Streptomycin

Nihon Kyobu Shikkan Gakkai Zasshi, 1997 Jan, 35(1), 67 - 71
{Spontaneous recovery from cytomegalovirus pneumonia}; Matsuki H et al.; A 30-year-old woman with systemic lupus erythematosus was admitted to our hospital because of a slight fever and diffuse interstitial shadows on a chest X-ray film . She had taken prednisolone (60 mg per day) at another hospital for six weeks . At the time of admission to our hospital, she had been treated with antituberculosis drugs (streptomycin, isoniazid, and rifampicin) for two weeks because of suspected miliary tuberculosis . Chest radiography on admission revealed diffuse nodular and micronodular shadows in the middle and lower lung fields on both sides . Examination of transbronchial lung biopsy specimens revealed intranuclear viral inclusion bodies in infected alveolar epithelial cells, which suggested the diagnosis of cytomegalovirus infection . The elevation of serum IgM antibody to cytomegalovirus and positive results of in situ hybridization for cytomegalovirus DNA supported this diagnosis . The symptoms and radiographic abnormalities resolved completely without ganciclovir . Although we cannot exclude the possibility that the antituberculosis drugs caused the resolution of the cytomegalovirus pneumonia, it appears most probable that the cytomegalovirus pneumonia resolved spontaneously.

Curr Eye Res, 1997 Jan, 16(1), 64 - 70
Effect of electric pulses and antiproliferative drugs on cultured bovine retinal pigment epithelial cells; Oshima Y et al.; PURPOSE: The effect of antiproliferative agents with high voltage electric pulses (EP) on the proliferation of retinal pigment epithelial (RPE) cells was investigated . METHODS: Bovine RPE cells were cultured and exposed briefly to an antiproliferative agent: 0.005 to 500 microM of bleomycin (BLM), 0.005 to 500 microM of mitomycin C (MMC) or 0.05 to 5000 microM of 5-fluorouracil (5-FU) with or without high voltage electric pulses (EP: 2,000V/cm, 98 microseconds, 8 pulses) . Streptomycin (SM) was used as a negative control . Cell proliferation with or without antiproliferative agents was assessed on day 3 . DNA fragmentation was assessed by flow cytometric analysis . RESULTS: Treatment with BLM, MMC or 5-FU inhibited cell proliferation in a dose-dependent manner, with and without EP (p < 0.05) . EP enhanced the inhibitory effect of BLM as much as 3,000 times (ID50: BLM without EP; 163.7 microM, BLM with EP; 0.0574 microM, MMC without EP; 132.4 microM, MMC with EP; 26.2 microM, 5-FU without EP; 616.4 microM, 5-FU with EP; 873.8 microM) . EP treatment showed an inhibitory effect of BLM on cell proliferation more prominently than BLM alone . The cell numbers of 0.5 microM BLM treatment without EP were 87.4 +/- 11.7% (mean +/- SD), whereas the cell numbers of 0.5 microM BLM with EP were 21.1 +/- 2.16% (p < 0.005) . BLM treatment with EP increased the apoptosis like DNA fragmentation in the flow cytometric DNA histogram, showing dominant accumulation in the A0 region, which is the population of DNA fragmentation . (The cell population of the A0 region: control, 3.4%; EP alone, 18.9%; BLM treatment without EP, 32.0%; with EP, 93.8%.) CONCLUSIONS: EP treatment enhances the inhibitory effect of BLM on RPE cell proliferation . The combination of electric pulse and BLM treatment can localize the drug effect and reduce the necessary dose of the antiproliferative agent in comparison to BLM treatment alone.

J Bacteriol, 1997 Jan, 179(1), 180 - 6
Use of rpsL for dominance selection and gene replacement in Streptomyces roseosporus; Hosted TJ et al.; We developed a gene replacement system using the rpsL gene of Streptomyces roseosporus and demonstrated its utility by constructing a deletion in the S . roseosporus glnA gene . A 1.3-kb BamHI fragment that hybridized to the Mycobacterium smegmatis rpsL gene was subcloned from an S . roseosporus cosmid library and sequenced . Plasmid pRHB514 containing the rpsL gene conferred streptomycin sensitivity (Sm(S)) to the Sm(r) S . roseosporus TH149 . The temperature-sensitive plasmid pRHB543 containing rpsL and the S . roseosporus glnA gene disrupted with a hygromycin resistance (Hm(r)) gene was introduced into S . roseosporus TH149, and recombinants containing single and double crossovers were obtained after a temperature increase . Southern hybridization analysis revealed that single crossovers occurred in the glnA or rpsL genes and that double crossovers resulted in replacement of the chromosomal glnA gene with the disrupted glnA . Glutamine synthetase activity was undetectable in the recombinant containing the disrupted glnA gene.

Drug Saf, 1996 Dec, 15(6), 394 - 405
Hepatotoxicity of antitubercular treatments . Rationale for monitoring liver status; Durand F et al.; The standard antitubercular regimen currently includes a combination of 3 antitubercular agents: isoniazid, rifampicin (rifampin) and pyrazinamide . Administration of a fourth agent, ethambutol, is recommended when isoniazid resistance is suspected . Two of these 4 agents (isoniazid and pyrazinamide) are major hepatotoxins . The remaining 2 agents (rifampicin and ethambutol) are rarely or not hepatotoxic . However, rifampicin, which is a powerful enzyme inducer, may enhance the hepatotoxicity of isoniazid . In patients receiving a combination of isoniazid, rifampicin and pyrazinamide, 2 patterns of fulminant liver injury can be observed . The first pattern is characterised by an increase in serum transaminase activity that occurs soon (usually within the first 15 days) after initiation of treatment . This pattern is likely to be caused by rifampicin-induced isoniazid hepatotoxicity . The prognosis is good in most cases . The second pattern is characterised by an increase in serum transaminase activity that occurs late (usually more than 1 month) after the initiation of treatment . It has been suggested that this pattern may be related to pyrazinamide hepatotoxicity . The prognosis of this type of hepatitis is generally poor . In order to reduce the risk of severe hepatic adverse effects during antitubercular treatment, several measures are proposed . First, patients with underlying liver test abnormalities should not be given pyrazinamide . Second, isoniazid and pyrazinamide should be administered at the lowest dosage within their respective therapeutic ranges . Third, serum transaminase levels should be determined twice weekly during the first 2 weeks of treatment, every 2 weeks during the rest of the first 2 months, and every month thereafter . When serum transaminase levels increase to greater than 3 times the upper limit of normal, therapy with isoniazid, rifampicin and pyrazinamide should be stopped . After serum transaminase levels have returned to normal, isoniazid can be re-introduced at a low daily dose, without rifampicin . Pyrazinamide may not be re-introduced because of the risk of recurrence and the poor prognosis of pyrazinamide-induced hepatitis . Although it is nephrotoxic, streptomycin is an alternative in patients with liver test abnormalities during antitubercular treatment.

Ned Tijdschr Geneeskd, 1996 Nov 2, 140(44), 2187 - 91
{Drug resistance in Mycobacterium tuberculosis in The Netherlands}; Lambregts-van Weezenbeek CS et al.; OBJECTIVE: To determine magnitude, trend and specific features of the resistance problem . DESIGN: Descriptive . SETTING: Royal Netherlands Tuberculosis Association, The Hague, the Netherlands . METHODS: The data of the National Institute of Public Health and Environmental Protection concerning the prevalence of drug-resistant tuberculosis during the period 1990-1994 were analysed . Also, features of patients with and without drug resistance were compared (Dutch National Tuberculosis Register: cohort 1993) . RESULTS: Isoniazid and streptomycin resistance were each observed in approximately 6% of susceptibility tests, showing no clear trend over the study period . Rifampicin resistance increased from 0% to 1.5% in 1994 . In the 1993 patient cohort, 809 cases were analysed, showing resistant organisms in 103 (13%) . The resistance group included 84 (82%) foreigners versus 387 (55%) among the 'sensitives' (p < 0.001) . The percentages of (known) HIV infections were equal in both groups (5-6%) . The percentage of isoniazid-resistance varied from 1.8% in Dutch patients to 7.8% in foreign patients . Recent immigrants and refugees waiting for official status were important risk groups for resistance (p < 0.005) . Foreign tuberculosis patients defaulted more often from treatment than Dutch patients (p < 0.001) . CONCLUSION: Drug-resistant tuberculosis in the Netherlands is mainly due to import of resistant strains . Transmission and further development of resistance within the country must be prevented.

Trans R Soc Trop Med Hyg, 1996 Nov-Dec, 90(6), 692 - 5
Resistance to antituberculosis drugs in rural South Africa: rates, patterns, risks, and transmission dynamics; Wilkinson D et al.; This study describes the rate, pattern, and transmission dynamics of, and risk factors for, isolates of Mycobacterium tuberculosis resistant to antituberculosis drugs in a rural South African health district . Twenty-one of 254 (7.6%; 95% confidence interval {CI} 4.8-11.4) isolates from incident cases were resistant to at least one drug (isoniazid, rifampicin, streptomycin, ethambutol) . A random sample of 28 otherwise susceptible isolates and all 21 resistant isolates were susceptible to pyrazinamide . There was one case of combined isoniazid/rifampicin resistance . The rate of initial resistance was 8.1% (95% CI 4.9-12.4) and of acquired resistance 6.2% (95% CI 1.9-14.2) . Age, sex, known human immunodeficiency virus status, and previous treatment history were not associated with drug resistance . Restriction fragment length polymorphism (RFLP) analysis of 13 of the 21 resistant specimens showed 12 different banding patterns . Rates of drug resistance were low in this representative sample of patients from a defined geographical area . Previous treatment history was probably not a risk factor because of the use of multiple drug regimens, directly observed therapy, and high completion rates in those previously treated . Although limited in number, the RFLP data suggested that recent local transmission of resistant strains was not occurring to a significant extentPIP: Drug resistance in patients with tuberculosis (TB) is a cause of treatment failure and relapse, and contributes to the development of multiple-drug resistance . Consecutive incident adult patients diagnosed with sputum smear-positive TB during 1994 in Hlabisa Hospital, northern KwaZulu/Natal, were studied to describe the rate, pattern, and transmission dynamics of, and risk factors for, isolates of Mycobacterium tuberculosis resistant to antituberculosis drugs . Cases currently being treated and followed were excluded from study . There were 354 incident cases of sputum smear-positive pulmonary TB registered at the hospital in 1994, although sputum specimens for culture were obtained from only 335 patients . 21 isolates from incident cases were at least partially resistant to at least either isoniazid, rifampicin, streptomycin, or ethambutol . A random sample of 28 otherwise susceptible isolates and all 21 resistant isolates were susceptible to pyrazinamide . There was one case of combined isoniazid/rifampicin resistance . The rates of initial and acquired resistance were 8.1% and 6.2%, respectively . Age, sex, known HIV status, and previous treatment history were not associated with drug resistance . Restriction fragment length polymorphism (RFLP) analysis of 13 of the 21 resistant specimens identified 12 different banding patterns, suggesting the absence of any significant recent local transmission of resistant strains .

Acta Otolaryngol, 1996 Nov, 116(6), 812 - 6
Incorporation of tetracycline into otoconia of the guinea-pig following streptomycin intoxication; Zhang DM et al.; The effects of streptomycin on the calcium ion turnover into otoconia of adult guinea-pigs investigated by the use of tetracycline . The oral administration of tetracycline induced the deposition of tetracycline (fluorescence) on the outer surface of otoconia indicating the existence of dynamic exchange and/or uptake of calcium ions in the otoconia . The significant finding is that streptomycin specifically interfered with calcium uptake into the otoconia which indicated that the decrease in calcium uptake caused by streptomycin may be closely related to the loss of otoconia as well as to a decrease in the calcium contents of otoconia . The decrease in calcium incorporation into otoconia caused by streptomycin was recovered within 6 weeks after the last injection of streptomycin . The number of otoconia with fluorescence in the central portion as well as their outer surface was increased . It is therefore suggested that the recovery of calcium uptake as well as new otoconial regeneration may play an important role for the recovery from loss of otoconia.

J Bacteriol, 1996 Nov, 178(22), 6496 - 507
Biosynthesis of diaminopimelate, the precursor of lysine and a component of peptidoglycan, is an essential function of Mycobacterium smegmatis; Pavelka MS Jr et al.; Diaminopimelate (DAP) is a unique metabolite used for both the biosynthesis of lysine in bacteria and the construction of the peptidoglycan of many species of bacteria, including mycobacteria . DAP is synthesized by bacteria as part of the aspartate amino acid family, which includes methionine, threonine, isoleucine, and lysine . Aspartokinase, the first enzyme in this pathway, is encoded by the ask gene in mycobacteria . Previous attempts to disrupt this gene in Mycobacterium smegmatis were unsuccessful, even when the cells were supplied with all the members of the aspartate family, suggesting that unlike other bacteria, mycobacteria may have an absolute requirement for this pathway even when growing in rich medium containing DAP . The purpose of this study was to determine if the ask gene and the aspartate pathway are essential to M . smegmatis . This study describes a test for gene essentiality in mycobacteria, utilizing a counterselectable marker (streptomycin resistance) in conjunction with a specially constructed merodiploid strain . We have used this system to show that the ask gene could not be disrupted in wild-type M . smegmatis, using selective rich medium supplemented with DAP unless there was an extra copy of ask provided elsewhere in the chromosome . Disruption of ask was also possible in a lysine auxotroph incapable of converting DAP to lysine . The ask mutant, mc21278 (ask1::aph), exhibits multiple auxotrophy (Met-, Thr-, DAP-, and Lys-) and is complemented by the ask gene . This is the first description of DAP auxotrophy in mycobacteria . The ask mutant lyses when deprived of DAP in culture, a characteristic which can be exploited for the reproducible preparation of protoplasts and mycobacterial extracts . The evidence presented here indicates that the aspartate pathway is essential to M . smegmatis and that DAP is the essential product of this pathway.

J Neurophysiol, 1996 Nov, 76(5), 3301 - 12
Hair cell regeneration and recovery of the vestibuloocular reflex in the avian vestibular system; Carey JP et al.; 1 . Although auditory and vestibular hair cells are known to regenerate after aminoglycoside intoxication in birds, there is only sparse evidence that the regenerated hair cells are functional . To address this issue, we examined the relation of hair cell regeneration to recovery of the vestibuloocular reflex (VOR), whose afferent signal originates at hair cells in the vestibular epithelium . Hair cell damage was produced by treating white Leghorn chicks (Gallus domesticus, 4-8 days posthatch) with streptomycin sulfate in normal saline (1,200 mg.kg-1.day-1 im) for 5 days . 2 . In the 1st wk after treatment, the VOR gain was essentially 0, and hair cell density as assessed by light microscopy was approximately 40% of normal . Between the 1st and 3rd wk after treatment, the VOR was present . Although VOR gain varied considerably from one chick to another, it increased, on average, between the 1st and 3rd wk, as did the average hair cell density . At the end of 8-9 wk, the gain and phase of the VOR had returned to normal values, as had the average density of hair cells . 3 . Therefore, despite the catastrophic initial effect of hair cell loss on the VOR, recovered hair cells appeared to restore the VOR completely . Average hair cell density increased with average VOR gain . VOR gain correlated better with recovery of type 1 hair cells than with recovery of type II hair cells . 4 . In contrast to hair cell density, the appearance of the vestibular epithelia as assessed by hair cell stereocilia in scanning electron micrographs was a poor indicator of VOR gain . In both treated and control birds, epithelia with the same appearance could have quite different VOR gains, suggesting a variation in the functional viability of the hair cells . 5 . This observation suggests that several factors, such as the repair of stereocilia, the efficacy of hair cell synapses on afferent fibers, and the extent of compensation by central vestibular pathways, may affect the recovery of VOR gain . However, our data suggest that hair cell regeneration plays an important role in this recovery.

Antimicrob Agents Chemother, 1996 Nov, 40(11), 2452 - 4
Correlation of molecular resistance mechanisms and phenotypic resistance levels in streptomycin-resistant Mycobacterium tuberculosis; Meier A et al.; Quantitative susceptibility testing of clinical isolates of streptomycin-resistant Mycobacterium tuberculosis demonstrated that there is a close correlation between the molecular resistance mechanism and the in vitro activity of streptomycin: mutations in rpsL were mainly associated with high-level resistance, mutations in rrs were associated with an intermediate level of resistance, and streptomycin-resistant isolates with wild-type rpsL and rrs exhibited a low-level resistance phenotype . Investigations of streptomycin-resistant isolates with wild-type rpsL and rrs revealed that (i) there is no cross-resistance to other drugs and (ii) a permeability barrier may contribute to resistance, because resistance was significantly lowered in the presence of a membrane-active agent.

Am J Respir Crit Care Med, 1996 Nov, 154(5), 1473 - 7
Rifampin preventive therapy for tuberculosis in Boston's homeless; Polesky A et al.; An epidemic of isoniazid (INH)- and streptomycin (SM)-resistant tuberculosis began among Boston's homeless population in 1984 . Individuals with skin test conversions who agreed to preventive therapy received either INH, rifampin, or a combination of INH and rifampin . A total of 204 individuals with documented tuberculin skin test conversions who did not have active tuberculosis at the time of the clinical evaluation for their positive skin test were eligible for preventive therapy . Data on type and length of preventive therapy were obtained from the Tuberculosis Clinic and the Boston Tuberculosis Registry records at Boston City Hospital . The individuals were followed for development of active tuberculosis . Six of 71 (8.6%) individuals who received no therapy, 3 of 38 (7.9%) in the INH group, and none in the rifampin or rifampin plus INH groups (49 and 37 persons, respectively) developed active tuberculosis . Patients in the rifampin group were significantly less likely to develop tuberculosis than patients in the no therapy group (p = 0.04; odds ratio {OR} = 0.00, 95% confidence interval {CI} = 0.00-0.91) . Treatment with any rifampin-containing preventive therapy (rifampin or rifampin plus INH) was effective (p < 0.01 ) in preventing development of active disease . The three INH failures were with organisms that were resistant to INH.

Recenti Prog Med, 1996 Oct, 87(10), 457 - 9
{Tuberculosis and immigrants . A study of its prevalence in the Umbria region}; Cerami F et al.; In 1995, 463 patients were admitted in the medical service of Perugia (Sanitary District n . 6) . Only 20% of them were enrolled in the TBC programme . Mantoux was: < 10 mm in 35%, 10-15 mm in 25%, > 15 mm in 40% . Chest Rx in 30 subjects demonstrated: normality in 19; old TBC in 7, active TBC in 4 (miliary, bilateral upper lobe pneumonitis, left subapical upper lobe pneumonitis and right lobitis of the upper lobe) . All patients were admitted in hospital and showed positive sputum culture for Mycobacterium Tuberculosis . They were treated with isoniazid, rifampin, pyrazinamide, ethambutol/streptomycin for 2 months and with isoniazid, rifampin for other 4-8 months . Two patients showed Mycobacterium tuberculosis with isoniazid resistance . Seven patients were treated with isoniazid chemoprophylaxis without side effects . Migrants should receive information about health care service and be encourage to register themselves with a general practitioner . Skin test screening and chest radiographs for those with positive results should be provided at a convenient location.

J Craniomaxillofac Surg, 1996 Oct, 24(5), 289 - 92
Use of streptomycin-lidocaine injections in the treatment of the cluster-tic syndrome . Clinical perspectives and a case report; Kreiner M; Trigeminal neuralgia and cluster headache syndrome are complex pain conditions of the craniofacial region . Both diseases can coexist in the same patient, comprising the cluster-tic syndrome . This article reviews the literature on this condition and reports a new case who responded well to peripheral streptomycin-lidocaine injections.

J Acquir Immune Defic Syndr Hum Retrovirol, 1996 Oct 1, 13(2), 155 - 9
Human immunodeficiency virus infection in children with tuberculosis in Santo Domingo, Dominican Republic: prevalence, clinical findings, and response to antituberculosis treatment; Espinal MA et al.; We studied human immunodeficiency virus (HIV)-seroprevalence among children with clinically diagnosed tuberculosis (TB) and compared the clinical features and response to short-term anti-TB therapy of children with and without HIV infection in Santo Domingo, Dominican Republic . Children aged 18-59 months with new-onset, clinically diagnosed TB were tested for HIV antibodies, their clinical features were recorded and their response to a standard 6-month regimen of daily isoniazid and rifampicin with daily streptomycin and pyrazinamide for the first 2 months was assessed . To increase the number of HIV-infected children with TB available for study, we also included children previously known to be HIV infected who developed new-onset TB . Eleven (5.8%) of 189 consecutively enrolled children with clinically diagnosed TB were HIV infected . Fifteen other children with previously documented HIV infection and new-onset TB were available for study, yielding 26 HIV-positive and 178 HIV-negative children with TB . Of these 204 children with clinically diagnosed TB, 25 HIV-positive and 156 HIV-negative children were successfully followed for 6 months or until death . The proportion of HIV-positive children who failed treatment was 6 (29%) of 21 as compared with only 5 (3%) of 156 HIV-negative children {relative risk = 8.9; 95% confidence interval (CI) 2.9, 26.6; p = 0.0004} . HIV-infected children with clinically diagnosed TB are substantially more likely to fail standard treatment for TB than are HIV-uninfected children . If standard treatment regimens are used in such children, response to treatment must be monitored very closely and appropriate changes in the regimen must be made expeditiously.

Arch Otolaryngol Head Neck Surg, 1996 Sep, 122(9), 1001 - 4
Audiovestibular findings in patients with deafness caused by a mitochondrial susceptibility mutation and precipitated by an inherited nuclear mutation or aminoglycosides; Braverman I et al.; OBJECTIVE: To characterize the audiological and vestibular changes associated with a mitochondrial DNA mutation in an Arab-Israeli family and in other families with mitochondrial predisposition to aminoglycoside-induced hearing loss . DESIGN: Evaluation of audiological (pure tone thresholds, speech reception thresholds, speech discrimination, tympanometry, acoustic reflex thresholds, tone decay, and auditory brain-stem evoked response recording) and vestibular (complete history, physical examination, and 2-channel electronystagmography) systems . In 5 patients, structural evaluation of the inner ear was done by magnetic resonance imaging . PATIENTS: Fifteen members of an Arab-Israeli family, and 1 Chinese woman with the same mitochondrial DNA mutation who experienced hearing loss after short-term exposure to streptomycin . RESULTS: Most of the patients had a profound hearing loss due to cochlear involvement . The hearing loss usually was not accompanied by notable peripheral vestibular dysfunction . In the patient with severe hearing loss after exposure to aminoglycoside, the vestibular function was completely normal . CONCLUSIONS: In most of the Arab-Israeli patients with congenital deafness, the vestibular system function was normal, in contrast to the frequency of vestibular abnormality among deaf children, which was described in the literature . This may be related to genetic predisposition to aminoglycoside-induced deafness.

Spine, 1996 Aug 15, 21(16), 1898 - 903
Duration of antituberculosis chemotherapy in conjunction with radical surgery in the management of spinal tuberculosis; Upadhyay SS et al.; STUDY DESIGN: The effectiveness of duration of antituberculous chemotherapy in conjunction with radical surgery for tuberculosis of the spine is reported . One hundred fourteen patients were followed prospectively for a mean period of 14.6 years after radical resection of the tuberculous lesion and reconstruction of the resultant gap with bone graft . OBJECTIVE: To evaluate the efficacy of short-course antituberculous chemotherapy in relation to the standard 18-month chemotherapy in conjunction with radical surgery for tuberculosis of the spine . SUMMARY OF BACKGROUND DATA: One hundred fourteen patients who were subjects of the Medical Research Council's (London, UK) prospective study underwent radical resection of the lesion and anterior arthrodesis of the spine . These patients received 6, 9, and 18 months of antituberculous chemotherapy . Those who received 6- and 9-month chemotherapy received streptomycin, rifampicin, and isoniazid . Streptomycin was given for the first 3 months, and the other two drugs were continued for 6 or 9 months . Those who received 18 months of chemotherapy were given streptomycin (first 3 months), sodium para-aminosalicylic acid, and isoniazid . METHODS: These patients were followed longitudinally, and at each visit, clinical and radiologic data were collected at 1-month intervals up to 3 months postoperatively, at 3-month intervals to 30 months postoperatively, at 6-month intervals up to 5 years postoperatively, and at 12-month intervals to the conclusion of study (minimum, 10 years) . For assessment of spinal deformity, the "deformity angle" was measured on lateral spinal radiographs obtained at each visit . RESULTS: Six-month, 9-month, and 18-month chemotherapeutic regimens in association with radical surgery produced similar clinical results with no recurrence or reactivation of tuberculosis . The changes in deformity angles at final follow-up evaluation compared with 6-month postoperative values were not statistically significantly different in the groups who underwent 6 months, 9 months, and 18 months of chemotherapy . CONCLUSIONS: The authors' findings show that a 6-month chemotherapeutic regimen combined with surgical excision and bone grafting is adequate for management of tuberculosis of the spine, as it produced clinical and radiologic results comparable with the 18-month chemotherapeutic regimen.

J Invest Dermatol, 1996 Aug, 107(2), 229 - 34
In the absence of streptomycin, minoxidil potentiates the mitogenic effects of fetal calf serum, insulin-like growth factor 1, and platelet-derived growth factor on NIH 3T3 fibroblasts in a K+ channel-dependent fashion; Sanders DA et al.; There is considerable evidence to suggest that the opening of K+ channels plays an important role in stimulating mitogenesis . K+ channel blockers have been shown to inhibit mitogenesis in vitro, mitogens increase cytosolic membrane K+ channel permeability, K+ channel openers stimulate hair growth in vivo, and the Ras/Raf signal transduction pathway induces K+ channel activity . Paradoxically, however, K+ channel openers such as minoxidil have been reported in vitro not to modulate, or even to inhibit, mitogenesis in a range of cell types . Only untherapeutic concentrations have stimulated mitogenesis . These experiments, however, appear to have been carried out in the presence of aminoglycoside antibiotics, which inhibit potassium channel activity . We now report that in the absence of aminoglycoside antibiotics, minoxidil at 10 microg/ml (0.05 mM) causes a significant stimulation of proliferation of NIH 3T3 fibroblasts maintained over a 10-d period in 5% fetal calf serum-supplemented medium . Further, we show that in the presence of 100 microg streptomycin per ml, minoxidil at 10 microg/ml produces an initial inhibition of proliferation, which apparently confirms, in NIH 3T3 fibroblasts, that the inhibition of mitogenesis by minoxidil in the presence of streptomycin is an artifact . The potentiation of NIH 3T3 cell growth by minoxidil can be attributed to the opening of potassium channels, because the potassium channel blocker tolbutamide (5 mM) or combinations of the blockers tolbutamide (1 mM)/tetraethylammonium (2 mM) or glibenclamide (1 microM)/apamin (10 nM) block the minoxidil-induced stimulation of growth . We also demonstrate that minoxidil is able to significantly potentiate the mitogenic effects of both platelet-derived growth factor and insulin-like growth factor 1 on NIH 3T3 fibroblasts in the presence of CPSR-2 (a cytokine free serum substitute) . Thus we have shown that minoxidil potentiates the mitogenic effects of fetal calf serum in vitro on NIH 3T3 fibroblasts by opening potassium channels and is also able to potentiate the mitogenic effects of the growth factors platelet-derived growth factor and insulin-like growth factor 1.

Avian Dis, 1996 Jul-Sep, 40(3), 533 - 9
Analysis of plasmids cloned from a virulent avian Escherichia coli and transformed into Escherichia coli DH5 alpha; Wooley RE et al.; Three of four plasmids from a virulent wild-type avian Escherichia coli were cloned or transformed into an avirulent laboratory recipient E . coli DH5 alpha and tested for the ability to confer a virulence phenotype . The three plasmids transformed into E . coli DH5 alpha were 5, 6, and 56 kb . A fourth plasmid of 64 kb was not successfully transformed . Parameters used to measure virulence included presence of type 1 pili and a smooth lipopolysaccharide (LPS) layer, motility, production of Colicin V, resistance to host complement, and embryo lethality . The 5-kb plasmid encoded for ampicillin resistance, whereas the 6-kb plasmid encoded for tetracycline resistance . The 56-kb plasmid encoded for streptomycin, sulfisoxazole, and tetracycline resistance . Twelve-day embryos inoculated with 467 colony-forming units of E . coli DH5 alpha containing the 56-kb plasmid had increased death rates (45%) in the embryo lethality assay and a decreased weight of surviving embryos with cranial hemorrhages as compared with embryos inoculated with similar amounts of E . coli DH5 alpha (0%) and phosphate-buffered saline (0%) . Embryos inoculated with the wild-type virulent E . coli had 90% deaths . The 56-kb plasmid also had homology with a probe for Colicin V production (cvaC) . No differences in LPS layer, complement resistance, motility, Colicin V activity, type 1 pili, cell-free supernatant proteins, or outer membrane proteins were observed in the transformants when compared with nontransformed E . coli DH5 alpha.

Cell Mol Biol (Noisy-le-grand), 1996 Jul, 42(5), 719 - 27
In vitro studies on ppGpp synthetase I from polyamine-starved and unstarved Escherichia coli; Goldemberg SH; We have studied the in vitro formation of guanosine 5'-diphosphate 3'-diphosphate (ppGpp) using a partially purified ppGpp synthetase I (PSI) from Escherichia coli BGA8, a polyamine auxotrophic strain . A comparison of the enzyme obtained from polyamine-supplemented or deprived bacteria showed similar requirements for the reaction, Mg+2 optimum levels and sparing effect of spermidine . No differences in the inhibitory effects of tetracycline, puromycin and fusidic acid were detected either . However, a modified subcellular distribution, as well as a larger specific activity and a larger stimulation by streptomycin was observed when PSI was prepared from polyamine-depleted bacteria . The role of ribosome assembly and subunit distribution on the altered properties of the enzyme are discussed.

Cardiovasc Res, 1996 Jul, 32(1), 131 - 7
Previous-beat contraction history is not influenced by mechanosensitive ion channel blockade; Slinker BK et al.; OBJECTIVES: Prior studies have shown that the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, a phenomenon called "previous-beat contraction history" . This previous-beat contraction history, which appears to be an interplay between the mechanical events of one contraction and the activation state of the next contraction, could depend, at least in part, on mechanosensitive ion channels . The purpose of this study, therefore, was to test the hypothesis that mechanosensitive ion channels contribute to previous-beat contraction history: If previous-beat contraction history depends on mechanosensitive ion channels, the magnitude of its effect should be decreased by blocking mechanosensitive ion channels . METHODS: We performed experiments in buffer-perfused isolated rabbit hearts in which left ventricular pressure and volume were controlled with a servo-motor system . We evaluated the pulse interval-dependent expression of previous-beat contraction history under control conditions (no drug) and in the presence of 100 and 500 microM streptomycin, a blocker of mechanosensitive ion channels . RESULTS: Under control conditions, previous-beat contraction history nor its dependence on pulse interval was influenced significantly by either concentration of streptomycin . CONCLUSION: Mechanosensitive ion channels do not play a role in the expression of previous-beat contraction history in the left ventricle of the isolated rabbit heart.

J Histochem Cytochem, 1996 Jul, 44(7), 733 - 41
Internalization of styryl dye FM1-43 in the hair cells of lateral line organs in Xenopus larvae; Nishikawa S et al.; We used a fluorescent dye, FM1-43 to investigate mechanotransduction mechanisms in the hair cells of lateral line organs of Xenopus larvae . FM1-43 specifically labeled the hair cells . The photo-oxidation technique was performed with election microscopy to examine the labeling sites and their mechanisms . The results showed that the labeling sites were mitochondria and rough endoplasmic reticulum throughout the cytoplasm . Endocytic activity of the hair cells was limited to endosomes and small granules located at the apical part of the cells . Blockers of the mechanosensitive cation channel (neomycin, gentamicin, streptomycin, and amiloride) effectively inhibited FM1-43 labeling . One of the blockers, amiloride, was found to bind to hair cells when its fluorescence was examined . Divalent cations such as Mg2+ and Ca2+, but not monovalent cations such as Na+ and K+, inhibited FM1-43 labeling when they were added in excess amounts . These results suggest that FM1-43 internalizes hair cells via the putative mechanosensitive cation channel in the plasma membrane.

Biochem Biophys Res Commun, 1996 Jun 25, 223(3), 496 - 501
Mutant mtDNA at 1555 A to G in 12S rRNA gene and hypersusceptibility of mitochondrial translation to streptomycin can be co-transferred to rho 0 HeLa cells; Inoue K et al.; Human skin fibroblast line 95-119, which had been isolated from the mother of a Japanese patient with aminoglycoside-induced deafness and a 1555 A to G mutation at 12S rRNA gene in mitochondrial DNA (mtDNA), was used to investigate the relationship between the 1555 mtDNA mutation and its pathogenicity . By the intercellular transfer of mtDNA with or without the 1555 mutation to mtDNA-less (rho 0) HeLa cells, we isolated cybrid clones and found that the mitochondrial translation in a cybrid clone repopulated with the homoplasmic 1555 mutation showed the highest susceptibility to streptomycin . These observations suggest that the genotype of the mutant mtDNA and the phenotype of hypersusceptibility to streptomycin observed in 95-119 fibroblasts were co-transferred simultaneously to rho 0 HeLa cells, supporting the idea that the homoplasmic 1555 mtDNA mutation is involved in the pathogenesis leading to aminoglycoside-induced hearing loss.

Southeast Asian J Trop Med Public Health, 1996 Jun, 27(2), 257 - 62
Pulmonary tuberculosis in a BCG vaccinated area: relationship of disease severity with immunological and hematological parameters and drug resistance patterns; Hussain R et al.; Clinical hematological and immunological parameters were studied in a group of 145 pulmonary patients with active tuberculosis, from a defined area of Karachi (Kharadar) belonging to the lower socioeconomic strata . Although clinical symptomatology could not differentiate the extent of lung involvement, a majority (69.6%) of the patients were diagnosed radiologically as having moderately advanced pulmonary disease . The peak number of patients were in their second decade of life . No differences were observed in the extent of disease based on age or gender . All hematological parameters for the group were in the normal ranges except for low levels of hemoglobin (9.58 +/- 1.55 SD; normal range 12-14 mg/dl) and a high ESR (90 +/- 31 SD; normal range 0-13 mm/hour) . A negative correlation of PPD skin test induration (r = 0.21, p = 0.02), and a positive correlation of total white blood cell (r = 0.20; p = 0.015) was observed with the amount of lung tissue involved . The resistance amongst the strains for the four first line anti-tuberculosis agents was found to be: isoniazid = 27.4%; ethambutol = 14.5%; rifampicin = 11.29% and streptomycin = 12.9% . Multi-drug resistance to the most commonly prescribed combination (rifampicin and ethambutol) was 8.06% . Drug resistance patterns to individual drugs were comparable with resistance patterns observed in strains from greater Karachi at The Aga Khan Hospital during the same period . Such studies should provide improved rationale for patients diagnosis and treatment.

Am J Respir Crit Care Med, 1996 Jun, 153(6 Pt 1), 1977 - 81
Predictors of survival in human immunodeficiency virus-infected patients with pulmonary tuberculosis . The Makerere University-Case Western Reserve University Research Collaboration; Whalen C et al.; Infection with the human immunodeficiency virus (HIV) has changed both the epidemiology and natural history of tuberculosis . Despite a generally good response to effective antituberculous therapy, the prognosis remains poor . The objective of this analysis was to determine the independent predictors of survival in HIV-infected Ugandan adults with smear-positive pulmonary tuberculosis . A total of 191 HIV-infected Ugandan adults with smear-positive pulmonary tuberculosis were enrolled into a clinical trial of chemotherapy for tuberculosis . The subjects received either rifampin, isoniazid, and pyrazinamide for two months, followed by rifampin and isoniazid for six months (n = 101) or streptomycin, thiacetazone, and isoniazid for two months followed by thiacetazone and isoniazid for eight months (n = 90) . After standard measurements were made at baseline, the group was followed at regular intervals for a mean of 16 months to determine survival . During the course of follow-up, 82 (43%) of the patients died, six within the first month of therapy . The one-year survival proportion was 68% with an estimated median survival of 26 months and did not differ according to treatment regimen . The hazard for death was biphasic, high early in the course of therapy, and then again after about one year . After controlling for the treatment regimen, four independent predictors of survival were found: anergy to purified protein derivative, atypical chest roentgenogram, previous HIV-related condition, and lymphopenia . In this cohort of Ugandan adults, four simple and inexpensive predictors of survival were found . These factors suggest that the degree of immunosuppression was a major determinant of survival.

Am J Respir Crit Care Med, 1996 Jun, 153(6 Pt 1), 1766 - 72
Clarithromycin regimens for pulmonary Mycobacterium avium complex . The first 50 patients; Wallace RJ Jr et al.; Intermediate results of the first 50 patients treated with clarithromycin (CLARI) regimens for Mycobacterium avium-intracellulare (MAI) lung disease were evaluated . Patients were HIV negative, and pretreatment isolates were susceptible to CLARI . Patients received CLARI 500 mg twice daily, ethambutol, rifampin (RMP), or rifabutin (RBT) and initial streptomycin, and they were treated until culture-negative 1 yr . Eleven of 50 patients (22%) were dropped in the first 3 mo . Of the remaining 39 patients, 36 (92%) converted their sputa to negative, and 32 (82%) remain culture negative to date . This includes 11 of 16 (69%) with prior drug therapy and 21 of 23 (91%) with no prior therapy . One or more companion drugs were discontinued in 16 of 39 (41%) of patients because of adverse events . Isolates from six of 39 patients (15%) became CLARI-resistant . Of 23 patients who are alive and were culture-negative a mean of 12.0 mo while receiving therapy, all remain culture-negative without therapy a mean of 19.1 mo . Despite reduced CLARI serum levels in patients also receiving RMP, 10 of 13 patients (77%) receiving this regimen were successfully treated . Although not directly compared with previous regimens, the success of this regimen strongly suggests it is superior to previous non-CLARI-containing regimens.

Mutat Res, 1996 May 17, 360(1), 1 - 14
A novel positive detection system of in vivo mutations in rpsL (strA) transgenic mice; Gondo Y et al.; To positively detect the in vivo mutations accumulated in different mouse organs, we have developed a transgenic mouse system . This transgenic mouse carried an Escherichia coli (E . coli) plasmid pML4 as a shuttle vector that consisted of a replication origin (ori), the kanamycin-resistant gene (KanR) and the rpsL+ gene (strAS) derived from E . coli . These E . coli elements were expected to be inert in the transgenic mouse system; thus, neutral mutations would be accumulated on the shuttle plasmid in the transgenic mice . The shuttle plasmid vector was recovered from the mouse genomic DNA and introduced into kanamycin-sensitive (KmS) and streptomycin-resistant (SmR) E . coli cells by using electroporation . The original pML4 shuttle plasmid transformed the host E . coli to KmR and SmS, since both the KanR and rpsL genes exhibited dominant traits of KmR and SmS, respectively . On the other hand, when the retrieved pML4 shuttle plasmid carried a mutated rpsL gene, it could be positively detected as both KmR and SmR . Based on this principle, we were able to positively detect the in vivo mutations accumulated in the rpsL transgene of the shuttle vector pML4 integrated into the mouse genome . The total number of rescued shuttle plasmids were counted on the plates containing Km alone, while only mutants were detected on the plates containing both Km and Sm . We have so far established 22 independent transgenic mouse lines that carried up to approx . 750 copies of the shuttle plasmid pML4 in a haploid genome . By using high-copy-number transgenic mouse lines which carried 350 copies or more of the shuttle vector, we also developed a simple and proficient method for retrieving the shuttle plasmid from various tissues of the transgenic mice . The background mutant frequency was approx . 5 x 10(-5) . In order to validate the applicability of the positive-detection transgenic system for the induced mutagenicity assay, methylnitrosourea (MNU) was administered to the transgenic mice, and an increase in the number of mutant frequencies was seen in all tested organs including spleen, liver and brain . The rpsL transgenic mouse system was therefore considered to provide a quick-and-easy risk assessment test for in vivo tissue-specific mutagenicity, using positive detection by streptomycin.

Am J Otol, 1996 May, 17(3), 401 - 9
What is the minimal vestibular function required for compensation?
Black FO, Wade SW, Nashner LM.
Living with an uncompensated, abnormal vestibular system requires oppressive modification of life style and often prevents return to work and activities of daily living . Patients with vestibular abnormalities were studied to determine the minimal residual vestibular function required to achieve compensation . Three groups of patients with (a) complete unilateral loss of vestibular function with normal horizontal canal-vestibulo-ocular (HCVOR) function in the opposite ear, (b) complete unilateral loss with abnormal HCVOR function in the opposite ear, and (c) bilateral reduction of vestibular function from aminoglycoside toxicity underwent vestibuloocular (VOR), optokinetic (OKN), visual-VOR (VVOR), and computerized dynamic posturography (CDP) tests before and after therapeutic procedures . Results suggest that a minimal VOR response amplitude must be present for compensation of VVOR function to occur . The roles of VOR and OKN phase shifts in vestibular compensation are more complicated and require further study . Compensation of vestibulospinal function does not necessarily accompany VOR or VVOR compensation . Ascending and descending vestibular compensatory mechanisms may involve different spatial sensory inputs . Results of these studies have important implications for the diagnosis and treatment of patients with vestibular disorders, including selection and monitoring of patients for therapeutic regimens such as vestibular nerve section and streptomycin therapy.

