Streptomycin

Probl Tuberk, 1989, (2), 50 - 1
{Effect of antitubercular preparations on the function of the ciliary epithelium of the respiratory tract mucosa}; Syrovatka IuA; The effect of various concentrations of streptomycin, isoniazid, rifampicin and ethambutol on the function of the siliated epithelium of the frog oral mucosa was studied (110 experiments with 50 frogs) . The level of inhibition of the siliated epithelium function depended on the properties of the drugs and their concentration in solution . More pronounced inhibition was induced by 15 per cent ethambutol solution and 10 per cent isoniazid solution . The least inhibition of the siliated epithelium function was observed with the use of 6.25 per cent streptomycin solution, 5 per cent isoniazid solution, 7.5 per cent ethambutol solution and 3.75 per cent rifampicin solution.

Scand J Infect Dis, 1989, 21(3), 333 - 6
Brucellosis in a child complicated with multiple brain abscesses; Guvenc H et al.; A 4-year-old boy developed symptoms consistent with brucellosis and was treated with combined streptomycin and tetracycline . He had a high brucella agglutinin titer . However, he continued to have headache and papilledema . A brain CT revealed 6 large abscesses . Brucella melitensis was isolated from abscess material . The boy recovered completely after drainage therapy.

Cell Mol Biol, 1989, 35(2), 129 - 36
An attempt to prevent or delay denervation changes in rat muscles; Schwartz J et al.; A number of drugs which are known to affect lysosomes and their enzyme activities were used in an attempt to inhibit or delay the onset of denervation changes in rat muscles . The following parameters were used: the occurrence of fibrillations in electromyographs; diameters of muscle fibers; acid phosphatase activity; acetylcholinesterase activity and distribution in end plates . Differences between denervated and non-denervated limbs were evaluated and compared in the different treatment groups . The various parameters were differently affected by the different drugs . Chloroquin, thiouracil and streptomycin appeared to be more effective than other treatments in the inhibition of denervation changes.

Scand J Infect Dis, 1989, 21(1), 81 - 5
Treatment of tuberculous meningitis in adults with a combination of isoniazid, rifampicin and streptomycin: a prospective study; Doganay M et al.; 15 patients with tuberculous meningitis were treated with isoniazid, streptomycin and rifampicin and 14 with isoniazid, streptomycin and ethambutol for 12 months . Both groups received prednisolone at the beginning of treatment . The two groups were compared with regard to clinical improvement, presence of neurological sequelae and mortality . No difference in recovery rate between the groups was observed . 6 patients (21%) died (5 in group I and 1 in group II) . Residual sequelae developed in 9 cases (5 in group I and 4 in group II; 31%) . The difference between the groups was not significant . The regimen including rifampicin for tuberculous meningitis did not result in any superiority compared to standard therapy.

Zhonghua Er Bi Yan Hou Ke Za Zhi, 1989, 24(2), 79 - 81, 127
{Experimental study of Rhizoma drynariae (Gusuibu) in the treatment of streptomycin ototoxicity}; Wang Z; According to Chinese traditional medical theory, kidney governs ear . Gusuibu is a kind of traditional Chinese drug which has nutritive effect to the kidney . The present study was intended to show whether Gusuibu could reduce streptomycin ototoxicity . Changes in cochlear hair cells, the Preyer's reflexes and auditory brain stem responses in guinea pigs were examined . Statistical analysis showed that hair cell loss in Gusuibu group was significantly milder then that in the control group; hearing threshold was also significantly different between these two groups . It was suggested that Gusuibu may have protective effect against streptomycin ototoxicity.

Z Erkr Atmungsorgane, 1989, 173(1), 6 - 17
Overview and epidemiological assessment of the current global tuberculosis situation: with an emphasis on tuberculosis control in developing countries; Styblo K; This paper reviews the global epidemiological situation to tuberculosis, with an emphasis on the disappointing tuberculosis control achievements in developing countries over the last three decades . It is concluded tht in low prevalence developed countries it will take at least 35-40 years to eliminate tuberculosis because of endogenous exacerbation in subjects remotely infected . In developing countries most of the estimated 4 million new smear-positive and 4 million new smear-negative and extra-pulmonary cases with some 2-3 million deaths from tuberculosis occur each year . It is evident that a low cure rate is the most important reason for failure of tuberculosis control programmes in poor developing countries . Canetti stressed the urgent need to develop chemotherapeutic methods adapted to the conditions prevailing in developing countries . Based on a 9-year experience in IUATLD-assisted national tuberculosis programmes in 10 developing countries, it became apparent that the basic chemotherapeutic regimen consisting of Thiazina (combined tablet of isoniazid and thiacetazone) for 12 months supplemented by streptomycin for the first 2 months is not suitable for achieving a high cure rate in those countries . A high cure rate (90%) under routine conditions can be achieved with an inexpensive 8-month short-course regimen with a 2-month strictly supervised initial intensive phase with daily isoniazid, rifampicin, pyrazinamide and streptomycin, followed by 6 months of self-administered Thiazina daily . A substantial decrease in the risk of tuberculous infection in developing countries is essential, since we are facing their serious problems concerning tuberculosis with the increasing number of AIDS patients . BCG vaccination alone at least with the present type of vaccine, cannot substantially influence the epidemiological situation . It goes without saying that it should be applies to children to prevent tuberculosis whenever its use is justified for its purpose.