Antimicrob Agents Chemother, 1996 May, 40(5), 1186 - 8
Characterization of streptomycin resistance mechanisms among Mycobacterium tuberculosis isolates from patients in New York City; Cooksey RC et al.; From a collection of 367 isolates of Mycobacterium tuberculosis from patients in New York City in 1994, 45 isolates (12.3%) were resistant in vitro to 2 micrograms or more of streptomycin (SM) per ml . We further evaluated these isolates for levels of SM resistance and for mutations previously associated with resistance in the rpsL (S12 ribosomal protein) gene and the rrs (16S rRNA)-coding region . Twenty-four isolates, representing nine distinct patterns of susceptibility to antituberculosis drugs, were resistant to 500 micrograms of SM per ml and shared a common point mutation at nucleotide 128 in the rpsL gene . This mutation, which substitutes lysine for arginine in the S12 ribosomal binding protein, was not present in isolates with low-level SM resistance or in SM-susceptible control isolates . Among 20 isolates with low-level SM resistance, one possessed a substitution (C-->G865) in the 912 loop of the rrs gene . No mutations in the 530 loop of the rrs coding region were detected, suggesting the presence of an alternative SM resistance mechanism in 19 isolates . Single-strand conformation polymorphisms of mutants were readily detected by a nonradioactive gel screen.

J Med Assoc Thai, 1996 May, 79(5), 285 - 7
Effect of isoniazid prophylaxis on incidence of active tuberculosis among Thai HIV-infected individuals; Saenghirunvattana S; A prospective comparative study was conducted to determine the effect of isoniazid prophylaxis on the incidence of active tuberculosis among Thai HIV-infected patients for 1 year . Among those 36 HIV-infected patients without prophylaxis, the incidence of active tuberculosis was 2.7 per cent while in 10 HIV-infected patients with isoniazid prophylaxis, there was no incidence of active tuberculosis during the first yearPIP: In Thailand during 1994-1995, 46 HIV-seropositive asymptomatic patients were followed-up monthly for 1 year to evaluate the prophylactic effect of isoniazid against tuberculosis among these patients . 36 patients did not receive isoniazid; the remaining 10 patients received 300 mg isoniazid daily for 1 year . The 2 groups were matched for age and sex . Three controls and 1 case dropped out of the study during the second half . Only 1 (2.7%) of the controls developed active tuberculosis . Active tuberculosis in this case developed on the fifth month of follow-up . This patient responded well to anti-tuberculosis drugs (300 mg isoniazid, 600 or 450 mg rifampicin depending on weight, 20-30 mg/kg pyrazinamide daily, and 1 g streptomycin daily for 2 weeks and 15 mg/kg thereafter) . No cases developed active tuberculosis . Despite study weaknesses (e.g., low sample size), prophylactic isoniazid is recommended for HIV-positive asymptomatic patients .

Rinsho Byori, 1996 May, 44(5), 456 - 64
Multicenter evaluation of a colorimetric microplate antimycobacterial susceptibility test: comparative study with the NCCLS M24-P; Yamane N et al.; A colorimetric test method using the microplate culture technique for the determination of susceptibility of Mycobacterium tuberculosis against antimycobacterial agents was developed and evaluated by the multicenter study . The test method utilizes an oxidation-reduction dye, 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC), as an indicator of mycobacterial growth . When compared to the presently available test method, some modifications were also included; lower inoculum density (10-fold dilution), inclusion of an inoculum diluted 1:100 as a growth control, and the preparation of inoculum preincubated in Middlebrook 7H9 broth and spectrophotometrically adjusted to McFarland #1 turbidity . The test method evaluated was highly precise and reliable to detect antimycobacterial resistances when the ATCC reference strains were tested . Also, the interpretations of the test result were highly comparable to those determined by the method of NCCLS M24-P, the % agreements ranging from 76.1% (ethambutol) to 91.3% (streptomycin) . The test results were also comparable to those determined by Ogawa media; > 90% agreed with susceptible, intermediate, or resistant . The appearance of mycobacterial colonies on the test media was easily read, and the test results were more comparable to those of NCCLS M24-P . With these results, it can be concluded that the colorimetric microplate susceptibility test method described will be more suitable for clinical mycobacteriology laboratories.

Infect Immun, 1996 May, 64(5), 1569 - 76
Activation of Shiga-like toxins by mouse and human intestinal mucus correlates with virulence of enterohemorrhagic Escherichia coli O91:H21 isolates in orally infected, streptomycin-treated mice; Melton-Celsa AR et al.; The enterohemorrhagic Escherichia coli (EHEC) O91:H21 isolates B2F1 and H414-36/89 are virulent in an orally infected streptomycin-treated mouse model . Previous studies demonstrated that B2F1 and H414-36/89 grow to high levels in mucus isolated from mouse small intestine and colon and that growth in small-intestine mucus is related to virulence . We measured the levels of Shiga-like toxins (SLTs) SLT-IIvha and SLT-IIvhb produced by B2F1 after growth in Luria-Bertani (LB) broth supplemented with mouse intestinal mucus by assaying the cytotoxicity of culture supernatants on Vero cells . Culture supernatants from B2F1 grown in mouse intestinal mucus, but not EHEC strains that produce SLT-II or SLT-IIc, were approximately 35- to 350-fold more toxic for Vero cells than supernatants from B2F1 grown in LB broth . This increased toxicity was not reflected by a concomitant increase in SLT antigen content . Furthermore, when culture supernatants from B2F1 or K-12 strains carrying plasmids encoding SLTs cloned from H414-36/89 or purified SLT-IIvhb from B2F1 were incubated with mouse intestinal mucus, the samples exhibited greater cytotoxicity than when they were incubated with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer alone . These toxin preparations also showed increased cytotoxicity after incubation with human colonic mucus . In contrast, culture supernatants from LB-grown EHEC isolates that produced SLT-I, SLT-II, SLT-IIc or SLT-IIe did not show increased cytotoxicity after incubation with mouse or human intestinal mucus . The A subunits of purified SLT-II and SLT-IIvhb that had been treated with mouse intestinal mucus or trypsin were cleaved to A1 fragments by the mucus, but trypsin-mediated cleavage, unlike treatment with mouse intestinal mucus, did not result in increased Vero cell cytotoxicity activity . This finding implies that the increased cytotoxicity of SLT-IIvhb detected after incubation with mucus is probably not due to cleavage of the A subunit into the A1 and A2 fragments . Taken together, these results indicate that mouse or human intestinal mucus directly activates SLT-II-related toxins from B2F1 and H414-36/89 and suggest that toxin activation may explain the low 50% lethal doses of B2F1 and H414-36/89 in streptomycin-treated mice.

Ear Nose Throat J, 1996 Apr, 75(4), 239 - 43
Very high-dose streptomycin labyrinthectomy; Sataloff RT et al.; Medical labyrinthectomy by systemic administration of streptomycin has proven safe and effective for treatment of selected patients with intractable vertigo . In most patients, 40 grams or less of streptomycin sulfate are required . However, otolaryngologists should be aware that much higher doses can be used safely in selected patients; and a small number of patients may be resistant to streptomycin toxicity even in doses over 100 grams.

Otolaryngol Clin North Am, 1996 Apr, 29(2), 353 - 8
Dexamethasone perfusion of the labyrinth plus intravenous dexamethasone for Ménière's disease; Shea JJ Jr et al.; Recent clinical and laboratory evidence indicates that Meniere's disease is an immune-mediated disease . Dexamethasone perfusion of the inner ear through the round window plus intravenous dexamethasone often will stop the dizzy spells, reduce the fullness and low-frequency tinnitus, and sometimes improve the hearing in patients with Meniere's disease . The dexamethasone must act mostly on the endolymphatic sac and, to a lesser extent, on the stria vascularis and spiral ligament, the known targets of immune response in the inner ear, to reduce the endolymphatic hydrops and restore the fluid dynamics of the endolymph . Despite the good results with streptomycin perfusion, the number of patients with further hearing loss is large, so dexamethasone perfusion with intravenous dexamethasone should be tried first . The initial response to dexamethasone perfusion plus intravenous dexamethasone has been very good, with very little risk of further hearing loss, and it holds great promise for the future.

Antimicrob Agents Chemother, 1996 Apr, 40(4), 1024 - 6
Characterization of rpsL and rrs mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from diverse geographic localities; Sreevatsan S et al.; Two genes (rpsL and rrs) with mutations associated with streptomycin resistance in Mycobacterium tuberculosis were characterized in 78 streptomycin-resistant and 61 streptomycin-susceptible isolates recovered from patients living in the United States, South America, Europe, Africa, and Asia . Fifty-four percent of the 78 resistant organisms had missense mutations in codon 43 of rpsL resulting in a K-43-->R substitution . Mutations in codon 88 of rpsL were also identified in four Asian isolates.

Arch Biochem Biophys, 1996 Apr 1, 328(1), 9 - 16
Rate of translation of natural mRNAs in an optimized in vitro system; Pavlov MY et al.; We report results on in vitro translation of an mRNA coding for elongation factor TuB which was in vitro transcribed from the tufB gene from Escherichia coli . Translation occurs at a rate of about 10 codons per second, which is close to the in vivo rate . Protein elongation obeys Michaelis-Menten kinetics with respect to the concentrations of the elongation factors EF-Tu and EF-G in the translation system . The measured K(m) values for EF-Tu and EF-G are 10 and 0.25 microM, respectively . The obtained k(cat) and K(m) values were used to estimate the average k(cat)/K(m) of about 24 x 10(6) s-1 M-1 for the interaction of individual EF-Tu*GTP*aa-tRNA complexes with ribosomes . The estimated k(cat)/K(m) value for EF-G is 36 x 10(6) s-1 M-1 . We have also studied translation with a "hyperaccurate" ribosome variant that is pseudodependent on streptomycin (SmP) . We have found that SmP ribosomes translate the TuB mRNA significantly slower than wild-type ribosomes do . This is mainly due to a threefold lower k(cat)/K(m) for the interaction of EF-Tu*GTP*aa-tRNA complexes with SmP ribosomes.

Lancet, 1996 Mar 23, 347(9004), 807 - 9
Tuberculosis programme changes and treatment outcomes in patients with smear-positive pulmonary tuberculosis in Blantyre, Malawi; Harries AD et al.; PIP: The rates of tuberculosis (TB) notifications and treatment outcomes in Queen Elizabeth Central Hospital in Blantyre, Malawi, and the measures introduced to improve treatment were assessed by analyzing patient records and treatment outcomes . From 1989 to 1991, the number of TB cases registered increased by 58% . From 1991 to 1993, the number of cases per year did not change . However, from 1991 onward the number of TB patients within Blantyre district continued to rise, and treatment outcomes in new smear-positive TB patients deteriorated substantially . In 1991 the cure rate for the last two quarters was 32% and the default rate was more than 40% . The increase in TB patients between 1989 and 1991 strained TB services and contributed to the deterioration in treatment outcomes . In 1991 measures were taken to counter the worsening trend with a focus on staffing, staff activities, treatment regimens, and sputum-collection procedures . The arrival of a physician in July 1991 and another in October 1992 led to improved diagnosis and more extensive health education of patients . In May 1993 a health surveillance assistant was hired for health education and supervision of patients . In July 1993 a district health TB officer was appointed to supervise TB activities in health centers . Also, monthly TB meetings were started for all health staff . At the end of 1993 the number of nurses were also increased . In October 1991 an outpatient regimen for smear-negative pulmonary TB and moderate extrapulmonary TB replaced the standard regimen . This new regimen consisted of 2 months of rifampicin, isoniazid, and pyrazinamide each given three times per week, followed by 2 months of daily isoniazid and ethambutol, and then 4 months of isoniazid . Then, in March 1992, another regimen was introduced: 1 month of daily streptomycin, rifampicin, isoniazid, and pyrazinamide followed by 1 month of these drugs three times per week, and then 6 months of maintenance treatment with isoniazid and thiacetazone .

Schweiz Med Wochenschr, 1996 Mar 9, 126(10), 392 - 7
{Fulminant, rapidly reversible hepatitis and life-threatening anaphylaxis following rifampicin in an HIV-positive female patient with latent adrenal cortex insufficiency}; Canova CR et al.; We report the case of a 28-year-old-prostitute from Thailand with HIV infection stage B2 associated with retroperitoneal lymph node tuberculosis . 6 days after the beginning of anti-tuberculous therapy (isoniazid, rifampicin, pyrazinamid and ethambutol) the temperature rose to 40.5 degrees C, diarrhea, vomiting, and tachycardia developed and systolic blood pressure fell to 80 mm Hg . Liver function tests revealed acute hepatic failure (ALT 800 IU/l rising to 1500; serum bilirubin 89 mumol/l rising to 238.0; alkaline phosphatase 199 IU/l; glucose 1.8 mmol/l; prothrombin time 20%) . Isoniazid, rifampicin, and pyrazinamid were replaced by streptomycin and PAS . A few days after withdrawal the liver profile returned to normal . Hours after the reintroduction of rifampicin total body erythema, pruritus, vomiting and severe hypotension developed, requiring saline methylprednisolone and epinephrine administration . The next reexposure to intravenous rifampicin produced a rash and was rapidly discontinued . Liver function tests remained normal . Later mild adverse reactions to streptomycin and pyrazinamid occurred, two drugs which had been well tolerated before . Subsequently the diagnosis of adrenal insufficiency was established . After initiation of steroid replacement (50 mg prednisolone) the antituberculous therapy with isoniazid, pyrazinamid and ethambutol was well tolerated . We conclude that the shock in this HIV-infected patient was either due to severe anaphylaxis to rifampicin or acute adrenal insufficiency ensuing on this drug . The reversible fulminant acute hepatic failure represents either an adverse effect of antituberculous drugs, especially hepatotoxic interactions of drug combinations, or an ischemic liver injury during hypotension caused by anaphylaxis . The case illustrates the complex nature of side effects of antituberculous drugs in HIV patients and their aggravation by adrenal insufficiency.

Biochem Mol Biol Int, 1996 Mar, 38(3), 493 - 500
Purification and partial characterization of Ca(2+)-dependent ribonucleotide reductase from Streptomyces aureofaciens; Racay P et al.; Ribonucleotide reductase (EC 1 . 17 . 4 . 1.) is an essential enzyme providing 2'-deoxy-ribonucleotides for DNA replication . Ribonucleotide reductase from Streptomyces aureofaciens was purified 3365-fold with a yield of 6.5% . After homogenization of cells by ultrasonic homogenizer and DNA removing by 7% (w/v) solution of streptomycin sulphate, the sample was chromatographed on a DEAE-Sepharose CL 6 B, Phenyl-Sepharose CL 4 B, Heparin-Sepharose CL 6 B and a Sephacryl S-200 . The specific activity of the purified protein was 1740 pmol per s per mg . Sephacryl S-200 chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed that in the presence of calcium ions the enzyme appears to be a dimer with an apparent molecular weight of 125.9 kDa . In the absence of calcium dimer dissociates into a monomer with the apparent molecular weight of 64.3 kDa . On the basis of these results, we suggest that calcium plays a role in the formation of the dimer, which is the biologically active form of ribonucleotide reductase.

Nihon Kyobu Shikkan Gakkai Zasshi, 1996 Mar, 34(3), 374 - 9
{Pulmonary and endobronchial tuberculosis with subclavian artery-pulmonary artery shunts}; Ando M et al.; A 77-year-old woman with a productive cough and fever was admitted to the hospital . Pulmonary and endobronchial tuberculosis, pneumonia of the left upper lobe, and stenosis of the left main bronchus were diagnosed . She was given the antimycobacterial drugs isoniazid, rifampin, and streptomycin, and her condition improved . Two months later, bronchoscopy revealed semilunar-shaped stenosis of the left main bronchus, and auscultation revealed wheezing in the middle-end expiratory phase . A continuous flow murmur (Levine III) was also heard at the left anterior chest wall . Cardiac catheterization with subclavian arteriography revealed two left subclavian-pulmonary shunts . In a case of systemic-pulmonary shunt such as this, the bronchial stenosis could be surgically repaired, but the result would be an increase in dead space . If left untreated, the pulmonary hypertension would progress and symptoms of pulmonary disease would become more severe . Subclavian-pulmonary artery shunt is a very rare complication of pulmonary tuberculosis . Surgical treatment should consist of open bronchoplasty along with lobectomy and removal of the shunt, rather than embolization of the shunt and endoscopic bronchoplasty.

J Commun Dis, 1996 Mar, 28(1), 15 - 9
Initial and acquired drug resistance of Mycobacterium tuberculosis in east Delhi; Mahajan M et al.; One hundred and fifty six strains of Mycobacterium tuberculosis, isolated from cases of pulmonary tuberculosis were subjected to sensitivity test to detect initial and acquired drug resistance to Streptomycin, isoniazid, Rifampicin, Ethambutol and Pyrazinamide . Initial and acquired drug resistance was observed to one or more drugs in 16% and 24.4% of the patients respectively . Strains resistant to Rifampicin and Ethambutol were resistant to Isoniazid also . Drug resistance was unrelated to age and sex of the patients.

Arch Bronconeumol, 1996 Mar, 32(3), 118 - 21
{Resistance of Mycobacterium tuberculosis in the province of Castellón}; Moreno R et al.; We conduced a cross-sectional study to determine the prevalence of resistant mycobacteria in our setting . All patients in whom M . tuberculosis had been isolated in cultures of clinical samples (119) between January 1992 and December 1993 took part in the study . Canetti's method of percentages was used for the study of sensitivity to the following drugs: isocyanide, rifampicin, streptomycin, ethambutol and para-aminosalicylic acid . Overall resistance of M . tuberculosis was 9.24% . Specifically, we found resistance to isocyanide in 5.9%, to streptomycin in 4.20%, to rifampicin in 5.04% and to ethambutol in 1.68% . Resistance was primary in 7% and secondary in 21.05%; 2% showed primary resistance to isocyanide, 1% to isocyanide and rifampicin, 2% to streptomycin, 1% to ethambutol and 1% to streptomycin and rifampicin . These resistance indices are in keeping with those published for other areas of Spain.

EMBO J, 1996 Mar 1, 15(5), 1149 - 54
Dissociation rates of peptidyl-tRNA from the P-site of E.coli ribosomes; Karimi R et al.; We studied the dissociation rates of peptidyl-tRNA from the P-site of poly(U)-programmed wild-type Escherichia coli ribosomes, hyperaccurate variants altered in S12 (SmD, SmP) and error-prone variants (Ram) altered in S4 or S5 . The experiments were carried out in the presence and absence of streptomycin, and the effects of neomycin were tested in the wild-type ribosomes . Binding of peptidyl-tRNA to the P-site of wild-type ribosomes is much stronger than to their A-site . Addition of streptomycin dramatically reduces its affinity for the P-site . The S12 alternations make the P-site binding of peptidyl-tRNA much tighter, and the S4, S5 alterations make it weaker than in the case of the wild-type . We find that when binding of peptidyl-tRNA to the A-site is weak, then the affinity for the P-site is stronger, and vice versa . From these results, we formulate a hypothesis for the actions of streptomycin and neomycin based on deformations of the 16S rRNA tertiary structure . The results are also used to interpret some in vivo experiments on translational processivity.

Biochem Pharmacol, 1996 Feb 23, 51(4), 437 - 45
Purification and characterization of an Ah receptor binding factor in chromatin; Dunn RT 2nd et al.; Dioxin induces biological responses through interaction with a specific intracellular receptor, the Ah receptor, and the subsequent interaction of the Ah receptor with chromatin . We previously reported the binding of the Ah receptor, partially purified form rabbit liver, to receptor binding factors (termed AhRBFs) in chromatin . Rabbit liver chromatin proteins (CP) were isolated by absorption of chromatin to hydroxylapatite followed by sequential extraction with 3 M NaCl and 1-8 M guanidine hydrochloride (GdnHCl) . In the present study, we continued the purification of the CP5 fraction, which exhibited AhRBF activity . The proteins in CP5 were separated by CL-Sepharose 6B column chromatography resolving lower molecular weight fractions . To assay for receptor binding, a portion of each Cl-Sepharose 6B fraction was reconstituted to rabbit double-stranded DNA (dsDNA) using a reverse gradient dialysis of 7.5 to 0.0 M GdnHCl . These reconstituted chromatins were then examined for binding to {3H}-2,3,7,8-tetrachlorodibenzo-p-dioxin ({3H}TCDD)-receptor complexes by the streptomycin filter binding assay . Two protein fractions with a molecular weight in the range of 10,000-14,000 demonstrated high affinity binding to the Ah receptor . The binding of AhRBFs reconstituted to dsDNA was shown, by competition experiments with Ah receptor bound by unlabeled TCDD (TCDD-R), to be > 90% specific for {3H}TCDD-R . Further purification was achieved by preparative ADS-PAGE, and AhRBF activity was attributed to two fractions with molecular weights between 12,000 and 10,000 . A kDa protein with AhRBF activity was found to have an isoelectric point (pI) of > or = 10 . The 12 kDa AhRBF was sequenced by Edman degradation after cyanogen bromide cleavage and identified as histone H4 . Although histone H4 has been postulated to interact with transcription factors in a variety of systems, this is the first report of a specific interaction of AhR with histone H4.

Gene, 1996 Feb 22, 169(1), 91 - 5
The aerial mycelium-defective phenotype of Streptomyces griseus resulting from A-factor deficiency is suppressed by a Ser/Thr kinase of S . coelicolor A3(2); Ueda K et al.; A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) is essential for aerial mycelium formation and streptomycin (Sm) production in Streptomyces griseus . A protein Ser/Thr kinase (AfsK), the product of the Streptomyces coelicolor A3(2) afsK gene, controlling secondary metabolism in this strain, reversed the aerial mycelium-negative phenotype of an A-factor-deficient mutant strain, S . griseus HH1, and induced sporulation without affecting A-factor productivity or Sm production . A mutant AfsK protein lacking kinase activity failed to induce aerial mycelium formation which indicates the importance of the kinase activity for suppression in S . griseus . These data suggest that a Ser/Thr kinase functionally similar to S . coelicolor A3(2) AfsK plays a regulatory role in aerial mycelium formation in S . griseus, either as a member in the A-factor regulatory network or independently of this network.

Lancet, 1996 Feb 10, 347(8998), 358 - 62
Results of directly observed short-course chemotherapy in 112,842 Chinese patients with smear-positive tuberculosis . China Tuberculosis Control Collaboration; Occurrence of silent RNA editing in chloroplasts: its species specificity and the influence of environmental and developmental conditions; Center for Gene Research, Nagoya University, JapanWe have identified three new C-to-U RNA editing sites, one in atpF and two in atpA transcripts from tobacco chloroplasts . Two of them lead to amino acid substitutions to restore the conserved amino acid found in the corresponding genes of other plants . However, one editing site in the atpA transcript was found to take place partially at the third base of a serine codon (CUC_ to CUU_), thus not leading to an amino acid substitution . This is the first report of silent editing in chloroplasts . The extent of silent editing depends on plastid stage and light conditions, while editing as another site (found 4 nt upstream from the silent editing site) takes place constitutively even in non-photosynthetic cultured cells and bleached white seedlings grown in the presence of spectinomycin and streptomycin . In pea and spinach, despite a conservation in sequence, no editing at the site corresponding to the silent site in tobacco was found . This observation suggests that the silent editing detected in this study is species-specific.

S Afr J Commun Disord, 1996, 43, 3 - 6
Ototoxicity of aminoglycoside drugs in tuberculosis treatment; Voogt GR et al.; The possible ototoxic effect of kanamycin, streptomycin and a standard anti-TB drug combination, used in the treatment of 92 TB patients (7-71 years old), was examined by measuring the highest audible electric bone conduction frequency before and after treatment, using an Audimax 500 audiometer . At the so-called "safe" levels of drug administration it was found that kanamycin was markedly ototoxic, streptomycin very slightly ototoxic and the standard anti-TB drug combination had practically no ototoxic effect . Furthermore, it was found that none of these drugs were gender specific . Lastly, the possible effects of ageing on highest audible bone conduction frequency is discussed.

Biochimie, 1996, 78(11-12), 959 - 69
Dual functions of ribosome recycling factor in protein biosynthesis: disassembling the termination complex and preventing translational errors; Janosi L et al.; We summarize in this communication the data supporting the two functions of ribosome recycling factor (RRF, originally called ribosome releasing factor) . The first described role involves the disassembly of the termination complex which consists of mRNA, tRNA and the ribosome bound to the mRNA at the termination codon . This process is catalyzed by two factors, elongation factor G (EF-G) and RRF . RRF stimulated protein synthesis as much as eight-fold in the in vitro lysozyme synthesis system, when ribosomes were limiting . In the absence of RRF, ribosomes remain mRNA-bound at the termination codon and translate downstream codons . In the in vitro system, the site of reinitiation is the triplet codon 3' to the termination codon . RRF is an essential protein for bacterial life . Temperature sensitive (ts) RRF mutants were isolated and in vivo translational reinitiation due to inactivation of ts RRF was demonstrated using the beta-galactosidase reporter gene placed downstream from the termination codon . A second function of RRF involves preventing errors in translation . In polyphenylalanine synthesis programmed by polyuridylic acid, misincorporation of isoleucine, leucine or a mixture of amino acids was stimulated upto 17-fold when RRF was omitted from the in vitro system . RRF did not influence the large error (10-fold increase) induced by streptomycin . This means that RRF participates not only in the disassembly of the termination complex but also in peptide elongation . Extending this concept and its conventional role for releasing ribosomes from mRNA, involvement of RRF in the reinitiation in the 3A' system (a construct using S aureus protein A, a collaborative work with Dr Isaksson), in programmed frame shifting, in trans-translation with 10Sa RNA (collaborative work with Dr Muto), and in the reinitiation downstream from the ORF A of the IS 3 (insertion sequence of a transposon, collaborative work with Dr Sekine) are discussed on the basis of preliminary data to be published elsewhere . Finally, we review the known RRF sequences from various organisms including eukaryotes and discuss the possible mechanism for disassembly of the eukaryotic termination complex.

Probl Tuberk, 1996, (6), 52 - 4
{Dynamics of isolation of mycobacterium tuberculosis during 2-stage standard chemotherapy}; Khomenko AG et al.; Two-stage standard chemotherapy was performed in 149 newly detected patients with pulmonary tuberculosis, by isolating Mycobacteria . Within the first 2 months, the patients received 4 drugs: isoniazid, rifampicin, pyrazinamide, streptomycin or ethambutol . Treatment with two agents (isoniazid and rifampicin) was continued for 4 months . Mycobacterial isolation was stopped in 104 patients after 2 months of treatment, in other 26 after 3 months, which amounts to 80.2% . Higher therapeutical results were observed in patients who had isolated Mycobacteria resistant to 1 and even 2 drugs.

Arch Virol, 1996, 141(8), 1453 - 62
Evidence that neomycin inhibits human cytomegalovirus infection of fibroblasts; Lobert PE et al.; The effect of phosphoinositide-binding aminoglycosides, such as neomycin, gentamicin and streptomycin, on human cytomegalovirus (HCMV) infection of human fibroblasts MRC-5 was studied . The inhibition of HCMV infection was obtained with all of these molecules but neomycin was more effective than the others . We showed that the inoculation of the cells with cell-free viral suspension in presence of neomycin concentrations above 5 mM at 37 degrees C, inhibited more than 98% the HCMV infection . However, the preincubation of the fibroblasts with neomycin at 4 degrees C, before the removal of the drug and the inoculation of the cells, induced only a 30% decrease in the number of infected cells . Addition of neomycin after the HCMV-binding at 4 degrees C or the infection of the cells was less efficient to inhibit HCMV infection than the standard incubation of neomycin during inoculation of the fibroblasts . Indeed, 1 hour after the inoculation of the cells at 37 degrees C, neomycin still inhibited HCMV infection, but 4 hours after the inoculation, this drug had no effect on HCMV infection . Our findings demonstrated that neomycin must be present at the time of infection in order to exert a full inhibiting effect . The effect of neomycin on the HCMV infection was almost immediate upon the addition of the drug (binding and/or internalization) and after the virus internalization (inhibition of immediate-early events) . We suggest that neomycin and other aminoglycoside antibiotics may interact with HCMV glycoproteins for binding to similar structural features of cell surface heparan sulfate proteoglycans and may inhibit HCMV infection in fibroblasts by disrupting phosphoinositide-mediated events in the cells.

Pneumologie, 1996 Jan, 50(1), 28 - 35
{Incidence of resistance and risk factors for resistance in Mycobacterium tuberculosis . A retrospective study of 1,055 patients of a specialty hospital 1984 to 1993}; Borchardt J et al.; For the past decade, there have been no data on the time course of drug-resistant tuberculosis and on risk factors for drug resistance in former West Germany . We reviewed the medical records of all patients with positive cultures for Mycobacterium tuberculosis from 1984 until 1993 in a hospital near Hamburg . Drug-susceptibility testing was performed for isoniazid, rifampicin, ethambutol, and streptomycin, using the modified proportion method . Of 1,055 patient, 9.6% had isolates resistant to one or more drugs . Of the isolates, 5.8% showed resistance to isoniazid or rifampicin and 1.8% to both isoniazid and rifampicin . There was no significant change of the resistance rate during the study period . Twenty six percent of 89 patients from South America, Africa or Asia had isolates resistant to one or more drugs, compared with 7.6% of 799 patients born in Germany (odds ratio (OR) 4.2; 95% confidence interval (95% CI) 2.5-7.3) . Among patients born in Germany, 32% of 101 patients with a history of prior antituberculosis drug therapy had resistant organisms, versus 4.2% of 698 patients without prior therapy (OR 10.7; 95% CI 6.1-18.7) . Resistance orates for 35 patients, who had been treated within the last 5 yrs, and for 65 patients, who had been treated more than 5 yrs ago, were 57 and 17%, respectively (OR 6.6; 95% CI 2.9-16.6) . Our results suggest that there is no increase in the proportion of drug-resistant tuberculosis in our hospital, and that patients with a recent history of antituberculosis drug therapy and patients from South America, Africa, or Asia are at high risk for drug resistance.

Eur J Pediatr, 1996 Jan, 155(1), 1 - 6
Childhood brucellosis in north-western Greece: a retrospective analysis; Galanakis E et al.; Fifty-two cases of childhood brucellosis which occurred in north-western Greece during the 15-year period 1979-1993, are reviewed . It is believed that they represent very closely the total incidence of the disease in the region which has a population of 100,000 children aged 0-14 years old . Brucellosis-affected children were almost exclusively from goat- or shepherd families and of both sexes and all age groups . A broad spectrum of clinical manifestations ranging from malaise only to brain abscess was observed . Fever and arthralgia were the most common manifestations followed by malaise, myalgia, sweating, rash, cough, and gastro-intestinal, cardiac and CNS involvement . Splenomegaly was found more often than hepatomegaly and lymphadenopathy . Laboratory findings included anaemia, leukopenia, neutropenia, lymphocytopenia, monocytosis, eosinophilia, thrombocytopenia and pancytopenia . Leukocytosis and lymphocytosis were extremely rare and ESR and serum C-reactive protein levels were mildly elevated . All patients had positive Rose Bengal slide agglutination tests and standard tube agglutination titres of 1:160 or more . When performed, blood culture was often diagnostic . The children were treated with streptomycin for 2 weeks plus either tetracyclines or trimethoprim-sulphamethoxazole for 3 weeks . Treatment was well tolerated . Relapse was observed in one case . CONCLUSION: Brucellosis nowadays affects children in an occupational pattern . As symptoms, signs and first-line laboratory findings are not characteristic, agglutination tests and blood culture should be performed in any child with prolonged fever . Treatment is effective, but prevention of the disease by animal testing and education of high risk families is indicated.

Yi Chuan Xue Bao, 1996, 23(2), 158 - 62
{Molecular mechanism of suppressing lambda N gene's expression in E . coli ribosomal protein S12 streptomycin-dependent mutant}; Jiang X et al.; Using the polymerase chain reaction (PCR) method, the rpsLd gene was amplified and cloned, which encodes the streptomycin-dependent (Smd) mutant of ribosomal protein S12 in E.coli T83 . The result of DNA sequencing showed an AAA to CAA mutation at codon 42, leading to the substitution of glutamine (Gln, Q) for lysine (Lys, K) . According to the principle of Garnier, we predicted that there might be alterations in the secondary structural propensity of protein S12 due to the mutation . The outcome indicated that the beta-turn propensity at position 42 and its nearby region was increased evidently and the relative position of relevant subdomains were changed . As a result, the special conformation of the whole protein S12 was influenced . In view of that ribosomal proteins and ribosomal RNAs (rRNA) mutually adapted in structures and functions, the probable molecular mechanism . That how protein S12 Smd mutant in E.coli T83 suppressed lambda N gene's expression is discussed.

Am J Otol, 1996 Jan, 17(1), 15 - 8
Cochlear fistula in chronic otitis media with cholesteatoma; Chao YH et al.; Labyrinthine fistula in chronic otitis media with cholesteatoma most commonly involves the horizontal semicircular canal . We report three cases of cochlear fistula in chronic otitis media with cholesteatoma . All of them had a long history of otorrhea . One patient had total hearing loss of the affected side . The other two patients had conductive hearing loss . Radical mastoidectomy had been done in all cases . Cholesteatoma in the tympanic cavity destroyed the basal turn of the cochlea . These fistulas were sealed with muscle or Gelfoam with streptomycin . We found no fistula in the semicircular canal in any of the three cases . We report three cases of cochlear fistula in chronic otitis media with cholesteatoma, and review the literature.

Planta, 1996, 199(2), 193 - 201
Integration of foreign sequences into the tobacco plastome via polyethylene glycol-mediated protoplast transformation; Koop HU et al.; A new vector, pFaadAII, for transformation of plastids of Nicotiana tabacum L . has been developed . It harbours a chimeric gene consisting of the aadA coding region from Escherichia coli, the 16S rDNA promoter from tobacco combined with a synthetic ribosome-binding site, a 500-bp fragment containing the 3' untranslated transcript region (UTR) of the Chlamydomonas rbcL gene and 3.75-kb (5') and 0.95-kb (3') tobacco plastome sequences allowing for targeting the foreign sequences to the intergenic region between the rpl32 and trnL genes of the tobacco plastome . The vector thus targets foreign sequences to the small single-copy region of the plastome, which has so far not been modified by transformation . Leaf protoplasts of Nicotiana tabacum L . were treated with polyethylene glycol (PEG) in the presence of the vector . The protocol for PEG treatment aiming at plastome transformation was optimized . Cell lines were cultured in the presence of spectinomycin and streptomycin using a novel and efficient protoplast culture and selection system . Regenerants were characterized by polymerase chain reaction (PCR) analysis, Southern hybridization and reciprocal crossing . The transformation procedure is described in detail and parameters influencing its efficiency are presented . Special effort is placed on analyzing suitable selection conditions . Only a proportion of the cell lines with a resistant phenotype could be confirmed by molecular analysis and/or reciprocal crossings to represent plastome transformants . Integration of the plastome specific aadA cassette into the nuclear genome accounted for a fraction of the resistant cell lines . Still, as many as 20-40 plastome transformants can be expected from the treatment of 10(6) protoplasts . Therefore, the improved protocol for PEG-mediated plastome transformation in combination with the new aadA-vector supplies a simple, reproducible and cost-efficient alternative to the biolistic procedure.

Can J Microbiol, 1996 Jan, 42(1), 12 - 8
Characterization of the drug resistance plasmid R2418: restriction map and role of insertion and deletion in its evolution; Guessouss M et al.; Escherichia coli 2418 strain is resistant to beta-lactam antibiotics (ampicillin, carbenicillin, and cephalothin), streptomycin, tetracycline, kanamycin, and chloramphenicol . This strain contains at least two conjugative plasmids (R2418 and R2418S) encoding resistance to beta lactam antibiotics and resistance to both beta-lactam antibiotics and streptomycin, respectively . Restriction endonuclease mapping of plasmid DNAs indicates that the plasmid R2418S has evolved from R2418 DNA by the insertion of 2.5-kb DNA between BamHI and PvuII sites, and deletion of 0.5-kb DNA within the EcoRI-EcoRV region . The 2.5-kb DNA insert is responsible for streptomycin resistance . This evolution is also associated with a reduction in the efficiency of conjugal transfer for the plasmid R2418S . The conjugal transfer of streptomycin resistance occurs only through the coresidence of the conjugative plasmid R2418 or R2418S in the donor cell . In accordance with the hypothesis that the Smr determinant is due to a putative transposon, plasmid-free transconjugants resistant to streptomycin only were isolated . Southern blot analysis of HindIII chromosomal digests extracted from these transconjugants shows that the Smr determinant is inserted into different sites in chromosomal DNA.

J Diarrhoeal Dis Res, 1995 Dec, 13(4), 238 - 41
Treatment of diarrhoea in infants by medical doctors in Balochistan, Pakistan; Kasi M et al.; Diarrhoea is an important public health problem in Balochistan, the westernmost province of Pakistan . Although the use of oral rehydration solutions (ORS) has been widely promoted, no studies have been reported on the actual uses of ORS in treating infant diarrhoea by the medical doctors in this region . The medical practices of 30 doctors in Balochistan were surveyed . The surveyors posed as the mothers of infants with diarrhoea . The questions asked by the doctors, the physical examinations performed, and the treatments prescribed were noted . The histories and physical examinations were incomplete, as performed by most practitioners . In addition, 80% of the doctors prescribed drugs, usually kaolin preparations to treat diarrhoea . However, 18 of the 30 (60%) practitioners also prescribed ORS for treating diarrhoea and most of them gave some recommendations about ORS use . It is concluded that many medical practitioners have incorporated ORS treatment into their practices . Ongoing educational programmes and refresher courses would likely improve the use of ORS further in this regionPIP: Diarrhea is an important public health problem in Baluchistan, the western province of Pakistan . Although the use of oral rehydration solution (ORS) has been widely promoted, no studies have been reported on the actual uses of ORS in treating infant diarrhea by the doctors in this region . The medical practices of 30 doctors in the cities of Quetta and Loralai were surveyed . The surveyors posed as the mothers of three infants aged 6-8 months with diarrhea . The questions asked by the doctors, the physical examinations performed, and the treatment regimens prescribed were recorded . The outcome indicated that the case histories and physical examinations were incomplete as performed by most practitioners . None of the doctors asked about the frequency of stools, the time of the infant's recent urination, or the health of family members . Most physical examinations were severely deficient . Only two doctors performed adequate examinations (taking of temperature, pulse, respirations, skin pinch, evaluation of fontanelle and mucus membranes, and abdominal examination) . Two doctors ordered laboratory tests: both requested stool examination for parasites, ova, and leukocytes, dipstick urinalysis, and blood leucocyte count with differential . 24 doctors (80%) prescribed drugs, usually a kaolin preparation, to treat diarrhea, although only 11 of them gave instructions on how to take the medication . 46% of the doctors prescribed commercially prepared mixtures of kaolin and pectin or neomycin and pectin, while two doctors prescribed streptomycin . Other medication prescribed included: fosfomycin, amoxycillin, co-trimethoxazole, metronidazole, paracetamol, vitamin drops, and colic drops . However, 18 of the 30 (60%) practitioners also prescribed ORS for treating diarrhea, and most of them gave some recommendations about ORS use . 14 doctors (46%) recommended breast feeding to prevent diarrhea, while 6 (20%) commented on food hygiene, recommending hand washing and clean drinking water . Ongoing education programs and refresher courses would likely improve the use of ORS further in this region .

Kansenshogaku Zasshi, 1995 Dec, 69(12), 1402 - 7
{A case of tuberculous meningitis followed by tuberculoma with pan-hypopituitarism}; Tomono N et al.; We reported a case who suffered from tuberculous meningitis at 10 months of age, and progressed to basal tuberculoma despite intensive drug therapy with isoniazid, rifampin, and streptomycin . Pan-hypopituitaliam due to basal tuberculoma was effectively replaced by the administration of anti-diuretic hormone (DDAVP) and levothyroxine sodium . Basal tuberculoma was finally removed by surgical operation . Histopathological examination of the tuberculoma revealed Mycobacterium tuberculosis and Langhans giant cells . During the 6 years after the operation, her growth rate was found to be retarded, and the administration of human growth hormone was started . Remarkable catch-up growth was demonstrated . We like to emphasize that infantile tuberculosis, mostly a result of intafamilial transmission, may manifest meningitis in the early phase of the disease, and it sometimes progresses to basal tuberculoma unresponsive to anti-mycobacterial drug therapy.