Chemotherapy, 1989, 35(2), 146 - 52
Comparative trial of doxycycline plus streptomycin versus doxycycline plus rifampin for the therapy of human brucellosis; Colmenero Castillo JD et al.; Effectiveness and therapeutic value of the doxycycline plus streptomycin and doxycycline plus rifampin schedules of treatment of human brucellosis have been assessed by carrying out a prospective study on 111 patients randomly distributed into two groups . Patients in group A were treated with doxycycline plus streptomycin sulphate and those in group B with doxycycline plus rifampin . The temperature of all patients reverted to normal, and 54 patients from group A (91.6%) and 45 from group B (86.5%) achieved total recovery with a single therapeutic cycle . Two therapeutic failures and 3 relapses in group A (8.4%) and 7 relapses in group B (13.46%) were observed . The tolerance to both regimens was good . Although the combination doxycycline plus rifampin offers a more convenient oral administration, in the light of these results, until more extensive research is carried out, it should be considered as an alternative rather than a first choice in the treatment of human brucellosis.

Med Cutan Ibero Lat Am, 1989, 17(1), 9 - 12
{Surgical treatment of mycetoma located in the face}; Orellano Ocampo F et al.; The first case described in Mexico, was studied by Cicero in 1900 and 1911 Ocaranza, in Sonora, reports some cases, pointing out that the first known case dates back to 1874 . In USA Gonzalez Ochoa identifies the causative agent of the cases he studied, as the same identified in USA, but he calls attention to the fact that it has already been described under the name of Actinomyces brasiliensis, finally, taxonomically it is included among the nocardias . In Mexico the micetoma is caused in 90% of the cases by Nocardia brasiliensis, and 8% by Streptomysis and other actinomycetos and only in 1.5% it is determined by true fungi . Until the observation of the present case, mycetomas had been reported located or scattered in different places of the human body, except the face . This case is observed in a 24 years old woman patient, of peasant extraction, who presents tumoration of the left hemiface, irregularly oval, 18 x 25 cm . of anfractous surface, with nodes and fistulas that secrete suppuration . The evolution is of seven years duration, and begins after a trauma . The mycologic and histopathologic study, confirms N . brasiliensis as the causative agent . X rays prove that the skull bones are not affected, but the mycosis cause anemia . Specific treatment for anemia is installed with trimetropryn and sulphametoxazol plus sulphone, for a period of six months . A change is made to streptomycin to a total of 40 g . and then this is replaced by isonizasyn, adding to both these drugs alphamatoxipyridazine, for a period of six months and in last months, riprampycin plus sulphone are given; always with bad results.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Nephrol, 1989, 9(2), 155 - 61
Tuberculous peritonitis complicating long-term peritoneal dialysis . Report of 5 cases and review of the literature; Cheng IK et al.; The characteristics of 5 patients who developed tuberculous peritonitis while receiving long-term peritoneal dialysis (PD) are presented . There were 2 males and 3 females . 3 patients were on intermittent and 2 were on continuous ambulatory peritoneal dialysis when tuberculous peritonitis was first diagnosed . None of the patients had recently received immunosuppression therapy or were diabetics . The clinical presentations were similar to other forms of peritonitis complicating PD except for a more insidious onset . As extraperitoneal involvement and peritoneal lymphocytosis were rarely present, the diagnosis was mainly dependent on the direct demonstration of Mycobacterium tuberculosis with smear (1 patient) and culture (4 patients) . In 1 patient with a pleuroperitoneal communication, the diagnosis was made by pleural biopsy and a positive response to antituberculous therapy . All patients responded to treatment with a combination of three antituberculous drugs which included streptomycin, isoniazid, rifampicin and pyrazinamide . Two patients were transferred to hemodialysis . In 3 patients, peritoneal dialysis was continued . Peritoneal clearance and ultrafiltration capacity were unchanged for up to 16 months after treatment in 2 patients who continued peritoneal dialysis but was reduced by 30 and 50%, respectively, in the remaining patient . Only 1 patient died, but her death was not directly related to tuberculous peritonitis . It was concluded that with a high index of suspicion and early institution of treatment, tuberculous peritonitis complicating PD can be successfully treated with low mortality and without compromising the dialysis capacity of the peritoneal membrane.

Microbiol Immunol, 1989, 33(12), 1001 - 11
Different correlations of drug susceptibilities to colonial morphology in Mycobacterium avium complex strains; Tsukamura M et al.; In Mycobacterium avium and Mycobacterium intracellulare complex strains isolated from patients who were not treated previously by any antituberculosis drugs or from fowls, the colonial morphology, smooth, domed, opaque (SmD) or smooth, flat, transparent (SmT) colonial forms, significantly correlated with susceptibilities to rifampicin, minocycline, streptomycin, kanamycin, enviomycin, ethambutol, and sulfadimethoxine, whereas it did not correlate with susceptibilities to isoniazid, cycloserine, and ethionamide . Strains with the SmT colonial morphology were more resistant to the former seven drugs than strains with the SmD colonial morphology . Since the susceptibilities to antituberculosis drugs with large molecules correlated with the colonial morphology, it has been suggested that a permeability barrier that allows passage of small molecules but prevents passage of large molecules exists in the strains with the SmT colonial morphology.

Henry Ford Hosp Med J, 1989, 37(2), 73 - 5
Ulceroglandular tularemia: a typical case of relapse; Miller SD et al.; Tularemia is an infectious disease that continues to occur sporadically and in epidemics in the United States . It is characterized as an acute febrile illness with constitutional symptoms associated with skin, glandular, respiratory, or gastrointestinal involvement . Tularemia usually can be treated effectively with streptomycin . Relapse most often occurs when patients are treated with bacteriostatic agents such as chloramphenicol or tetracycline . We present a case of ulceroglandular tularemia distinguished by its relapse after initial streptomycin/doxycycline therapy and subsequent slow response to additional streptomycin.

Vestn Akad Med Nauk SSSR, 1989, (7), 20 - 8
{Glucocorticoid receptors as targets for pharmacologic action}; Golikov PP et al.; Experimental data demonstrate the influence of certain drugs on the interaction of Type II and III glucocorticoid receptors of the liver cytosol and labelled natural and synthetic glucocorticoids . Preparations of the phenothiazine (aminazine, tizercine) and pyrazolone (amidopyrine, analginum) series and non-steroid anti-inflammatory drugs (acetylsalicylic acid, sodium salicylate) exert a significant effect on the glucocorticoid-receptor interplay . Certain drugs (tizercine, analginum) have an anti-stress effect by lowering the level of Type II glucocorticoid receptors of liver cytosol and corticosterone concentration in the blood plasma of rats . The phenothiazine and no-spa derivatives inhibit the matrix activity of the thymocyte DNA in adrenalectomized rats . Pyracetam, caffeine, adrenaline, noradrenaline, verapamil, digoxin, and streptomycin do not influence the thymocyte DNA matrix activity in the presence of triamcinolone acetonide . Based on the literature data and original research findings, the problem of glucocorticoid receptors employment as targets for medication to control the glucocorticoid effect and stress is discussed.

J Bacteriol, 1989 Jan, 171(1), 24 - 9
Genetic relationship of two highly studied Synechococcus strains designated Anacystis nidulans; Golden SS et al.; The cyanobacteria Synechococcus sp . strain PCC 7942 and Synechococcus sp . strain PCC 6301 are very closely related and both have been designated by the binomial Anacystis nidulans . The only established difference between the two strains is the superior transformation properties of strain PCC 7942 . Significant homology between the rRNA genes of these strains was demonstrated by the ability of an rRNA operon from strain PCC 6301, interrupted by a spectinomycin and streptomycin resistance marker, to transform strain PCC 7942 by recombining with and replacing an endogenous rRNA operon . Restriction fragment length polymorphism data indicated that the chromosomes of the two strains were conserved around the three psbA loci, the two rRNA operons, and the psbDI locus . However, multiple polymorphisms were detected downstream of the psbDII locus, identifying a DNA rearrangement such as an inversion, insertion, or deletion within the chromosome . Analysis of genome structure by pulsed-field gel electrophoresis of large NotI restriction fragments showed only two bands that were visibly shifted between the chromosomes of the two strains . These data support their very close genetic relationship and the feasibility of studying genes derived from strain PCC 6301 in the highly transformable PCC 7942 strain.