Biochem Cell Biol, 1995 Nov-Dec, 73(11-12), 907 - 13
Pleiotropic effects of mutations at positions 13 and 914 in Escherichia coli 16S ribosomal RNA; Brakier-Gingras L et al.; Mutations at position 13 or 914 of Escherichia coli 16S ribosomal RNA exert pleiotropic effects on protein synthesis . They interfere with the binding of streptomycin, a translational miscoding drug, to the ribosomes . They increase translational fidelity, and this effect can be related to a perturbation of the higher order structure of the 530 stem-loop, a key region for tRNA selection . In contrast, the structure of the decoding center is not perturbed . The mutations also affect translational initiation, slowing down the formation of the 30S initiation complex . This effect can be related to a destabilization of the pseudoknot helix (17-19/916-918), at the convergence of the three major domains of 16S ribosomal RNA.

Kekkaku, 1995 Nov, 70(11), 621 - 8
{A clinical study of non-tuberculous pulmonary mycobacteriosis}; Kurasawa T et al.; We studied the clinical features of sixty-one patients with non-tuberculous pulmonary mycobacteriosis (NTM), who were newly diagnosed at five national hospitals in Kinki area during 1993 . The study subjects were composed of 31 patients with M . avium complex (MAC) disease (20 males and 15 females), 21 with M . kansasii (MK) disease (19 males and 3 females), 2 males with M . szulgai (MS) disease and 2 females with M . chelonae (MC) disease . The rate of NTM to all culture proven mycobacteriosis was 20.2% and the rate of NTM to all culture proven, newly discovered mycobacteriosis was 18.2% and the rates were higher than Sakatani's report in 1994 (14% in 1991) . The ratio of MK to MAC was 22:35, and the ratio of MK was higher than the report of Sakatani . The mean age of patients with MK was 57.9 in male and 76.7 in female, that with MAC was 71.0 in male and 70.1 in female, that with MS was 57.0 in male and that 72.5 with MC in female . The proportion of elderly patients was higher than the former reports in Japan, especially in female with MK . The main lesions on chest X-ray was found in bilateral S1, 2(S1+2), particularly in the cases with cavitary lesions, but right middle lobe and left lingular lobe were mainly affected in some patients with MAC and S6 was often affected in elderly patients with MK . The chemotherapy with isoniazid, rifampicin, ethambutol and/or streptomycin (or kanamycin) w as highly effective in case with MK and MS disease, the efficacy was similar to pulmonary tuberculosis . Some patients with MAC were treated with combination of anti-tuberculosis drugs and new quinolons and/or clarythromycin, but the efficacy was not yet revealed.

Pneumologie, 1995 Nov, 49(11), 590 - 5
{Monitoring ototoxic side effects in streptomycin therapy of tuberculosis patients with transitory evoked otoacoustic emissions TEOAE}; Furst G et al.; The transient stimulated otoacoustic emissions TEOAE's from 10 patients treated with Streptomycin for tuberculosis, were measured . The patients received a combination of four drugs consisting of isoniazid, rifampicin, pyrazinamid and streptomycin . All patients received a total of 30 grams of streptomycin during 30 days of treatment . Pure tone audiograms between 125 Hz and 8000 Hz were performed before, during and at the end of the treatment . The TEOAE's were measured in a soundproof cabin before during and after the streptomycin treatment . None of the patients experienced subjective dizziness, hearing loss or tinnitus . The pure tone audiograms showed no significant fluctuations . However, 14 of the 20 examined ears showed a significant decrease in the amplitudes of the TEOAE's . An observation of the TEOAE-amplitudes of each patient during the treatment allows an assessment of impending cochlear dysfunction before subjective hearing loss can be recognized.

Neurologia, 1995 Nov, 10(9), 375 - 9
{Neurobrucellosis . A report of 13 cases}; Marzo Sola ME et al.; Thirteen patients with nervous system brucellosis are described . The clinical signs were heterogeneous: meningoencephalitis in 5 cases, meningoradiculitis in another 5, meningomyelitis with cranial neuropathy in 1 and of a vascular nature in 2 others . Neurologic signs appeared during the active phase in 5 patients and later in 8 . Diagnosis was based on clinical manifestations, serum and cerebrospinal fluid (CSF) serology, quantitative changes in CSF and favorable response to treatment . Therapy consisted of a combination of 2 or 3 of the following drugs: rifampin, doxycycline, streptomycin and trimethoprim sulfamethoxazole . In spite of favorable evolution, 5 patients suffered sequelae . We suggest that brucellosis be investigated when neurologic deficit ensues with no known etiology, especially in endemic countries.

J Bacteriol, 1995 Nov, 177(22), 6401 - 10
Cloning and characterization of a gene involved in aerial mycelium formation in Streptomyces griseus; Kudo N et al.; A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) is essentially required for aerial mycelium formation and streptomycin production in Streptomyces griseus . A DNA fragment which induced aerial mycelium formation and sporulation in an A-factor-deficient mutant strain, S . griseus HH1, was cloned from this strain on a high-copy-number plasmid . Subcloning and nucleotide sequencing revealed that one open reading frame with 218 amino acids, named AmfC, served as a multicopy suppressor of the aerial mycelium-defective phenotype of the A-factor-deficient strain . The amfC gene did not restore A-factor or streptomycin production, indicating that amfC is involved in aerial mycelium formation independently of secondary metabolic function . Disruption of the chromosomal amfC gene in the wild-type S . griseus strain caused a severe reduction in the abundance of spores but no effect on the shape or size of the spores . The infrequent sporulation of the amfC disruptant was reversed by introduction of amfC on a plasmid . The amfC-defective phenotype was also restored by the orf1590 gene but not by the amfR-amfA-amfB gene cluster . Nucleotide sequences homologous to the amfC gene were distributed in all of 12 Streptomyces species tested, including Streptomyces coelicolor A3(2) . The amfC homolog of S . coelicolor A3(2) was cloned and its nucleotide sequence was determined . The AmfC products of S . griseus and S . coelicolor A3(2) showed a 60% identity in their amino acid sequences . Introduction of the amfC gene of S . coelicolor A3(2) into strain HH1 induced aerial mycelium formation and sporulation, which suggests that both play the same functional role in morphogenesis in the strains.

J Bacteriol, 1995 Nov, 177(21), 6083 - 92
Cloning and characterization of the A-factor receptor gene from Streptomyces griseus; Onaka H et al.; A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) and its specific receptor protein control streptomycin production, streptomycin resistance, and aerial mycelium formation in Streptomyces griseus . The A-factor receptor protein (ArpA) was purified from a cell lysate of S . griseus IFO 13350 . The NH2-terminal amino acid sequences of ArpA and lysyl endopeptidase-generated fragments were determined for the purpose of preparing oligonucleotide primers for cloning arpA by the PCR method . The arpA gene cloned in this way directed the synthesis of a protein having A-factor-specific binding activity when expressed in Escherichia coli under the control of the T7 promoter . The arpA gene was thus concluded to encode a 276-amino-acid protein with a calculated molecular mass of 29.1 kDa, as determined by nucleotide sequencing . The A-factor-binding activity was observed with a homodimer of ArpA . The NH2-terminal portion of ArpA contained an alpha-helix-turn-alpha-helix DNA-binding motif that showed great similarity to those of many DNA-binding proteins, which suggests that it exerts its regulatory function for the various phenotypes by directly binding to a certain key gene(s) . Although a mutant strain deficient in both the ArpA protein and A-factor production overproduces streptomycin and forms aerial mycelium and spores earlier than the wild-type strain because of repressor-like behavior of ArpA, introduction of arpA into this mutant abolished simultaneously its streptomycin production and aerial mycelium formation . All of these data are consistent with the idea that ArpA acts as a repressor-type regulator for secondary metabolite formation and morphogenesis during the early growth phase and A-factor at a certain critical intracellular concentration releases the derepression, thus leading to the onset of secondary metabolism and aerial mycelium formation . The presence of ArpA-like proteins among Streptomyces spp., as revealed by PCR, together with the presence of A-factor-like compounds, suggests that a hormonal control similar to the A-factor system exists in many species of this genus.

Gene, 1995 Oct 16, 164(1), 41 - 4
Detection of exonuclease activities in restriction endonuclease preparations using an enforcement plasmid for kanamycin-resistance selection; Hashimoto-Gotoh T et al.; A new enforcement (kyosei-) cloning plasmid vector, designated pKF4, was constructed which confers kanamycin resistance (KmR) and enforces streptomycin sensitivity (SmS) . Since it is important to employ restriction endonuclease (ENase) preparations free of exonuclease (Exo) activities for effective use of the kyosei-cloning procedure {Hashimoto-Gotoh et al., Gene 137 (1993) 211-216}, ENases such as HpaI and SmaI purchased from four different suppliers were examined for possible contamination by exonucleases using pKF4 . The plasmid DNA was digested with either ENase, ligated and transformed into Escherichia coli mutants, rpsL, supE, trpR . With pKF4 intact DNA (approx . 8 ng), 2.3 x 10(5) KmR transformant and four KmRSmR transformant colonies were obtained; the efficiency of transformation plating (ETP) of the intact DNA was approx . 2 x 10(-5) . On the other hand, the ETP values were significantly higher by one to three orders of magnitude when cut and re-joined DNAs were used under the same conditions in six out of eight ENase samples examined . The results indicate that even commercially supplied ENases, that should have passed their quality control test, could have been contaminated with Exo sufficient to interfere with effective use of the kyosei-cloning method . Therefore, it is advisable to examine ENase samples for possible contamination with Exo activities, in order to choose the right preparations for this method at the beginning of the experiments.

Anal Biochem, 1995 Oct 10, 231(1), 230 - 6
Quantitative determination of effective nibbling activities contaminating restriction endonuclease preparations; Hashimoto-Gotoh T; A simple and sensitive procedure with which to detect residual exonucleolytic nibbling activities contaminating restriction endonuclease preparations is described . The procedure uses the kyosei-plasmid, pKF4, which confers kanamycin resistance and enforces streptomycin sensitivity encoded by the trp promoter/operator-driven rpsL+amber(PO(trp)-rpsL+4(am)) gene onto Escherichia coli streptomycin-resistant, amber-suppressive, trp repressor-negative strains such as TH5 . When TH5 cells transformed by pKF4 were selected on agar medium containing kanamycin plus streptomycin, the efficiency of transformation plating was substantially lower than that on agar containing kanamycin alone . However, when pKF4 DNA was digested by restriction enzymes that cut once per molecule within PO(trp)-rpsL+4(am) and relegated, the plating efficiency increased depending on the degree of contamination of exonucleolytic nibbling activities in the enzyme preparations, due to deletion mutation at the ligand junction . Plating efficiency was converted to inverted question markeffective nibbling activity inverted question mark corresponding to Bal31 nuclease-equivalent units . Using this procedure, effective nibbling activities were detected in 17 of 34 commercial samples of restriction enzymes tested . The method is simple and more sensitive than the procedures used by the commercial suppliers and it is applicable to the quality control testing of more than 100 restriction enzymes.

Ned Tijdschr Geneeskd, 1995 Oct 7, 139(40), 2050 - 2
{Extrapulmonary tuberculosis in 3 Dutch patients}; Kruijtzer CM et al.; In three patients, two women aged 71 and 59 years and a man aged 49 who had been living in the Netherlands for a long time and who were admitted because of vague symptoms, extrapulmonary manifestations of tuberculosis were diagnosed: tuberculosis of the lumbar spine with psoas abscess, tuberculous peritonitis and adrenal tuberculosis with Addison's disease in a patient with open pulmonary tuberculosis . All three recovered with tuberculostatic therapy (isoniazid, streptomycin, pyrazinamide and rifampicin).

Mol Microbiol, 1995 Oct, 18(1), 151 - 62
The regulator of streptomycin gene expression, StrR, of Streptomyces griseus is a DNA binding activator protein with multiple recognition sites; Retzlaff L et al.; In Streptomyces griseus the expression of at least one streptomycin biosynthetic gene, strB1, is dependent on the pathway-specific activator protein StrR . We show here that StrR is a DNA-binding protein which specifically interacts with the strB1 promoter fragment . Footprinting experiments demonstrate that the StrR protein binds to an inverted repeat located upstream of the strB1 promoter . Further StrR-binding sites having the consensus sequence GTTCGActG(N)11CagTcGAAc were identified in the str-sts gene clusters of S . griseus and Streptomyces glaucescens by sequence comparison, gel retardation, and footprinting studies . The genetic and biochemical evidence strongly supports the model of the StrR protein activating the expression of streptomycin biosynthetic genes by interacting with multiple binding sites within the str-sts gene clusters of S . griseus and S . glaucescens.

J Bacteriol, 1995 Oct, 177(20), 5840 - 5
Physiological state of Escherichia coli BJ4 growing in the large intestines of streptomycin-treated mice; Poulsen LK et al.; Growth rates of Escherichia coli BJ4 colonizing the large intestine of streptomycin-treated mice were estimated by quantitative hybridization with rRNA target probes and by epifluorescence microscopy . The ribosomal contents in bacteria isolated from the cecal mucus, cecal contents, and feces were measured and correlated with the ribosomal contents of bacteria growing in vitro at defined rates . The data suggest that E . coli BJ4 grows at an overall high rate in the intestine . However, when taking into account the total intestinal volume and numbers of bacteria present in cecal mucus, cecal contents, and feces, we suggest that E . coli BJ4 in the intestine consists of two populations, one in the mucus which has an apparent generation time of 40 to 80 min and one in the luminal contents which is static.

Microbiology, 1995 Oct, 141 ( Pt 10), 2511 - 8
Depression of streptomycin production by Streptomyces griseus at elevated growth temperature: studies using gene fusions; Deeble VJ et al.; Streptomyces griseus ATCC 12475 fails to produce streptomycin when grown at 34 degrees C or above, although growth is appreciable up to at least 37 degrees C . This depression of streptomycin production at elevated growth temperature is manifest equally in liquid and on solid, and with complex and minimal, media . We report studies with gene fusions of the reporter genes aph or xyIE to restriction fragments containing the streptomycin biosynthesis promoter PstrB1 . aph constructs were in high, and xyIE constructs in low, copy number vectors . Two strB1 promoter fragments were used, one requiring activation by the pathway-specific activator StrR of S . griseus, the other reportedly activator independent . PstrB1 expression in the aph constructs in S . griseus and in S . lividans was significantly reduced at 37 degrees C compared to 30 degrees C . Some of this reduction could be explained by lower plasmid copy number at the higher temperature, but strR-dependent expression was clearly temperature controlled . Using the xyIE reporter system, the temperature dependence of PstrB1 expression was confirmed but, surprisingly, the strR dependence of the two promoter fragments differed from that observed in the multicopy aph constructs . These data identify a temperature-dependent promoter which may contribute to the depressive effect of elevated growth temperature on streptomycin production.

Endocrinology, 1995 Oct, 136(10), 4448 - 53
Hypothyroidism prevents postnatal changes in rat liver mitochondrial populations defined by rhodamine-123 staining; Almeida A et al.; The effect of hypothyroidism on the percentages of low fluorescence population (LFP) and high fluorescence population (HFP) rhodamine-123-stained mitochondria, respiratory parameters, and ATPase activity were studied in liver mitochondria from early newborn rats . Hypothyroidism prevented the decrease in the percentage of HFP and the subsequent increase in LFP that occurs immediately after birth . This effect coincides with the impairment of mitochondrial respiratory function, as shown by the low respiratory control ratio and the low activity of F0,F1-ATPase found in hypothyroid newborns . All of these changes were reversed by the administration of thyroid hormones . ATP in vitro promotes the conversion of HFP into LFP and increases the respiratory control ratio in hypothyroid newborns, although this effect was not observed after thyroid hormone treatment . The effect of thyroid hormones on both the postnatal changes in mitochondrial populations and in F0,F1-ATPase activity was prevented by cycloheximide, but not by streptomycin . Thus, the observed effects of thyroid hormones on neonatal mitochondria must be accomplished by the induction of the synthesis of some nuclei-coded protein, possibly involved in F0,F1-ATPase assembly.

Tuber Lung Dis, 1995 Oct, 76(5), 463 - 7
Failure of drug penetration and acquisition of drug resistance in chronic tuberculous empyema; Elliott AM et al.; We describe a patient with drug-resistant chronic tuberculous empyema in whom substantial differences between achievable pleural fluid and serum drug concentrations were displayed . The ratio of maximum concentration in pleural fluid to serum was especially low for rifampin (4%) but was also low for streptomycin (34%) and ofloxacin (48%) . Subtherapeutic drug concentrations in the pleural fluid may have contributed to acquisition of drug resistance in this case.

Lancet, 1995 Sep 9, 346(8976), 675 - 7
Tuberculosis control in resource-poor countries: alternative approaches in the era of HIV; De Cock KM et al.; PIP: WHO projections suggest that the annual number of tuberculosis (TB) cases worldwide will reach 10.2 million by the year 2000 . HIV plays a dominant role in this increase in many resource-poor countries . The internationally recommended treatment regimens for TB combine some of the six major antituberculosis drugs: isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, and thiacetazone . WHO treatment guidelines give priority to patients according to the nature of their disease and recommend two regimens of 6-8 months duration, the longer regimen incorporating thiacetazone . Recently, WHO has favored a 6-month treatment regimen given as directly observed therapy (DOT) . The disadvantages of the standard approach are the heavy workload of smear examinations, the complexity of some drug regimens, and the low rates of therapy completion . With the increasing TB case load in areas of high HIV infection prevalence, laboratories cannot do initial as well as follow-up smear examinations . In Botswana the proportion of smear-positive TB cases declined to 40% in 1992, but the overall proportion of patients who had smears performed had declined (52% in 1992) . The multiple regimens in use cause confusion and nonadherence to guidelines . Nonadherence is the major risk factor for the emergence of drug resistance, and low completion rates are the most obvious signs of inadequate control programs . Alternative approaches mean ensuring high completion rates and using the most effective drugs . Regarding diagnosis, research might show that the number of smears could be reduced depending on the initial reading . There is no reason why a rifampicin-based short-course regimen could not replace the multiple regimens now in use . Rifampicin-containing regimens of 62-78 doses given intermittently have been effective and are suitable for use within a DOT program . For prevention of drug resistance, only pills combining different drugs should be used and rifampicin should be limited to the treatment of TB and leprosy .

Rev Sci Tech, 1995 Sep, 14(3), 719 - 32
Control of Brucella melitensis infection in a large camel herd in Saudi Arabia using antibiotherapy and vaccination with Rev . 1 vaccine; Radwan AI et al.; The authors describe an attempt to control Brucella melitensis infection in a large camel herd in Saudi Arabia . Sera from the entire herd (2,536) were examined by the Rose Bengal and standard United States of America buffered plate agglutination tests . The overall Brucella seroprevalence was 8% . Milk samples from the 120 seropositive milking camels were cultured on Brucella-selective media . B . melitensis biovars 1, 2 and 3 were isolated from 41 camels (34%) . Seropositive camels (202) were treated for the first time with a combination of long-acting oxytetracycline (OTC) at a dose of 25 mg/kg administered intramuscularly (i.m.) every 2 days for 30 days and streptomycin at 25 mg/kg i.m . every 2 days for 16 days . In addition, milking camels were given OTC-intramammary infusion at a rate of 10 ml/teat every 2 days for 8 days . This regimen was found to be effective in eliminating the shedding of Brucella organisms by camels, with no relapse . Moreover, all treated camels became seronegative within 16 months after treatment . Seronegative camels (2,331) were vaccinated for the first time with the B . melitensis Rev . 1 strain vaccine, as follows: a) 175 young camels (aged three months to one year) were each inoculated subcutaneously with a full dose (1-2 x 10(9) viable organisms in 1 ml) . Brucella antibody titres between 1:50 and 1:200 were detected 2-4 weeks post-vaccination . Brucella antibodies decreased gradually until the animals became seronegative 8 months after vaccination . b) 2,156 camels aged more than one year were each inoculated subcutaneously with a reduced dose (1-2 x 10(6) viable organisms in 1 ml) . Antibody titres measured 2-4 weeks post-vaccination varied from 1:25 to 1:200 . The titres decreased gradually, until the animals became seronegative 3 months post-vaccination . No Brucella organisms were recovered from repeated udder secretion samples from all vaccinated milking camels, and no abortions were recorded among pregnant vaccinated camels.

Rev Sci Tech, 1995 Sep, 14(3), 593 - 601
Contagious bovine pleuropneumonia vaccines: the need for improvements; Rweyemamu MM et al.; Contagious bovine pleuropneumonia (CBPP) vaccines are routinely used only in Africa . The vaccines are usually produced from one of two strains (T1/44 and KH3J), each of which has a streptomycin-resistant variant . The necessity for a 'master seed strain' is evident . At least one manufacturer in Africa produces a broth culture vaccine, while others produce a freeze-dried product . A standardised manufacturing protocol needs to be developed, together with in-process and final product quality control procedures . Some CBPP vaccine manufacturing procedures do not allow sufficient leeway for the execution of typical quality control practices . For example, it is difficult to perform batch testing on broth culture vaccine, as the vaccine is produced in its final container . Quality control test results from the Pan African Veterinary Vaccine Centre (PANVAC) are analysed in terms of causes of batch failure and indicators for process development . Taking potency as an example, most vaccine batches tested by PANVAC pass only at the limit of the OIE minimum requirement of 10(7) colony-forming units per dose . To improve the titre of the vaccine, it will be necessary to modify the manufacturing process, either by increasing mycoplasma yield during the culture phase or by minimising losses during downstream processes, especially freeze-drying . Data on inactivated vaccines are scarce . Duration of the immunity achieved with live CBPP vaccines is relatively short, in comparison with other live vaccines . Data may be required on the molecular basis of virulence and immunogenicity, as well as on the molecular immunology of CBPP, to enable the development of improved vaccines.

Microb Pathog, 1995 Sep, 19(3), 185 - 91
Increased oral virulence of Escherichia coli expressing a variant Shiga-like toxin type II operon is associated with both A subunit residues Met4 and Gly102; Paton AW et al.; We have previously demonstrated that Escherichia coli DH5 alpha clones expressing closely-related Shiga-like toxin type II operons (designated SLT-II/OX3b and SLT-II/O48) had similar cytotoxicity for Vero cells, but differed in oral virulence for streptomycin-treated mice . Studies with chimeric toxin operons indicated that increased virulence was associated with the A subunit of SLT-II/OX3b, which differs from that of SLT-II/O48 by two amino acids (at positions 4 and 102) . In the present study, we have constructed a series of additional chimeric derivatives of the SLT-II/OX3b and SLT-II/O48 operons and assessed the effect of single A subunit amino acid substitutions on oral virulence . Maximal virulence, as judged by median survival time after oral challenge, was associated only with the combination of Met4 and Gly102, as found in the A subunit of SLT-II/OX3b.

Mutagenesis, 1995 Sep, 10(5), 463 - 6
Growth rate effects of mutations conferring streptomycin-dependence and of ancillary mutations in the rpsL gene of Escherichia coli: implications for the clustering (hypermutation) hypothesis for spontaneous mutation; Timms AR et al.; Colonies of newly arising streptomycin-dependent (SmD) mutants frequently contain a high proportion of cells with additional mutations (ancillary mutations) in the same gene (rpsL) . The ancillary mutations appear to have arisen at a rate greatly above expectation . To better estimate this rate it is necessary to allow for any selective advantage conferred by the ancillary mutations . We have previously measured their effect on growth rate of established SmD strains in the presence of streptomycin . In the present work a pair of single and double mutant alleles (rpsL832 and rpsL852 respectively) has been employed together with the wild-type allele to model the situation soon after such mutations first arise, i.e . when the cell still contains wild-type S12 protein (the rpsL gene product) . When these alleles, under the control of an IPTG-inducible promoter and carried on a plasmid, were expressed in the presence of a chromosomal wild-type allele, the double mutant allele permitted much faster cell growth than the single mutant allele . In the presence of streptomycin, and with rpsL+ on a plasmid, bacteria with a double mutant chromosomal gene grew faster than those with a single mutant chromosomal gene . If these results can be extrapolated to a bacterial cell in which an SmD mutation has just occurred, the ancillary mutation should be able to confer a selective advantage during a limited period when wild-type S12 protein is still present, both in the absence and in the presence of streptomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1995 Sep, 39(9), 2061 - 7
Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis . The GECMEI Group . Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas; Solera J et al.; Brucellosis is a common zoonosis in many parts of the world; the best regimen for the treatment of brucellosis has not been clearly determined . We have carried out a multicenter, open, controlled trial in five general hospitals in Spain to compare the efficacy and safety of doxycycline and rifampin (DR) versus doxycycline and streptomycin (DS) for the treatment of human brucellosis . The study included 194 ambulatory or hospitalized patients with acute brucellosis, without endocarditis or neurobrucellosis . The diagnostic criterion was isolation of Brucella species from blood or other tissues (n = 120) or a standard tube agglutination titer of 1/160 or more for anti-Brucella antibodies with compatible clinical findings (n = 74) . Patients were randomly assigned to receive either 100 mg of doxycycline twice daily plus rifampin, 900 mg/day, in a single morning dose for 45 days (DR group) or the same dose of doxycycline for 45 days plus streptomycin, 1 g/day, intramuscularly for 14 days (DS group) . A lack of therapeutic efficacy developed in 8 of the 100 patients in the DR group (8%) and in 2 of the 94 patients in the DS group (2%)(P = 0.10) . Relapses occurred in 16 of the 100 patients in the DR group (16%) but in only 5 of the 94 patients in the DS group (5.3%) (P = 0.02) . When relapse was considered in combination with initial lack of efficacy, 26 patients in the DR group (24%) and 7 patients in the DS group (7.45%) failed to respond to therapy (P = 0.0016) . In general, therapy was well tolerated and only four patients (4%) in the DR group and two (2%) in the DS group had episodes of adverse effects necessitating discontinuation of treatment (P> 0.2) . We conclude that a doxycycline-and-rifampin regimen is less effective than the doxycycline-and-streptomycin regimen in patients with acute brucellosis.

Cornea, 1995 Sep, 14(5), 457 - 62
Positive donor rim culture in penetrating keratoplasty; Gomes JA et al.; A 3-year retrospective study on the risk factors of positive donor rim cultures in penetrating keratoplasty was performed . One thousand and ninety-seven consecutive donor rim cultures were reviewed from the period between June 1990 and October 1993 to determine the rate of culture positivity . The sex, age, diabetes status, use of respirator at time of death, cause of death, harvesting technique, storage time, and corneal storage medium utilized for the donors with positive donor rim culture were compared to those for 100 randomly selected culture negative donor controls . Logistic analysis was performed to eliminate confounding effects . Forty-six of the 1,097 (4.19%) donor rim cultures were positive . We found an association between the in situ technique for donor harvesting and culture negativity (p = 0.03) . None of the other donor characteristics was associated with culture positivity . None of the 46 recipients who received the positive culture corneas developed endophthalmitis . In situ cornea harvesting promotes less contamination than enucleation and enriched gentamicin and streptomycin storage medium may further decrease donor rim culture positivity.

Bull Pan Am Health Organ, 1995 Sep, 29(3), 226 - 36
Restriction fragment length polymorphism (RFLP) analysis and tuberculosis epidemiology; Gomez Marin JE et al.; In order to study polymorphisms of the DNA insertion sequence 6110 (IS6110) in Mycobacterium tuberculosis strains isolated from Colombian patients, together with resistance to antituberculous medications in the Department of Quindio, Colombia, a prospective study was conducted using a consecutive sample of 59 patients with symptomatic pulmonary tuberculosis whose cases had been confirmed by bacilloscopy, both with and without a history of treatment . The patients, who were participating in the Tuberculosis Control Program of the Regional Health Institute of Quindio in Armenia, included all individuals attending local health centers and hospitals between March and July 1993 who were referred to the regional institute . Sputum specimens from each patient were cultured and subjected to drug sensitivity tests . Subsequently, restriction fragment length polymorphisms (RFLP) of IS6110 from 27 patients were analyzed . The patients' treatment histories were used to classify their cases according to WHO criteria . Forty-five cultures were found positive, 44 for M . tuberculosis and 1 for M . africanum . Initial drug resistance was observed in 4 of 42 new cases, or 9.5% (95% CI: 0.6, 18), 2 showing resistance to isoniazid (INH) and 2 to isoniazid plus streptomycin (INH-SM) . Acquired resistance was observed in 2 of the 3 chronic cases and relapses, the bacteria being resistant to isoniazid, rifampicin, and streptomycin (INH-RM-SM) in one case and to isoniazid, ethambutol, rifampicin, and streptomycin (INH-EMB-RM-SM) in the other . In those 27 strains subjected to RFLP analysis, the number of copies of IS6110 ranged from 6 to 17 . Similarity coefficients revealed five distinct groups of strains . Overall, the RFLP analysis permitted most of the strains to be distinguished from one another, implying that the polymorphisms involved are sufficient to permit effective employment of this technique, which appears to have considerable potential for use in epidemiologic studies and in work designed to provide a basis for tuberculosis control program decision-making.

Prep Biochem, 1995 Aug, 25(3), 89 - 97
Interference of nucleases in cyanobacterium ferredoxin purification; Bes MT et al.; Isolation of cyanobacterial ferredoxin is normally carried out using nucleases in order to degrade the nucleic acids that accompany this protein during the purification procedure . However, this practice presents the inconvenience that these proteins remain in trace amounts in the purified ferredoxin preparations, although they are not visible by electrophoretical techniques . Evidence of that fact is shown in this report and an alternative procedure is described for the rapid preparation of ferredoxin from crude extracts of Anabaena PCC 7119 . The method involves a treatment of the crude extract with streptomycin sulphate, a high molecular weight polication that precipitates the nucleic acids in the beginning of the purification.

Tuber Lung Dis, 1995 Aug, 76(4), 286 - 9
Impact of the change from an injectable to a fully oral regimen on patient adherence to ambulatory tuberculosis treatment in Dar es Salaam, Tanzania; Chum HJ et al.; OBJECTIVE: To measure the impact on patient adherence to directly observed ambulatory tuberculosis treatment substituting an all-oral treatment regimen for a regimen containing streptomycin . METHODS: The expected and observed attendance of patients during the intensive phase of anti-tuberculosis treatment was measured daily at two out-patient clinics in Dar es Salaam . During the observation period, treatment was changed from a regimen containing streptomycin to an all-oral regimen, and attendance proportions were compared for the three periods during which patients always, sometimes or never received streptomycin during the intensive phase of treatment . RESULTS: In Kinondoni, an average of 98 patients was expected every day, in Ilala 127 . No significant difference was observed in attendance in Kinondoni between periods when patients always (median attendance 95.9%) and never (median 95.7%) received streptomycin injections as part of their intensive phase treatment for tuberculosis . In Ilala, no difference was noted in attendance between the period in which patients received streptomycin for at least part of their treatment (median 91.3%) and the period when ethambutol had fully replaced streptomycin (median 91.8%) . CONCLUSIONS: In these two districts of Dar es Salaam, patient adherence to a completely oral treatment regimen was indistinguishable from that to a streptomycin-containing regimen . Given the potential of iatrogenic transmission of HIV and the advantages in reduced staff time and drug costs, the results clearly justify the replacement of streptomycin with ethambutol in Tanzania for new patients receiving an ambulatory rifampicin-containing regimenPIP: In a comparative study conducted among outpatients at tuberculosis clinics in the Ilala and Kinondoni districts of Dar es Salaam, no difference in patient compliance was recorded between streptomycin injection and an all-oral treatment regimen . An all-oral regimen was considered desirable because of concerns about injection-related human immunodeficiency virus (HIV) transmission, the high cost of streptomycin, and the staff time involved in providing injections; on the other hand, it was unclear whether patients would accept a change to oral ethambutol . In Kinondoni District, where an average of 127 tuberculosis patients are expected daily, 95.9% of the expected patients attended in the initial phase when streptomycin was still given, 97.1% in the transition period, and 95.7% once the oral regimen had been fully implemented . In Ilala, where there was no baseline survey due to nonavailability of streptomycin, attendance was 91.8% of expected when the oral regimen was put into place . Encouraged by these findings, Tanzania's national tuberculosis control program has replaced streptomycin injection with oral ethambutol administration . It is speculated that the shorter clinic waiting times involved in this regimen have helped to maintain a high level of attendance . In this culture, at least, oral regimens do not appear to be perceived as less effective or important than injections .

Z Gastroenterol, 1995 Aug, 33(8), 440 - 4
{Tuberculous anal fistula in acquired immunologic deficiency syndrome}; Musch E et al.; We report here on a 36-year old, HIV-positive patient, who was sent to hospital with an anal fistula . A short time later during the course of an extensive diagnosis the anal fistula was recognized as an extrapulmonary manifestation of a miliary tuberculosis stemming from an immunodeficiency syndrome . A rapid conversion of the sputum, a normalization of the radiological findings and the absence of relapse are the results of the classic systemic fourfold therapy with myambutol, isoniazid, rifampicin and streptomycin . The danger of overlooking the fact that an anal fistula can be the clinically primary manifestation of a tuberculosis and the problems of a mixed infection within the scope of the acquired immunodeficiency syndrome are discussed . Tuberculosis as a frequent complicating infection of HIV-positive patients--often diagnosed some time before the AIDS-infection as in our patient--can be successfully cured by a high dose of intravenous pharmacotherapy, even when additional complications (parasitic stomatitis, increasing deterioration of the immunological parameters) are present . In order to show the large spectrum of the problems involved in the diagnosis, the therapy and the course of the active acquired immunodeficiency syndrome, we have focused here on the detailed description of the case report.

Spine, 1995 Aug 1, 20(15), 1709 - 12
Latent solitary tuberculous psoas abscess 52 years after healed thoracolumbar tuberculous spondylitis; Korovessis P et al.; STUDY DESIGN . This study reports on an extremely rare case of tuberculous psoas abscess and describes the mode of diagnosis and treatment . OBJECTIVE . This patient is presented to emphasize that cases of solitary psoas abscess resulting from tuberculosis exist today . SUMMARY OF BACKGROUND DATA . No recent cases of latent solitary tuberculous psoas abscess have been reported, to the authors' knowledge . METHODS . A tuberculous psoas abscess associated with fistula to the greater trochanter may remain dormant for years after tuberculous spondylitis has healed, as a distinct entity without concomitant active bone infection . In our 58-year-old female patient, the diagnosis of a psoas abscess was greatly aided by the "three pass" technetium bone scan and computed tomography, but the anamnesis also was important . RESULTS . Anti-tuberculosis medication (streptomycin, aminosalicylic, and isoniazid) combined with open drainage, curettage of the psoas, and simultaneous revision of the fistula eradicated the disease, making the course of the disease uneventful until the 5-year follow-up evaluation . CONCLUSIONS . Orthopedic surgeons must be aware of the rare, delayed appearance of a solitary psoas abscess after tuberculous spondylitis.

Infect Immun, 1995 Jul, 63(7), 2450 - 8
Comparative toxicity and virulence of Escherichia coli clones expressing variant and chimeric Shiga-like toxin type II operons; Paton AW et al.; Shiga-like toxin (SLT)-producing strains of Escherichia coli are known to cause diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome in humans . The SLTs, particularly those related to type II (SLT-II), are a diverse family of toxins which may have differing in vitro or in vivo properties . To examine the impact of naturally occurring SLT-II sequence variation on the capacity of a given E . coli strain to cause disease, operons encoding four different SLT-II-related toxins, designated SLT-II/O111, SLT-II/OX3a, SLT-II/OX3b, and SLT-II/O48, were cloned in the same orientation in pBluescript . French pressure cell lysates of E . coli DH5 alpha derivatives carrying these plasmids differed markedly in cytotoxicity for Vero cells, with 50% cytotoxic doses ranging from 20 to 328,000/ml . The strains also differed in oral virulence for streptomycin-treated mice, as judged by survival rate and/or median survival time, but virulence did not necessarily correlate with in vitro cytotoxicity . The SLT-II type associated with the lowest oral virulence was SLT-II/O111 . Both the overall survival rate and the median survival time of mice challenged with clones producing this toxin were significantly greater than that for mice challenged with a clone producing the closely related SLT-II/OX3a . Experiments with clones carrying chimeric O111/OX3a SLT-II operons indicated that the reduced virulence was associated with an Arg-176-->Gly substitution in the mature A subunit . Clones producing SLT-II/O48 and SLT-II/OX3b had similarly high cytotoxicities for Vero cells, but the latter was more virulent when fed to streptomycin-treated mice, as judged by median survival time . Experiments with clones carrying chimeric O48/OX3b SLT-II operons indicated that the increased virulence was a function of the A subunit of SLT-II/OX3b, which differs from the A subunit of SLT-II/O48 by only two amino acids (Met-4-->Thr and Gly-102-->Asp, respectively) . These findings raise the possibility that naturally occurring SLT-II sequence variations may impact directly on the capacity of a given SLT-producing E . coli strain to cause disease.

Food Chem Toxicol, 1995 Jul, 33(7), 597 - 600
Protection by lysosomal hydrolase inhibitors against cytotoxicity of 2-chloroethylethyl sulfide; Sok DE et al.; A possible participation of lysosomal hydrolases in the cytotoxicity of 2-chloroethylethyl sulfide in spleen lymphocytes was investigated using inhibitors of lysosomal phospholipases and proteases . Pepstatin (6 microM) and leupeptin (60 microM), inhibitors of lysosomal proteases, raised the viability of lymphocytes exposed to 2-chloroethylethyl sulfide from 63 to 87 and 88% of control, respectively . Serine protease inhibitors showed no significant effect on viability . Aminoglycoside inhibitors of lysosomal phospholipases were also found to prevent the decrease in viability of spleen lymphocytes exposed to 2-chloroethylethyl sulfide, and the effectiveness of these aminoglycosides (30 microM) was as follows: gentamicin > kanamycin > streptomycin, with viability increased to 89, 79 and 67%, respectively . In contrast to a co-operative action between leupeptin and gentamicin, the protection by pepstatin was reduced in the presence of gentamicin . Moreover, the order of the aminoglycosides in terms of the extent to which they antagonized the protective action of pepstatin was the same as their order of efficacy in preventing the cytotoxicity of CEES . It is suggested that inhibitors of lysosomal hydrolases reduce the cytotoxicity of 2-chloroethylethyl sulfide, presumably through lysosomal stabilization in spleen lymphocytes.

Eur Respir J, 1995 Jul, 8(7), 1076 - 83
Drug-resistant tuberculosis in northern Germany: a retrospective hospital-based study of 1,055 patients from 1984 until 1993; Borchardt J et al.; For the past decade, there have been no data on the time course of drug resistant tuberculosis and on risk factors for drug resistance in former West Germany . We reviewed the medical records of all patients with positive cultures for Mycobacterium tuberculosis from 1984 until 1993 in a hospital near Hamburg . Drug-susceptibility testing was performed for isoniazid, rifampicin, ethambutol, and streptomycin, using the modified proportion method . Of 1,055 patients, 9.6% had isolates resistant to one or more drugs . Of the isolates, 5.8% showed resistance to isoniazid or rifampicin and 1.8% to both isoniazid and rifampicin . There was no significant change of the resistance rate during the study period . Twenty six percent of 89 patients from South America, Africa or Asia had isolates resistant to one or more drugs, compared with 7.6% of 799 patients born in Germany (odds ratio (OR) 4.2; 95% confidence interval (95% CI) 2.5-7.3) . Among patients born in Germany, 32% of 101 patients with a history of prior anti-tuberculosis drug therapy had resistant organisms, versus 4.2% of 698 patients without prior therapy (OR 10.7; 95% CI 6.1-18.7) . Resistance rates for 35 patients, who had been treated within the last 5 yrs, and for 65 patients, who had been treated more than 5 yrs ago, were 57 and 17%, respectively (OR 6.6; 95% CI 2.9-16.6) . Our results suggest that there is no increase in the proportion of drug-resistant tuberculosis in our hospital, and that patients with a recent history of antituberculosis drug therapy and patients from South America, Africa, or Asia are at high risk for drug resistance.

Eur J Surg, 1995 Jul, 161(7), 471 - 3
Tuberculosis of the breast; Goksoy E et al.; OBJECTIVE: To present our 20 years experience of tuberculosis of the breast . DESIGN: Retrospective study . SETTING: Teaching hospital, Turkey . SUBJECTS: 9 women with tuberculous mastitis . MAIN OUTCOME MEASURE: Cure . RESULTS: All cases underwent frozen section and excision . One required a simple mastectomy because of the extent of destruction; the remainder underwent lumpectomy . All patients were given rifampicin, ethambutol, and isoniazid, and the three who had tuberculosis of other organs were also treated with streptomycin . Mean follow up was 87 months (range 6-178) and two patients were lost to follow up, at three and six years, respectively . Histological examination showed the presence of tubercle and central caseation in 8 cases and granulomatous infiltration in one . CONCLUSION: Tuberculous mastitis is rare, and should be suspected in any woman with persistent breast abscesses and sinuses, particularly if she lives in an area from which tuberculosis has not been eradicated . Conservative surgery and antituberculous drugs are the treatment of choice.