Res Commun Chem Pathol Pharmacol, 1988 Dec, 62(3), 447 - 60
Synergistic toxicity of cyclosporin A and streptomycin in renal epithelial cell cultures; Walker RJ et al.; Cyclosporin A (CSA) nephrotoxicity was examined in two renal epithelial cell cultures, the LLC-PK1 cell line and the MDCK cell line . Acute changes in cell growth and cellular DNA and protein synthesis were investigated at 2 hours, 20 hours and 5 days . The potential synergistic interaction between streptomycin (a standard additive to most culture media) and CSA was examined . CSA produced significant alterations in cell function as early as 2 hours after exposure and this became more noticeable with increased exposure to CSA . Streptomycin potentiated the toxicity effects on cellular metabolism that was seen with CSA . The use of cell culture models to investigate CSA toxicity must avoid the use of potential agents which may have a synergistic effect on the development of toxicity.

Biochimie, 1988 Dec, 70(12), 1715 - 8
High fidelity of guanine translation in a plasmid-directed in vitro system; Negre D et al.; The extent of misreading of individual bases in the first or second codon position has been measured in vitro in a simplified plasmid-directed coupled system in which natural messenger translation is restricted to the formation of the N-terminal di- or tripeptide . Experiments were performed under conditions of competition between cognate and noncognate tRNAs in the presence of streptomycin to maximize the frequency of reading errors . A striking lack of susceptibility to mistranslation of guanine, as compared to the other 3 bases, was observed.

J Bacteriol, 1988 Dec, 170(12), 5913 - 5
Allele replacement in Escherichia coli by use of a selectable marker for resistance to spectinomycin: replacement of the lexA gene; Hill SA et al.; We replaced the Escherichia coli lexA gene by a segment of DNA coding for resistance to spectinomycin and streptomycin . The use of this segment expands the range of selectable markers usable for allele replacement . The availability of this null lexA mutation will facilitate genetic analysis of lexA and the SOS regulon.

Acta Paediatr Scand, 1988 Nov, 77(6), 890 - 4
INH and streptomycin in Ethiopian children with tuberculosis and different nutritional status; Eriksson M et al.; The plasma concentration of INH and streptomycin was followed in 45 Ethiopian children with tuberculosis . The children were grouped according to their nutritional status as normal, underweight, marasm and kwashiorkor . INH was well absorbed in all nutritional groups to give therapeutically active plasma levels . When terminal half life (t1/2) of INH was calculated for individual patients there were more children in all nutritional groups with t1/2 greater than or equal to 2 hours than less than 2 hours, indicating a slow acetylation of INH . Streptomycin was well absorbed in all nutritional groups and therapeutic levels were obtained with 20 mg/kg i.m . After 30 mg/kg i.m . of streptomycin kwashiorkor children had an increased t1/2 of streptomycin indicating a decreased renal excretion of the drug in kwashiorkor . The clinical follow-up of the children indicated that serious tuberculosis could be successfully treated with INH and streptomycin in the doses used.

Mol Gen Genet, 1988 Nov, 214(3), 456 - 9
Improved expression of streptomycin resistance in plants due to a deletion in the streptomycin phosphotransferase coding sequence; Maliga P et al.; Previous studies have shown that a chimeric streptomycin phosphotransferase (SPT) gene can function as a dominant marker for plant cell transformation . The SPT marker previously described by Jones and co-workers has a limited value since it conferred a useful level of resistance only to a fraction (10%) of Nicotiana plumbaginifolia transgenic lines . Expression of resistance was species specific: no such resistant transformants were found in N . tabacum . In this paper we describe an improved SPT construct that utilizes a mutant Tn5 SPT gene . The mutant gene, SPT*, encodes a protein with a two amino acid deletion close to its COOH-terminus . In N . tabacum cell culture the efficiency of transformation with the improved streptomycin resistance marker was comparable to kanamycin resistance . When the chimeric SPT* gene was introduced linked to a kanamycin resistance gene, streptomycin resistance was expressed in most of the transgenic N . tabacum lines.

Nucleic Acids Res, 1988 Oct 25, 16(20), 9631 - 9
A mutation in the 530 loop of Escherichia coli 16S ribosomal RNA causes resistance to streptomycin; Melancon P et al.; Oligonucleotide-directed mutagenesis was used to introduce an A to C transversion at position 523 in the 16S ribosomal RNA gene of Escherichia coli rrnB operon cloned in plasmid pKK3535 . E . coli cells transformed with the mutated plasmid were resistant to streptomycin . The mutated ribosomes isolated from these cells were not stimulated by streptomycin to misread the message in a poly(U)-directed assay . They were also restrictive to the stimulation of misreading by other error-promoting related aminoglycoside antibiotics such as neomycin, kanamycin or gentamicin, which do not compete for the streptomycin binding site . The 530 loop where the mutation in the 16S rRNA is located has been mapped at the external surface of the 30S subunit, and is therefore distal from the streptomycin binding site at the subunit interface . Our results support the conclusion that the mutation at position 523 in the 16S rRNA does not interfere with the binding of streptomycin, but prevents the drug from inducing conformational changes in the 530 loop which account for its miscoding effect . Since this effect primarily results from a perturbation of the translational proofreading control, our results also provide evidence that the 530 loop of the 16S rRNA is involved in this accuracy control.