Arch Biochem Biophys, 1995 Jun 20, 320(1), 106 - 14
Protein oxidation and aging . I . Difficulties in measuring reactive protein carbonyls in tissues using 2,4-dinitrophenylhydrazine; Cao G et al.; A current hypothesis explaining the aging process implicates the accumulation of oxidized protein in animal tissues . This hypothesis is based on a series of reports showing an age-dependent increase in protein carbonyl content and an age-dependent loss of enzyme function . This hypothesis is also supported by the report of a novel effect of N-tert-butyl-alpha-phenylnitrone (PBN) in reversing these age-dependent changes . Here we specifically study the method that was used to measure reactive protein carbonyls in tissues . This method uses 2,4-dinitrophenylhydrazine (DNPH) and includes a washing procedure . Our results indicate that reactive protein carbonyls in normal crude tissue extracts cannot be reliably measured by this method, although it does reliably measure reactive carbonyls in purified proteins which have been oxidatively modified in vitro . The nucleic acids in tissues could be a major problem encountered in the assay . Using the streptomycin sulfate treatment combined with a dialysis step, we were successful in removing most nucleic acids from a crude tissue extract, but then the reactive carbonyl level in the crude tissue extract was too low to be reliably measured . This streptomycin sulfate treatment procedure, however, had no effect on the reactive carbonyl measurement of an oxidized protein sample . The unwashed free DNPH was another major problem in the assay because of its very strong absorption around 370 nm, where reactive carbonyls were quantitated . Nevertheless, on using the procedure described in the literature to measure total "reactive carbonyls" in rat liver and gerbil brain cortex, no change with age or PBN treatment was found . Then, we investigated a HPLC procedure which uses sodium dodecyl sulfate in the mobile phase but this was also found to be unsuitable for the reactive protein carbonyl assay in tissues.

Circulation, 1995 Jun 1, 91(11), 2712 - 6
Suppression of ventricular arrhythmias during ischemia-reperfusion by agents inhibiting Ins(1,4,5)P3 release; Du XJ et al.; BACKGROUND: Reperfusion following myocardial ischemia causes a rapid and transient release of inositol (1,4,5)triphosphate {Ins(1,4,5)P3} . The aim of this study was to test whether this increased Ins(1,4,5)P3 release was important for the development of ventricular arrhythmias and whether agents that inhibit this signal transduction pathway, such as aminoglycoside antibiotics, suppress arrhythmias . METHODS AND RESULTS: In perfused rat hearts, ventricular tachycardia (VT), ventricular fibrillation (VF), and accumulation of Ins(1,4,5)P3 were measured during early reperfusion . A number of different compounds, including neomycin, gentamicin, streptomycin, spermine, reserpine, and prazosin, were effective in inhibiting the reperfusion-induced Ins(1,4,5)P3 release and the onset of VT and VF in parallel . A strong correlation existed between Ins(1,4,5)P3 content, measured at 2 minutes of reperfusion, and the incidence of reperfusion VT and VF . In addition, intravenous gentamicin suppressed the onset of arrhythmias under ischemic and reperfusion conditions in vivo . CONCLUSIONS: Our results are consistent with the view that Ins(1,4,5)P3 release plays a pivotal role in mediating arrhythmias during early reperfusion . Agents inhibiting Ins(1,4,5)P3 release are antiarrhythmic and may have potential use clinically.

Kekkaku, 1995 Jun, 70(6), 369 - 76
{A clinical experience of DNA probe method for identifying Mycobacterium avium and Mycobacterium intracellulare}; Tsuda M et al.; In Japan the number of patient infected with M . avium complex (MAC) has been increasing in contrast to a decrease of pulmonary tuberculosis . DNA probe method enabled us be able to differentiate an isolated MAC into M . avium and M . intracellulare . From 1991 to 1992, we performed an investigation to apply this new technique of the DNA probe method on 52 patients of atypical mycobacteriosis diagnosed as infected with MAC by the ordinary method at the Higashi Nagoya National Hospital . The group consisted of 27 males and 25 females . M . avium infection was found in 39 patients (M . avium group) and M . intracellulare in 16 patients (M . intracellulare group) . No significant gender difference was found between two groups . The M . avium group showed more complications in contrast to the M . intracellulare group . As complications in the M . avium group, pulmonary aspergillus infection, bacterial pneumonia and bronchiectasis were found in 4, 3 and 2 cases, respectively . The rate of drug resistance to antituberculosis drugs was high in the both groups . Chemotherapy with isoniazid (INH) rifampin (RFP) and streptomycin (SM) in five patients, that with INH, RFP and ethambutol (EB) in three were found to be effective after 4 months treatment . Three patients in M . avium group died of respiratory failure, aspergillus infection and renal failure . In contrast the prognosis of patients in the M . intracellulare group seemed to be better as there was no fatal case . We conclude that DNA probe method is useful to differentiate between M . avium and M . intracellulare, and enable us to select more appropriate selection of the chemotherapy and to assess of the prognosis.

Hua Xi Yi Ke Da Xue Xue Bao, 1995 Jun, 26(2), 167 - 71
{Study on the lung targeting gelatin microspheres of streptomycin sulphate}; Zhang Z et al.; This paper is reported the technology of lung targeting gelatin microspheres of streptomycin sulphate (SMS) . The microspheres were prepared with natural biodegradable gelatin as the load material and castor oil as the oil phase . The experimental conditions were optimized, the mean volume diameter obtained being 9.7 microns and the mean rate of encapsulation 15.69% . The content, shape and size of the microspheres showed no remarkable change after storage at 37 degrees C RH 75% for 3 months . Activation energy of heat decomposition E = 75.86kJ/mol . In vitro, the SMS release rate was found to accord with Higuchi equation with t1/2 = 8.6h . In vivo (rabbits) the gelatin microspheres were proved to be concentrated in the lung.

Mol Microbiol, 1995 Jun, 16(5), 991 - 1000
rpsL+: a dominant selectable marker for gene replacement in mycobacteria; Sander P et al.; Molecular genetic manipulations in mycobacteria would benefit from procedures which efficiently select for double-crossover events by homologous recombination . Here we describe a vector-host system for gene replacement in mycobacteria, the utility of which was investigated using functional inactivation of the pyrF gene in Mycobacterium smegmatis as a model . This system is based on the expression of the wild-type rpsL gene coding for ribosomal protein S12 in a streptomycin-resistant host . Owing to the absence of a mycobacterial origin the plasmids are unable to replicate autonomously in mycobacteria . The first selection for maintenance of cloned sequences is conferred by the kanamycin-resistance gene . The second simultaneous selection by streptomycin is against maintenance of cloned sequences which contain the gene encoding the streptomycin-sensitive allele of the rpsL gene . By placing the gene for positive selection and that used for negative selection within and outside the target gene of interest, respectively, gene replacement is obtained . A one-step double selection procedure provides a means to distinguish strictly between gene replacement by double crossover versus homologous recombination by single crossover events . The system should have considerable potential for genera or species where single-crossover events or even illegitimate recombination are the predominant recombination mechanisms . It should also be of wide use for the construction of mutants without a selectable phenotype.

Mol Gen Genet, 1995 May 10, 247(3), 295 - 305
The chloroplast gene encoding ribosomal protein S4 in Chlamydomonas reinhardtii spans an inverted repeat--unique sequence junction and can be mutated to suppress a streptomycin dependence mutation in ribosomal protein S12; Randolph-Anderson BL et al.; The ribosomal protein gene rps4 was cloned and sequenced from the chloroplast genome of Chlamydomonas reinhardtii . The N-terminal 213 amino acid residues of the S4 protein are encoded in the single-copy region (SCR) of the genome, while the C-terminal 44 amino acid residues are encoded in the inverted repeat (IR) . The deduced 257 amino acid sequence of C . reinhardtii S4 is considerably longer (by 51-59 residues) than S4 proteins of other photosynthetic species and Escherichia coli, due to the presence of two internal insertions and a C-terminal extension . A short conserved C-terminal motif found in all other S4 proteins examined is missing from the C . reinhardtii protein . In E . coli, mutations in the S4 protein suppress the streptomycin-dependent (sd) phenotype of mutations in the S12 protein . Because we have been unable to identify similar S4 mutations among suppressors of an sd mutation in C . reinhardtii S12 obtained using UV mutagenesis, we made site-directed mutations {Arg68 (CGT) to Leu (CTG and CTT)} in the wild-type rps4 gene equivalent to an E . coli Gln53 to Leu ribosomal ambiguity mutation (ram), which suppresses the sd phenotype and decreases translational accuracy . These mutants were tested for their ability to transform the sd S12 mutation of C . reinhardtii to streptomycin independence . The streptomycin-independent isolates obtained by biolistic transformation all possessed the original sd mutation in rps12, but none had the expected donor Leu68 mutations in rps4 . Instead, six of 15 contained a Gln73 (CAA) to Pro (CCA) mutation five amino acids downstream from the predicted mutant codon, irrespective of rps4 donor DNA . Two others contained six- and ten-amino acid, in-frame insertions at S4 positions 90 and 92 that appear to have been induced by the biolistic process itself . Eight streptomycin-independent isolates analyzed had wild-type rps4 genes and may possess mutations identical to previously isolated suppressors of sd that define at least two additional chloroplast loci . Cloned rps4 genes from streptomycin-independent isolates containing the Gln73 to Pro mutation and the 6-amino acid insertion in r-protein S4 transform the sd strain to streptomycin independence.

Eur Respir J, 1995 May, 8(5), 866 - 8
Ethambutol-induced pulmonary infiltrates with eosinophilia and skin involvement; Wong PC et al.; A 67 year old woman presented with miliary tuberculosis . She was treated with streptomycin, isoniazid, rifampicin, ethambutol and pyrazinamide . However, she developed rifampicin-induced thrombocytopenia after 6 weeks of treatment, and skin rash, blood eosinophilia and pulmonary infiltrates after 8 weeks of therapy . The latter was found to be ethambutol related . Additional evidence, including blood and sputum eosinophilia and the rapidity of its response to corticosteroid, suggested that the pulmonary infiltrates might also be eosinophilic in nature . To the best of our knowledge, this constitutes the first report of such adverse drug reaction, induced by ethambutol.

J Clin Microbiol, 1995 May, 33(5), 1231 - 7
Rapid susceptibility testing of Mycobacterium tuberculosis (H37Ra) by flow cytometry; Norden MA et al.; The resurgence of tuberculosis has caused considerable effort to be focused on the development of rapid methods for determining the susceptibility of Mycobacterium tuberculosis to antimycobacterial agents . We demonstrated that susceptibility testing of M . tuberculosis can be accomplished rapidly by using flow cytometry . Results of tests were available within 24 h after M . tuberculosis organisms were incubated with ethambutol, isoniazid, rifampin, or streptomycin . The method was based on the ability of viable M . tuberculosis organisms to hydrolyze fluorescein diacetate (FDA) and the detection of fluorescent mycobacteria by flow cytometric analysis . The assay system also did not require multiplication of the mycobacteria . In contrast, M . tuberculosis organisms exposed to antimycobacterial agents hydrolyzed significantly less FDA . The use of flow cytometry and FDA staining shows considerable promise as a rapid method for obtaining susceptibility test results.

Lancet, 1995 Apr 8, 345(8954), 907 - 10
Patterns of initial and acquired antituberculosis drug resistance in Karonga District, Malawi; Glynn JR et al.; There is concern that drug-resistant tuberculosis is increasing and may be concentrated among HIV-positive patients . Little information is available from developing countries, where surveillance studies are often unable to distinguish resistance in previously untreated patients (initial resistance) from resistance acquired following drug therapy, and where information on the HIV status of the patients is rare . Initial resistance patterns reflect the strains being transmitted in the community . We have studied patterns of resistance in northern Malawi, where the Lepra Evaluation Project has been collecting data on drug resistance since 1986 . Initial drug sensitivity results were available for 373 new cases of tuberculosis . Initial resistance to at least one drug was found in 44 of these patients (11.8%, 95% CI 8.5-15.1): 13 were resistant to streptomycin alone, 13 to isoniazid alone, and 17 to more than one drug . Only 3 patients showed initial rifampicin resistance-1 in isolation, 1 in combination with streptomycin, and 1 with triple resistance . Drug resistance was not related to age, sex, or HIV status of the patient and there was no evidence of any increase over the period studied . There was no evidence of geographic clustering of the resistant strains, or of any increased risk of resistant strains in households with previous tuberculosis cases . Acquired resistance during follow-up was found in 5 of 329 patients with documented initially fully sensitive strains . 5 patients with initial resistance seemed to show reversion to sensitivity . The absence of an increase in drug resistance, despite an increase in tuberculosis cases over the period, is encouraging for the control programme . It emphasises the need to collect information from many areas before assuming that increases in antituberculosis drug resistance are occurring worldwide.

Can J Microbiol, 1995 Apr-May, 41(4-5), 407 - 17
Dependence on reporter gene of apparent activity in gene fusions of a Streptomyces griseus streptomycin biosynthesis promoter; Lindley HK et al.; The adjacent genes strR-strA-strB1 lie within the large cluster of genes of streptomycin biosynthesis and resistance in Streptomyces griseus . strR encodes a pathway-specific activator StrR, suggested by previous work to be either an antiterminator or a conventional activator, binding to its DNA target via a helix-turn-helix motif . strB1 is transcribed in an StrR-dependent fashion from a promoter (PstrB1) that lies downstream from strA; between PstrB1 and strB1 there is a 300-bp leader region containing numerous inverted repeats that could represent modulatable transcription termination sites . Hybrid plasmids were constructed in vitro with transcriptional fusions in which fragments containing PstrB1 and either the entire leader region ("long" fragments) or a small part of it (the "short" fragment) were cloned upstream of (i) aph as reporter gene, in a high copy number plasmid background, or (ii) xylE as reporter gene, in a low copy number plasmid background . The short fragment directed high levels of APH (aminoglycoside 3'-phosphotransferase) whether StrR was present or not, while the long fragments did not do so in the absence of StrR; one long fragment directed high levels in wild-type S . griseus, in which StrR would be present . Insertion of an extraneous fragment into PstrB1 in the short fragment construct led to loss of APH activity, demonstrating that no adventitious promoter had been formed in the short construct . In vitro deletion of part of the leader region in a long fragment construct led to high APH expression with or without StrR present . Although these results are consistent with the target of StrR being within the leader region, and thus with an antiterminator role, it was found that both long and short fragments in the low copy number background failed to direct high expression of catechol oxygenase (the product of xylE) unless strR was also present on a compatible plasmid . Transfer of PstrB1-xylE fragments to the high copy number vector did not increase catechol oxygenase expression . We interpret these results in terms of an effect, in the hybrid constructs, of one of the reporter genes on promoter function, possibly by affecting local DNA topology.

Presse Med, 1995 Apr 1, 24(13), 601 - 5
{Tuberculosis in Africans hospitalized in Paris . Impact of infection by the human immunodeficiency virus}; Cabie A et al.; OBJECTIVES: Human immunodeficiency virus (HIV) infection has greatly modified the epidemiology and clinical course of tuberculosis . The aim of this study was to analyze the characteristics of tuberculosis in African patients hospitalized in Paris by comparing clinical features in patients with and without HIV infection . METHODS: Hospital records of 71 patients from Africa hospitalized between 1989 and 1992 in Paris with a certain or probable diagnosis of tuberculosis were studied retrospectively . RESULTS: There were 30 patients (42%) with HIV infection . In 12 of them (40%) HIV positivity was discovered at diagnosis of tuberculosis . Age, sex, and duration of residence in France before diagnosis were similar between HIV+ and HIV- patients . Pulmonary tuberculosis was found in 23 patients and extrapulmonary forms (mainly lymph node involvement) were seen in 34; both in 14 patients . There was no difference in localization between HIV+ and HIV- patients except for disseminated tuberculosis which was more frequent in HIV+ patients . Skin reactions to tuberculin were positive in 76% and 97% of the HIV- and HIV+ patients respectively (p < 0.02) . Drug resistance was observed in 8 patients (6 HIV+): streptomycin (n = 6), pyrazinamide (n = 2), isoniazide (n = 2), ethambutol (n = 1) and rifampicin (n = 1) . Drug therapy was successful in controlling the initial manifestations of tuberculosis in both HIV+ and HIV- patients . CONCLUSION: Extrapulmonary forms of tuberculosis, especially lymph node infection was more frequent in Africans hospitalized in Paris, whether the patients were HIV positive or negative . HIV infection was associated with disseminated tuberculosis, non-excavated pulmonary tuberculosis and undesirable side effects of antituberculosis drugs.

J Infect Dis, 1995 Apr, 171(4), 954 - 60
Molecular mechanisms of multiple drug resistance in clinical isolates of Mycobacterium tuberculosis; Morris S et al.; The molecular mechanisms of resistance to streptomycin, rifampin, and isoniazid in 53 Mycobacterium tuberculosis clinical isolates were examined . Twenty-five of 44 streptomycin-resistant strains had mutations in the rpsL gene and 5 of these had rrs gene perturbations . The region of the rpoB gene that is associated with resistance to rifampin was altered in 28 of 29 rifampin-resistant strains . Mutations in known genetic markers of isoniazid resistance were detected in 25 of 42 isoniazid-resistant isolates: 20 strains had katG gene alterations and 5 had perturbations in the inhA operon . Of the 20 multiply resistant strains with reduced sensitivity to streptomycin, rifampin, and isoniazid, 11 had mutations in genetic markers associated with resistance to each of these three drugs . These studies suggest that the primary mechanism of multiple drug resistance in tuberculosis is the accumulation of mutations in individual drug target genes.

Scanning Microsc, 1995 Mar, 9(1), 283 - 8
Scanning electron microscopic observation of dark cells after streptomycin perfusion of the vestibule in guinea pigs; Ge X et al.; Hearing has been stabilized in the majority of patients studied in the treatment of Meniere's disease with streptomycin . This observation suggests that effects of streptomycin may ameliorate endolymphatic hydrops, possibly by attenuating the activity of secretory tissue . The purpose of this study is to observe the dark cells of the utricle in guinea pigs after streptomycin perfusion of the vestibule . Twelve pigmented guinea pigs weighing 250-350 grams were used in this study . The vestibules in five guinea pigs were perfused monolaterally with 150 micrograms of streptomycin in artificial perilymph and, in seven, the vestibules were perfused only with artificial perilymph as a control group . Specimens were processed for observation with a scanning electron microscope . After streptomycin perfusion, the margin of the dark cells became indistinct . The luminal surface of the cells bulged out like a dome . The microvilli decreased or were absent, and some debris was deposited on the surface . In four of the five animals, the luminal membrane of the dark cell ruptured . The cytoplasm and organelle extruded into the endolymphatic space . After the cellular debris moved out into the endolymph, either a vanished cell or a nucleus in an empty nest was observed . These cells appeared damaged and destroyed . The results indicate that the dark cells in the membranous wall of the utricle were affected by streptomycin . The results lead to the assumption that streptomycin may reduce the volume of endolymph by damaging the dark cells of the utricle.

J Bone Joint Surg Br, 1995 Mar, 77(2), 319 - 26
Tuberculosis of the hip in children; Campbell JA et al.; We have reviewed 74 tuberculous hips in 73 children treated from 1950 to 1991 . From 1979 to 1991 we treated 28 patients with rifampicin, isoniazid and pyrazinamide given for nine months (series A), using active mobilisation for the more recent cases . Before this, 46 hips had been treated with streptomycin and isoniazid with or without para-aminosalicyclic acid given for a mean of 18 months (series B), and all these patients were immobilised for a mean of 2.2 years . The radiological appearances at presentation as classified by Shanmugasundaram (1983) predicted the outcome . Most hips were of the 'normal' type (50% and 59% of series A and B respectively) followed by the dislocating type (25% and 13%) and the atrophic type (8% and 9%) . There were good or excellent results in 93% of the 'normal' type . All the atrophic type had poor results . The dislocating type had a poor result if the joint space was narrow after reduction of the hip . Early mobilisation had no effect on the outcome of the 'normal' type of disease . The newer drug regimens allowed for shorter courses of treatment, but did not necessarily give a better outcome.

Antimicrob Agents Chemother, 1995 Mar, 39(3), 769 - 70
Novel mutation in 16S rRNA associated with streptomycin dependence in Mycobacterium tuberculosis; Honore N et al.; Molecular characterization of a streptomycin-dependent mutant of Mycobacterium tuberculosis revealed the presence of a novel mutation in the rrs gene encoding 16S rRNA . Insertion of an additional cytosine in the 530 loop of 16S rRNA, a region known to be involved in streptomycin susceptibility and resistance, was associated with streptomycin dependence.

J Inorg Biochem, 1995 Feb 15, 57(3), 209 - 18
Unsymmetrical borole complexes as biocides: synthetic, structural and biological aspects; Saxena C et al.; Triisopropoxyborane on treatment with catechol in equimolar ratio in excess of benzene affords the formation of 2-isopropoxybenzo-1,3-dioxa-2-borole {OC6H4OB(OPri)} . The interaction of {OC6H4OB(OPri)} with benzothiazolines, prepared by the condensation of {1-(2-thienyl)ethanone}, {1-(2-pyridinyl)ethanone}, {1-(2-furanyl)ethanone}, and {1-(2-naphthenyl)ethanone} with 2-mercaptoaniline, yields complexes that have B--O, B--S, and B<--N bonds . The unsymmetrical borole complexes were subjected to microestimations and spectral analyses comprised of UV, IR, proton-1, boron-11, and carbon-13 nuclear magnetic resonance studies . The spectral studies point to a tetracoordinated environment around boron because the stereochemically active lone pair is also included in the coordination sphere . X-ray powder diffraction of a representative complex also has been carried out . In the quest for better fungicides and bactericides, studies were conducted to assess the growth-inhibiting potential of the synthesized complexes along with the ligands against various fungal and bacterial strains . The studies demonstrate that the concentrations reach levels that are sufficient to inhibit and kill the pathogens . Furthermore, the results achieved from biological activity also have been compared with the conventional fungicide, Bavistin, and conventional bactericide, Streptomycin.

J Trop Med Hyg, 1995 Feb, 98(1), 9 - 21
The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia; Elliott AM et al.; To examine the effect of HIV on response to treatment and recurrence rate in patients with tuberculosis (TB), we have followed 239 previously untreated, adult, TB patients in a prospective cohort study in Lusaka, Zambia . One hundred and seventy-four (73%) were HIV-1 antibody positive . Patients with sputum smear positive, miliary, or meningeal TB were prescribed 2 months daily streptomycin, thiacetazone, isoniazid, rifampicin, pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid . Thirty-five per cent of HIV-positive (HIV+ve) and 9% of HIV-negative (HIV-ve) patients were known to have died before the scheduled end of treatment . Surviving HIV+ve patients showed weight gain and improvement in symptoms and laboratory and radiological findings similar to HIV-ve patients . The risk of cutaneous drug reaction was 17% (95% CI: 12-25%) in HIV+ve, and 4% (1-13%) in HIV-ve patients . Severe rashes were attributed to thiacetazone . Recurrence of active TB was examined among 64 HIV+ve and 37 HIV-ve patients who successfully completed treatment, with mean follow-up after the end of treatment of 13.5 and 16.8 months, respectively . The rate of recurrence was 22/100 person years (pyr) for HIV+ve patients and 6/100 pyr for HIV-ve patients, giving a recurrence rate ratio of 4.0 (95% CI 1.2-13.8, P = 0.03)PIP: In 1989, researchers followed 239 newly diagnosed adult patients with tuberculosis (TB), never previously treated for TB, for two years to examine the response to TB treatment among patients with and without HIV infection and the TB recurrence rate . They were patients in the medical wards and the chest clinic outpatients' department of the University Teaching Hospital in Lusaka, Zambia . 174 (73%) tested positive for HIV . HIV-positive patients were more likely than HIV-negative patients to have extrapulmonary and both pulmonary and extrapulmonary TB (35% and 26% for both, respectively vs . 17% and 12%, respectively; p 0.001) . They were less likely to have positive sputum tests than HIV-negative patients (36% vs . 57% for smear; p = 0.005 and 39% vs . 55% for culture; p = 0.03) . HIV-positive patients were more likely to receive standard TB therapy (62% vs . 37%), while HIV-negative patients were more likely to receive short course therapy (62% vs . 37%; p = 0.001) . HIV-positive patients were more likely than HIV-negative patients to die before completion of treatment (35% vs . 9%) . Surviving HIV-positive patients gained weight and experienced improvement in symptoms at the same rate as did surviving HIV-negative patients . They also had similar laboratory and radiological findings . HIV-positive patients had a higher risk of cutaneous drug reaction than HIV-negative patients (17% vs . 4%; hazard ratio = 5.1; p = 0.03) . One HIV-positive patient with a rash died . Thiacetazone was responsible for the rashes . Among the HIV-positive and HIV-negative patients who successfully completed treatment, the active TB recurrence rate was greatest for HIV-positive patients (22 vs . 6/100 person years; rate ratio = 4; p = 0.03) . Yet, all but one of the HIV-positive cases with recurrent TB responded well to TB treatment . High recurrence rates pose renewed potential sources of infection and a high cost of renewed treatment .

Baillieres Clin Rheumatol, 1995 Feb, 9(1), 161 - 77
Bacterial infections: osteoarticular brucellosis; Rajapakse CN; Osteoarticular brucellosis has been documented extensively from the Middle East and Spain in the last 5 years, but it has only been reported infrequently from the UK and USA . Brucella melitensis from goat and sheep is the most frequently isolated organism . Peripheral articular pain, particularly of the large joints, is the commonest osteoarticular manifestation, while effusions that seldom yield organisms on culture, also occur frequently . Sacroiliitis which most frequently is unilateral, often presents acutely and dramatically with severe pain that is poorly localized to the lower back and buttock, leading to difficulty in walking and even standing . Tapping the heel and springing the sacrum is probably the best way of localizing the pain to the sacroiliac joint in this acute stage . Lack of awareness of this pattern of presentation could lead to misdiagnosis . Spondylitis is the third major manifestation of osteoarticular brucellosis . It occurs in older patients and is insidious and chronic in onset and course . The lumbar spine is most frequently involved, although cervical involvement is frequently associated with more complications, particularly compressive neurological deficits . Osteomyelitis occurs unusually . Several large series have been reported among children . In them peripheral large joint involvement in association with systemic features predominate while sacroiliitis may occur unusually . Plain X-rays often demonstrate vertebral damage, involving the upper anterior margin most frequently . CT scans define better vertebral damage that is characterized by bony sclerosis and the less frequently encountered extradural extension and para-vertebral abscess formation . Technetium bone scan is the most sensitive technique for detecting acute sacroiliitis and other sites of early osteoarticular involvement . A four-fold rise in Brucella agglutination titre is the most frequently utilized diagnostic aid . A 6 week culture in a CO2-enriched medium is recommended for growing Brucella . Tetracycline or doxycycline 200 mg per day for 6 weeks is the mainstay of most medical treatment schedules . Combination with streptomycin for 3 weeks or rifampicin for 6 weeks is recommended, to reduce significantly the failure and relapse rate . Spinal involvement is associated with an increased failure and relapse rate while they occurred least among those with no osteoarticular involvement . Surgical intervention to stabilize the spine and relieve neurological compression may become necessary . With the use of these various measures, the outlook for complete recovery is good.

Eur J Pediatr, 1995 Feb, 154(2), 120 - 2
Neurobrucellosis in children; Estevao MH et al.; Neurobrucellosis is an uncommon disease in children . The authors present two cases of brucellar meningo-encephalitis . Headache and vomiting were the main complaints and one child had also some behavioural disturbance as well as papilloedema and sixth cranial nerve palsy . The clinical diagnosis was suggested by epidemiological data in both cases . Blood and CSF cultures confirmed brucellar aetiology in one of the cases and positive serum and CSF specific antibodies in both . Clinical course was favourable after treatment with doxycycline, rifampicin and streptomycin . No relapse occurred and there were no sequelae . CONCLUSION: Neurobrucellosis should be considered in the differential diagnosis of neurobehavioural disturbance of children living in areas where brucellosis is endemic.

Tuber Lung Dis, 1995 Feb, 76(1), 39 - 42
Silicotuberculosis: long-term outcome after short-course chemotherapy; Cowie RL; SETTING: A medical facility for approximately 90,000 gold miners employed on 24 South African gold mines . OBJECTIVE: To establish the long-term risk attributable to silicosis of relapse from pulmonary tuberculosis treated with short-course chemotherapy . DESIGN: A consecutive sample of gold miners with pulmonary tuberculosis allocated to receive rifampicin, isoniazid, pyrazinamide and streptomycin given on weekdays for 5 months . Radiographs were assessed at the time of diagnosis for the presence of silicosis . All of the men were followed for at least 5 years after completing their treatment, or until they left mine service or suffered a relapse of tuberculosis . RESULTS: The sample included 549 men of whom 167 had silicosis . The incidence density for relapse in silicosis was 1.55 (95% CI 0.97, 2.48) times that for the men without silicosis . There was no difference in the pattern of relapse over time between the two groups: the mean period to relapse in the men with silicosis was 2.6 years (SD 1.89 years) and for the men without silicosis was 3.1 years (SD 2.23 years) (P = 0.6) . CONCLUSION: Silicosis causes a small increase in the risk of relapse of tuberculosis . Relapses in both groups were not confined to the first 2 years after completion of treatment.

Zhonghua Er Bi Yan Hou Ke Za Zhi, 1995, 30(6), 329 - 31
{Effect of streptomycin placing in the fenestra of semicircular canals on the function and morphology of the normal and hydropic ears in guinea pigs}; Peng A et al.; The effect of streptomycin placed in the fenestra of lateral semicircular canal (LSC) on the function and morphology of the normal and artificial hydropic inner ears in guinea pigs was studied in order to explore the method and possibility of treating Meniere's disease by using aminoglycosides . After placing the drug in the fenestra of LSC, no change in AP threshold of ECochG in normal ears but an increase of that in hydropic ears were found caloric induced nystagmus in both groups were disappeared . Under light microscope, severe damage of vestibular epithelium of three canal cristae and utricular macula was noted, while no insult of cochlear hair cells was found in normal ears . More severe damage of vestibular epithelium with part of them degenerated and atrophied and lesions of cochlear hair cells in basal turns and part of second turns occurred in hydropic ears . These demonstrated that the ototoxicity of streptomycin was higher in hydropic ears than in normal ears . In order to destroy vestibular function and preserve cochlear function, further study for adequate dosage of streptomycin and correct route of administration is needed.

Zhonghua Er Bi Yan Hou Ke Za Zhi, 1995, 30(4), 227 - 9
{Alternation of intracellular Ca2+ caused by streptomycin in the isolated cochlear OHC}; Li Y et al.; Stained with fluorescence, the intracellular free calcium concentration (Ca2+) of the cochlear out hair cell (OHC) isolated from guinea pigs was measured using ACAS 570 . Streptomycin caused a remarkable rise in Ca2+ and reached peak value in 60s, decreased gradually after lasting for 60s in that value . The Ca2+ fell back to primary level in another 100s and followed by a slight drop . The distribution of free calcium in the OHC was showed . The rise of intracellular free calcium in the OHC was assumed to be a period in the ototoxicity caused by aminoglycoside antibiotics.

Scand J Infect Dis, 1995, 27(4), 339 - 43
Clinical and therapeutic features of childhood neurobrucellosis; al-Eissa YA; Brucellosis is a multisystem disease with diverse clinical presentations, and involvement of the nervous system is considered to be rare in childhood . Five children with meningitis (n=2), meningoencephalitis (n=1), meningomyelitis (n=1), or cerebellar ataxia (n=1) are described, all of whom had a history of exposure to a possible source of brucellosis . Examination of cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis in 4 patients, high protein concentration in 5 and low glucose concentration in 3 . Reciprocal brucella agglutination titers were significantly elevated in serum (> or = 160) and in CSF (> or = 80) of all patients . Brucella melitensis was isolated from blood and CSF in one patient, from blood only in 2, and from bone marrow only in another one . All patients were treated successfully by a three-drug combination of streptomycin (4 patients) or doxycycline (one patient) with trimethoprim-sulfamethoxazole and rifampin, and in one patient dexamethasone was also added . In endemic areas, neurobrucellosis should be suspected in the evaluation of patients with unexplained neurologic symptoms.

Arch Inst Pasteur Madagascar, 1995, 62(1), 72 - 6
{Comparison of routine therapeutic protocols used in Madagascar for the treatment of smear-positive pulmonary tuberculosis (preliminary results)}; Boisier P et al.; A survey was undertaken in April 1993 to compare the respective benefits of 2 regimens containing either streptomycin (SHRZ) or ethambutol (EHRZ) in the first two months of treatment of smear-positive pulmonary tuberculosis in Madagascar . This operational research was justified by the risks related to the use of parenteral streptomycin in a country where single use material is rare and its purpose was to provide arguments for an eventual recommendation to replace this drug by oral ethambutol which is also less expensive . 907 patients were included . The compliance was not significantly different between the 2 groups, although it was traditionally assumed to be better with streptomycin . The frequency of side effects was significantly lower with EHRZ . Overall treatment failure rates were not significantly different, but all of 6 patients who were negative at 5 months and were again positive at 8 months had received EHRZ . This point obliged to be careful before concluding, because 24% of patients were lost for follow-up . A 2 years surveillance will be necessary to compare the frequency of recurrences.

Urol Int, 1995, 55(3), 141 - 2
Epididymo-orchitis as a complication of brucellosis; Yurdakul T et al.; A study of 84 patients who were diagnosed with epididymo-orchitis between July 1987 and September 1993 is presented . Brucellosis was a complication in 14 cases (17%) . All 14 cases had elevated agglutination titers . Brucella blood culture was found to be positive in 4 of 14 cases (28.5%) . Standard therapy regime (streptomycin plus tetracycline) was effective in 13 of 14 (93%) cases.

New Microbiol, 1995 Jan, 18(1), 69 - 72
Drug resistance of Mycobacterium tuberculosis strains isolated from HIV-infected Italian patients: preliminary report from a multicentric study . The Italian Tuberculosis Drug Resistance Study Group; Angarano G et al.; A multicentric prospective study started in March '93 to describe both initial and acquired resistance of Mycobacterium Tuberculosis in Italian HIV+ patients (pts.) to first line drugs: Rifampin (R), Isoniazid (I), Pyrazinamide (P), Ethambutol (E), Streptomycin (S) . All tuberculosis (TB) cases diagnosed in HIV+ patients (pts.) were included, along with clinical-anamnestical data . Drug-susceptibility tests were performed centrally . Preliminary results indicate an overall low frequency of TB resistance to first line drugs: R = 2%, P = 4%, S = 9%, I/E = none . However, a relevant nosocomial outbreak of multiple drug resistant (DR) TB was detected . This finding, along with some previous Italian reports of DR-TB clusters, may herald a further spread of DR-TB . Surveillance, therefore, is mandatory in Italy from now on.

Trans R Soc Trop Med Hyg, 1995 Jan-Feb, 89(1), 78 - 82
The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia; Elliott AM et al.; We have examined the impact of human immunodeficiency virus (HIV) on mortality of patients treated for tuberculosis in a prospective study in Lusaka, Zambia . Patients with sputum smear-positive, miliary, or meningeal tuberculosis were prescribed 2 months' daily streptomycin, thiacetazone, isoniazid, rifampicin, and pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid . 239 patients (65 HIV-negative and 174 HIV-positive) were followed to 2 years from start of treatment . The crude mortality rate ratio for HIV-positive compared with HIV-negative patients over 2 years was 5.00 (95% confidence interval 2.30-10.86) . Median survival for HIV-positive patients from the start of treatment was 22 months . At least 34% of HIV-positive patients for whom cause of death was known died from tuberculosis, three-quarters of these during the first month of treatment . Risk factors for death in HIV-positive patients included multi-site tuberculosis, history of prolonged diarrhoea or fever, oral thrush, splenomegaly, anergy to tuberculin, low weight, anaemia or lymphopenia, and poor compliance with regimens containing rifampicin and pyrazinamide . Tuberculosis, even treated, was a major cause of death in patients with HIV infectionPIP: The impact of HIV on mortality is described in a prospective study of tuberculosis patients in Lusaka, Zambia, where more than 70% of newly diagnosed tuberculosis patients have concurrent HIV infection . Patients attending the University Teaching Hospital in Lusaka, Zambia, were recruited to a prospective cohort study from April to December 1989 . Of the 239 patients included in the follow-up study, 174 (73%) were HIV-1 positive by ELISA . A higher proportion of HIV-positive patients were 25-34 years old, and they more often had a negative tuberculin response, anemia, or lymphopenia at recruitment . The probability of survival for HIV-negative and HIV-positive patients was, respectively: at 2 months 95% and 89%; at 6 months 95% and 76%; at 12 months 91% and 66%; at 18 months 87% and 55%; and at 24 months 87% and 48% . The median survival of HIV-positive patients was 22 months . The crude, 2-year mortality rate ratio for HIV-positive compared with HIV-negative patients was 5 (p 0.001) . Mortality was higher for patients with both pulmonary and extrapulmonary disease than for those with either pulmonary or extrapulmonary disease alone; for individual sites, only lymph node disease was associated with a significantly higher mortality than other sites (p = 0.01) . At presentation prolonged fever, prolonged diarrhea, oral Candida or splenomegaly, negative tuberculin response, anemia or lymphopenia and low weight were associated with higher mortality . Among the 39 patients seen at 2 months who had been prescribed short-course chemotherapy, subsequent mortality was lower in the group who reported receiving all 60 doses of either rifampicin or pyrazinamide or both (20 patients) than among those who had not (19 patients inverted question mark (rate ratio 0.24, p = 0.02) . 47 of the 81 patients died within 24 months of the start of treatment, 5 HIV-negative and 42 HIV-positive . 3 of 5 HIV-negative patients for whom information was available died of active tuberculosis . Among HIV-positive patients, 14 of 42 died of active tuberculosis and 2 more of complications of tuberculosis .

Hear Res, 1995 Jan, 82(1), 125 - 33
Hair cell replacement in avian vestibular epithelium: supporting cell to type I hair cell; Weisleder P et al.; Previous investigations have demonstrated that the sensory epithelium of the avian vestibular system possesses the capacity to replace hair cells both on an ongoing basis and following severe damage . Supporting cells, within the sensory epithelium, are believed to be the progenitors of the regenerated hair cells . In the present study we describe the series of events leading to the formation of a regenerated vestibular hair cell in post-hatched birds . Young chickens received injections of streptomycin sulfate in order to damage the sensory epithelium of the vestibular system . These injections were followed by injections of the cell proliferation marker tritiated-thymidine . At predetermined intervals, the animals were killed, and the vestibular organs were processed for tissue autoradiography . Our results confirm that hair cells originate from supporting cells . The data also indicate that postmitotic cells migrate towards the lumen of the epithelium where they differentiate into Type II hair cells . At a later time, some of the new Type II hair cells further differentiate into Type I hair cells . These results suggest that both types of avian vestibular hair cells have a common ancestor . The data also provide evidence in support of the hypothesis that calyx enclosed Type I hair cells, only present in birds and mammals, are a more differentiated stage of Type II hair cells.

Scand J Infect Dis, 1995, 27(2), 135 - 8
Treatment of tuberculous meningitis in Turkey; Doganay M et al.; A prospective study was performed on 72 cases of tuberculous meningitis studying various treatments . 37 patients were treated with a combination of isoniazid, rifampicin, pyrazinamide and streptomycin for 2 months, followed by a combination of isoniazid and rifampicin for 6 months . 35 patients were treated with various combinations of antituberculous drugs for 12-16 months . Disappearance of symptoms took (mean) 17 days . Mean duration of therapy for the hospitalized patients was 36 +/- 4 days . Seven (9.7%) patients died, 5 in the short-course therapy group and 2 in the long-course therapy group . Sequelae persisted in 18 (31%) cases, 8 of which cases were in the short-course therapy group and 10 in the long-course therapy group . No relapse was observed in either of the groups.

Acta Otolaryngol Suppl, 1995, 519, 71 - 3
Changes in calcium distribution in the utricular supporting cells of the guinea pig; Mori N et al.; Changes in calcium distribution in cultured utricular supporting cells following streptomycin sulfate (SM) intoxication were investigated by means of an organ culture system using potassium pyroantimonate (PA) precipitation . PA precipitation showed that calcium ions are located in the otoconia and in the secretory granules of the supporting cells . Exposure of the supporting cells to SM increased the number of lysosomes and reduced the secretory granules in the cytoplasm . These lysosomes had many granules containing calcium ion . It is suggested that calcium secretion from the secretory granules was inhibited by SM and that this might lead to reduction of otoconia.