Am Rev Respir Dis, 1988 Oct, 138(4), 878 - 81
Susceptibility of Mycobacterium avium complex to various two-drug combinations of antituberculosis agents; Ozenne G et al.; The drug susceptibility of two untypable strains of Mycobacterium avium complex were studied in 7H10 agar plates containing ethambutol (EMB), isoniazid (INH), rifampicin (RMP), ethionamide (ETH), and streptomycin (SM) alone and in two-drug combinations . The effective dose inhibiting 75% of the mycobacterial population (ED 75) was estimated by a regression analysis on the probit transformed inhibition percentages and plotted on an isobologram for each combination . No major discrepancies were found between strains . Five combinations (RMP plus INH, RMP plus EMB, EMB plus SM, INH plus EMB, and ETH plus INH) showed synergistic effect, whereas five other combinations (ETH plus EMB, ETH plus RMP, ETH plus SM, SM plus RMP, and SM plus INH) showed antagonistic effect . These in vitro results are not in combination with the known results of treatment of the M . avium diseases . We conclude that the effect of drug combinations against M . avium may be strain dependent and that it is important to determine this effect in vitro before setting up a treatment protocol.

Laryngoscope, 1988 Oct, 98(10), 1040 - 3
Binaural cochlear implantation: comparison of 3M/House and Nucleus 22 devices with evidence of sensory integration; Balkany T et al.; Direct comparison of the efficacy of cochlear implant designs has been difficult for several reasons . There have been wide variations in patients implanted and many differences in testing protocols for each device . In most instances, even a single patient may have unequal degrees of pathology and duration of deafness in the two ears . Implantation of a 3M/House device in the left ear and a Nucleus 22 device in the right ear of a 55-year-old woman, deafened to a similar degree and simultaneously in both ears by streptomycin, allows an opportunity to compare function under presumably similar circumstances . The Nucleus 22 cochlear implant was superior in this case in providing speech discrimination . Perhaps of greater interest, however, is evidence of a binaural effect . Presumably, central integration of sensory stimuli presented through two dissimilar processing strategies resulted in enhanced function on certain measures.

Am Rev Respir Dis, 1988 Oct, 138(4), 999 - 1001
Minimal inhibitory concentrations of isoniazid, rifampin, ethambutol, and streptomycin against Mycobacterium tuberculosis strains isolated before treatment of patients in Taiwan; Suo J et al.; Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and streptomycin (SM) for susceptible "wild" M . tuberculosis strains isolated from Taiwanese patients were within the limits previously reported for strains isolated in the United States . The highest agar-determined MICs (in 7H10 and 7H11 agar) corresponded well with the critical concentrations established for these media . The highest MICs found radiometrically in 7H12 broth were significantly lower than the critical concentrations proposed for this medium . On the basis of an evaluation of the highest broth-determined MICs found in this and in the previous study (1), we suggest that the following MICs, when determined radiometrically, should be used as breakpoints to classify the strain as "susceptible": for INH, 0.1 microgram/ml or less; for RMP, 0.5 microgram/ml or less; for EMB, 4.0 micrograms/ml or less; for SM, 2.0 micrograms/ml or less.

Genetica, 1988 Sep 30, 77(2), 113 - 21
Parental age dependent changes as a source of genetic variation in Drosophila melanogaster; Marinkovic D et al.; It has been shown repeatedly that numerous cumulative changes occur in chromosomes of D . melanogaster, as an effect of ageing which, especially in the homozygous state, significantly affect different fitness components of their carriers . It appears that the observed age-affected events are produced by systematic and ontogenetically programmed changes in genetic loads at specific chromosomes, which are transferable to following generations . It has been suggested that such changes could be of mutational origin, and that they could be more frequent at gene loci which are epigenetically active during ontogenesis . It was demonstrated that a large sample of identical chromosomes behave quite differently in the homozygous state when obtained from aged compared to non-aged parents, producing a significant decrease in relative viability, length of preadult development, and longevity of their carriers, as well as in the frequency of recombinations of corresponding chromosomes . A specific treatment by streptomycin resulted in remarkably milder effects of ageing, which is in accordance with the statement of some authors that such a treatment may diminish the frequency of spontaneous recessive mutations in their carriers . Thus the observed age-affected changes could be an important source of developmental and evolutionary variation of living organisms.