Acta Otolaryngol Suppl, 1995, 519, 238 - 43
Effect of streptomycin on the supporting cells of the utricular macula; Oda Y et al.; Morphological changes in utricular supporting cells in the guinea pig following streptomycin sulfate (SM) intoxication were investigated ultrastructurally in vitro, using an organ culture system . The intracellular structures of the supporting cells, such as the nucleus, mitochondria, and Golgi apparati were well preserved after 7 days in culture . After 10 and 14 days in culture, the supporting cells degenerated . The organ culture system was applied to ototoxicity studies on the supporting cells in utricular macula within 7 days after explanation . When the utricles were exposed to 3, 10 and 30 mg/ml of SM for 3 days, the number of granules in the supporting cells decreased markedly and the number of lysosomes increased daily . The lysosomes contained mitochondria, myeloid bodies, granules and vesicles . Acid phosphatase (AcPase) activity decreased in Golgi apparati and lysosomes . When the concentration of SM was reduced to 3 and 10 mg/ml, the damage to the supporting cells was less marked than that in cells exposed to 30 mg/ml . The supporting cells showed a dose-dependent response with respect to morphological damage . After 3 days culture with 30 mg/ml of SM, the specimens were subsequently cultured for 4 days in a medium without SM . After removal of SM from the medium, lysosomes decreased in number, and the granules and the endoplasmic reticulum showed a gradual increase . The AcPase activity was determined in both lysosomes and Golgi apparatus . This study revealed that the morphological changes in the supporting cells can be reversible.

Acta Otolaryngol Suppl, 1995, 519, 140 - 2
Otoconia on the vestibular dark cells of the ampullar areas; Fujii M et al.; Morphological and metabolic differences in the otoconia on vestibular dark cells of the ampullar area before and after streptomycin treatment were studied by scanning electron microscopy and X-ray microanalyser . Young adult pigmented guinea pigs were used in this study . In the control group, distribution of the otoconia showed a regular pattern . In the SM group the otoconia decreased in numbers and the regularity of the distribution pattern seemed to disappear . Calcium content of the otoconia in SM group also decreased . From these findings, it was concluded that SM might affect not only the sensory and supporting cells but also the vestibular dark cells.

Pneumonol Alergol Pol, 1995, 63(5-6), 293 - 7
{Analysis of course and treatment results after treatment of pulmonary tuberculosis with early introduction of interrupted observation--preliminary report}; Sedlaczek AM et al.; The results of the treatment 33 patients for smear-positive pulmonary tuberculosis with Isoniazid, Rifampicin, Pyrazinamide and Streptomycin administrated during first two weeks daily, from 3 to 8 week also with these four drugs but in a little higher doses twice weekly and next Isoniazid and Rifampicin during 9-26 weeks also twice weekly as in standard Polish model were described . After therapy with above described regimen all patients became smear-negative and radiological improvement was observed . Drugs in higher doses were well tolerated . Only abnormality in laboratory findings was temporary elevated level of uric acid, which recovered to normal values before the end of therapy . Costs of antituberculous drugs were used in this regimen is approximately 35% lower than standard model in Poland.

Biochem J, 1994 Dec 15, 304 ( Pt 3), 937 - 43
Purification and characterization of the short-chain alkylsulphatase of coryneform B1a; Matts PJ et al.; Using a combination of streptomycin sulphate precipitation, and DEAE-cellulose and butyl-agarose chromatography, an alkylsulphatase active towards short-chain alkyl sulphates has been purified approx . 70-fold from extracts of coryneform B1a grown on butyl-1-sulphate . The enzyme protein is dimeric with a subunit molecular mass of 77.6 kDa, has an isoelectric point of pI 7.2, and converts butyl-1-sulphate stoichiometrically into butan-1-ol and inorganic sulphate . Stoichiometric incorporation of 18O from H2(18)O into sulphate during the reaction showed that enzymic hydrolysis occurred at the O-S bond of the C-O-S ester linkage . The enzyme was active on C3-C7 linear primary alkyl sulphates but not on higher (C8,9) or lower (C1,2) homologues, although the latter pair were competitive inhibitors . The specificity constant (kcat./Km) was highest for pentyl sulphate (Km 1.89 +/- 0.38 mM; kcat . 6.86 +/- 0.52 s-1) and decreased for higher and lower homologues . No activity was detected towards C3-C9 racemic alkyl-2-sulphates, D- or L-enantiomers of butyl-2-sulphate, the symmetrical secondary alkyl sulphates pentyl-3-sulphate, heptyl-4-sulphate, nonyl-5-sulphate, C1-C8 alkane sulphonates, choline sulphate, or butyric acid-4-sulphate; none of these compounds (except the symmetrical esters and butyric acid-4-sulphate, which were not tested) was demonstrably inhibitory . The enzyme was compared with other alkylsulphatases in terms of substrate specificity and mode of action.

Eur J Biochem, 1994 Dec 1, 226(2), 355 - 60
Dissociation rate of cognate peptidyl-tRNA from the A-site of hyper-accurate and error-prone ribosomes; Karimi R et al.; The binding stability of the aminoacyl-tRNA site (A-site), estimated from the dissociation rate constant kd, of AcPhe-Phe-tRNA(Phe) has been studied for wild-type (wt), for hyperaccurate ribosomes altered in S12 {streptomycin-dependent (SmD) and streptomycin-pseudodependent (SmP) phenotypes}, for error-prone ribosomes altered in S4 (Ram phenotype), and for ribosomes in complex with the error-inducing aminoglycosides streptomycin and neomycin . The AcPhe2-tRNA stability is slightly and identically reduced for SmD and SmP phenotypes in relation to wt ribosomes . The stability is increased (kd is reduced) for Ram ribosomes to about the same extent as the proof-reading accuracy is decreased for this phenotype . kd is also reduced by the action of streptomycin and neomycin, but much less than the reduction in proof-reading accuracy induced by streptomycin . Similar kd values for SmD and SmP ribosomes indicate that the cause of streptomycin dependence is not excessive drop-off of peptidyl-tRNAs from the A-site.

Epidemiol Mikrobiol Imunol, 1994 Dec, 43(4), 162 - 5
{External control of drug sensitivity determination in mycobacteriologic laboratories in the Czech Republic}; Havelkova M et al.; In 1992 and 1993 an external control of sensitivity assessment of coded strains of M . tuberculosis to five basic antituberculotics was made: isoniazide, streptomycin, pyrazinamide, ethambutol and rifampicin . In 1992 from 11 participating laboratories an erroneous result was recorded in 9 (3 laboratories made two mistakes, 6 laboratories one mistake), two laboratories did not provide complete results . Unsatisfactory results were obtained during external controls in 1993 . Of 15 participating laboratories four laboratories made one mistake, two laboratories two mistakes, four laboratories three mistakes . Five laboratories (i.e . one third) made more than three mistakes . Analysis of the results revealed a low reproductibility of results of drug sensitivity tests . To eliminate these shortcomings it will be necessary to make systematic external controls with subsequent solution of the shortcomings, restriction of the number of laboratories making these examinations to those who will systematically produce correct results . And it will be also necessary to test the sensitivity tests to antituberculotics in resistant strains in the National reference laboratory for mycobacteria.

Epidemiol Mikrobiol Imunol, 1994 Dec, 43(4), 158 - 61
{Drug resistance in M . tuberculosis in Prague 1987-1992}; Havelkova M et al.; In 1987-1992 in Prague drug resistance of M . tuberculosis to four standard antituberculotics (isoniazide, streptomycin, rifampicin, ethambutol) was recorded in 39 patients, i.e . in 1.5-5% of patients with bacillary tuberculosis . Initial resistance was found in 25, secondary resistance in 13 subjects, in one patient both types of resistance were observed . In both groups men and patients born before 1941 predominated . In patients with initial resistance findings rated as small or medium-sized predominated, while in secondary resistance half the findings were medium-sized or extensive; an extrapulmonary form was recorded in one female patient . In the group of patients with an initially resistant M . tuberculosis monoresistant strains predominated and the highest ratio was accounted for by strains resistant to isoniazide; in patients with secondary resistance strains with combined resistance to two or more drugs predominated, however in all instances a combination of isoniazide with other antituberculotics was involved . With regard to the changing epidemiological situation as regards tuberculosis (in particular the arrested decline of the incidence of bacillary tuberculosis and the increase of drug resistance of M . tuberculosis), the authors recommend further monitoring and epidemiological analysis of the incidence of strains with initial and secondary resistance, systematic external checks of laboratory technique used for testing the sensitivity to antituberculotics and its centralization as well as the introduction of analyses of restrictive fragments of the DNA genome (RFLP method) to monitor the spread of tuberculous mycobacteria in the population.

Antimicrob Agents Chemother, 1994 Dec, 38(12), 2798 - 802
Possible implications of doxycycline-rifampin interaction for treatment of brucellosis; Colmenero JD et al.; We studied the possible interaction between rifampin and doxycycline in 20 patients with brucellosis treated randomly with either doxycycline and streptomycin or doxycycline and rifampin . The doxycycline levels in the plasma of patients in the group treated with rifampin were significantly lower than those in the plasma of patients treated with doxycycline and streptomycin . Furthermore, clearance in patients treated with rifampin was significantly higher than that in patients treated with doxycycline and streptomycin, and consequently, the elimination half-life and the area under the concentration-time curve were significantly lower . There was no therapeutic failure or relapse in the group treated with doxycycline and streptomycin, whereas 2 of 10 patients in the group treated with doxycycline and rifampin had a therapeutic failure or relapse . The plasma doxycycline levels had an inverse correlation with plasma rifampin levels . In the group treated with rifampin, those who were rapid acetylators had lower levels of doxycycline . In conclusion, combined treatment with rifampin reduces the levels of doxycycline in plasma . These data suggest that therapeutic failures or relapses may result from this interaction.

Infect Immun, 1994 Nov, 62(11), 5191 - 4
Spatial distribution of Escherichia coli in the mouse large intestine inferred from rRNA in situ hybridization; Poulsen LK et al.; Fluorescent oligonucleotide probes targeting rRNA were used to develop an in situ hybridization technique by which the spatial distribution of Escherichia coli in the large intestines of streptomycin-treated mice was determined . Single E . coli cells were identified in thin frozen sections from the large intestines by the use of a probe specific for E . coli 23S rRNA . Furthermore, the total bacterial population was visualized with an rRNA probe targeting the domain Bacteria . By this technique, all E . coli cells were seen embedded in the mucosal material overlying the epithelial cells of the large intestine, and no direct attachment to the epithelium was observed.

Clin Infect Dis, 1994 Nov, 19(5), 938 - 40
Drug susceptibility of Mycobacterium tuberculosis isolates from recent Haitian migrants: correlation with clinical response; Malone JL et al.; Between November 1991 and June 1993, approximately 11,000 Haitian migrants were screened for active tuberculosis and human immunodeficiency virus type 1 (HIV-1) infection at the U.S . Naval Base in Guantanamo Bay, Cuba . Cultures of specimens from 37 of these patients yielded Mycobacterium tuberculosis; eight (22%) of these isolates were resistant to standard medications, including isoniazid (22%), rifampin (0), ethambutol (3%), and streptomycin (3%) . Two isolates (5.4%) were resistant to two drugs simultaneously . All but one of 340 patients who were treated for presumptive active tuberculosis and who were followed up for about 1 month had a favorable initial clinical response to a standard four-drug regimen . Among 259 HIV-1-infected patients who had normal findings on screening chest radiographs and who received prophylaxis with isoniazid, there were 1.8 incident cases of active tuberculosis per 100 person-years; this rate was 76% lower than that (reported by others) among HIV-1-infected Haitian patients who were not treated with isoniazid . No serious toxic effects due to standard four-drug regimens or to prophylaxis with isoniazid were observed . These data suggest that standard empirical therapeutic interventions for tuberculosis are adequate and well tolerated in Haitian migrants.

Kekkaku, 1994 Nov, 69(11), 733 - 8
{Evaluation of aerosol therapy of streptomycin for tracheobronchial tuberculosis}; Rikimaru T; The clinical features of tracheobronchial tuberculosis are distinct from those of pulmonary tuberculosis in some aspects . Streptomycin (SM) is claimed by some investigators that it has a tendency to promote the development of bronchial stenosis . The purpose of the present investigation is to point out that aerosol therapy of SM is useful for patients with tracheobronchial tuberculosis . Prior to clinical application of the inhalation therapy, we confirmed that the therapy was not harmful . Serum concentration of SM, when inhaled, was measured in 9 volunteers . Before and after administration of SM aerosol, spirograms were examined in 4 volunteers, and no special abnormality was recognized . It seemed that serum concentration of SM after the administration was too low to evoke adverse reactions (less than 3.0 gamma) . In 6 patients, blood gases were measured, and no obvious change was observed . In 41 patients with bronchial tuberculosis, bronchofiberscopic examinations were performed twice or more . We observed the ulcerous lesions of bronchial tuberculosis at various stages of healing, and could classify the ulcerous lesions into the following three stages . Active Stage: stage A; ulcer formation without regenerating epithelium, Healing Stage: stage H; ulcer formation with regenerating epithelium, Scarring Stage: stage S; and no ulcer formation . Only the lesions of stage A were observed before treatment . In many patients during the first and second month of treatment, the lesions were at stage A or H . It was found that healing of the lesions of tracheobronchial tuberculosis progressed through the stages A, H, and S, in this order.(ABSTRACT TRUNCATED AT 250 WORDS)

J Mol Biol, 1994 Oct 7, 242(5), 644 - 54
Synergism between the GTPase activities of EF-Tu.GTP and EF-G.GTP on empty ribosomes . Elongation factors as stimulators of the ribosomal oscillation between two conformations; Mesters JR et al.; A remarkable positive cooperativity between the GTPase activities of EF-Tu and EF-G on empty ribosomes from Escherichia coli has been discovered . This cooperativity implies a decrease of the corresponding apparent KM values of the empty ribosome for either elongation factor: from more than 10 microM to 0.5 microM for EF-Tu.GTP by the addition of 0.25 microM EF-G and from 0.7 microM to 0.5 microM for EF-G.GTP by the addition of 3 microM EF-Tu . In a further analysis of this phenomenon, the effects of various specific antibiotics were studied: thiostrepton, fusidic acid, tetracycline, pulvomycin and kirromycin appeared to inhibit the synergistic effect, whereas streptomycin was found to stimulate it . Even in the present minimal system the ribosomes respond to the above-mentioned antibiotics in a way surprisingly similar to that in the coupled system with mRNA and tRNAs . The cooperativity seems not to be due to a simultaneous binding of the two elongation factors to the ribosome as revealed by studying the effects of fusidic acid and kirromycin, and by band-shift experiments by means of gel electrophoresis under non-denaturing conditions . Our experimental data and the kinetic analysis of alternative models provide evidence that EF-Tu.GTP and EF-G.GTP interact sequentially with empty ribosomes that oscillate between two different conformations, one for each elongation factor . Apparently, ribosomes have an intrinsic property for oscillation as normally observed during protein synthesis with a frequency paced by the events of tRNA binding and translocation.

J Bacteriol, 1994 Oct, 176(19), 6153 - 6
Cloning and sequence analysis of the rpsL and rpsG genes of Mycobacterium smegmatis and characterization of mutations causing resistance to streptomycin; Kenney TJ et al.; The Mycobacterium smegmatis rpsL and rpsG genes, encoding the ribosomal proteins S12 and S7, were cloned, and their DNA sequence was determined . The third nucleotide of the S12 termination codon overlapped the first nucleotide of the S7 translation initiation codon . A collection of 28 spontaneous streptomycin-resistant mutants of M . smegmatis were isolated . All had single-base-pair substitutions in the rpsL gene which were changed to a streptomycin-sensitive phenotype by complementation with a low-copy-number plasmid carrying the wild-type M . smegmatis rpsL gene . A total of eight different mutations were found in two specific regions of the rpsL gene . Fifty-seven percent (16 of 28) altered the Lys codon at position 43 . Forty-six percent of the mutations (13 of 28) were due to a transition changing an AAG Lys codon to an AGG Arg codon, with eight changes at codon 43 and five at codon 88.

Tuber Lung Dis, 1994 Oct, 75(5), 324 - 8
High initial and acquired drug resistance in pulmonary tuberculosis in Turkey; Tahaoglu K et al.; SETTING: Sureyyapasa Center for Chest Diseases and Thoracic Surgery, Istanbul, Turkey between January 1992 and December 1992 . OBJECTIVE: To evaluate the prevalances of initial and acquired resistance to antituberculosis drugs in our center . DESIGN: 785 patients with pulmonary tuberculosis (both old = 525/785 and new = 260/785 cases) referred to our center were evaluated with respect to their drug resistance patterns . RESULTS: The overall resistance rate (1 or more drugs) was 35.5%, with initial resistance 26.6% (140 of 525) and acquired resistance 53.4% (139 of 260) . Initial resistance to streptomycin was the most frequent (20.6%), followed by rifampicin (10.8%), isoniazid (5.1%) and ethambutol; (4.2%) . Initial resistance was noted as 16.4% to 1 drug, 7.7% to 2 drugs, 1.2% to 3 drugs and 1.3% to 4 drugs . Acquired resistance to rifampicin was the most frequent (36.2%) followed by streptomycin 31.9%, and isoniazid 30% . Acquired resistance was found as 18.7% to 1 drug, 19.3% to 2 drugs, 9.6% to 3 drugs and 5.8% to 4 drugs . CONCLUSION: High initial drug resistance in Turkey may well threaten the success rates of antituberculosis treatment and it is therefore mandatory to begin antituberculosis treatment in routine practice in our country with at least 4 first-line drugs, replacing streptomycin with ethambutol due to high resistance to streptomycin . In conclusion there is an urgent need for a nationwide tuberculosis control programme in Turkey, where the treatment of old cases is still challenging, in order to combat the grave situation of high initial and acquired drug resistance.

J Med Assoc Thai, 1994 Oct, 77(10), 520 - 5
Clinical aspects and treatment outcome in HIV-associated pulmonary tuberculosis: an experience from a Thai referral centre; Hongthiamthong P et al.; This case-control study examined the impact of HIV infection on clinical presentation, response to treatment, and outcome of pulmonary tuberculosis . Symptoms, radiographic pattern, sputum direct smear, drug susceptibility, treatment outcome and adverse reactions of 88 HIV-infected patients with newly-diagnosed, culture-proved, untreated pulmonary tuberculosis were compared with those of age and gender-matched HIV-seronegative patients . No differences in the frequency of pyrexia, dyspnoea, cough or haemoptysis were evident . Cavitary lesions and upper zone infiltrates were observed significantly less often in the HIV-infected group (p = 0.02 and 0.01, respectively) . Direct smear positivity was comparable in the 2 groups . The resistance rates to antituberculous drugs were not different except for Streptomycin which was higher among the HIV-infected patients (p = 0.01) . Cutaneous hypersensitivity reactions and drug-induced hepatitis occurred more often in the HIV-seropositive group, albeit not reaching statistical significance . Default was much higher in the HIV-infected patients (33%); however, the culture conversion rate was satisfactory among those completed treatment . Twelve HIV-infected patients died during the course of treatment, four of whom as a result of tuberculosis . Based on these observations, physicians should maintain a high index of suspicion for tuberculosis among HIV-seropositive patients for short-course chemotherapy to be promptly institutedPIP: HIV-associated tuberculosis (TB) poses an immediate and serious threat to public health, especially in the developing world . Moreover, atypical clinical presentation and unfavorable outcome have been observed in HIV-infected patients with TB . The authors report their findings from an investigation of the impact of HIV infection upon the clinical presentation, response to treatment, and outcome of pulmonary TB . The symptoms, radiographic pattern, sputum direct smear, drug susceptibility, treatment outcome, and adverse reactions of 88 HIV-infected patients seen during January-October 1993 at the Central Chest Hospital, Nonthaburi, Thailand, with newly-diagnosed, culture-proven, untreated pulmonary TB were compared with those of age- and gender-matched HIV-seronegative patients . There were 82 men and six women in each group of mean age 35.6 years, with the majority being aged 16-40 . Heterosexual contact was the most common risk factor for HIV infection, with homosexuality implicated in only 1% of all cases of infection . No difference was observed between the two groups in the frequency of pyrexia, dyspnoea, cough, or hemoptysis, although cavitary lesions and upper zone infiltrates were observed significantly less often in the HIV-infected group . Direct smear positivity was comparable in the two groups . Resistance rates to anti-TB drugs were not different except for Streptomycin which was higher among the HIV-infected patients . Cutaneous hypersensitivity reactions and drug-induced hepatitis occurred more often in the HIV-seropositive group, but the difference was not statistically significant . Default was much higher among the HIV-infected, although the culture conversion rate was satisfactory among those who completed treatment . Twelve HIV-infected patients died during the course of treatment, four due to TB . The authors that their findings lead physicians to suspect TB among HIV-seropositive patients and provide them with the appropriate and timely short-course chemotherapy .

Mol Gen Genet, 1994 Sep 1, 244(5), 491 - 500
Enhanced frequency of transposition of the maize transposable element Activator following excision from T-DNA in Petunia hybrida; Robbins TP et al.; Many of the systems currently employed for heterologous transposon tagging in plants rely on an excision assay to monitor transposon activity . We have used the streptomycin phosphotransferase (SPT) reporter system to assay Ac activity in Petunia hybrida . In other species, such as tobacco or Arabidopsis, excision of Ac from the SPT gene in sporogenous tissue gives rise to streptomycin-resistant seedlings in the following generation . The frequency of fully streptomycin-resistant seedlings in petunia was low (0.4%) but molecular analysis of these indicated that the actual excision frequency may be as low as 0.05% . This indicates that the SPT assay is not a reliable selection criterion for germinal excision in petunia . Extensive molecular screening for reinsertion of Ac was consistent with a low primary transposition frequency (0%-0.6%) . In contrast to these findings, the progeny of confirmed germinal transpositions for three independent transformants showed frequent transposition to new sites (9.5%-17.0%) . This suggests a high frequency of secondary transposition compared with primary transposition from the T-DNA . Segregation analysis indicates that the high transposition activity is closely associated with transposed copies of Ac . No evidence was found for an altered methylation state for Ac following transposition . The implications of these results for heterologous transposon tagging in petunia are discussed in the context of the reliability of excision reporter systems in general.

Kekkaku, 1994 Sep, 69(9), 559 - 63
{Evaluation of the streptomycin twice weekly with INH and RFP for initial therapy of pulmonary tuberculosis}; Toyota E et al.; For the purpose to compare the effectiveness of SM and EB as a third drug in the standard regimens and to know whether the addition of SM twice weekly to INH and RFP could be acceptable for the treatment of pulmonary tuberculosis, the efficacy, adverse effects and results of long-term follow-up of the groups consisting of 105 patients treated with SM twice weekly for 6 months in addition to INH and RFP for 9 months (S2 group) and 107 patients treated with EB for 6 months in addition to INH and RFP for 9 months (E group) were observed . The speed of negative conversion of sputum and that of X-ray findings improvement were slightly faster in S2 group than E group but the difference was statistically not significant . The incidence of adverse effects such as elevation of serum transaminase values, gastrointestinal troubles, drug allergy and others was not similar in two groups . The relapse was observed in 2 cases of S2 group and 5 cases of E group . We concluded that SM twice weekly to INH and RFP is similarly effective as EB in combination with INH and RFP, and the this regimen could be used as standard regimen for pulmonary tuberculosis.

Public Health Rep, 1994 Sep-Oct, 109(5), 632 - 6
Drug resistance among tuberculosis patients, New York City, 1991 and 1992; Driver CR et al.; The authors assessed drug susceptibility patterns among tuberculosis patients reported to the New York City Department of Health in the first quarters of 1991 and 1992 . Resistance to one or more drugs was seen in 26 percent (137 divided by 520) in 1991 and 24 percent (122 divided by 517) in 1992 . Resistance to isoniazid was seen in 22 percent and 19 percent of patients in 1991 and 1992, respectively; resistance to rifampin in 15 percent and 14 percent; and to both isoniazid and rifampin in 15 percent and 14 percent . Combined resistance to four first line drugs (isoniazid, rifampin, streptomycin, and ethambutol) was seen in 6 percent (1991) and 8 percent (1992) . Patients with organisms resistant to both isoniazid and rifampin were as likely among U.S . born as among foreign born, and younger patients were more likely than older patients to have isoniazid and rifampin resistant organisms . These findings underscore the importance of obtaining susceptibility testing in all patients who have cultures positive for Mycobacterium tuberculosis.

Hear Res, 1994 Sep, 79(1-2), 26 - 38
Scar formation in the vestibular sensory epithelium after aminoglycoside toxicity; Meiteles LZ et al.; Hair cell degeneration and the repair process due to differing types of trauma have been studied extensively in the organ of Corti . It has been determined that, during scar formation, after differing types of trauma to the auditory sensory system, the reticular lamina is maintained with adherens junctions and tight junctions . We investigated the repair process within the vestibular epithelium . Hair cell degeneration was induced by the unilateral application of streptomycin to the inner ears of guinea pigs . Whole mount preparations of all five vestibular organs were processed and examined by fluorescence, light and electron microscopy . Scar formation was seen as early as 4 days post-treatment with streptomycin and was noted to coincide with hair cell degeneration . Neighboring supporting cells swelled and filled the space beneath the degenerating hair cell . Between three and five supporting cells participate in the reparative process . The distribution of cytokeratin is also altered during scar formation . The area once occupied by the hair cell becomes filled with cytokeratin-rich processes of supporting cells . It appears that differing numbers of supporting cells are involved in the reparative process within the vestibular sensory epithelium as compared to the auditory system . The reticular lamina remains intact at all times . This may possibly prevent mixing of fluids between different compartments in the inner ear and dysfunction of the vestibular sensory organs.

Int J Lepr Other Mycobact Dis, 1994 Sep, 62(3), 353 - 8
Relapse rates in patients treated with dapsone monotherapy and combinations of dapsone and thiambutosine, thiacetazone, isoniazid and streptomycin in the pre-MDT era; Smith TC et al.; Relapse rates were studied in patients from northern Thailand who were started on dapsone monotherapy between 1949 and 1976 . Included are a group of patients who, for various reasons, also received combinations of dapsone and thiambutosine, thiacetazone, isoniazid and streptomycin . The overall relapse rate in paucibacillary patients on dapsone monotherapy only was 2.7 per 1000 person-years at risk (PYR) (average observation period 13.9 years) . In the multibacillary patients who received dapsone monotherapy only, the relapse rate was 10.5 per 1000 PYR (average observation period 12.4 years) . In both groups it was found that 50% of the relapses occurred after the seventh year of follow up . The overall relapse rate in those patients whose treatment included thiambutosine, thiacetazone, isoniazid and/or streptomycin for at least 3 months was 17.9 per 1000 PYR (average observation period 11.9 years) . The difference with the multibacillary patients treated with dapsone monotherapy only is not significant . It is concluded that alternative antileprosy drugs included in therapy regimens with dapsone in the pre-MDT era did not result in relapses occurring less often.

Infect Immun, 1994 Aug, 62(8), 3447 - 53
Direct evidence of neuron impairment by oral infection with verotoxin-producing Escherichia coli O157:H- in mitomycin-treated mice; Fujii J et al.; We developed a mouse model of acute encephalopathy induced by verotoxin 2 variant (VT2v)-producing Escherichia coli . Three-week-old mice were inoculated intragastrically with approximately 10(10) CFU of E . coli O157:H- strain E32511/HSC and simultaneously given an intraperitoneal injection of mitomycin (MMC; 2.5 mg/kg) . Drinking water containing 5 g of streptomycin sulfate per liter was given ad libitum from 3 days before the infection . From 1 to 2 days after bacterial inoculation, clinical features including weight loss, weakness, and flaccid paralysis of the extremities developed, usually culminating in death within 4 days . Diarrhea was not observed during the course of disease . No mice died in the absence of streptomycin or MMC treatment for 2 weeks after the oral bacterial infection . Judging from the clinical course and the biochemical and histological examination, the cause of death was not likely to be attributable to renal failure or to a side effect of MMC . To better understand the cause of death, we examined the brain cortex and spinal cord of the moribund mice by electron microscopy . Mice showing mortal symptoms were given horseradish peroxidase intravenously . The tracer was present in the endothelial basal lamina, in the surrounding extracellular spaces, and even in the neuron fibers of the brain cortex . Furthermore, immunoreactivity of VT2v, proved by the use of rabbit anti-VT2 serum, was localized selectively in the damaged myelin sheaths of neuron fibers which were accompanied by edematous axons in the brain cortex and spinal cord . These findings strongly suggest that VT2v is toxic to both endothelial cells and neurons in the central nervous system and subsequently causes fatal acute encephalopathy.

Curr Genet, 1994 Aug, 26(2), 132 - 5
Point mutations in the chloroplast 16s rRNA gene confer streptomycin resistance in Nicotiana plumbaginifolia; Yeh KC et al.; In a previous paper we reported the isolation of streptomycin-resistant mutants from Nicotiana plumbaginifolia and presented evidence for chloroplast control of the resistance trait . To understand the molecular basis of the resistance in these mutants, we sequenced three regions in the chloroplast 16s rRNA gene, which correspond to the 5' terminus, the 530 loop, and the 900 stem/loop of Escherichia coli 16s rRNA, and compared them with the sequences of the wild-type . Our results show that: (1) nine mutants have a C to T change at position 912, (2) one mutant (SR1021) has a G to A change at position 885, (3) one mutant has a C to T change at position 526, based on E . coli numbering; and (4) three mutants do not have any change in the regions analyzed . The point mutation detected in SR1021 has not been reported previously . In E . coli 16s rRNA, position 885 is protected from chemical probing by ribosomal protein S12 and is closely juxtaposed with the streptomycin-binding region (positions 912-915) in the predicted secondary structure . It is likely that the G to A transition at this position is a novel mutation for streptomycin resistance.

Tuber Lung Dis, 1994 Aug, 75(4), 245 - 50
4-, 5- and 6-month regimens containing isoniazid, rifampicin, pyrazinamide and streptomycin for treatment of pulmonary tuberculosis under program conditions in Hong Kong; Chan SL et al.; SETTING: Ten full time urban government chest clinics in Hong Kong . OBJECTIVE: To assess the effectiveness of 4-, 5- and 6-month fully supervised thrice-weekly regimens containing 4 months of isoniazid, rifampicin, pyrazinamide and streptomycin followed by nil, 1 or 2 months of isoniazid and rifampicin for the treatment of smear-negative culture-negative, smear-negative culture-positive and smear-positive pulmonary tuberculosis . DESIGN: Retrospective study of the 3 antituberculosis treatment regimens given under program conditions during a 6-month period in 1983 . RESULTS: Of the 1616 patients assessed, 953 (59%) completed their treatment strictly as planned, 443 (27%) had their treatment prolonged, 107 (7%) had their treatment modified and 113 (7%) defaulted or did not complete their treatment as planned . There were 2 treatment failures at the end of chemotherapy . At 60 months of follow-up, 67 patients died, 2 from the sequelae of tuberculosis . Of 1287 patients assessable up to 60 months, a total of 47 (3.7%) patients relapsed and were eventually treated successfully . 11 (20%) relapses occurred among the 55 patients who had defaulted and did not complete treatment as planned . CONCLUSION: The effectiveness of the 3 treatment regimens depended very much on the patient's adherence to treatment . The necessity of prolongation of treatment is not known and requires further assessment.

Am J Otol, 1994 Jul, 15(4), 540 - 4
Long-term results of low dose intramuscular streptomycin for Menière's disease; Shea JJ et al.; The initial results of partial ablation of vestibular function are evident to control vertigo attacks and stabilize hearing as well as to reduce the severity of ataxia . The purpose of this study is to observe the long-term results of low dose intramuscular streptomycin in the treatment of bilateral Meniere's disease . Eleven patients with disabling bilateral Meniere's disease were treated with low doses of intramuscular streptomycin (20-40 g, mean = 25 g) . Follow-up was 5-12 years (mean = 8 yr) . All 11 patients achieved relief of their disabling vertigo . One patient had recurrent vertigo 1 year after treatment and streptomycin perfusion of the labyrinth was performed subsequently . Four patients reported feeling slightly off balance during follow-up . None experienced oscillopsia in this series . In the entire group of 11 patients (22 ears), hearing was unchanged in 17 ears, improved in two and worse in three . A hearing threshold of < 30 dB was found in two ears before and two after treatment; 30-60 dB was found in seven ears before and six after treatment; and > 60 dB was found in 13 ears before and 14 after treatment . The mean PTA of the 22 ears was 58 dB before and 65.5 dB after treatment . The mean speech discrimination scores were 61.4 percent before and 51.3 percent after treatment . The long-term results suggest that partial ablation of vestibular function by streptomycin has long-lasting effects of controlling vertigo attacks, stabilizing hearing, and reducing the severity of ataxia . Administration of low doses of intramuscular streptomycin is the treatment of choice for bilateral Meniere's disease.

J Biol Chem, 1994 Jul 1, 269(26), 17556 - 60
Cloning and sequencing of rat kidney L-arginine:glycine amidinotransferase . Studies on the mechanism of regulation by growth hormone and creatine; Guthmiller P et al.; L-Arginine-glycine amidinotransferase (transamidinase) is the first and rate-limiting step in creatine biosynthesis . Rats fed a creatine-supplemented diet or hypophysectomized rats have only 20% of the kidney transamidinase activity as intact rats fed a creatine-free diet . A cDNA clone corresponding to transamidinase was isolated by immunoscreening of a lambda gt11 expression library prepared from rat kidney mRNA . The transamidinase cDNA had an open reading frame containing the known sequence of the amino-terminal peptide of transamidinase . Based on the cDNA sequence, transamidinase is synthesized as a precursor with an amino-terminal extension of 50 amino acids, consistent with its mitochondrial localization . Comparison of the transamidinase sequence with the protein data base identified only a single, related protein . Remarkably, this protein, which has a 37% amino acid identity with transamidinase, is also an amidinotransferase, catalyzing streptomycin biosynthesis in Streptomyces griseus . Transamidinase cDNA was used to investigate the regulation of mRNA levels by creatine and growth hormone . Hypophysectomized rats were fed a creatine-free or a creatine-supplemented diet and maintained with and without injections of growth hormone . An excellent correlation was found between changes in transamidinase activity and mRNA levels in response to creatine and growth hormone . Thus, the regulation of transamidinase by creatine and growth hormone is at a pretranslational level . In addition, the two effectors do not act independently but interact at a pretranslational level to control transamidinase gene expression.

Minerva Pediatr, 1994 Jun, 46(6), 295 - 301
{Tuberculosis of the spine in children . Personal experience}; Mantero E et al.; We are currently witnessing a worldwide return of tuberculosis . An extremely rare form is tuberculosis of the spine which is reported above all in extra-European studies . The authors report a case of Pott's disease in a child aged 3 years and 3 months who was referred to their attention due to the appearance of left inguinal swelling, fever and anemia . Diagnostic tests (ETG, CT, MR) showed an abscess involving the L5-S1 intersomatic space, the intervertebral disc and osteolytic lesions of S1, with impairment of the left psoas muscle and diffusion as far as the inguinal region . Chemotherapy was commenced using isoniazid, ethambutol, rifampicin, and streptomycin and lasted 24 months associated with drainage of the ileopsoas abscess . Conservative orthopedic treatment lasting for one year initially took the form of decubitus in bed with hyperdistension of the vertebral column, followed by the creation of a plaster-cast cot on the back and lastly a glass-reinforced resin orthopedic jacket . The follow-up of 2 years and 10 months showed recovery with reconstruction of the vertebral elements and the preservation of intervertebral space.

Med Clin (Barc), 1994 May 21, 102(19), 731 - 8
{Meta-analysis of the efficacy of the combination of +rifampicin and doxycycline in the treatment of human brucellosis}; Solera J et al.; BACKGROUND: The aim of this study was to determine whether a conclusion could be obtained through meta-analysis of the published trials on the relative efficacy of rifampicin and doxycycline versus streptomycin and doxycycline or another tetracycline (SD) . METHODS: The comparative and randomized trials identified by a search in the reference data base MEDLINE from 1967 to 1992 and through manual review of the articles cited in these studies or other reviews were included . The evaluation of quality was performed by a standardized scale . The differences in efficacy were expressed as odds ratio and the results were contrasted by the Mantel-Haenszel method . Heterogenicity was graphically analyzed by the Woolf method with an adjustment being made for small subgroups . The confidence intervals were calculated for each trial and for the combined data by the Cornfield method . RESULTS: Six trials including 581 patients of whom 544 were considered evaluable were analyzed . In the RD treatment group 261 (242 valid) patients were included with 268 (253 valid) being included in the SD group . Five cases of initial therapeutic failure were observed in each group without significant differences . The secondary effects described were very variable . Nonetheless no secondary effects obliging discontinuation of treatment were presented in the RD group with only one in the SD group with no differences between the two groups . Recurrences were presented in 5% and 39% in the RD group and in 0 and 17% in the SD group . In total 37 (16%) in the former group and 13 (5%) in the latter group . The Mantel-Haenszel odds ratio with respect to recurrence was 3.81 (CI 95%, 1.82-8.17; p = 0.00009) . The total number of cures was 196 (81%) in the RD group and 232 (92%) in the SD group (Mantel-Haenszel odds ratio 0.36; CI 95%, 1.19-0.64; p = 0.0004) . The inclusion of the quality index of the trials did not modify the statistical significance achieved . CONCLUSIONS: In human brucellosis the treatment of rifampicin and doxycycline presents a greater number of recurrence and lower number of cure than the classical treatment with streptomycin and tetracycline drugs.

FEBS Lett, 1994 May 9, 344(1), 50 - 4
Postnatal changes in rhodamine-123 stained mitochondrial populations are sensitive to protein synthesis inhibitors but mimicked in vitro by ATP; Almeida A et al.; The incubation of term fetus mitochondria with ATP mimicked in vitro the increase in the respiratory control index and in the percentage of the rhodamine-123-low fluorescence population that occurred in vivo immediately after birth, suggesting that both phenomena are closely associated . The administration of streptomycin inhibited the increase in the percentage of the low fluorescence population that occurred immediately after birth, while the administration of cycloheximide even reversed these changes . These results suggest that the in vivo interconversion between mitochondrial forms depends on both cytosolic and mitochondrial protein synthesis.

J Bacteriol, 1994 May, 176(10), 2892 - 7
Plasmid and transposon transfer to Thiobacillus ferrooxidans; Peng JB et al.; The broad-host-range IncP plasmids RP4, R68.45, RP1::Tn501, and pUB307 were transferred to acidophilic, obligately chemolithotrophic Thiobacillus ferrooxidans from Escherichia coli by conjugation . A genetic marker of kanamycin resistance was expressed in T . ferrooxidans . Plasmid RP4 was transferred back to E . coli from T . ferrooxidans . The broad-host-range IncQ vector pJRD215 was mobilized to T . ferrooxidans with the aid of plasmid RP4 integrated in the chromosome of E . coli SM10 . pJRD215 was stable, and all genetic markers (kanamycin/neomycin and streptomycin resistance) were expressed in T . ferrooxidans . By the use of suicide vector pSUP1011, transposon Tn5 was introduced into T . ferrooxidans . The influence of some factors on plasmid transfer from E . coli to T . ferrooxidans was investigated . Results showed that the physiological state of donor cells might be important to the mobilization of plasmids . The transfer of plasmids from E . coli to T . ferrooxidans occurred in the absence of energy sources for both donor and recipient.

Allergy, 1994 May, 49(5), 388 - 9
Streptomycin-induced anaphylactic reaction during in vitro fertilization (IVF); Abeck D et al.; Indications for in vitro fertilization (IVF) have been cautiously extended over the years . IVF is usually considered to be a technically complex method with only minimal side-effects . We report the case of a woman who developed an anaphylactic reaction during IVF immediately after the embryo transfer.

Indian J Exp Biol, 1994 May, 32(5), 318 - 23
Effect of combination therapy in Mycobacterium paratuberculosis infected rabbits; Mondal D et al.; Rabbits, infected with M paratuberculosis of caprine origin, were treated with streptomycin sulphate and rifampicin in combination with levamisole hydrochloride for a period of 2 months . Marked clinical response including significant rise in total serum protein, albumin and globulin were recorded in treated groups . Highly significant higher leucocyte migration inhibition indicating enhanced CMI reaction, occurred in rabbits treated for 4 weeks . Complete elimination of M . paratuberculosis from faeces, intestines and mesenteric lymph nodes was observed . They were also absent from spleen, kidneys, lungs and liver of rabbits treated with rifampicin and levamisole, whereas were present in lungs of the rabbits administered with streptomycin and levamisole . Absence of characteristic lesions of paratuberculosis and evidence of regenerative reaction were observed in visceral organs of rabbits treated with rifampicin and levamisole . Effectiveness of rifampicin is attributed to its effect on lymphocyte, the primary cell involved in cell mediated immunity . Rifampicin-levamisole combination appeared superior to streptomycin-levamisole in eliminating the infection of M . paratuberculosis from infected rabbits . Approximate cost of treatment was calculated to be Rs 8.50 per kg body weight . Cattle, sheep and goats, if treated in early stage of infection may recover from paratuberculosis.

J AOAC Int, 1994 May-Jun, 77(3), 765 - 7
Analysis of streptomycin and dihydrostreptomycin in milk by liquid chromatography; Gerhardt GC et al.; A method developed for the determination of the aminoglycoside antibiotics streptomycin and dihydrostreptomycin in tissues was applied to the analysis of fluid milk . Samples are extracted with 3.6% perchloric acid, and then injected onto a trace enrichment column, from which they are eluted onto a reversed-phase analytical column . The analytes are detected by fluorescence following postcolumn derivatization with 1,2-naphthoquinone-4-sulfonic acid . Recovery of analytes was in the range of 50-65% for skim or partially defatted fluid milk, while recoveries for homogenized whole milk were lower . Limits of quantitation were 10 ppb for streptomycin and 20 ppb for dihydrostreptomycin.