J Biol Chem, 1988 Sep 15, 263(26), 13103 - 11
The allosteric three-site model for the ribosomal elongation cycle . New insights into the inhibition mechanisms of aminoglycosides, thiostrepton, and viomycin; Hausner TP et al.; According to the allosteric three-site model for the ribosomal elongation cycle (Rheinberger, H.J . and Nierhaus, K.H . (1986) J . Biol . Chem . 261, 9133-9139), two types of A site (aminoacyl-tRNA site) occupation exist . First is the A site occupation after initiation (i-type), with only one site, the P site (peptidyl-tRNA site), being prefilled with a tRNA (initiator tRNA) . Second is the A site occupation after an elongation cycle (e-type), with two prefilled sites, namely the P and E sites containing peptidyl-tRNA and deacylated tRNA, respectively . The individual reactions of the elongation cycle were tested, including both types of A site occupation in the presence of various antibiotics . A test system was used allowing the functional studies to be made with quantitative tRNA binding at 6 mM Mg2+ . The following results were obtained: 1) thiostrepton (5 x 10(-6) M) induced a complete block of both EF-(elongation factor) G dependent and EF-G independent translocation, in agreement with older observations . The A-site occupation of the e-type was severely inhibited in contrast to that of the i-type . Thus, thiostrepton blocks the allosteric transitions in both directions, i.e . the transition from pre- to post-translocational state (translocation) and that from the post- to the pre-translocational state (A site occupation of the e-type) . In addition the ribosomal binding of EF-G.{3H} GMPPNP was inhibited by about 60% . 2) Similarly, viomycin (5 x 10(-5) M) appears to be an inhibitor of both allosteric transitions, since it strongly inhibited the e-type (but not the i-type) A site occupation in addition to translocation . 3) The aminoglycosides streptomycin, hygromycin B, neomycin, kanamycin, and gentamicin prevented A site occupation of the e-type (residual activity below 15%) . Neomycin and hygromycin, in addition, blocked the translocation reaction . Only marginal effects were observed with A site occupation of the i-type . It appears that the inhibition of the A site binding of the e-type (allosteric transition from the post- to the pretranslocational state) is the predominant effect of the misreading-inducing aminoglycosides.

J Am Acad Dermatol, 1988 Sep, 19(3), 451 - 7
Cutaneous manifestations of human immunodeficiency virus in Lusaka, Zambia; Hira SK et al.; Of the 1124 human immunodeficiency virus (HIV)-infected patients studied, one or more cutaneous lesions were found in 113 (98.3%) of the 115 patients with acquired immunodeficiency syndrome (AIDS) and in 541 (53.6%) of 1009 patients with AIDS-related complex (ARC) . Kaposi's sarcoma, multidermatomal, necrotic herpes zoster, and pruritic maculopapular rashes are common cutaneous manifestations of AIDS and its related complex (ARC) in Zambia . The maculopapular rash results from a lymphoplasmacytic angiitis in the dermis, possibly in response to the presence of HIV in the dermis . Candidiasis, severe genital herpes, extensive molluscum contagiosum, and tinea corporis were less frequent and usually refractory to treatment . Drug reactions are also frequent in Zambians with AIDS . In seven patients given streptomycin, thiacetazone, and rifampicin for treatment of pulmonary tuberculosis, Stevens-Johnson syndrome occurred shortly after therapy was begun, and two died despite high-dose prednisone and discontinuance of tuberculosis therapy . Extensive seborrheic dermatitis refractory to topical fluorinated corticosteroids is also an associated condition in AIDS patients who have pulmonary tuberculosisPIP: Cutaneous manifestations of AIDS and AIDS-related complex were studied in a population of 1124 HIV seropositive patients at a hospital in Lusaka, Zambia . 115 of the patients had AIDS, and 1009 had AIDS-related complex . Drug eruptions occurred in 22 patients; 2 died of Stevens-Johnson syndrome subsequent to drug therapy for tuberculosis . The most frequently seen cutaneous manifestations were candidiasis, Kaposi's sarcoma, herpes zoster, seborrheic dermatitis, herpes genitalis, and papular dermatoses . The pruritic maculopapular eruption occurred in crops, healed, and recurred . It was one of the most unique dermatologic manifestations of AIDS found in Africa . Seborrheic dermatitis occurred frequently in patients who also had pulmonary tuberculosis .

Antimicrob Agents Chemother, 1988 Aug, 32(8), 1208 - 12
Rapid susceptibility testing of Mycobacterium tuberculosis by bioluminescence assay of mycobacterial ATP; Nilsson LE et al.; Mycobacterial growth was monitored by bioluminescence assay of mycobacterial ATP . Cultures of Mycobacterium tuberculosis H37Rv and of 25 clinical isolates of the same species were exposed to serial dilutions of ethambutol, isoniazid, rifampin, and streptomycin . A suppression of ATP, indicating growth inhibition, occurred for susceptible but not resistant strains within 5 to 7 days of incubation . Breakpoint concentrations between susceptibility and resistance were determined by comparing these results with those obtained by reference techniques . Full agreement was found in 99% of the assays with the resistance ratio method on Lowenstein-Jensen medium, and 98% of the assays were in full agreement with the radiometric system (BACTEC) . A main advantage of the bioluminescence method is its rapidity, with results available as fast as with the radiometric system but at a lower cost and without the need for radioactive culture medium . The method provides kinetic data concerning drug effects within available in vivo drug concentrations and has great potential for both rapid routine susceptibility testing and research applications in studies of drug effects on mycobacteria.

J Antibiot (Tokyo), 1988 Aug, 41(8), 1116 - 23
Strain- and species-specific distribution of the streptomycin gene cluster and kan-related sequences in Streptomyces griseus; Hotta K et al.; The streptomycin (SM) gene cluster was investigated for its distribution in streptomycetes by Southern hybridization using nick-translated DNA probes, which were isolated from the SM-6-phosphotransferase (SPH) and amidinotransferase (ADT) regions of the SM gene cluster of Streptomyces griseus SS-1198 . Bgl II-digested genomic DNAs from SM-producing strains of S . griseus yielded the same size fragment (7.0 kb) which hybridized to both the SPH and ADT probes as expected from the restriction endonuclease cleavage map of the SM gene cluster . By contrast, no genomic DNA fragments from heterologous Streptomyces strains hybridized to the probes . Thus, only SM-producing strains of S . griseus possess the highly homologous SM gene cluster . Similarly, distribution of DNA sequences homologous to the kanamycin (KM)-resistance determinant (kan) from a KM-resistant regenerant of S . griseus SS-1198 protoplasts was also examined . Using the kan gene fragment as the probe it was revealed that the kan-related sequences are present in all the strains of S . griseus tested, irrespective of the type of antibiotics they produce . However, no hybridization to the kan gene probe (KAN) was observed with DNA digests derived from other Streptomyces species.

J Bacteriol, 1988 Aug, 170(8), 3756 - 60
Is efficiency of suppressor tRNAs controlled at the level of ribosomal proofreading in vivo?
Faxen M, Kirsebom LA, Isaksson LA.
Ribosomal rpsD mutations did not stimulate nonsense suppressor tRNAs in a general manner according to their increased ribosomal ambiguity and decreased proofreading efficiency . Streptomycin, which stimulates error production by blocking proofreading in vitro, did not increase efficiency of suppressor tRNAs in strains with normal or streptomycin-resistant (rpsL) ribosomes . It did so only in combination with one rpsL mutation which is associated with streptomycin pseudodependence.

Clin Pharm, 1988 Jul, 7(7), 545 - 51
Treatment of nontuberculous mycobacterial infections in pediatric patients; Levin RH et al.; Two cases of Mycobacterium avium-intracellulare complex (MAC) infections are described, and the diagnosis, clinical features, and management of MAC infections are reviewed . In case 1, a four-year-old boy was diagnosed as having both acquired immunodeficiency syndrome (AIDS) and disseminated MAC infection . He was treated with a combination of isoniazid, ethambutol hydrochloride, rifabutin, and clofazimine . Results of susceptibility testing showed that the MAC was susceptible to rifabutin and ethambutol with intermediate susceptibility to isoniazid . The child developed severe adverse effects that necessitated the discontinuation of rifabutin therapy . Despite therapy, blood cultures remained positive for MAC . The child died of disseminated human immunodeficiency virus and MAC infection . In case 2, a 20-month-old girl was found to have a prevertebral retropharyngeal mass caused by MAC . The child did not have evidence of immunologic deficiency . She was treated with streptomycin, ethambutol, clofazimine, and rifabutin . Streptomycin was discontinued after three months . After seven months the mass decreased in size, allowing for surgical resection . Intraoperative cultures were negative for mycobacteria . Ethambutol, rifabutin, and clofazimine were continued for a total of 12 months, at which time the child was determined to be clinically and radiologically cured . Empiric multidrug antituberculous therapy should be initiated in patients with suspected disseminated nontuberculous mycobacterial infection because final isolation, identification, and susceptibility testing may take several weeks . Clofazimine and rifabutin, in combination with isoniazid and ethambutol, may be useful in the treatment of some MAC infections . At least four drugs are given, and regimens often consist of six drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