J Am Vet Med Assoc, 1994 Apr 15, 204(8), 1168 - 75
Animals as a source of Escherichia coli pathogenic for human beings; Whipp SC et al.; Symptoms of SLT E coli-induced enteric disease in human beings include watery diarrhea, hemorrhagic diarrhea, and, in some cases, HUS . The most frequent serotype associated with HUS is O157:H7, although several other serotypes have also been implicated . These organisms produce SLT-I, SLT-II, or both toxins . Factors other than SLT are implicated as virulence attributes, such as adhesins and enterohemolysins, but roles for these factors in the pathogenicity of these organisms have not been defined . Colonization mechanisms for enterohemorrhagic E coli have not been defined, nor is there a defined set of characteristics by which enterohemorrhagic E coli pathogenic for human beings can be identified . Because virulence attributes are ill-defined, experimental animal models are useful in studies of pathogenicity . Gnotobiotic pigs, infant rabbits, streptomycin-treated mice, and one-day-old chickens have been used . Although the epidemiologic evidence implicating cattle as a source of zoonotic SLT E coli is strong, there is a paucity of direct evidence documenting this relationship . Until we have a better set of criteria with which to identify SLT E coli that are human pathogens, we are probably limited to epidemiologic criteria . Cattle excrete a variety of SLT E coli that includes many serotypes, in addition to O157:H7, that have been associated with disease in human beings . Surveys of the incidence of O157:H7 indicate a low incidence of these organisms in healthy cattle . However, much of these data have been derived from surveys of clinically normal cattle in daries.(ABSTRACT TRUNCATED AT 250 WORDS)

Kekkaku, 1994 Apr, 69(4), 301 - 6
{Efficacy of the standard regimen for initial treatment of pulmonary tuberculosis: results of long-term followed-up}; Wada M et al.; In 1986, the regimen with isoniazid, rifampicin and streptomycin or ethambutol for 9 or 6 months was introduced as the standard therapy for the initial treatment of pulmonary tuberculosis in Japan . Since then, several reports have been published on the relapse rate after such standard regimen, but follow-up observation was limited to relatively short period in these studies, except one study . Further, none of these studies reported overall efficacy rate of the treatment which was the most important index to evaluate the regimen . So we investigated the deaths, defaults, treatment failures, and relapses during and after the initial treatment of pulmonary tuberculosis patients to calculate the efficacy rate . Three hundred and six patients with newly diagnosed pulmonary tuberculosis, who had admitted to Fukujuji Hospital and started initial treatment with standard regimen, were followed-up, retrospectively . At the start of the initial treatment, mean age of the male patients were 47.0 and those of the female patients were 42.2 years old (male: 232 cases, female: 74 cases) . Of the total 306 patients, 84.5% were basically positive and 50.7% were cavitary tuberculosis . Resistance to isoniazid, rifampicin, streptomycin and ethambutol was noticed in 3.5%, 0.4%, 4.3% and 0.4% of the patients tested . Their medical records in Fukujuji Hospital were reviewed, and for the patients who had not visited the hospital more than one year letters were sent to request to visit the hospital and to answer to questionnaire . The questionnaire were also sent to the referred hospitals and the concerned health-centers . Of 306 patients enrolled in the present investigation, 7 have dropped out.(ABSTRACT TRUNCATED AT 250 WORDS)

Sci China B, 1994 Apr, 37(4), 430 - 6
Purification and characterization of DNA methylase from HL-60 cells; He ZX et al.; A solid leukemia sarcoma has been successfully developed after subcutaneous inoculation of the cultured human promyelocytic leukemia cells (HL-60 cells) into nude mice . The solid leukemia sarcoma is a more plentiful source than the cultured cells for enzymatic study and its growing environment is closer to that of the human body than the cultured cells . We established an efficient procedure of purifying HL-60 cells DNA methylase which includes: disruption of HL-60 cells by homogenization and sonication, removing the cell fragments and cellular particles by centrifuge and ultracentrifuge (105,000 g); removing endogenous DNA by streptomycin sulfate, salting out by (NH4)2SO4, ion exchange chromatography on DEAE-cellulose (DE-52), gel filtration over Sephadex G-100 column . The DNA methylase from HL-60 cells has been purified 204 fold by this procedure . The purified enzyme shows a single-band on PG-PAGE . A 479-kD molecular weight of this enzyme is measured by PG-PAGE . The enzyme properties of HL-60 DNA methylase are also studied.

Arch Bronconeumol, 1994 Apr, 30(4), 222 - 5
{Pulmonary infection by M . kansasii following cytomegalovirus pneumonia in a kidney transplant patient}; Leon M et al.; We report the case of a 55-year-old woman who developed a lung infection by cytomegalovirus (CMV) with overlapping infection by M . kansasii after receiving a kidney transplant . The second germ infection was subclinical, with unusual nodules showing in X-rays . We describe procedures used and diagnostic criteria applied in determining the nature of this atypical mycobacteria in an immunosuppressed patient . The outcome was good with treatment that included rifamycin, cyprofloxacin, streptomycin and ethambutol.

Otolaryngol Clin North Am, 1994 Apr, 27(2), 317 - 24
Streptomycin perfusion of the labyrinth through the round window plus intravenous streptomycin; Shea JJ Jr et al.; Streptomycin perfusion of the labyrinth through the round window membrane in the middle ear is a simple, safe, and effective way to stop the dizzy spells, fullness, and tinnitus of Meniere's disease without making the hearing worse . My results with 24 patients in the last 8 months are presented . Although the long-term effect of this operation remains to be seen, my experience with streptomycin perfusion of the labyrinth through the lateral semicircular canal leads me to believe these good results will be maintained in the future . Although the caloric response is not usually eliminated completely in the operated ear, it is reduced enough that the patient no longer has dizzy spells . Because the vestibular receptors are not completely destroyed, and the afferent and efferent nerves coming to and from them are undamaged, the patient compensates after this operation more quickly than when the vestibular receptors are completely destroyed by intramuscular or middle ear aminoglycoside, or when the afferent and efferent nerves of the vestibular receptors are cut as in labyrinthectomy or vestibular neurectomy . Hyaluronan is used to carry the streptomycin into the inner ear because it is known to penetrate the round window easily, and because being hygroscopic, it may reduce the amount of endolymph by osmosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Otolaryngol Clin North Am, 1994 Apr, 27(2), 307 - 15
Pharmacologic labyrinthectomy; Hellstrom S et al.; Pharmacologic labyrinthectomy has become an alternative to surgery for treatment of severe Menier's disease . The use of systemic streptomycin has been replaced by intratympanal instillations of gentamicin that are administered once daily for a limited number of days . Gentamicin provides a high success rate for ablation of vertigo without causing any unnecessary negative effects on hearing . Future development of more selective vestibulotoxic chemicals could mean that pharmacologic labyrinthectomy will become a simple and ultimate treatment for disabling Meniere's disease.

Appl Environ Microbiol, 1994 Apr, 60(4), 1387 - 9
Selective enumeration of Fusobacterium necrophorum from the bovine rumen; Tan ZL et al.; A culture medium containing lactate as the sole energy source and antibiotics (bacitracin, gentamicin, and streptomycin) was used for selection and enumeration of Fusobacterium necrophorum from bovine ruminal contents . F . necrophorum growth was determined by indole production, and enumeration was performed by the most-probable-number technique . The number of F . necrophorum cells in cattle fed a 100% forage diet was 7 x 10(5)/g of ruminal contents . The number increased (P < 0.05) 10-fold after the diet was changed to 85% corn grain.

Acta Otolaryngol, 1994 Mar, 114(2), 130 - 4
Effect of experimental acidosis on nystagmus in rabbits; Morinaka S; Vertigo related to acidosis in Meniere's disease has been reported . This study was undertaken to ascertain whether acidosis has any effect on vertigo . Since patients with Meniere's disease usually show unilateral vestibular dysfunction, unilateral intratympanic injection of streptomycin sulfate (SM) was used to induce unilateral vestibular dysfunction in rabbits . Intratympanic SM injections induced vestibular destruction and elicited severe spontaneous nystagmus and ataxia . Then symptoms of acute vestibular upset gradually subsided and eventually disappeared completely . Three weeks after SM injections, in compensated rabbits, NH4Cl injection or CO2 inhalation was used to induce acidosis . Intravenous NH4Cl injection or CO2 inhalation induced nystagmus and ataxia again . In normal rabbits, no nystagmus was induced by NH4Cl injection or by CO2 inhalation . These results suggest that acidosis might be a cause of recurrence of vertigo in patients with unilateral vestibular dysfunction.

Plant Mol Biol, 1994 Mar, 24(5), 789 - 98
The presence of enhancers adjacent to the Ac promoter increases the abundance of transposase mRNA and alters the timing of Ds excision in Arabidopsis; Balcells L et al.; Two copies of domain B of the CaMV 35S promoter were inserted ca . 300 bp upstream of the transcriptional start site of the Ac transposase gene . Four independent Arabidopsis transformants containing this fusion (35SenhAc::TPase) were made and the abundance of transposase mRNA in each of them was determined . The presence of the enhancers increased the abundance of the transposase mRNA by about 12-fold compared to that found in plants containing an Ac promoter fusion to the transposase gene (Ac::TPase) . Hybrid plants carrying 35SenhAc::TPase and a Ds element inserted in a streptomycin phosphotransferase (SPT) gene were constructed and the frequency with which Ds excision occurred in the developing cotyledons was measured . Moreover, the number of progeny of these hybrid plants which inherited an SPT gene activated by Ds excision was studied in individual F2 families . Those derived from 35SenhAc::TPase often contained higher proportions of streptomycin-resistant (strepR) F2 progeny than those derived from Ac::TPase . These high frequencies of strepR seedlings were comparable to those previously detected after activation of Ds by a CaMV 35S promoter fusion to transposase (35S::TPase), but occurred in fewer families . The higher frequency with which this occurred in families derived from 35SenhAc::TPase compared to Ac::TPase suggests that the presence of enhancers adjacent to the native Ac promoter can influence transposase gene expression, and in this case often results in earlier excision of Ds during plant development.

Scanning Microsc, 1994 Mar, 8(1), 107 - 21; discussion 121-4
Ultrastructural changes of the vestibular sensory organs after streptomycin application on the lateral canal; Lee KS et al.; Early changes in the vestibular sense organs resulting from the application of a streptomycin sulfate soaked Gelfoam pledget on the fenestra of the lateral semicircular canal were studied by transmission and scanning electron microscopy . Three days after the application, lesions were present in the central part of the lateral crista . The type I sensory cells were more affected than the type II cells . These sensory cells showed mitochondrial swelling, cytoplasm protrusion at the cell apex, inclusion of multiple vacuoles, fusion or loss of stereocilia, and pyknotic nuclei . Seven days after the drug application, the sensory cell damage extended to all three cristae and macula utriculi . The lesions were very extensive after ten days and the sensory cells had almost equally disappeared in all three cristae; the lesion in the macula utriculi was smaller and the macula sacculi was unaffected . At fourteen days, the lesions appeared less severe . Thus, a single application of a small amount of streptomycin on the lateral canal fenestra affected all vestibular sense organs, except the saccule, in a short time . The strong affinity of aminoglycosides for the cristae suggests possible entrapment of the drug at the ampullae . This local drug application technique to the canal will be useful in studying vestibular function in animals, and it is applicable to controlling severe vestibular symptoms in human patients.

Comp Biochem Physiol Comp Physiol, 1994 Mar, 107(3), 473 - 81
Evidence for calcium channels involved in regulating nematocyst discharge; Watson GM et al.; In the tentacles of sea anemones, nematocyst discharge is regulated by cnidocyte/supporting cell complexes (CSCCs) of which three functional types have been identified: A, B and C . Type A CSCCs respond to contact by vibrating targets . Types B and C CSCCs respond to contact by static targets . Whereas type C CSCCs respond to contact alone, type B CSCCs require that surface chemoreceptors bind ligands before becoming responsive . Reducing Ca2+ levels in artificial seawater to below 1 mM inhibits discharge from each type of CSCC . The calcium channel inhibitors, nifedipine or verapamil, selectively inhibit discharge from type B CSCCs . The calcium channel activator, Bay K-8644, mimics the biphasic dose response of type B CSCCs to natural chemosensitizers such as N-acetylated sugars . Discharge from type A CSCCs is unaffected by inhibitors of L-type calcium channels, but is selectively inhibited by the aminoglycoside antibiotics, gentamicin and streptomycin . While each type of CSCC requires extracellular calcium, the calcium channels employed may vary according to CSCC type.

J AOAC Int, 1994 Mar-Apr, 77(2), 334 - 7
Determination of streptomycin and dihydrostreptomycin in animal tissue by on-line sample enrichment liquid chromatography; Gerhardt GC et al.; A method for the determination of streptomycin and dihydrostreptomycin in pork and bovine muscle and kidney was developed . Dilute perchloric acid solution is used to precipitate proteins and extract the analytes from the tissue . The extract is loaded onto a cation-exchange, solid-phase extraction column, and the drugs are eluted with pH 8 phosphate buffer . The eluant is chromatographed by using an on-line column enrichment liquid chromatographic system with postcolumn derivatization using 1,2-naphthoquinone-4-sulfonic acid and detection by fluorescence . The recoveries were 61.1% (coefficient of variation {CV}, 7.3%) for streptomycin and 55.3% (CV, 8.2%) for dihydrostreptomycin . The detection limits were 10 ppb for streptomycin and 20 ppb for dihydrostreptomycin.

Nucleic Acids Res, 1994 Feb 25, 22(4), 619 - 24
Positions 13 and 914 in Escherichia coli 16S ribosomal RNA are involved in the control of translational accuracy; Pinard R et al.; Using a conditional expression system with the temperature-inducible lambda PL promoter, we previously showed that the single mutations 13U-->A and 914A-->U, and the double mutation 13U-->A and 914A-->U in Escherichia coli 16S ribosomal RNA impair the binding of streptomycin (Pinard et al., The FASEB Journal, 1993, 7, 173-176) . In this study, we found that the two single mutations and the double mutation increase translational fidelity, reducing in vivo readthrough of nonsense codons and frameshifting, and decreasing in vitro misincorporation in a poly(U)-directed system . Using oligodeoxyribonucleotide probes which hybridize to the 530 loop and to the 1400 region of 16S rRNA, two regions involved in the control of tRNA binding to the A site, we observed that the mutations in rRNA increase the binding of the probe to the 530 loop but not to the 1400 region . We suggest that the mutations at positions 13 and 914 of 16S rRNA induce a conformational rearrangement in the 530 loop, which contributes to the increased accuracy of the ribosome.

Infect Immun, 1994 Feb, 62(2), 623 - 31
The specific activities of Shiga-like toxin type II (SLT-II) and SLT-II-related toxins of enterohemorrhagic Escherichia coli differ when measured by Vero cell cytotoxicity but not by mouse lethality; Lindgren SW et al.; Characteristically, enterohemorrhagic Escherichia coli (EHEC) strains produce Shiga-like toxin type I (SLT-I), SLT-II, or both of these immunologically distinct cytotoxins . No antigenic or receptor-binding variants of SLT-I have been identified, but a number of SLT-II-related toxins have been described . Because EHEC O91:H21 strain B2F1, which produces two SLT-II-related toxins, is exquisitely virulent in an orally infected, streptomycin-treated mouse model (oral 50% lethal dose {LD50}, < 10 organisms), we asked whether the pathogenicity of strain B2F1 was a consequence of SLT-II-related toxin production . For this purpose, we compared the lethality of orally administered E . coli DH5 alpha (Strr) strains that produced different cytotoxic levels of SLT-II, SLT-IIvha (cloned from B2F1), SLT-IIvhb (also cloned from B2F1), or SLT-IIc (cloned from EHEC O157:H7 strain E32511) on Vero cells . We also calculated the specific activities of purified SLT-IIvhb and SLT-II in intraperitoneally injected mice and on Vero cells . The two purified toxins were equally toxic for mice, but SLT-IIvhb was approximately 100-fold less active than SLT-II on Vero cells and bound to the glycolipid receptor Gb3 with lower affinity than did SLT-II . In addition, characterization of SLT-II-related toxin-binding (B) subunit mutants generated in this study revealed that the reduced in vitro cytotoxic levels of the SLT-II-related toxins were due to Asn-16 in the B subunit . Taken together, these findings do not support the idea that B2F1 is uniquely virulent because of the in vivo toxicity of SLT-II-related toxins but do demonstrate differences in in vitro cytotoxic activity among the SLT-II group produced by human EHEC isolates.

Antimicrob Agents Chemother, 1994 Feb, 38(2), 228 - 33
Genetic alterations in streptomycin-resistant Mycobacterium tuberculosis: mapping of mutations conferring resistance; Meier A et al.; We report on the identification of mutations associated with streptomycin resistance in Mycobacterium tuberculosis . Two isolates (3656 and 3976) showed a wild-type ribosomal protein, S12, but exhibited a single point mutation at 16S rRNA position 491 (C-->T) or 512 (C-->T), respectively . Sequence analysis of a third isolate (2438) revealed a single base change at 16S rRNA position 904 (A-->G) . This position is equivalent to invariant position 913 of the Escherichia coli 16S rRNA gene, an A-->G transition of which has been shown previously to impair streptomycin binding and streptomycin-induced misreading in vivo . Surprisingly, strain 2438 harbors an additional mutation in the ribosomal protein S12 (Lys-88-->Gln).

Eur Respir J, 1994 Feb, 7(2), 247 - 50
Mycobacterium avium complex develop resistance to synergistically active drug combinations during infection; Hoffner SE et al.; Isolates of Mycobacterium avium complex from five patients on longterm (3-5 yrs) anti-mycobacterial drug treatment were collected during the early and late phase of disease, and studied in vitro for their susceptibility to anti-mycobacterial drugs and drug-combinations . All isolates were resistant or moderately resistant to ethambutol, rifampicin and streptomycin when given singly; however, all strains isolated early in the disease were susceptible to the combination of ethambutol with either rifampicin or streptomycin . All late isolates had developed resistance to one or both of these combinations . Three of the patients died within a year after the last isolation of M . avium complex, and the two remaining patients still have severe chronic disease . It is concluded that the susceptibility of M . avium strains to combinations of drugs should be monitored during the course of treatment, in order to guide the selection of effective drug-combinations throughout the infection.

Mol Microbiol, 1994 Feb, 11(3), 449 - 58
Initiation and termination of DNA transfer at F plasmid oriT; Gao Q et al.; DNA sequences within the F plasmid transfer origin (oriT) were tested for their ability to initiate or terminate conjugal transfer . Mutant and wild-type oriT elements were cloned as direct repetitions flanking the rpsL gene on a pBR322-based plasmid, and the frequency of deletion of this segment during matings sponsored by F'lac (F42) with streptomycin-resistant recipients was measured . Shortened oriT elements that lacked adjacent TraM-binding sites allowed efficient initiation and termination . Some truncated oriT segments lacking the TraM-binding sites and the TraY-binding site, sbyA, initiated transfer inefficiently, but nevertheless promoted efficient termination . Removal of TraM-, TraY-, and IHF-binding sites severely reduced both nicking and termination . Point mutations that previously had been reported to prevent nicking caused reduced levels of both initiation and termination . These results indicate that regions of oriT supporting initiation are more extensive than those needed for termination, although some regions are required for both . Moreover, termination can be effective for some mutant loci that do not support efficient nicking.

Otolaryngol Head Neck Surg, 1994 Feb, 110(2), 162 - 7
Intratympanic gentamicin in bilateral Menière's disease; Pyykko I et al.; Treatment of bilateral Meniere's disease is a delicate task . Streptomycin has demonstrated its ability to successfully control the vertigo attacks, but in some cases it results in oscillopsia and transforms the periodic attacks to permanent instability . If the site of the active labyrinth can be determined, a more specific treatment can be tried . We have treated 14 patients with intractable bilateral Meniere's disease with intratympanic gentamicin (Garamycin, 40 mg/ml) administered initially in either 1, 2, 3, or 4 injections . The patients were tested at frequent intervals and followed up for 2 years . The work capacity, severity of vertigo, and gait difficulties were scored before treatment and during each test occasion . The postural stability was evaluated on a force platform and sway velocity was analyzed . Before treatment, moderate or severe reduction of work capacity was experienced by all of the subjects, which correlated to severity of vertigo and gait problems . Two years after treatment, the vertigo attacks were eliminated in 11 subjects and controlled in three subjects . The work capacity of three subjects was still moderately or severely reduced . This reduction depended on gait disturbance and Tumarkin attacks . The average postural stability returned to pretreatment level 2 years after the treatment was begun . The outcome of the caloric responses did not correlate with the outcome of the treatment . Hearing was not significantly affected by the treatment . Intratympanic gentamicin treatment is a relatively safe and effective way to treat bilateral Meniere's disease when the symptoms can be localized to one ear.

J Bacteriol, 1994 Feb, 176(4), 1093 - 8
Transfer of a genetic marker from a megaplasmid of Anabaena sp . strain PCC 7120 to a megaplasmid of a different Anabaena strain; Muro-Pastor AM et al.; The 410-kb alpha megaplasmid of the heterocyst-forming cyanobacterium Anabaena sp . strain PCC 7120 was found to bear the nucA gene that encodes a sugar-nonspecific nuclease . That gene was mutated by insertion of a cassette that confers resistance to neomycin . The resulting strain, AMP2, was mated with a streptomycin-resistant derivative of Anabaena sp . strain PCC 7118, a strain that does not form heterocysts . Cells resistant to both neomycin and streptomycin that were derived from such matings were found to bear the neomycin resistance cassette of the donor strain in a larger megaplasmid characteristic of the recipient strain and did not form heterocysts . This is the first example of transfer of a genetic marker directly between strains of cyanobacteria in which incontrovertible physical evidence of transfer has been obtained . DNA sequences homologous to the nucA gene were present in 13 heterocyst-forming cyanobacteria that were tested but in none of six diverse unicellular strains that were examined.

J Mol Biol, 1994 Jan 21, 235(3), 813 - 24
Mutations in 23 S ribosomal RNA perturb transfer RNA selection and can lead to streptomycin dependence; Bilgin N et al.; Escherichia coli ribosomes with a G to C transversion at position 2661 in 23 S ribosomal RNA are more accurate in tRNA selection than wild-type ribosomes . This enhanced accuracy is due to improved initial selection of ternary complexes rather than proofreading of aminoacyl tRNAs . The 2661C mutation reduces the binding rate of cognate ternary complexes to the A-site . This binding rate deficiency becomes dramatic when ribosomes also harbour an S12 mutation with a streptomycin-resistant, hyperaccurate phenotype . In this case, severe loss of kinetic efficiency in EF-Tu function leads to cell death . Streptomycin restores viability by increasing the association rate of ternary complex to these doubly altered ribosomes . The binding rate of EF-G to 2661C ribosomes is also reduced while the translocation rate is unaffected.

J Mol Biol, 1994 Jan 7, 235(1), 156 - 72
Selective perturbation of G530 of 16 S rRNA by translational miscoding agents and a streptomycin-dependence mutation in protein S12; Powers T et al.; Previous studies have shown that a concise set of universally conserved bases in 16 S rRNA are strongly protected from attack by chemical probes when tRNA is bound specifically to the ribosomal A site . Two of these bases, A1492 and A1493, are located in the cleft of the 30 S subunit, the site of codon-anticodon interaction . A third residue, G530, is located within the highly conserved 530 stem-loop, a region that is involved in interactions with proteins S4 and S12, mutations in which perturb the translational error frequency . The 530 loop is also thought to be located at or near the site of interaction of elongation factor Tu on the 30 S subunit, a location that is distinct from the decoding site . This study monitors the response of these two A-site-related regions of 16 S rRNA to a variety of translational miscoding agents . Several of these agents, including streptomycin, neomycin and ethanol, selectively potentiate tRNA-dependent protection of residue G530 from kethoxal modification; in contrast, little change in reactivity of residues A1492 and A1493 is observed . These results are consistent with the previously demonstrated importance of G530 for A-site function and, moreover, suggest a common mechanism of action for these miscoding agents, even though they appear to have distinctly different modes of interaction with 16 S rRNA . In contrast to the miscoding agents, we find that a streptomycin-dependence (SmD) mutation in protein S12, which causes ribosomes to be hyperaccurate, antagonizes tRNA-dependent protection of G530 . The possibility that 5' or 3' flanking regions of mRNA could be involved in tRNA-dependent protection of G530 was tested by using different lengths of oligo(U) to promote binding of tRNA(Phe) to the A site . The relative levels of protection of G530, A1492 and A1493 were unchanged as the size of the mRNA fragment was decreased from 16 to 6 bases in length . We conclude, therefore, that for protection of G530 to be the result of direct contact with message, it must necessarily be located directly at the decoding site; otherwise, its protection is best explained by allosteric interactions, either with mRNA, or with the codon-anticodon complex . These results are discussed in terms of a model wherein the conformation of the 530 loop is correlated with the affinity of the ribosome for elongation factor Tu.

J Exp Biol, 1994 Dec, 197(1), 399 - 403
THE RELATIONSHIP BETWEEN THE LENGTH OF THE CUPULAE OF FREE NEUROMASTS AND FEEDING ABILITY IN LARVAE OF THE WILLOW SHINER GNATHOPOGON ELONGATUS CAERULESCENS (TELEOSTEI, CYPRINIDAE)
Mukai Y, Yoshikawa H, Kobayashi H.
Free mechanosensory neuromasts of larval fishes have been described as playing a complementary role to vision in feeding behaviour (Disler, 1971; Iwai, 1972a,b) . In certain species or under limited conditions, free neuromasts play a major role in detecting prey . The larvae of mottled sculpin Cottus bairdi can feed on Artemia in the dark by using free neuromasts (Jones and Janssen, 1992) . Artificially blinded surface-feeding Aplocheilus lineatus can detect insects on the water surface by means of free neuromasts (Muller and Schwarts, 1982; Tittel et al . 1984; Bleckmann, 1988; Bleckmann et al . 1989) . Furthermore, vibrations produced by swimming crustaceans are known to be a potent natural stimulus for the lateral line system in the Antarctic fish Pagothenia borchgrevinki (Montgomery and Macdonald, 1987; Montgomery, 1989) . We found that larvae of a plankton feeder, the willow shiner Gnathopogon elongatus caerulescens (Sauvage) (Cypriniformes, Cyprinidae), fed on nauplii of Artemia in complete darkness . Ototoxic compounds, such as streptomycin, have been shown to disturb the function of the lateral line organ or free neuromasts (Kaus, 1987; Blaxter and Fuiman, 1989; Janssen, 1990; Jones and Janssen, 1992) . Willow shiner larvae treated with streptomycin sulphate no longer feed on Artemia in the dark (Y . Mukai, in preparation) . The willow shiner inhabits calm lakes and feeds on zooplanktonic prey (Nakamura, 1949) . The larvae show a high sensitivity to minute water displacements . From these observations and from our findings, it appears that larval willow shiner must feed on zooplankton by using free neuromasts in the dark . In larval willow shiner, the vane-like cupulae of the free neuromasts protrude from the body surface and the long cupulae are 100-250 microm in length (Mukai and Kobayashi, 1991) . The prey is detected by the free neuromasts as a result of a slight bending of the cupula in response to local water movements . The shape of the cupula, especially its length, must therefore be related to the sensitivity of the free neuromast, as inferred from the results of Coombs and Janssen (1989) and van Netten and Kroese (1989).

Chest, 1994 Jan, 105(1), 318 - 9
Endoscopic classification of tracheobronchial tuberculosis with healing processes; Rikimaru T et al.; We established an endoscopic classification of tracheobronchial tuberculosis with healing processes . According to this classification, the period of time needed for healing was found to be shorter in patients who were treated by aerosolized streptomycin than in those treated with the conventional triple-drug oral regimen.

Bull Soc Pathol Exot, 1994, 87(1), 19 - 21
{Therapeutic approach in Mycobacterium ulcerans infections}; Darie H et al.; In Cote d'Ivoire, 88 patients of a series of 124 cases with Buruli ulcer have been able to be treated and supervised . All of them have received local cares and various antibiotics, and 23 have been treated by islet skin graft . Among the numerous antibiotics used, only Streptomycin seems to be accompanied by an acceptable failure rate . The islet-graft presents the advantage of the technical simplicity, of the good tolerance face the infection and of a good successful rate, which permits to shorten the evolution of this disabling affection . It seems to be the best adapted procedure taking into account available medical means in most of tropical countries.

Folia Microbiol (Praha), 1994, 39(2), 129 - 32
In vitro measurement of translation accuracy of ribosomes isolated from streptomycin-resistant mutant of Streptomyces granaticolor; Weiser J et al.; Accuracy of activity of ribosome isolated from UV-light-induced streptomycin-resistant R-21 mutant of Streptomyces granaticolor was measured in an E . coli-derived system translating poly(U) with a high rate and accuracy . Ribosomes from the R-21 mutant strain were shown to be resistant to streptomycin and about two-fold more accurate than those from the wild type . The mutant strain was found to be resistant to 1000 mg/L streptomycin (Stm) during vegetative growth while it sporulated on agar plates containing only up to 200 mg/L of Stm . The growth rate of the R-21 mutant in complex liquid medium was indistinguishable from that of the wild-type strain.

Eur J Anaesthesiol Suppl, 1994, 9, 93 - 8
Interaction between rocuronium bromide and some drugs used during anaesthesia; Muir AW et al.; In cats anaesthetized with i.p . chloralose and pentobarbitone, neuromuscular blockade produced by various doses of rocuronium was measured and dose response curves constructed in the presence of halothane, enflurane, nitrous oxide, propofol, alfentanil, thiopentone, ketamine, diazepam, chlorpromazine, morphine or streptomycin . In general, when a shift in the dose response curve was produced, it was a parallel shift to the left, indicating potentiation . Both halothane and enflurane produced a left shift and a small increase in the time from maximum block to 90% recovery . Nitrous oxide had no effect on the depth of block but delayed recovery . Thiopentone and ketamine potentiated the blocking effect of rocuronium but propofol and alfentanil had no effect . Chlorpromazine and morphine caused potentiation which took 1-1.5 h to develop . Streptomycin had a potentiating effect in four cats but not in two others . Diazepam displaced the dose-response curve to the right in four cats . Prior treatment with suxamethonium had no effect.

Bull World Health Organ, 1994, 72(4), 603 - 10
A random sample survey of initial drug resistance among tuberculosis cases in Latin America; Laszlo A et al.; A random sample survey of initial drug resistance among cases of tuberculosis in Latin America was carried out during the second half of the 1980s and the early 1990s . A total of 948 cultures of Mycobacterium tuberculosis isolated from patients presumed never before to have been treated for tuberculosis were collected from 30 randomly selected clusters in Latin America and tested for resistance to isoniazid, streptomycin, rifampicin, ethambutol, and thioacetazone . Initial drug resistance, although unevenly distributed, was detected in all the clusters tested and characterized one out of every six tuberculosis cases . Both single and multiple resistance to streptomycin and to isoniazid were the most prevalent forms throughout the region but were not sufficiently frequent to jeopardize significantly the outcome of short-course chemotherapy . However, localized pockets of high drug resistance occurred throughout the region and are cause for concern, especially in the case of rifampicinPIP: The survey was conducted in Argentina, Bolivia, Brazil, Chile, Colombia, Cuba, Haiti, Mexico, Paraguay, and Peru . A random sample survey of initial drug resistance among cases of tuberculosis in Latin America was carried out during the second half of the 1980s and the early 1990s . A total of 948 cultures of Mycobacterium tuberculosis isolated from patients who presumably had never previously been treated for tuberculosis were collected from 30 randomly selected clusters in Latin America and tested for resistance to isoniazid (H), streptomycin (SM), rifampicin (R), ethambutol (E), and thiacetazone (Th) . Unevenly distributed, initial drug resistance was detected in all the clusters tested and characterized one out of every six tuberculosis cases . A total of 159 of the 948 clusters tested (16.8%) exhibited some type of drug resistance, ranging from 2.7% to 54.5 . Resistance to one drug was 12.2%, to two drugs was 3.4%, and to more than two drugs was 1.2% . A total of 116 (12.2%) strains exhibited single-drug resistance: H-26 strains from all 10 countries; SM-70 strains also from all 10 countries; Th-16 strains from Colombia, Cuba, Mexico, Paraguay, and Peru; and R-four strains from Colombia, Mexico, and Peru . Another 32 (3.3%) strains exhibited simultaneous resistance to two drugs, distributed as follows: H-SM: 25 strains (2.6%) from Argentina, Bolivia, Brazil, Chile, Colombia, Mexico and Peru; SM-Th: five strains (0.5%) from Colombia and Peru; R-E: one strain (0.1%) from Haiti; and H-R: one strain (0.1%) from Peru . Another 10 (0.1%) strains exhibited simultaneous resistance to three drugs: H-SM-Th: four strains (0.4%), from Bolivia, Brazil, Cuba, and Peru; H-SM-R: three strains (0.3%) from Peru; H-SM-E: two strains, one from Mexico and one from Peru; and H-E-Th: one strain (0.1%) from Cuba . Finally, one strain (0.1%) from Brazil exhibited resistance to four drugs: H-SM-R-Th . The total resistance was as follows: H (6.5%); SM (11.6%); R (1.1%); E (0.4%); and Th (2.6%) .

Rev Pneumol Clin, 1994, 50(5), 256 - 9
{Treatment of tuberculosis in France}; Dautzenberg B; In France, the treatment of tuberculosis must take into account both the low rate of multiresistance and the relatively low cost of drugs (the cost of 6 months treatment is about equivalent to the cost of 1 day of hospitalization) . A six-month regimen has been recommended in France since 1981 . Streptomycin is no longer used routinely . A combination of rifampicin, isoniazid and pyrazinamide is the basis of initial treatment either in as a single medication (Rifater) or taken separately . Ethambutol is added at treatment onset, especially when there was a doubt about resistance . The second phase uses isoniazid and rifampicin, together (Rifanah) or separate.

Ann Otolaryngol Chir Cervicofac, 1994, 111(4), 201 - 7
{Current aspects of laryngeal tuberculosis . Apropos of 4 cases and review of the literature}; Gallas D et al.; After the discovery of streptomycin 1944, laryngeal tuberculosis became a rare complication of advanced pulmonary tuberculosis . Since that time the clinical aspects of the disease have changed . We analyzed these changes by reviewing 65 papers in English and in French published from 1965 to 1991 involving 738 cases and added our 4 new personal cases . To our knowledge, we report the first two well-documented cases of laryngeal tuberculosis in HIV positive patients . We propose a therapeutic and follow-up protocol for laryngeal and chest specialists treating such patients.

J Neurosci, 1994 Jan, 14(1), 140 - 52
Identification of hair cell progenitors and intermitotic migration of their nuclei in the normal and regenerating avian inner ear; Tsue TT et al.; Postembryonic production of sensory hair cells occurs in both normal and aminoglycoside-damaged avian inner ears . The cellular source and mechanism that results in new differentiated hair cells were investigated in the avian vestibular epithelia using three distinct cell-cycle-specific labeling methods to identify proliferating sensory epithelial cells . First, immunocytochemical detection of the proliferating cell nuclear antigen, an auxiliary protein of DNA polymerase, allowed labeling of cells in late G1, S, and early G2 phases of the cell cycle . Second, a pulse-fix tritiated thymidine autoradiographic protocol was used to identify cells in S phase of the cell cycle . Finally, Hoechst 33342, a fluorescent DNA stain, was used to identify epithelial cells in mitosis . The distribution of cells active in the cell cycle within the normal and ototoxin-damaged vestibular epithelium suggests that supporting cells within the sensory epithelia are the cellular precursors to the regenerated hair cells . Differences between the proliferation marker densities in control and damaged end organs indicate that the upregulation of mitotic activity observed after streptomycin treatment is due primarily to an increase in the number of dividing progenitor cells . The differences between the extent of ototoxic damage and the level of reparative proliferative response suggest a generalized stimulus, such as a soluble chemical factor, plays a role in initiating regeneration . Finally, after DNA replication is initiated, progenitor cell nuclei migrate from their original location close to the basement membrane to the lumenal surface, where cell division occurs . This pattern of intermitotic nuclear migration is analogous to that observed in the developing inner ear and neural epithelium.

Gene, 1993 Dec 31, 137(2), 211 - 6
Construction and characterization of new host-vector systems for the enforcement-cloning method; Hashimoto-Gotoh T et al.; The Escherichia coli host strains, TH1, TH2, TH3 alpha, TH4 and TH5, all trpR-, rpsL- and supE-, were constructed to constitutively express a trp promoter/operator (POtrp)-driven synthetic rpsLam+ gene encoding the streptomycin sensitivity (Sms) determinant (ribosomal protein S12) . The applicability of these strains to the Sms-enforcement cloning procedure {Toba-Minowa and Hashimoto-Gotoh, Gene 121 (1992) 25-33} was examined on tryptophan-rich low-salt (LS) agar medium in combination with two reconstructed Sms-enforcement plasmid vectors, ampicillin-resistant (ApR) pKF2, and chloramphenicol-resistant (CmR) pKF3 . The results indicated that (1) pKF2 enforced the Sms phenotype on TH1, TH2, TH4 and TH5, but not TH3 alpha, while pKF3 was effective on all the strains, (2) even without Sm, strains TH1, TH2, TH4 and TH5 harboring pKF2 rarely formed colonies on LS+Ap agar, and (3) TH2 harboring pKF3 hardly grew, forming tiny colonies only after two overnight incubations at 37 degrees C on LS+Cm agar . By using the AseI, BclI, StuI and EcoRI sites in POtrp-rpsL+4am of pKF2 and pKF3, it was revealed that enforcement cloning was applicable in the new host-vector systems on normal nutrient agar medium, except for a combination of TH3 alpha and pKF2, with the TH2 strain in combination with pKF2 or pKF3 seeming to be most suitable for enforcement cloning, even without Sm.

J Nucl Biol Med, 1993 Dec, 37(4), 245 - 8
Gallium-67 scintigraphy in an AIDS patients presenting tuberculous pericarditis; Bertolaccini P et al.; The case of a 31-year-old HIV-positive male drug addict, with a history of recurrent intermittent fever is presented . Chest x-ray showed right ilar-node enlargement and moderate venous congestion . A 67Ga-citrate scan of the chest was highly suggestive of Mycobacterial infection . Scans showed right supraclavicular, right costophrenic, hilar node, pericardial and low grade pulmonary tracer uptake . Therapy with streptomycin, ethambutol, isoniazid and pyrazinamide was started . After 8 weeks, a chest roentgenogram was normal and 67Ga-citrate scintigraphy showed only right hilar node tracer uptake . Biopsy specimen cultures then confirmed the diagnosis of Mycobacterium tuberculosis infection . This case is interesting because of (1) the uncommon pericardial tracer uptake, and (2) because it confirms the usefulness of 67Ga-citrate scan for the early diagnosis of Mycobacterial infection.

Am J Otol, 1993 Nov, 14(6), 570 - 5
Factors influencing results with streptomycin perfusion of the labyrinth; Shea JJ et al.; Streptomycin perfusion of the labyrinth is the logical choice of treatment for the third stage of Meniere's disease with intractable vertigo . The results of streptomycin perfusion of the labyrinth are comparable to those of other treatments, including endolymphatic shunt and vestibular nerve section . Refinements must be made in the process of selecting candidates for the operation . To study the factors influencing the results of streptomycin perfusion of the labyrinth, 144 patients who had streptomycin perfusion of the labyrinth and were followed for 1 year were studied using the 1972 AAOO classification of results . The findings of this study indicate that only a low dosage of streptomycin and a small volume of perfusate are required to obtain good results . Patients who have long lasting severe endolymphatic hydrops with poor hearing preoperatively are less likely to achieve good results.

Nippon Jibiinkoka Gakkai Kaiho, 1993 Nov, 96(11), 1950 - 61
{Morphological changes in the supporting cells of the utricular macula due to streptomycin intoxication}; Oda Y; Morphological changes in cultured utricular supporting cells following streptomycin sulfate (SM) intoxication were investigated using an organ culture system . Utricles of guinea pig were exposed to 30 and 3mg/ml of SM for 1-3 days in culture . The number of lysosomes in the supporting cells increased daily, and mitochondria, myeloid bodies, granules and vesicles were observed within the lysosomes . As these components accumulated in the lysosomes, the number of granules and vesicles in the cytoplasma decreased . Acid phosphatase (AcPase) activity also decreased . After 1-3 days culture with SM, the culture medium was changed to a medium without SM . After removal of SM, the Golgi apparati appeared more developed and AcPase activity was higher . At the same time, lysosomes were markedly decreased in number and the endoplasmic reticulum showed a gradual reproduction . These findings suggest close relationships among the Golgi apparatus, lysosomes, secretory granules and the endplasmic reticulum.

Rev Med Chil, 1993 Nov, 121(11), 1269 - 73
{Acquired resistance of M tuberculosis to the antitubercular drugs in Chile from 1988 to 1991}; Guzman AM et al.; Acquired drug resistance appears in patients that are or have been in treatment for tuberculosis (relapses, abandons and failures) . The aim of this study was to maintain an epidemiologic surveillance on the incidence of acquired drug resistance among previously treated patients and treatment failures . In 896 strains (518 in 1988 and 378 in 1991) coming from these type of patients, the pattern of sensitivity towards agents used in the treatment of tuberculosis was studied . There was an increase in the frequency of acquired resistance from 24.5% in 1988 to 32.3% in 1991 . This increment was observed in the group of treatment failures, where the resistance to the combination streptomycin-isoniazid-rifampin had special relevance . This situation is epidemiologically and clinically negative since it generates primary resistance and chronicity . The increment in acquired resistance forces a revision of tuberculosis treatment, specially in its operational features.

Eur J Surg, 1993 Nov-Dec, 159(11-12), 609 - 12
Do diets enriched with oil prevent multiple organ failure in mice?
Gielen CJ, van As AB, Goris RJ.
OBJECTIVE: To examine the effects of various diets supplemented with fat in an experimental model of multiple organ failure in mice . DESIGN: Two randomised laboratory studies . SETTING: University hospital . MATERIAL: 177 female Swiss mice (weight 20-30 g) . INTERVENTIONS: Experiment I: 59 mice; 20 received no dietary supplement, 20 received 15% palm oil, and 19 received 14% fish oil plus 1% corn oil, eight weeks before injection of 100 mg zymosan/100 g in 4 ml liquid paraffin; 5 mice in each group killed after 1.5 hours, and the rest on day 12 . Experiment II: 118 mice; 29 received no dietary supplement, 30 received 15% palm oil, 30 1% corn oil, and 29 14% fish oil, 12 weeks before injection with zymosan . 20 mice in each group received streptomycin 5 g/l in drinking water starting five days before injection of zymosan and continued until the end of the experiment . All mice killed on day 12 . MAIN OUTCOME MEASURES: Mortality, body and organ weights, and culture of peritoneal fluid . Detection of tumour necrosis factor-alpha (TNF-alpha) in plasma . RESULTS: Experiment I: only 5 control mice, 2 in the fish oil, and 7 in the palm oil, groups survived to day 12 . Spleens in mice given fish oil were significantly heavier than those that had had palm oil (p = 0.03) . Experiment II: 108/118 mice survived until day 12, and most had macroscopic signs of multiple organ failure . Liver weights in the fish oil group were lower than in the control (p = 0.04) and palm oil (p = 0.03) groups, and kidney weights higher than in the corn oil group (p = 0.007); there were no differences in the amounts of TNF-alpha detected in the blood . One culture in each experiment grew bacteria . CONCLUSION: Diets supplemented with fish oil did not prevent multiple organ failure or reduce plasma concentrations of TNF-alpha . Decontamination of the gut did not alter these results.

Rinsho Ketsueki, 1993 Nov, 34(11), 1491 - 3
{Streptomycin-induced severe aplastic anemia successfully treated with high-dose methylprednisolone pulse therapy and rhG-CSF}; Umeno Y et al.; An 83-year-old male was admitted with pulmonary tuberculosis . He was started on rifampicin, isoniazid, and streptomycin (SM) . The hematological data at 12 weeks after the treatment showed pancytopenia (RBC: 2.14 x 10(6)/microliters, Hb: 7.2g/dl, Plt: 1.8 x 10(4)/microliters, WBC: 700/microliters) . All the above medicines were discontinued and he received bolus methylprednisolone (bmPSL) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) . After 3 cycles of bmPSL, red blood cells and platelets gradually increased . White blood cells also increased in response to rhG-CSF . Bone marrow aspirate and biopsy specimens showed normocellularity, indicating recovery from aplastic anemia . Drug lymphocyte stimulation test was positive for SM.

Enferm Infecc Microbiol Clin, 1993 Oct, 11(8), 415 - 9
{Incidence of tuberculostatic-resistant Mycobacterium tuberculosis . Clinical aspects and impact on therapy and clinical course}; Esteban J et al.; BACKGROUND: To know the incidence of Mycobacterium tuberculosis resistant to anti-tuberculin drugs in addition to the clinical features, treatment and evolution of the patients . METHODS: This was a retrospective study of the clinical histories of patients with isolation of Mycobacterium tuberculosis with some type of resistance studied from January 1980 to April 1992 . RESULTS: During the period studied 470 patients were diagnosed with tuberculosis by cultures . In 30 of these cases (6.4%) Mycobacterium tuberculosis resistant to Isoniazide (8), Streptomycin (6), Isoniazide + Rifampicin (4), Isoniazide + Streptomycin (3), Isoniazide + Ethambutol (2), Isoniazide + Rifampicin + Streptomycin (2), Isoniazide + Rifampicin + Ethambutol (2), Rifampicin (1), Ethambutol (1), Isoniazide + Pyrazinamide (1) and Isoniazide + Rifampicin + Streptomycin + Ethambutol (1) were isolated . Clinical information was obtained on 23 patients, with the most frequent clinical pictures being those of respiratory infection (15) . Five cases occurred in HIV+ patients . The resistance was considered as primary in 58.97% of the cases with modifications in empiric treatment being necessary in 6 cases . In 15 out of the 19 patients from whom the data of the follow up was obtained the evolution was good . CONCLUSIONS: Resistance to Mycobacterium tuberculosis was 6.4%, with the high number of strains resistant to Rifampicin being of note . In 79% of the cases in which follow up data was obtained the resistance had no impact on treatment due to the good evolution of the patients in relation with the treatment used.

Kekkaku, 1993 Oct, 68(10), 653 - 6
{Pulmonary disease due to Mycobacterium xenopi}; Terashima T et al.; A 54-year old man with pulmonary disease due to Mycobacterium xenopi is described . He had a history of pulmonary tuberculosis at 8 years of age . He was admitted to our hospital in October 1992, complaining of productive cough and fever . A chest X-ray on October 20 showed an infiltrative shadow with a cavity, although chest X-ray picture on October 2 showed only inactive shadow, in the right upper lobe . Acid-fast organisms were seen in his sputum specimens and M . xenopi was identified by culture . The isolates were confirmed to be M . xenopi by the DNA-DNA hybridization method . He was treated with isoniazid, rifampicin and streptomycin . The fever decreased within a week . After two months of therapy, sputum cultures became negative and chest X-ray findings improved . It was concluded that this is a case of rapidly progressed pulmonary disease caused by M . xenopi in the normal host . This patient's condition responded to antituberculosis drugs.

Otolaryngol Clin North Am, 1993 Oct, 26(5), 737 - 46
Therapeutic use of aminoglycosides in Ménière's disease; Monsell EM et al.; This article details the various effects of aminoglycosides used to treat individuals with Meniere's disease . Effects of aminoglycosides on hair cells and dark cells are described in addition to intramuscular streptomycin, intratympanic application of aminoglycosides, and the application of streptomycin to the lateral semicircular canal.

Plant Mol Biol, 1993 Oct, 23(1), 179 - 83
A point mutation in the chloroplast rps12 gene from Nicotiana plumbaginifolia confers streptomycin resistance; Hsu CM et al.; In an effort to understand the mechanism of streptomycin resistance in Nicotiana plumbaginifolia, we have sequenced the chloroplast rps12 gene, a potential molecular target . We report that a streptomycin-resistant mutant isolated from protoplast cultures of N . plumbaginifolia contains an A-to-G transition at nucleotide position 149 in exon 2 of the chloroplast rps12 gene . The detected point mutation predicts a substitution of arginine for lysine in a phylogenetically conserved region.

East Afr Med J, 1993 Oct, 70(10), 609 - 12
Anti-tuberculous initial drug resistance of Mycobacterium tuberculosis in Kenya: a ten-year review; Githui WA et al.; Our experience at the Respiratory Diseases Research Unit (RDRU), over the last 10 years (1981-1990) on the initial drug resistance pattern, focusing on three drugs viz: isoniazid (H), streptomycin (S) and rifampicin (R) is presented . Records on all isolates of M . tuberculosis from one specimen of every newly diagnosed patient recruited countrywide between 1981-1990 were reviewed . We analyzed records of 6,514 isolates and found that total resistance to the three drugs had increased from 8.9% to 14.4% . Resistance to H alone increased from 6.8% to 10.2% while that of S alone from 0.8% to 1.8% . Resistance to R was between 0.1% and 0.3% . Generally, the increase in the resistance trend to both H and S was statistically significant (p = < 0.05 and 0.03, respectively) . Although in our analysis we did not address the possible impact of HIV infection, we hope that these findings form a basis for evaluation of this and other possible factors on the emergence of anti-TB drug resistance in future studiesPIP: A retrospective review of medical records of 6514 Mycobacterium tuberculosis isolates of newly diagnosed patients at the Respiratory Diseases Research Unit of the Kenya Medical Research Institute between 1981 and 1990 aimed to determine the initial drug-resistance pattern for isoniazid, streptomycin, and rifampicin . Overall resistance increased from 8.9 to 14.4% (p 0.001) . The increase in the resistance trend to isoniazid and to streptomycin were statistically significant (6.8-10.2; p 0.05 and 0.8-1.8; p = 0.03, respectively) as well as the trend among isolates resistant to both isoniazid and streptomycin (1.2.4; p = 0.03) . The trend was more pronounced during 1987-1990 than during 1981-1986 . There was no trend in the resistance to rifampicin alone (0.1-0.3%) . Just 4 isolates were resistant to both isoniazid and rifampicin . Only 1 was resistant to both streptomycin and rifampicin . None were resistant to all 3 antibiotics . These first-line drugs are used widely in Kenya . These rates of initial resistance to the drugs are lower than those in other developing countries . The lower resistance rate is unlikely to continue, however, due to higher prevalence of HIV infection and the associated increase in tuberculosis incidence . These findings provide researchers a baseline with which to study M . tuberculosis drug resistance and other risk factors as drug resistance increases in Kenya .

Indian J Pathol Microbiol, 1993 Oct, 36(4), 383 - 8
HIV-1 seropositivity in pulmonary tuberculosis (study of 340 cases from Marathwada); Talib SH et al.; An investigative study was carried out in 340 cases of established pulmonary and presumed pleural tuberculosis for co-occurrence of HIV-1 infection in them . Confirmatory screening for HIV-1 was carried out with both ELISA (Vironostika) and Serodia commercial kits in all reactive samples on first screening . In all, 16 cases proved to be having HIV-1 coexistent infection with pulmonary tuberculosis . Their preliminary vital clinical observations and roentogenic finding are summarized and literature reviewed brieflyPIP: In Marathwada region of Maharashtra State, India, clinicians obtained blood samples from 340 pulmonary and presumed pleural tuberculosis (TB) patients at the TB Wing of the Government Medical College Hospital in Aurangabad to determine the HIV seropositivity rate of the cases . All samples testing positive for an ELISA would undergo another ELISA to confirm the first ELISA's results . The ELISA commercial kits were Serodia and Vironostika . 16 cases tested positive for HIV by both ELISA tests . The sexual preference of all 16 cases was heterosexual . Males and 20-39 year olds were the predominant groups (12 vs . 4 for both groups) . No case was younger than 20 years old . Six HIV-positive male TB patients had had multiple partners . Three of them also had genital ulcer disease, a cofactor facilitating HIV transmission . Six HIV-positive TB patients had a history of receiving streptomycin injections and 2 of them had also had multiple partners . 25% of HIV-positive TB patients had pleural effusion . 12 cases had TB clinical features (lower zone infiltration, hilar/mediastinal adenopathy, and diffuse infiltration without cavitation) associated with greater impairment of cell mediated immunity .

HNO, 1993 Oct, 41(10), 471 - 4
{Mechanical stimulation of isolated outer hair cells as a test system . Inhibition of transduction by streptomycin treatment}; Preyer S et al.; Deflection of the hair bundle of isolated outer hair cells from the guinea pig cochlea can induce a receptor potential . Outer hair cells from the third and fourth turns of the guinea pig cochlea were isolated according to the method described by Zenner et al . Cells were maintained in Hank's balanced salt solution at room temperature . The whole cell potential was measured by the patch-clamp technique with soda glass capillaries (resistance 3-5 M omega) filled with KCl-Ringer solution . After compensation for the junction potential the stable resting potential of 46 cells was -63 mV +/- 5 mV . The hair bundle was deflected sinusoidally, with amplitudes ranging from 6 degrees to a maximum of 31 degrees in the positive direction (i.e., in the direction of the longest stereocilium) . The stimulus was a piezo-driven glass capillary with an opening diameter of 5 microns . This mechanical stimulation induced in 33% of all stimulated cells (n = 46) a receptor potential response of 2.1 +/- 1.4 mV (maximally 5.5 mV) . Deflection of the hair bundle in the opposite direction led to no change in the membrane potential, i.e . the cells were not hyperpolarized (minimal resolution 0.5 mV) . Since the resting potential of the cells was more positive than the potassium equilibrium potential under our experimental conditions, the receptor current was most likely mediated by an influx of Na+ ions into the cell . The receptor potential response could be completely and reversibly blocked by the addition of dihydro-streptomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Dtsch Med Wochenschr, 1993 Sep 10, 118(36), 1281 - 6
{Generalized nocardiosis with meningoencephalitis in a nonimmunosuppressed female patient}; Hannemann J et al.; Four weeks after an attack of pneumonia of unknown aetiology a 40-year-old woman was hospitalized because of a nonpurulent, predominantly basal meningoencephalitis and infratentorial abscesses . She had dysarthria, mild right-sided motor hemiparesis and central paresis affecting the 7th cranial nerve . An area of fluctuating resistance, about 3 cm in diameter, was noticed over the left thigh . Serology indicated inflammatory disease, but there was no immunodeficiency . The CSF showed lymphocytic pleocytosis with mild protein increase but no evidence of infective agent . As tubercular meningitis was suspected she was treated with rifampicin (300 mg i.v . twice daily), isoniazid (300 mg i.v . once daily), streptomycin (800 mg i.m . once daily), cefotaxime (2.0 g i.v . three times daily), fluconazole (200 mg i.v . once daily) and dexamethasone (16-8-8 mg i.v.) . She suddenly died two days after admission, probably as the result of central regulatory failure . Generalized nocardiosis involving lung, subcutaneous tissue and brain was revealed at autopsy . Although nocardiosis occurs predominantly in patients under immunosuppression, this infection should be considered in the differential diagnosis of treatment-resistant pneumonia and meningoencephalitis without obvious predisposition.

Ann Thorac Surg, 1993 Sep, 56(3), 610 - 4
The history of thoracoscopic surgery; Braimbridge MV; The necessity for thoracoscopy became apparent with the adhesions that limited the success of Forlanini's introduction in 1882 of artificial pneumothorax in the treatment of pulmonary tuberculosis . The first thoracoscopy, using a modified cystoscope, was performed by H . C . Jacobaeus, a professor of medicine, not surgery, in Stockholm, publishing in 1910 . Thoracoscopy and division of adhesions (intrapleural pneumonolysis) then spread all over the world, with reports of series of 1,000 or more cases in spite of a significant incidence of complications . Its use declined rapidly after the introduction of streptomycin in 1945, becoming then confined to relatively minor diagnostic procedures except in a few European centers . The advent of video-assisted thoracoscopes and the development of ancillary instruments has allowed a new explosion of thoracoscopic surgery . Surgeons, in whose hands the procedure now rests, should nevertheless be aware of the five unacceptable thoracoscopic disasters--wrong side, kebab lung, "clotted hemothorax," artificial lunchothorax, and aorto-pleuro-cutaneous fistula.

Infect Immun, 1993 Sep, 61(9), 3832 - 42
Virulence of enterohemorrhagic Escherichia coli O91:H21 clinical isolates in an orally infected mouse model; Lindgren SW et al.; Escherichia coli K-12 strains producing high levels of Shiga-like toxin type II (SLT-II) but not SLT-I were previously shown to be virulent in an orally infected, streptomycin-treated mouse model . In this investigation, we tested the virulence of several SLT-II-producing enterohemorrhagic E . coli (EHEC) isolates from patients with hemorrhagic colitis or hemolytic uremic syndrome . All of the strains tested were able to colonize the mouse intestine . However, only two strains were consistently virulent for mice: O91:H21 strain B2F1 (Strr), which was previously shown to carry two copies of slt-II-related toxins, and O91:H21 strain H414-36/89 (Strr), which was found in this study to contain three genes from the slt-II group . The oral 50% lethal doses of strains B2F1 (Strr) and H414-36/89 (Strr) when fed to streptomycin-treated mice were less than 10 bacteria . Histological sections from moribund mice fed the O91:H21 strains demonstrated extensive renal tubular necrosis; however, hematological results were not consistent with a diagnosis of hemolytic uremic syndrome . The central role of SLT in the virulence of the O91:H21 EHEC strains was supported by the finding that streptomycin-treated mice preinoculated with monoclonal antibody specific for SLT-II survived oral challenge with either B2F1 (Strr) or H414-36/89 (Strr) . The basis for the variation in virulence among the SLT-II-producing EHEC strains tested was not determined . However, a correlation between the capacity of an EHEC strain to grow in small intestinal mucus and lethality in the streptomycin-treated mice was observed.

Infection, 1993 Sep-Oct, 21(5), 324 - 7
Short course intermittent chemotherapy in childhood tuberculosis; Gocmen A et al.; A total of 130 children diagnosed as having pulmonary and extrapulmonary tuberculosis who received short course intermittent chemotherapy between 1978-1992 were evaluated retrospectively . One hundred and ten children with tuberculosis were treated with isoniazid (10-15 mg/kg, maximum 400 mg), rifampin (10-15 mg/kg, maximum 600 mg), and streptomycin (30 mg/kg, maximum 1 g) daily, for 15 days . Treatment was completed with similar doses of isoniazid and rifampin twice a week for a period of 9 months . Since 1986, 20 children with tuberculosis were being treated with the same regimen but without streptomycin . The majority of patients in these cases had pulmonary tuberculosis (75%), followed by lymph nodes (9%), pleural (7%), bone and joint (5%), miliary (3%), and abdominal tuberculosis (1%) . The clinicoradiologic response to treatment was observed to be excellent . Only one case of relapse was detected, which was the case of a patient with lymph node tuberculosis that occurred 18 months after the completion of treatment . No serious adverse drug reaction was observed in any of the cases mentioned . In conclusion, short-course low-dose intermittent chemotherapy is an effective and economical treatment with minimal side effects for pulmonary and extrapulmonary tuberculosis in childhood.

Plasmid, 1993 Sep, 30(2), 90 - 105
Construction of shuttle plasmids which can be efficiently mobilized from Escherichia coli into the chromatically adapting cyanobacterium, Fremyella diplosiphon; Cobley JG et al.; In some strains of cyanobacteria the composition of the light-harvesting antennae is determined by the color of available light . The mechanism of this chromatic adaptation involves the regulation of gene expression by red and green light and has been most studied in Fremyella diplosiphon (Calothrix sp . PCC 7601), a filamentous cyanobacterium for which there has been no reported means of genetic manipulation . We have constructed shuttle plasmids which can be efficiently mobilized by RP4 from Escherichia coli into F . diplosiphon and which can be recovered from transconjugant F . diplosiphon and returned to E . coli by transformation . The ability of these plasmids to replicate in F . diplosiphon is conferred by an 8.0-kb DNA fragment isolated from pFDA, a plasmid native to F . diplosiphon . To create these shuttle plasmids the 8.0-kb fragment was cloned into pJCF22, a mobilizable plasmid constructed from oriV and bom from pBR322, cat from pACYC184 and aphA from pACYC177.pJCF22 lacks sites for the restriction enzymes FdiI and II . Transconjugant F . diplosiphon containing shuttle plasmid pJCF62 are resistant to chloramphenicol and highly resistant to the aminoglycosides, G418 and neomycin . When aadA from the omega interposon was incorporated into a shuttle plasmid transconjugant F . diplosiphon could also be selected with streptomycin or spectinomycin . In F . diplosiphon shuttle plasmid pJCF62 replicates with a minimum copy number of seven . The oriV for replication in F . diplosiphon was localized to a 2.8-kb region within the cyanobacterial part of pJCF62 . The presence on a shuttle plasmid of a single recognition site for FdiI reduced the efficiency of mobilization into F . diplosiphon by 5- to 10-fold . Restriction at this site was prevented when the E . coli donor strain in the mating contained the enzyme Eco47II methylase.

Rev Sci Tech, 1993 Sep, 12(3), 909 - 22
Successful therapeutic regimens for treating Brucella melitensis and Brucella abortus infections in cows; Radwan AI et al.; Three therapeutic regimens were evaluated in 121 cows naturally infected with Brucella melitensis or Brucella abortus, using a combination of long-acting oxytetracycline (LA-OTC), streptomycin (ST) and OTC-intramammary infusion (IMI) . Cessation of shedding of Brucella in udder secretions and absence of Brucella in selected tissues were considered criteria for successful treatment . Regimen A (tested on 35 cows) consisted of LA-OTC 25 mg/kg administered intramuscularly (i.m.) every 3 days for 42 days, ST 25 mg/kg i.m . daily for 8 days, and OTC-IMI 20 ml/teat daily for 4 days . Regimen B (tested on 53 cows) was similar to regimen A, except that ST was administered every 2 days for 16 days and OTC-IMI every 2 days for 8 days . Both regimens were equally effective in eliminating Brucella organisms from all cows involved in the tests and no relapses were recorded . However, regimen C, which was similar to regimen A, except that ST was administered every 3 days for 24 days and OTC-IMI every 3 days for 12 days, resulted in the elimination of Brucella organisms from only 30 (91%) of 33 cows . Before commencement of the therapeutic regimens, B . melitensis biovar 1 or 2 had been repeatedly isolated from udder secretions of 103 cows and B . abortus biovar 1 from mammary secretions of 18 cows.

Am J Otol, 1993 Sep, 14(5), 474 - 7
Titration streptomycin therapy in Menière's disease: current concepts; LaRouere MJ et al.; Soon after its discovery, streptomycin sulfate was found to be beneficial in the treatment of tuberculosis . However it also was found to have toxic effects, primarily vestibular and typically sparing the auditory nerve until higher doses were administered . The first reported use of streptomycin in the treatment of vertigo was in 1948 . This was soon followed by its use for treating Meniere's disease . Although excellent control of vertigo was achieved significant post-treatment oscillopsia was experienced by these completely ablated patients . A protocol of titration streptomycin therapy was established that effectively controls vertigo while decreasing the incidence of oscillopsia . This report presents three patients with Meniere's disease treated with this protocol.

Proc Natl Acad Sci U S A, 1993 Aug 15, 90(16), 7874 - 8
pDUAL: a transposon-based cosmid cloning vector for generating nested deletions and DNA sequencing templates in vivo; Wang G et al.; We describe a transposon gamma delta-containing cosmid cloning vector, pDUAL (previously called pJANUS), and demonstrate an efficient strategy for isolating nested deletions in both large-scale and small-scale DNA sequencing efforts . This "deletion factory" strategy takes advantage of the ability of gamma delta (Tn1000) to generate deletions that extend from an end of the transposon into adjacent DNA when gamma delta transposes to new sites in the same DNA molecule . pDUAL contains the contraselectable (conditional lethal) sacB+ (sucrose sensitivity) and strA+ (streptomycin sensitivity) genes just outside each end of an engineered gamma delta and selectable kan+ (Kanr) and tet+ (Tetr) genes between the cloning site and sacB and strA, respectively . Selection on sucrose tetracycline medium yields deletions that extend from one gamma delta end for various distances into the cloned DNA, while selection on streptomycin kanamycin medium yields comparable deletions in the other direction . Both types of deletions are recoverable because the essential plasmid replication origin is embedded in the gamma delta component and is thereby retained in each deletion product . Pilot experiments with pDUAL clones showed that deletion end points can be mapped or selected by plasmid size and that both DNA strands of any single clone can be accessed for sequencing by using a pair of universal primers specific for sequences that are just interior to the gamma delta ends.

Kekkaku, 1993 Aug, 68(8), 521 - 6
{The appearance and enlargement of localized pulmonary granuloma with eosinophilic infiltration during tuberculosis chemotherapy}; Saitoh Y et al.; A pulmonary tumorous shadow appeared and enlarged in a 25 years-old male patient undergoing intensive chemotherapy for tuberculosis . The chest X-rays taken on admission revealed effused pleura in the right lung and nodular shadows in the upper area of the right lung . After 40 days of using isoniazid (INH), rifampicin (RFP) and streptomycin (SM), a homogeneous opacity, not previously observed, appeared in the middle area of the right lung (S5) . Microscopic examination of the tissues obtained during a transbronchial lung biopsy disclosed epithelioid cell granulomas with marked eosinophilic infiltration . The presence of eosinophilic infiltration due to the admission of antituberculosis agents was disregarded because no change was observed in the new granulomatous shadows during the drug challenge tests and the lymphocyte stimulation test to INH, RFP and SM was negative . Transient aggravation during the initial phase of chemotherapy for pulmonary tuberculosis, such as in this case, is suspected cause by some eosinophilic allergic-induced mechanisms, against bacillary components.

Infect Immun, 1993 Aug, 61(8), 3392 - 402
Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice; Tesh VL et al.; In earlier studies using a streptomycin-treated mouse model of infection caused by enterohemorrhagic Escherichia coli (EHEC), animals fed Shiga-like toxin type II (SLT-II)-producing strains developed acute renal cortical necrosis and died, while mice fed Shiga-like toxin type I (SLT-I)-producing clones did not die (E . A . Wadolkowski, L . M . Sung, J . A . Burris, J . E . Samuel, and A . D . O'Brien, Infect . Immun . 58:3959-3965, 1990) . To examine the bases for the differences we noted between the two toxins in the murine infection model, we injected mice with purified toxins and carried out histopathological examinations . Despite the genetic and structural similarities between the two toxins, SLT-II had a 50% lethal dose (LD50) which was approximately 400 times lower than that of SLT-I when injected intravenously or intraperitoneally into mice . Histopathologic examination of toxin-injected mice revealed that detectable damage was limited to renal cortical tubule epithelial cells . Passive administration of anti-SLT-II antibodies protected mice from SLT-II-mediated kidney damage and death . Immunofluorescence staining of normal murine kidney sections incubated with purified SLT-I or SLT-II demonstrated that both toxins bound to cortical tubule and medullary duct epithelial cells . Compared with SLT-I, SLT-II was more heat and pH stable, suggesting that SLT-II is a relatively more stable macromolecule . Although both toxins bound to globotriaosylceramide, SLT-I bound with a higher affinity in a solid-phase binding assay . Differences in enzymatic activity between the two toxins were not detected . These data suggest that structural/functional differences between the two toxins, possibly involving holotoxin stability and/or receptor affinity, may contribute to the differential LD50s in mice.

Mol Microbiol, 1993 Jul, 9(2), 335 - 42
Double, independent mutational events in the rpsL gene of Escherichia coli: an example of hypermutability?
Timms AR, Bridges BA.
A proportion (up to 20%) of newly arising streptomycin-dependent (SmD) colonies of Escherichia coli WP2 contain bacteria where, in addition to a known SmD-determining (primary) mutation in the rpsL gene, there is a further ancillary mutation in the same gene . These ancillary mutations occur at 10 sites between 11 and 201bp away from the primary mutation . Ancillary mutations have been found in mutant colonies arising both spontaneously and after treatment with ultraviolet light and some have been found repeatedly . Ancillary mutations were frequently found to occur in mixed clones with an excess of bacteria carrying only the primary SmD mutation . No ancillary mutations were found in an adjacent non-coding region and there were no coding sequence changes that did not alter the amino acid specified . Although a selective advantage for bacteria containing ancillary mutations could not be demonstrated directly in every case, some small advantage must be presumed to have occurred to explain the absence of mutations at the other sites and particularly at third (wobble) codon positions . Ancillary mutations appear to occur fairly early in the life of a newly arisen SmD mutant clone in some sort of hypermutable process . Whether they are noticed appears to depend on their conferment of some selective advantage on the bacteria carrying them . While the ancillary mutations within rpsL lie close to, and may be consequent upon the formation of a primary SmD mutation, their mechanism of formation appears to be at least to some extent independent and does not involve the recA or umuC genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Otol, 1993 Jul, 14(4), 373 - 9
Acute and chronic effects of streptomycin applied to the lateral semicircular canal; Norris CH et al.; In developing the technique of selective chemical vestibulectomy, the destructive effect of streptomycin on the hair cells of the inner ear was well established . However, in both animal and human studies, a rapid onset of the drug's vestibular inhibition was observed in addition to a more slowly developing long-term destructive effect . In previous laboratory studies, streptomycin had been given only by a systemic route, and only the chronic long-term effects had been observed . In this study, an isolated semicircular canal was prepared and streptomycin was placed into the perilymph bathing the canal . The spontaneous and evoked afferent nerve activity were recorded prior to streptomycin application, during application, and after a washout period . During streptomycin application, the activity of the semicircular canal was reversibly inhibited in a dose dependent manner . After a sufficient washout period (5-10 min), the preparation had completely recovered from the drug's effect . Thus, there are two phases in the vestibular inhibition by streptomycin: an early reversible phase that subsequently can transform into a later irreversible phase.

Biochemistry, 1993 Jun 1, 32(21), 5539 - 47
Functional effects of a G to U base change at position 530 in a highly conserved loop of Escherichia coli 16S RNA; Santer M et al.; Any base change at position 530 introduced into Escherichia coli on a multicopy plasmid leads to cell death {Powers & Noller (1990) Proc . Natl . Acad . Sci . U.S.A . 87, 1042-1046} . It was suggested that these mutants cannot carry out chain elongation . To define more precisely the function of base 530, we have studied ribosomes in which G530 was mutated to U530 . In vivo, U530 16S rRNA was incorporated into 30S subunits and could combine with 50S to make 70S ribosomes . 16S rRNA in vitro transcripts containing U530 were assembled into 30S ribosomes, and their activity was tested in defined steps of protein synthesis . Mutant 30S ribosomes were as active as wild-type in poly(U)-dependent poly(Phe) synthesis, P- and A-site tRNA binding, and 30S initiation complex formation . 30S initiation complexes, in the presence of 50S, could react with puromycin like the wild-type . The rate, extent, and position of cross-linking of AcVal-tRNA in the P site to 16S RNA were identical in mutant and wild-type ribosomes . Although there appeared to be no defect in 70S initiation complex formation or in direct A-site binding of Phe-tRNA dependent on poly(U), U530 30S ribosomes were nevertheless defective in carrying out synthesis of fMet-Val dipeptide using natural mRNA . Mutant 30S ribosomes were also refractory to streptomycin-induced misreading although no misreading was observed in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

APMIS, 1993 Jun, 101(6), 449 - 54
Antimycobacterial activity of methdilazine (Md), an antimicrobic phenothiazine; Chakrabarty AN et al.; Methdilazine (Md) could inhibit various Mycobacterium spp . at 5-15 micrograms/ml concentrations in vitro as well as in vivo . When Md was tested in combination with streptomycin (Sm), rifampicin (Rf) or methyl-DOPA (m-D), it showed synergistic effects only with respect to methyl-DOPA.

Mol Gen Genet, 1993 May, 239(1-2), 241 - 50
Intermolecular ligation mediates efficient cotransformation in Phytophthora infestans; Judelson HS; The processing of DNA molecules during transformation was characterized in the oomycete Phytophthora infestans . Linear and circular forms of non-replicating transformation vectors supported similar rates of stable transformation . Remarkably, digestion of plasmids within the selectable marker genes neomycin phosphotransferase (npt) or hygromycin phosphotransferase (hpt) had little effect on the recovery of drug-resistant transformants, and the cleaved sites were shown to be reconstituted in the transformants . An assay for the transient expression of beta-glucuronidase (GUS) in protoplasts treated with partial or disrupted GUS genes demonstrated that active genes could be reconstituted through intramolecular and/or intermolecular ligation between compatible ends, while incompatible ends were inefficiently joined . Stable transformation studies also demonstrated that complementing portions of incomplete npt or hpt genes joined through homologous recombination . Based on the indication of efficient ligation between DNA molecules during transformation, an efficient procedure for cotransformation was developed . The frequency of cotransformation between vectors expressing selected genes (npt or hpt) and nonselected sequences (GUS, beta-galactosidase, or streptomycin phosphotransferase) approached unity when the plasmids were linearized with the same restriction enzyme before transformation . In contrast, cotransformation between circular plasmids or those cut with different enzymes occurred infrequently (10%) . Hybridization analysis of DNA from cotransformants demonstrated that linearized plasmids became colocalized within genomic DNA, while circular plasmids typically inserted at unliked sites.

J Bacteriol, 1993 May, 175(9), 2652 - 61
Detection of an A-factor-responsive protein that binds to the upstream activation sequence of strR, a regulatory gene for streptomycin biosynthesis in Streptomyces griseus; Vujaklija D et al.; DNA-binding assays using mobility shift polyacrylamide gel electrophoresis revealed the presence of a protein that specifically bound to a restriction fragment -288 to -191 bp upstream from the transcriptional start point of strR, a regulatory gene for streptomycin biosynthesis in Streptomyces griseus . The binding site corresponded to an upstream activation sequence predicted from the results of in vivo promoter assays . The binding was greatly enhanced by 5 mM Mg2+ . This binding was detected with the protein source only from the wild-type strain and not from an A-factor-deficient mutant strain . The exogenous supplementation of A-factor to the A-factor-deficient mutant strain caused the appearance of the protein in the DNA-binding assay . A synthetic nucleotide 52 bp in length (region from -293 to -242), which was synthesized on the basis of data obtained from both retardation assays with dissected DNA fragments and in vivo promoter assays, was retarded by the A-factor-dependent protein . In addition to this A-factor-dependent protein, at least three proteins with different recognition site affinities capable of binding to the upstream region of the strR promoter were detected . The binding of one of these proteins to both sides of the upstream activation sequence bound by the A-factor-dependent protein was completely abolished in the presence of ATP and Mg2+ in the incubation mixture . The region bound by these proteins showed anomalous electrophoretic mobility, like that of a bent DNA molecule, which is probably caused by the presence of many blocks consisting of A and T . The region bound by these proteins was found to be transcribed in the orientation opposite to that of strR.

CMAJ, 1993 May 1, 148(9), 1489 - 95
Antituberculous drug resistance in Manitoba from 1980 to 1989; Long R et al.; OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify the risk factors for its development in tuberculosis patients in Manitoba over a 10-year period . As well, to examine the clinical course of the patients whose initial or subsequent isolates of Mycobacterium tuberculosis were resistant to one or more drugs . DESIGN: Comparison of drug-resistant and non-drug-resistant cases of tuberculosis . SETTING: Manitoba . PATIENTS: All people with tuberculosis reported to the Central Tuberculosis Registry of Manitoba between Jan . 1, 1980, and Dec . 31, 1989 . MAIN OUTCOME MEASURES: Of 1478 cases of active tuberculosis 1086 were culture positive, and drug susceptibility testing was performed in these cases . The clinical course, including outcome of treatment, of all drug-resistant cases was described . RESULTS: Of 1086 culture-positive cases of tuberculosis 77 (7.1%) were drug resistant . Odds ratios suggested that the risk of drug resistance was significantly higher among the immigrants than among the other Canadians . Compared with the other Canadians the risk of drug resistance was 9.9 times greater among the immigrants in whom tuberculosis developed within the first year after arrival in Canada and 5.4 times greater among the immigrants in whom it developed 2 to 5 years after arrival in Canada . Of the 71 patients with drug-resistant disease whose type of resistance was known 62% had never taken antituberculous drugs before and 38% had . Most (91%) of the 77 cases of drug-resistant disease were resistant to first-line drugs, especially isoniazid and streptomycin . Thirty-two (42%) of the 77 cases were resistant to two or more first-line drugs . Of patients with drug-resistant disease a subgroup of 10 had disease that became resistant to several drugs over the 10-year period . The outcome of treatment in these individuals was poor, and they presented a particular public health problem . CONCLUSION: Resistance to one or more first-line antituberculous drugs continues to complicate the treatment of tuberculosis and may facilitate the spread of the disease.

Indian J Med Res, 1993 May, 97, 102 - 3
Prevalence of initial drug resistance in tuberculosis patients attending a chest hospital; Gupta PR et al.; Sputum samples from pulmonary tuberculosis patients attending a hospital for chest diseases and tuberculosis at Jaipur, India were directly subjected to sensitivity tests to detect drug resistance to streptomycin (S), isoniazid (I), rifampicin (R) and ethambutol (Emb) by slide culture technique . Drug resistance was observed to one or more drug in 19.9 per cent of the patients . I resistant organisms were present in 10.1 per cent of patients, S resistance in 7.6 per cent, R resistance in 3.0 per cent and Emb resistance in 2.6 per cent . Resistance was limited to a single drug in 16.7 per cent patients . Drug resistance was unrelated to age and sex of the patients.

Vet Microbiol, 1993 May, 35(1-2), 79 - 89
Inheritance of resistance to oedema disease in the pig: experiments with an Escherichia coli strain expressing fimbriae 107; Bertschinger HU et al.; Inheritance of resistance to intestinal colonization with E . coli causing oedema disease is hypothesized to be under the control of one locus consisting of two alleles with susceptibility (S) dominating resistance (s) . This mode of inheritance was investigated by mating pigs, resistant and susceptible to the disease, and examining the offspring . Weaned piglets were repeatedly inoculated orally with 5 x 10(5) CFU per pig per day of a streptomycin resistant strain of E . coli serotype O139:K12(B):H1:F(107) and susceptibility determined by daily semiquantitative cultural examination of rectal swabs . Using results obtained from offspring, 5 boars were retrospectively assigned the genotype ss, 1 was assigned Ss, and 2 were assigned SS . Nine sows were designated ss, 8 classified Ss and 4 SS . Ninety two pigs resulted from matings regarded as ss x ss; 89 (97%) of these were resistant to colonization and oedema disease . Of the 168 pigs from Ss x ss matings, 83 (49%) were resistant, while only 13 (9%) of 146 pigs from matings with at least one SS parent were classified resistant . The results are compatible with inheritance being controlled by one locus and with susceptibility dominating resistance to oedema disease.

J Gen Microbiol, 1993 May, 139 ( Pt 5), 995 - 1002
Functional and physiological characterization of the Tn21 cassette for resistance genes in Tn2426; Zuhlsdorf MT et al.; The Tn21 subgroup of class II transposons plays an important role in the dissemination of resistance genes and especially in the epidemic spread of multi-resistance . This ability reflects the variety of resistance genes that associate with the streptomycin/spectinomycin-resistance gene (aadA) of Tn21 . Deletion experiments with Tn2426, a typical member of the Tn21 subgroup, and sequencing of the region that accommodates additional resistance genes revealed significant structural characteristics . Each resistance gene was flanked by short, directly repeated recombinationally active sequences with unexpected variability in their sequence and length . The consensus for a recombinationally active sequence appeared to be 13 bp in length (TAAAACAANGNNA), compared to previous estimates of 54 bp . This sequence, in combination with the product of the integrase gene, is responsible for the genetic variability of members of the Tn21 family of transposable elements and the dissemination of multi-resistance.

Plant Cell, 1993 May, 5(5), 501 - 14
A genetic analysis of DNA sequence requirements for Dissociation state I activity in tobacco; English J et al.; Our objective was to test whether the double Ds structure correlated with Dissociation state I activity (i.e., high frequency of chromosome breakage and low frequency of reversion) in maize exhibited similar properties in tobacco . A genetic assay was established to test double Ds and related structures for their ability to cause loss of the linked marker genes streptomycin phosphotransferase and beta-glucuronidase in transgenic tobacco . An engineered double Ds element and a simple Ds element showed behavior consistent with that of state I and state II Ds elements, respectively, as described for maize . DNA structural rearrangements accompanied marker gene loss . Dissection of the double Ds structure showed that a left end and a right end of Ds in direct orientation were sufficient for the instability observed . This result suggested that left and right ends of Ds in direct orientation can participate in aberrant transposition events, consistent with two different models for double Ds-induced chromosome breakage proposed previously . Both models predict that the inversion of a half Ds element accompanies the aberrant transposition event . Such an inversion was detected by polymerase chain reaction experiments in tobacco and maize only when Activator activity was present in the genome.

Mol Microbiol, 1993 May, 8(4), 753 - 60
Aflagellated mutants of Helicobacter pylori generated by genetic transformation of naturally competent strains using transposon shuttle mutagenesis; Haas R et al.; Three out of 10 Helicobacter pylori clinical isolates were found to be naturally competent for genetic transformation to streptomycin resistance by chromosomal DNA extracted from a spontaneous streptomycin-resistant H . pylori mutant . The frequency of transformation varied between 5 x 10(-4) and 4 x 10(-6), depending on the H . pylori isolate used . Transposon shuttle mutagenesis based on this natural competence was established using the flagellin gene flaA as the target . The cloned flaA gene was interrupted by insertion of TnMax1, a mini-Tn1721 transposon carrying a modified chloramphenicol-acetyltransferase gene, the catGC cassette . Natural transformation of competent H . pylori strains with plasmid constructs harbouring a catGC-inactivated flaA gene resulted in chloramphenicol-resistant transformants at an average frequency of 4 x 10(-5) . Southern hybridization experiments confirmed the replacement of the chromosomal H . pylori flaA gene by the cat-inactivated cloned gene copy via homologous recombination resulting in allelic exchange . Phenotypic characterization of the mutants demonstrated the absence of flagella under the electron microscope and the loss of bacterial motility . Immunoblots of cell lysates of the H . pylori mutants with an antiserum raised against the C-terminal portion of recombinant H . pylori major flagellin (FlaA) confirmed the absence of the 54 kDa FlaA protein . This efficient transposon shuttle mutagenesis procedure for H . pylori based on natural competence opens up new possibilities for the genetic assessment of putative H . pylori virulence determinants.

J Comp Neurol, 1993 May 1, 331(1), 97 - 110
Hair cell regeneration after streptomycin toxicity in the avian vestibular epithelium; Weisleder P et al.; Recent reports documented the ability of the posthatch avian vestibular epithelia to produce hair cells continually at a low rate . This project was designed to investigate whether, in addition, the chicken vestibular system is capable of regenerating its sensory epithelium in response to a lesion . Aminoglycoside injections were given to young birds in order to damage the vestibular epithelium . Tritiated thymidine injections were used to label cells produced in response to the lesion . Treatment and age-matched control animals were killed at 1 day, 20 days, or 60 days after aminoglycoside injections, and vestibular organs were processed for autoradiography . Our results show that the chicken vestibular sensory epithelium is capable of regenerating hair cells after severe damage . Moreover, the epithelium is capable of complete anatomical recovery . Finally, drug damage increases the pace at which hair cells are replaced, compared to the rate of hair cell turnover in untreated tissue.

Am J Vet Res, 1993 May, 54(5), 701 - 8
Characterization of newly isolated plasmids from Actinobacillus pleuropneumoniae; Ishii H et al.; The genetic basis of drug-resistant strains of Actinobacillus pleuropneumoniae in Japan was studied . The A pleuropneumoniae strains AV277 and AV281 that belong to serotype 2 were resistant to streptomycin (SM) and sulfonamide (SA) . Both strains had an 8.1-kilobase (kb) SM-SA plasmid that was previously classified in the H1 group . The AV177 (serotype 1) strain was resistant to SM, SA, ampicillin, and kanamycin (KM), but did not have any plasmids . The AV319 and AV324 (serotype 1) strains were resistant to SM, SA, tetracycline (TC), and chloramphenicol (CP) . The AV318 (serotype 12) strain was resistant to SM, SA, TC, minocycline, and CP . These 3 strains (AV319, AV324, and AV318) had a 4.3-kb SM-SA plasmid and a 5.2-kb CP plasmid . The 4.3-kb plasmid was classified in the H2 group . The AV263 (serotype 1) strain was resistant to SM, SA, KM, TC, and CP . It had a 5.2-kb CP plasmid and a 6.6-kb SM-SA-KM plasmid . Both plasmids did not replicate stably in Escherichia coli strains . The former 5.2-kb plasmid was mobilized in E coli strains by plasmid RP4, which belonged to incompatibility P with broad host range, but the latter 6.6-kb plasmid was not so mobilized . Three 5.2-kb CP plasmids isolated from strains AV319, AV324, and AV318, had the same restriction endonuclease pattern after digestion with Ava I and EcoRI . They coexisted with H1 group plasmids in the incompatibility test, and coexisted also with H2 group plasmids of the original A pleuropneumoniae strains . Results indicated that the 5.2-kb CP plasmids could be classified in a new incompatibility group, H3 . In this study, 4 types of plasmids were isolated, but no plasmids encoded TC and minocycline resistance.

Arch Dis Child, 1993 May, 68(5), 665 - 8
Cutaneous hypersensitivity reactions due to thiacetazone in the treatment of tuberculosis in Zambian children infected with HIV-I; Chintu C et al.; Tuberculosis is one of the most common infections in Zambian adults and children infected with HIV . In Africa, cutaneous hypersensitivity reactions attributed to thiacetazone during treatment of tuberculosis in adults infected with HIV-I have been well documented . This study monitored adverse drug reactions during treatment for tuberculosis over an 18 month period (1 April 1990 to 31 October 1991) in 237 children with a clinical diagnosis of tuberculosis (125 boys and 112 girls; 88/237 (37%) infected with HIV-I) and 242 control children (149 boys and 93 girls; 26/242 (11%) infected with HIV-I) . Twenty two (9%) of the 237 children with tuberculosis developed hypersensitivity skin reactions during the course of treatment . Adverse skin reactions were seen more often in children infected with HIV than in those who were not (odds ratio 11.65, 95% confidence interval 3.07 to 34.88) . These represented 19 (21%) of 88 children infected with HIV and three (2%) of 149 children not infected with HIV . These skin reactions occurred after a period of treatment ranging between two and four weeks among 14 children receiving the HST (isoniazid, streptomycin, thiacetazone) regimen and eight children receiving the HSTR (isoniazid, streptomycin, thiacetazone, rifampicin) regimen . Twelve (55%) of the 22 children who reacted adversely to treatment developed the Stevens-Johnson syndrome . All 12 of these children with the Stevens-Johnson syndrome were infected with HIV . The mortality among these children who developed the Stevens-Johnson syndrome was 91% (11 of 12 died within three days of the onset of the reaction) . No further reactions were observed in the 11 children who recovered from the cutaneous hypersensitivity reactions after thiacetazone was discontinued over a period of six months of further treatment of tuberculosis . The results of this study were in part responsible for the recommendations put forward by the World Health Organization to avoid the use of thiacetazone in the treatment of tuberculosis in children infected with HIV.

Int J Syst Bacteriol, 1993 Apr, 43(2), 204 - 9
Mycobacterium intermedium sp . nov; Meier A et al.; Strains of a new type of slowly growing mycobacterium were repeatedly isolated from sputum from a patient with pulmonary disease . This photochromogenic organism grew at 22, 31, 37, and 41 degrees C, possessed catalase, acid phosphatase, esterase, beta-galactosidase, and arylsulfatase activities, and hydrolyzed Tween . It did not produce nicotinic acid or have nitrate reductase, acetamidase, benzamidase, isonicotinamidase, nicotinamidase, pyrazinamidase, succinidamidase, and acid phosphatase activities . Urease activity was variable . The organism is susceptible to ethambutol and resistant to isoniazid and streptomycin . A mycolic acid analysis revealed the presence of alpha-mycolates, alpha'-mycolates, and keto-mycolates . The results of comparative 16S rRNA sequencing placed this organism at an intermediate position between the rapidly and slowly growing mycobacteria . On the basis of the pattern of enzymatic activities and metabolic properties, the results of fatty acid analyses, and the unique 16S rRNA sequence, we propose that this organism represents a new species, for which we propose the name Mycobacterium intermedium . The type strain is strain 1669/91; a culture of this strain has been deposited in the Deutsche Sammlung von Mikroorganismen und Zellkulturen as strain DSM 44049.

Am Rev Respir Dis, 1993 Apr, 147(4), 958 - 61
Quantitative bacillary response to treatment in HIV-associated pulmonary tuberculosis; Brindle RJ et al.; A group of 122 patients with culture-proven pulmonary tuberculosis were recruited to examine the concentrations of Mycobacterium tuberculosis in sputum and the relationship to HIV-1 antibody status . They were followed for up to 28 days from the start of antituberculous chemotherapy to assess the early bacillary response to two chemotherapeutic regimens . Of 67 treated with streptomycin, thiacetazone, and isoniazid 17 were HIV positive, and subsequently 55, of whom 20 were HIV positive, were treated with streptomycin, rifampin, isoniazid, and pyrazinamide . The mean initial concentration of M . tuberculosis in the sputum of the HIV-negative patients was significantly higher than in HIV-positive patients (6.95 and 6.34 log colony-forming units respectively; p = 0.019) . The HIV-positive patients had less radiologic evidence of disease and significantly fewer zones of lung affected with cavities . The response to treatment was similar, but with HIV-positive patients more likely to become culture negative by 28 days . The differences that exist between HIV-positive and HIV-negative patients are minor, and standard regimens are at least as effective in HIV-positive patients in the first month of treatment.

Tuber Lung Dis, 1993 Apr, 74(2), 87 - 90
Effect of pyrazinamide on rifampicin kinetics in patients with tuberculosis; Jain A et al.; Rifampicin and pyrazinamide constitute an important part of drug regimens advocated for tuberculosis therapy, along with INH and streptomycin/ethambutol . The International Union against Tuberculosis and Lung Disease has also suggested the inclusion of these two drugs as part of short course chemotherapy for tuberculosis . Hence this study was undertaken to evaluate the influence of pyrazinamide on rifampicin kinetics when the two are given together . In a randomized, cross-over, single dose study, 16 patients with untreated pulmonary tuberculosis, after an overnight fast, were administered either rifampicin 450 mg + INH 300 mg (study A) or rifampicin 450 mg + INH 300 mg+pyrazinamide 1500 mg (study B) . Blood samples were collected for serum rifampicin estimation at 0, 0.5, 2, 4, 6 and 8 h . Various pharmacokinetic parameters (Cmax, Tmax, t1/2, Kel, area under plasma concentration time curve (AUC), Vd & Cpl of rifampicin) were calculated . It was observed that rifampicin concentration in study A in contrast to study B was significantly higher at 6 h (P < 0.01) and 8 h (P < 0.05), while there were no significant differences in serum rifampicin concentration at 0.5, 2 and 4 h . A significant difference was also observed in AUC and Cpl . In study A, AUC was higher (P < 0.05), while Cpl was lower (P < 0.02), than in study B . From the above data it appears that on concomitant administration of pyrazinamide in patients on rifampicin therapy, AUC of rifampicin is decreased while its clearance is increased.

Tuber Lung Dis, 1993 Apr, 74(2), 129 - 30
Drug susceptibility in Mycobacterium tuberculosis of a sample of patients in Guinea Bissau; Dias F et al.; Sputum samples from patients with known or suspected tuberculosis were collected in Bissau, Guinea Bissau, and isolates belonging to the Mycobacterium tuberculosis complex (M . tuberculosis, M . bovis or M . africanum) were examined for their susceptibility to the 4 drugs streptomycin, isoniazid, ethambutol and rifampicin . Of 59 M . tuberculosis complex isolates only 2 were resistant to any of the drugs (isoniazid) . Thus there is little resistance to these first line drugs among M . tuberculosis isolates from patients in Guinea Bissau.

FEMS Microbiol Lett, 1993 Mar 15, 108(1), 111 - 5
Escherichia coli K-12 ferrous iron uptake mutants are impaired in their ability to colonize the mouse intestine; Stojiljkovic I et al.; The streptomycin-treated mouse colonization model was used to investigate the role of the Fe2+ uptake system (Feo) of Escherichia coli K12 in the colonization of the mouse intestine . Mutants impaired in the uptake of Fe2+ ions were shown to be deficient also in their colonization ability . Both enterochelin-producing and enterochelin-nonproducing Escherichia coli feo mutants were unable to colonize the mouse intestine . These results demonstrated that Fe(II) is an essential source of iron for E . coli grown in the intestine.

Proc Natl Acad Sci U S A, 1993 Mar 15, 90(6), 2315 - 9
Increased ribosomal accuracy increases a programmed translational frameshift in Escherichia coli; Sipley J et al.; We have tested the effect of increased ribosomal fidelity on a modified version of the programmed release factor 2 (RF2) translational frameshift . In the constructs tested, the original UGA codon at the site of the shift was replaced by either of two sense codons, UGG (tryptophan), which allows a frameshift of approximately 13%, or CUG (leucine), which allows a frameshift of only approximately 2% . We confirmed the results of Curran and Yarus {Curran, J . F . & Yarus, M . (1989) J . Mol . Biol . 209, 65-77} in a wild-type ribosomal host, including a reduction of the UGG shift following induction of tRNA(Trp) from a plasmid copy of the tRNA gene . But to our surprise, in a hyperaccurate streptomycin pseudo-dependent host, the UGG frameshift increased to more than 50% . When we added a tRNA(Trp) plasmid to these cells, induction of the tRNA(Trp) gene reduced the shift back to approximately 7% . Messenger RNA levels did not vary greatly under these different induced conditions . Other increased accuracy alleles also showed increased frameshifting with UGG at the frameshift site . All increased accuracy alleles led to slower translation rates, and there appeared to be a proportionality between the extent of reduction of synthesis for the in-frame reporter and the extent of UGG frameshift for the out-of-frame reporter . There were little effects of increased accuracy on the lower level CUG frameshift . However, over-production of the cognate tRNA(1Leu) dramatically reduced even this lower level of shift, despite the fact that tRNA(1Leu) is already the most abundant isoacceptor in Escherichia coli . These results can be rationalized by following the hypothesis of Curran and Yarus as follows: with wild-type ribosomes, limited availability of tRNA(Trp) (about 1% of total tRNA) facilitates a pause at the UGG codon (due to the vacant A site), allowing increased opportunity for ribosome realignment . Excess tRNA(Trp) reduces the time the A site is vacant and thus reduces the frameshift . The slower hyperaccurate ribosomes increase the pause time and thus increase the opportunity for shifting, a process again reversed by increasing the in-frame cognate tRNA(Trp) . These data provide strong support for a model in which the extent of ribosome pause time at a programmed frameshift site is a major determinant in the efficiency of the frameshift and in which tRNA availability can be a major influence on this process.

Biochem Pharmacol, 1993 Mar 9, 45(5), 1121 - 8
Binding of the Ah receptor to receptor binding factors in chromatin; Dunn RT 2nd et al.; Dioxin induces biological responses through interaction with a specific intracellular receptor, the Ah receptor, and the subsequent interaction of the Ah receptor with chromatin . We report the binding of the Ah receptor, partially purified from rabbit liver, to receptor binding factors in chromatin . Rabbit liver chromatin proteins (CP) were isolated by adsorption of chromatin to hydroxylapatite followed by sequential extraction with 1-8 M GdnHCl . To assay for receptor binding a portion of each CP fraction was reconstituted to rabbit double-stranded DNA using a reverse gradient dialysis of 7.5 to 0 M GdnHCl . These reconstituted nucleoacidic proteins were then examined for binding to {3H}-2,3,7,8-tetrachlorodibenzo-p-dioxin ({3H}TCDD)-receptor complexes by the streptomycin filter assay . Prior to the binding assay, {3H}TCDD-receptor complexes were partially purified by step elution from DEAE-cellulose columns . CP fractions 2, 5, and 7 were found to bind to the Ah receptor with high affinity . Scatchard analysis yielded Kd values in the nanomolar range . Competition with 2-fold excess unlabeled TCDD-receptor complexes was demonstrated, and binding was reduced markedly when the receptor was prepared in the presence of 10 mM molybdate . Such chromatin receptor binding factors (RBFs) may participate in the interaction of receptor with specific DNA sequences resulting in modulation of specific gene expression.

Am J Otol, 1993 Mar, 14(2), 194 - 8
Effect on endocochlear potential of streptomycin perfusion of the cochlea in guinea pigs; Ge X et al.; Perilymphatic perfusion of the cochlea with streptomycin was performed on 17 guinea pigs . The first and second group, consisting of five animals each, received streptomycin 150 micrograms and 1500 micrograms respectively . In a control group, consisting of seven animals, the perilymph was perfused with artificial perilymph only . The endocochlear potential (EP) was recorded from the second turn of the cochlea in each animal . The results indicate that streptomycin in a low dosage that will destroy the vestibular receptors was not harmful to the function of either the stria vascularis or the hair cells in the cochlea, as measured by changes in the EP after streptomycin perfusion of the cochlea.

Headache, 1993 Mar, 33(3), 155 - 60
The effects of streptomycin/lidocaine block on trigeminal neuralgia: a double blind crossover placebo controlled study; Bittar GT et al.; This study investigated the long term effect of a peripheral sensory block using streptomycin sulphate on trigeminal neuralgia . A total of twenty subjects, thirteen with idiopathic trigeminal neuralgia (ITN) and seven with traumatic trigeminal neuralgia (TTN) were studied . A double-blind placebo controlled randomized design was used . After the clinical assessment subjects were randomly assigned to receive either 1 g of streptomycin with 3 ml 2% lidocaine, or 3 ml lidocaine alone . The injections were performed adjacent to the branches that served the painful site . These were intraoral injections, more specifically infraorbital and inferior alveolar blocks . Patients received five blocks of either streptomycin/lidocaine or lidocaine alone for a period of five consecutive weeks . On the sixth week they were crossed over . Measures of pain intensity and pain frequency were used to assess treatment outcome . Patients also recorded their side-effects . Repeated measures analysis of variance was used to compare the treatment outcomes between the active and placebo groups . There was no statistically significant differences in the treatment outcomes regarding frequency and intensity of pain attacks . The sensory function of the treated nerves was also not affected . Side effects including facial swelling and pain were a common finding in the patients receiving streptomycin . This study demonstrated no beneficial effects of streptomycin blockade for idiopathic and traumatic trigeminal neuralgia.

Int J Pediatr Otorhinolaryngol, 1993 Mar, 26(2), 109 - 15
Hearing loss and vestibular dysfunction in childhood from the use of streptomycin in Albania; Kastanioudakis J et al.; With the entry of a large number of Albanians in the area of Epirus over the past 8 months, a significant number of children with hearing problems or deafness has been examined in the out patient ward of the University Hospital of Ioannina . From the Pediatric-Neurologic-Psychiatric and Otorhinolaryngologic examination of these children, 18 cases with hearing problems and vestibular dysfunction due to administration of streptomycin sulfate have been defined . This article reports the ototoxic drug which has been used and is still being used in Albania, the procedure of audiological and vestibular investigation, and the damage which has been evoked in the auditory and vestibular pathway of the children in whom it has been administered.

Trans R Soc Trop Med Hyg, 1993 Mar-Apr, 87(2), 138 - 41
Brucellosis: imported and laboratory-acquired cases, and an overview of treatment trials; Luzzi GA et al.; Following the successful eradication of Brucella abortus infection in cattle, human brucellosis in England and Wales has become an uncommon imported disease . Culture of the organism presents a major laboratory hazard, and difficulties in identification may occur using a biochemical test-strip method . An overview of recent treatment trials of brucellosis indicates that regimens combining streptomycin and doxycycline are associated with a higher success rate (judged by the frequency of treatment failure and relapse following therapy) than combinations of rifampicin and doxycycline.

Am J Dis Child, 1993 Mar, 147(3), 320 - 4
Tuberculosis in human immunodeficiency virus-infected children . A family infection; Bakshi SS et al.; OBJECTIVE--To study the epidemiologic and clinical features of infection with Mycobacterium tuberculosis in human immunodeficiency virus (HIV)-infected children and their families . PATIENTS AND CLINICAL SETTING--Sixty families of children with HIV infection, children of HIV indeterminate status, and seroreverters underwent follow-up in a comprehensive multidisciplinary program for children and families . METHODS--Infection with M tuberculosis was diagnosed based on a positive Mantoux test result or a positive culture . RESULTS--Mycobacterium tuberculosis infection was diagnosed in seven children (three infected with HIV, three seroreverters, and one uninfected sibling of an infected child) from four families (6%) . All infections were detected in the period from March 1990 through January 1992 . Six of seven children had a history of exposure to M tuberculosis in an HIV-infected adult (parent) who was an intravenous drug user, homeless, and/or noncompliant with the medical regimen . All HIV-infected children and one seroreverter had pulmonary tuberculosis . One child died of complications of tuberculosis and HIV infection . The M tuberculosis isolated from this child was resistant to isoniazid, rifampin, and streptomycin sulfate . CONCLUSIONS--Tuberculosis is a growing problem among inner-city children born to HIV-infected parents . Children infected with HIV in this study had symptomatic and severe disease with tuberculosis, which reflected the drug susceptibility pattern of M tuberculosis seen in our community.

Tuber Lung Dis, 1993 Feb, 74(1), 16 - 9
Utilization of antituberculosis drugs expressed in defined daily doses in Klenovnik Hospital in the period between 1983 and 1987; Trkanjec Z et al.; In this paper the utilization of antituberculosis drugs was analyzed in defined daily doses per 1000 bed-days (DDD/1000 BD) in the Hospital for Pulmonary Diseases and Tuberculosis, Klenovnik, from 1983 to 1987 . The utilization of these drugs increased from 894 DDD/1000 BD in 1983 to 1112 DDD/1000 BD in 1984, and then decreased to 1077 DDD/1000 BD in 1986; but in 1987 it again increased to 1270 DDD/1000 BD . During the research period the following drugs were prescribed: ethambutol, rifampin, pyrazinamide, streptomycin, isoniazid, and two combinations of drugs: a combination of isoniazid with pyridoxine and a combination of ethambutol, isoniazid and pyridoxine . For the whole of that period the use of ethambutol, isoniazid with pyridoxine and rifampin made up more than 85% of the general utilization of antituberculosis drugs, while other drugs were prescribed in lesser quantities . The data presented indicate that tuberculosis in Klenovnik hospital was in most cases treated with ethambutol, the combination of isoniazid with pyridoxine, and rifampin.

Kansenshogaku Zasshi, 1993 Feb, 67(2), 127 - 36
{Biological characters of the clinically isolated strains of Escherichia coli O157:H7 in Canada}; Sakaguchi S et al.; Biological characters of enterohemorrhagic Escherichia coli (EHEC) strains isolated from food poisoning cases in Canada, 1987-1988 were examined in comparison with that isolated in Saitama, 1990 . The Saitama strain was found to belong to biotype I, and biotypes I and II were found in Canada . Most of the strains including the Saitama strain were found to have siderophilins suggesting their advantageous growth in vivo . An enteroinvasive strain with 140 megadalton (Md) plasmid and two colicinogenic strains with 4.8 Md plasmids were detected . All strains were found to have 60 Md plasmids . This plasmid might be specific for this serotype . A few strains were resistant to streptomycin (SM) and/or tetracycline (TC), and a strain transferred its SM-TC resistances by conjugation . Many strains including the Saitama strain were found to produce vero cytotoxin (VT) types 1 and 2 (VT1 and VT2) . A few type 2 and untypable toxin producing strains were also detected . VT titers produced by untypable toxin producing strains were over 10 times lower than those by other strains . High annealing temperature for PCR amplification of VT1 gene and a variety of annealing temperatures of VT2 gene suggested that the nucleotide sequences for VT1 gene were well preserved, but that those for VT2 might have some mutations.

Proc Natl Acad Sci U S A, 1993 Feb 1, 90(3), 913 - 7
High-frequency plastid transformation in tobacco by selection for a chimeric aadA gene; Svab Z et al.; We report here a 100-fold increased frequency of plastid transformation in tobacco by selection for a chimeric aadA gene encoding aminoglycoside 3"-adenylyltransferase, as compared with that obtained with mutant 16S rRNA genes . Expression of aadA confers resistance to spectinomycin and streptomycin . In transforming plasmid pZS197, a chimeric aadA is cloned between rbcL and open reading frame ORF512 plastid gene sequences . Selection was for spectinomycin resistance after biolistic delivery of pZS197 DNA into leaf cells . DNA gel-blot analysis confirmed incorporation of the chimeric aadA gene into the plastid genome by two homologous recombination events via the flanking plastid gene sequences . The chimeric gene became homoplasmic in the recipient cells and is uniformly transmitted to the maternal seed progeny . The ability to transform routinely plastids of land plants opens the way to manipulate the process of photosynthesis and to incorporate novel genes into the plastid genome of crops.

Isr J Med Sci, 1993 Jan, 29(1), 11 - 6
Effect of age and duration of disease on the clinical manifestations of brucellosis . A study of 73 consecutive patients in Israel; Yinnon AM et al.; We describe our experience with 73 patients diagnosed with brucellosis during the years 1979-91 at two Jerusalem hospitals: Hadassah Mount Scopus (37 patients from 1979-1984) and Shaare Zedek (36 patients from 1979-1991) . The patients included 32 children less than 14 years old and 41 adults; 70 of the patients were non-Jews . In all cases the pathogen was Brucella melitensis . The high proportion of children and the equal sex distribution was quite different from the age and sex distribution of brucellosis in Western countries where it is more common in adult males, and similar to that reported from other near-Eastern countries where household dairy products, and not occupational exposure, are the most common source of infection . The short duration of disease (< 2 weeks) prior to diagnosis in 70% of the patients is attributed to the ready availability of appropriate medical care, and a very high index of suspicion for brucellosis in the Jerusalem non-Jewish population . Abdominal symptoms were more common in adults, whereas enlarged lymph nodes and liver, skin rash and pharyngitis were more frequently observed in children . Some of these differences may be attributed to the very short duration of disease in most children at the time of presentation . Combination therapy with tetracycline-streptomycin or tetracycline-rifampin yielded superior results as compared with single-drug treatment in terms of early defervescence and relapse rates . The present experience underlines the importance of endemic brucellosis which still represents a significant public health problem in children and adults in Mediterranean countries.

Mol Gen Genet, 1993 Jan, 236(2-3), 163 - 70
Subcellular location of lincomycin resistance in Nicotiana mutants; Cseplo A et al.; Lincomycin-resistant Nicotiana plumbaginifolia plastid mutants were considered also to carry mitochondrial mutations on the basis of their ability to grow in the dark under selective conditions . To clarify the role of mitochondria, individual protoplasts of the green, lincomycin-resistant N . plumbaginifolia mutant LR400 were microfused with protoplasts of the N . tabacum plastid albino line 92V37, which possesses N . undulata cytoplasm . the production of lincomycin-resistant albino cybrid lines, with N . undulata plastids and recombinant mitochondria, strongly indicated a determining role for mitochondria in the lincomycin resistance . Sequence analysis of the region encompassing putative mutation sites in the 26S rRNA genes from the LR400 and several other lincomycin-resistant N . plumbaginifolia mutants revealed, however, no differences from the wild-type sequence . As an alternative source of the resistance of the fusion products, the N . tabacum fusion partner was also taken into account . Surprisingly, a natural lincomycin resistance of tobacco was detected, which was inherited as a dominant nuclear trait . This result compromises the interpretation of the fusion data suggested above . Thus, to answer the original question definitively, the mutant LR400 was crossed as a female parent with a N . plumbaginifolia line carrying streptomycin-resistant N . tabacum plastids . Calli were then induced from the seedlings . Occasional paternal plastid transmissions were selected as streptomycin-resistant calli on selective medium . These cell lines were shown by restriction enzyme analysis to contain paternal plastids and maternal mitochondria . They were tested for greening and growing ability in the presence of lincomycin . These resistance traits proved to be genetically linked and exclusively located in the plastids.

Kekkaku, 1993 Jan, 68(1), 63 - 9
{Clinical features of the lung diseases due to Mycobacterium avium and M . intracellulare}; Toyoda T et al.; In recent years, it has been made easy to identify Mycobacterium avium and M . intracellulare by DNA-probe test . To evaluate possible clinical differences between the lung diseases due to M . avium and those due to M . intracellulare, we studied a total of 248 cases (136 due to M . avium and 112 due to M . intracellulare) . M . avium cases were found more frequently in the eastern part of Japan, whereas M . intracellulare cases were seen more frequently in the western part of Japan . There was no significant difference between M . avium cases and M . intracellulare cases in sex, age, complications, chief complaint, body weight, tuberculin skin test, erythrocyte sedimentation rate, serum protein content, findings of chest X ray . M . avium cases were more frequently detected by health examination . M . avium was more susceptible to cycloserine than M . intracellulare . On the other hand, M . intracellulare was more susceptible to streptomycin and kanamycin . The prognosis of M . intracellulare cases were better than M . avium cases, when compared only the patients who showed positive tuberculin skin test.

Am J Otol, 1993 Jan, 14(1), 74 - 8
Intramuscular streptomycin effect on dark cells of utricle in guinea pigs; Ge X et al.; Streptomycin has been used in the treatment of Meniere's disease for almost half a century . Clinical studies showed that streptomycin may eliminate vertigo attacks and stabilize or improve hearing in the majority of patients . Animal experiments have demonstrated severe damage to the vestibular hair cells after streptomycin treatment . This study is to observe the effect of intramuscular streptomycin on dark cells of utricle . Guinea pigs that had received intramuscular injections of streptomycin sulfate 400 mg/kg per day for 1 and 2 weeks were studied . The dark cells of utricle were observed under transmission electron microscope . The pinocytotic vesicles and rough endoplasmic reticula markedly decreased and the plasmalemma infoldings in the lower part of the cell reduced in the 1-week group . The luminal membrane of the cells bulged out on the surface . After the cell membrane ruptured, the cytoplasmic organelle moved into the endolymphatic space and the cell dissolved . The morphologic changes indicated that streptomycin damaged the cytoplasmic granules and the plasma membrane infoldings of the dark cells . These cytologic characteristics are engaged in fluid secretion . The damage of secretory function of the dark cells may reduce the volume of endolymph.

Plant J, 1993 Jan, 3(1), 183 - 6
Detection of point mutations in the chloroplast genome by single-stranded conformation polymorphism analysis; To KY et al.; Single-stranded conformation polymorphism (SSCP) analysis was used to examine the mutations of the chloroplast 16S rRNA locus of streptomycin-resistant mutants in Nicotiana plumbaginifolia . DNA fragments of 121, 517, 968 and 1578 bp, each possessing a known point mutation, were generated by polymerase chain reaction (PCR) . The resulting fragments were denatured and separated by nondenaturing polyacrylamide gel electrophoresis . Compared to the patterns of the wild-type DNA fragments, the bands of the single-stranded DNA fragments of 121 and 517 bp with base changes were shifted . However, no pattern variations were detected from the DNA fragments of 968 and 1578 bp generated from both wild-type and mutants.

Plant Mol Biol, 1993 Jan, 21(1), 157 - 70
Effects of gene dosage and sequence modification on the frequency and timing of transposition of the maize element Activator (Ac) in tobacco; Keller J et al.; The effect of Ac copy number on the frequency and timing of germinal transposition in tobacco was investigated using the streptomycin phosphotransferase gene (SPT) as an excision marker . The activity of one and two copies of the element was compared by selecting heterozygous and homozygous progeny of transformants carrying single SPT::Ac inserts . It was observed that increasing gene copy not only increases the transposition frequency, but also occasionally alters the timing of transposition such that earlier events are obtained . The result is that some homozygous plants generate multiple streptomycin resistant progeny carrying the same transposed Ac (trAc) element . We have also investigated the effect of modification of the sequence in the region around 82 bp downstream of the polyadenylation site and 177 bp from the 3' end of the element on germinal excision frequencies . Alteration of three bases to create a Bgl II site at this location caused a minor decrease in germinal excision events, but insertion of four bases to create a Cla I site caused a 10-fold decrease in the transposition activity of the Ac element.

Eur Arch Otorhinolaryngol, 1993, 250(4), 237 - 9
Mycobacterial species causing cervicofacial infection in Turkey; Kanlikama M et al.; The aim of the study was to determine the mycobacterial species causing cervical lymphadenitis at Cukurova University Hospital, Adana, Turkey . To this end, culture and differential tests were performed on excisional or incisional biopsy specimens from patients with mycobacterial cervical disease (MCD) . The diagnosis was confirmed by skin tests, histopathological examination and positive cultures . In 15 of 40 cases diagnosed as MCD, mycobacteria were isolated in Lowenstein-Jensen medium . The etiological agents were tuberculous mycobacteria (Mycobacterium tuberculosis in 9 cases and M . bovis in 3 cases) . Of the 3 non-tuberculous cases, 2 were due to M . kansasii and the other to M . fortuitum . Antituberculous chemotherapy was given in all cases over an average period of 18 months . A combination of three of four drugs was used including isoniazid, ethambutol, rifampin and/or streptomycin . At the end a follow-up period of at least 3 years, there were no recurrences or persistences of infection and no surgical treatment was necessary to remove residual lymph nodes.

Pneumonol Alergol Pol, 1993, 61(5-6), 254 - 62
{Analysis of drug sensitivity of M . tuberculosis strains isolated from patients treated for tuberculosis in 1982-1991}; Zalewska-Schontaler N et al.; Analysis of drug-sensitiveness of 822 M . tuberculosis strains isolated from patients with pulmonary tuberculosis treated in the Institute of Tuberculosis and Lung Diseases and in Pediatric Clinic of Medical Academy in Warsaw in 1982-1991 years was performed for isoniazid (INH), streptomycin (SM), rifampicin (RMP) and ethambutol (EMB) . Drug sensitivity test was done on a basis of complexed proportional method according to Conethi and resistance index method according to Mitchinson . Examined strains were determined as resistant when the resistance index was 4 for INH, SM . RMP and EMB . During analysis the increase of resistance strains percentage (mean 25%) was observed in sputum-positive tuberculosis patients hospitalized in the Institute of Tuberculosis and Lung Diseases . The highest number of resistant strains was noticed in relation to CNH and RMP.

Probl Tuberk, 1993, (5), 21 - 3
{Combined chemotherapy of patients with tuberculosis - new regimens and dosage forms}; Sokolova GB et al.; 310 patients with pulmonary tuberculosis disseminating bacteria received isoniazid, rifampicin, streptomycin (ethambutol) and pirazinamid in different regimens and dosage forms . The drugs were administered in sequence or simultaneously, in single or divided doses . The best time and number characteristics as regards the discharge negativation were obtained in pirazinamid administration at a single dose daily or each other day irrespective of other drugs intake . 100 patients were given isoniazid, rifampicin and pirazinamid in multicomponent form tricox (Jemis, India) . Tricox proved effective under additional administration of isoniazid in the same dose as was fixed in tricox.

Acta Otolaryngol Suppl, 1993, 506, 7 - 13
Immunocytochemical localization of intermediate filaments in the guinea pig vestibular periphery with special reference to their alteration after ototoxic drug administration; Usami S et al.; The present study examined the immunocytochemical localization of various intermediate filaments (IFs), 68 kDa, 160 kDa and 200 kDa neurofilament protein (NFP), cytokeratin (CK) 1, 8, 10 and 19, vimentin, and glial fibrillary acidic protein (GFAP) in the vestibular end-organs and ganglia of normal and streptomycin-treated guinea pigs . In normal animals, 68 kDa, 160 kDa and 200 kDa NFP were found in afferent nerve fibers and nerve terminals (probably nerve chalices) . Fine nerve fibers (probably efferent and/or sympathetic nerve fibers) were also immunoreactive to NFP . In the vestibular ganglia, 68 kDa and 160 kDa NFP were predominantly distributed in larger cells, whereas 200 kDa NFP was also found in some small ganglion cells . Cytokeratin 8 and 19 were located in supporting cells, transitional cells, dark cells of vestibular end-organs, and the epithelial cell lining of the membranous labyrinth . Vimentin was observed in the hair cells distributed in the central region of the end organs, supporting cells, most connective tissue cells, and Schwann cells of the vestibular ganglion . Although GFAP-like immunoreactivity was evident in glial cells of the proximal vestibular nerve, no immunoreactivity was detected in the distal portion of the vestibular nerve, vestibular ganglion, or vestibular end-organs . These highly distinct staining patterns of IFs indicated that they may play different roles in the different cell types, and that they may serve as a specific marker for each cell type . In streptomycin-treated guinea pigs, immunoreactivities for NFP and vimentin (found in the hair cells) decreased after treatment, whereas immunoreactivities for the other IFs were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Zhonghua Er Bi Yan Hou Ke Za Zhi, 1993, 28(3), 146 - 8, 186
{The effect of streptomycin on energy metabolism in inner ear tissues in guinea pigs}; Wang SC; Fifty-four guinea pigs were divided into three groups . Group I was injected with streptomycin sulfate 200 mg/kg body wt.ip . for 8 days; group II was injected with streptomycin sulfate 200 mg/kg body wt . and Chinese angelica 2 ml/kg body wt . ip . for 8 days; group III, serving as control, was injected with corresponding volume of water for injection . Glucose and pyruvate levels were determined chemically, ATP, ADP and AMP were determined by HPLC . The hearing reflex thresholds were measured before injection of drug and sacrifice . The glucose content in inner ear tissues of group I and II was found to be lower than that of the control . The pyruvate content in group I and II was higher than that of the control . The ratio of pyruvate to glucose in the group I and II was significantly higher than that of the control, P < 0.05 . ATP level in inner ear tissues in group I (50.3 +/- 39.0 micrograms/mg protein) decreased significantly as compared with the control (167.7 +/- 115.4 micrograms/mg protein), P < 0.05, but not in group II (151.6 +/- 124.3 micrograms/mg protein) . The energy change in each group was in the range of 0.80-0.84 . The hearing reflex threshold attenuation in group I 8 days after injection of drug was slightly lower than that prior to the injection of the drug . The results suggest that streptomycin might inhibit the uptake and metabolism of glucose and decrease the ATP level in the inner ear tissues, and that the inner ear tissues accelerate the metabolism of amino-acids for compensation.(ABSTRACT TRUNCATED AT 250 WORDS)

FASEB J, 1993 Jan, 7(1), 173 - 6
The 5' proximal helix of 16S rRNA is involved in the binding of streptomycin to the ribosome; Pinard R et al.; Single mutations at the end of the 5' proximal helix and in the 915 region (13U-->A or C; 914A-->U or G), and double mutations (13U-->A and 914A-->U; 13U-->C and 914A-->G) were constructed into Escherichia coli 16S ribosomal RNA . The mutations were introduced into an expression plasmid containing the rrnB operon under the transcriptional control of the temperature-inducible lambda PL promoter . None of the mutant 16S rRNAs affected cell growth when expressed . Ribosomes extracted after induction of expression of the mutant 16S rRNAs were assayed for their capacity to bind the error-inducing drug streptomycin and for translational misreading in the presence of streptomycin . All mutations impaired the binding of streptomycin, and consequently its capacity to stimulate misreading . Our results demonstrate the involvement of the 5' proximal helix of 16S rRNA in the binding of streptomycin and confirm the participation of the 915 region . They do not support a previous suggestion {Leclerc, D . and Brakier-Gingras, L . (1991) FEBS Lett., Vol . 279, pp . 171-174} that base pairing between nucleotides 13 and 914 stabilizes the binding of streptomycin.

Ther Drug Monit, 1992 Dec, 14(6), 522 - 4
Bayesian estimation of streptomycin pharmacokinetics; Thomson AH et al.; Streptomycin dose requirements were determined in an 83-year-old man with renal impairment who was being treated for miliary tuberculosis . Concentration measurements were interpreted using a Bayesian parameter estimation program . Estimated creatinine clearance (1.1 L/h) was used as a starting value for streptomycin clearance, and volume was initially assumed to be 0.3 L/kg . Bayesian estimates of clearance were close to the starting value and declined from 1.4 L/h to 0.9 L/h during the course of therapy . Volume was higher than the initial estimate (0.4-0.5 L/kg), possibly due to the patient having a low albumin and being underweight . Satisfactory concentrations were maintained for several weeks with doses of 500 mg every 36-48 h.

J Bacteriol, 1992 Dec, 174(24), 7902 - 9
Identification and characterization of novel low-temperature-inducible promoters of Escherichia coli; Qoronfleh MW et al.; Escherichia coli promoters that are more active at low temperature (15 to 20 degrees C) than at 37 degrees C were identified by using the transposon Tn5-lac to generate promoter fusions expressing beta-galactosidase (beta-Gal) . Tn5-lac insertions that resulted in low-temperature-regulated beta-Gal expression were isolated by selecting kanamycin-resistant mutants capable of growth on lactose minimal medium at 15 degrees C but which grew poorly at 37 degrees C on this medium . Seven independent mutants were selected for further studies . In one such strain, designated WQ11, a temperature shift from 37 degrees C to either 20 or 15 degrees C resulted in a 15- to 24-fold induction of beta-Gal expression . Extended growth at 20 or 15 degrees C resulted in 36- to 42-fold-higher beta-Gal expression over that of cells grown at 37 degrees C . Treatment of WQ11 with streptomycin, reported to induce a response similar to heat shock, failed to induce beta-Gal expression . In contrast, treatment with either chloramphenicol or tetracycline, which mimics a cold shock response, resulted in a fourfold induction of beta-Gal expression in strain WQ11 . Hfr genetic mapping studies complemented by physical mapping indicated that in at least three mutants (WQ3, WQ6, and WQ11), Tn5-lac insertions mapped at unique sites where no known cold shock genes have been reported . The Tn5-lac insertions of these mutants mapped to 81, 12, and 34 min on the E . coli chromosome, respectively . The cold-inducible promoters from two of the mutants (WQ3 and WQ11) were cloned and sequenced, and their temperature regulation was examined . Comparison of the nucleotide sequences of these two promoters with the regulatory elements of other known cold shock genes identified the sequence CCAAT as a putative conserved motif.

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