J Mol Biol, 1988 Jun 20, 201(4), 683 - 95
Interaction of ribosomal proteins S5, S6, S11, S12, S18 and S21 with 16 S rRNA; Stern S et al.; We have examined the effects of assembly of ribosomal proteins S5, S6, S11, S12, S18 and S21 on the reactivities of residues in 16 S rRNA towards chemical probes . The results show that S6, S18 and S11 interact with the 690-720 and 790 loop regions of 16 S rRNA in a highly co-operative manner, that is consistent with the previously defined assembly map relationships among these proteins . The results also indicate that these proteins, one of which (S18) has previously been implicated as a component of the ribosomal P-site, interact with residues near some of the recently defined P-site (class II tRNA protection) nucleotides in 16 S rRNA . In addition, assembly of protein S12 has been found to result in the protection of residues in both the 530 stem/loop and the 900 stem regions; the latter group is closely juxtaposed to a segment of 16 S rRNA recently shown to be protected from chemical probes by streptomycin . Interestingly, both S5 and S12 appear to protect, to differing degrees, a well-defined set of residues in the 900 stem/loop and 5'-terminal regions . These observations are discussed in terms of the effects of S5 and S12 on streptomycin binding, and in terms of the class III tRNA protection found in the 900 stem of 16 S rRNA . Altogether these results show that many of the small subunit proteins, which have previously been shown to be functionally important, appear to be associated with functionally implicated segments of 16 S rRNA.

Tubercle, 1988 Jun, 69(2), 95 - 103
The management of tuberculosis in refugees along the Thai-Kampuchean border; Mastro TD et al.; The treatment of tuberculosis in refugees living in campus along the Thai-Kampuchean border has remained a controversial issue since the beginning of the Khmer relief operation in 1979 . During the 1984-85 dry season, war-related disruptions forced the evacuation of the 240,000 residents of 21 camps into evacuation sites in Thailand . Seven tuberculosis treatment programmes, using a fully supervised, daily protocol of isoniazid(H), rifampicin(R), pyrazinamide(Z) and streptomycin(S) 3 HRZS/HR, (6 months for pulmonary and 9 months for extrapulmonary tuberculosis), were able to continue operation, with acceptably low rates of default from therapy . During the 18 month period beginning in July 1984, 984 patients were started on treatment: 755 completed a full course while 86 defaulted . The programme design and organisation are described.

No Shinkei Geka, 1988 May, 16(6), 791 - 5
{A case of calcified intracranial tuberculoma presenting unique MRI findings}; Kinjo T et al.; A 41-year-old male patient was admitted in our Ryukyu University Hospital complaining of parosmia . He had a history of miliary tuberculosis 21 years ago . Neurologically he showed left anosmia and hyperreflexia of the right upper extremity . Plain skull X-P and CT scan revealed a calcified mass, 25mm in diameter, at the left frontal base . In MRI, the mass showed isointensity using the T1 weighted inversion recovery sequence and heterogenously low intensity using the T2 weighted spin echo sequence . Surgery was performed by bifrontal craniotomy . Then the tumor was removed totally including two coexisting small tumors . Histologically, they consisted of calcified caseous tissue and thick collagen capsule, suggesting old calcified tuberculomas . Postoperative course was uneventful and did not result in meningitis . Antituberculous therapy of streptomycin, isoniazid and rifampin was given for 2 weeks, started on the operative day . MRI findings were presented in detail and the guideline of antituberculous therapy to the tuberculoma was discussed.

Ann Clin Lab Sci, 1988 May-Jun, 18(3), 204 - 14
Cultured human proximal tubule cells as a model for aminoglycoside nephrotoxicity; Sens MA et al.; Despite numerous clinical and animal studies, the initial injury and pathogenesis of aminoglycoside nephrotoxicity remains unclear . To compliment and extend existing research avenues, a cell culture model system representative of the human proximal tubule (HPT) was tested to determine its applicability for use in studies assessing aminoglycoside-induced cellular toxicity . For this determination, the proximal tubule cell cultures were exposed to increasing concentrations of streptomycin and monitored for cell death and light and electron microscopic changes under both confluent (resting) and subconfluent (actively-dividing) culture conditions . Confluent cultures exposed to streptomycin were also assessed for possible alterations in transport activities by monitoring the electrical properties of the cells through Ussing chamber analysis . Both the confluent and subconfluent cultures demonstrated concentration-dependent toxicity to streptomycin . Ultrastructural analysis disclosed that both actively-dividing and stationary cultures contained "myeloid bodies" within the cytoplasm, consistent with those known to occur in vivo . In studies relating cell numbers to the dosage and time of exposure to streptomycin, the confluent cultures demonstrated and "insult-recovery" period at toxic, but sub-lethal, concentration, again correlating to the known in vivo experience with this class of antibiotics . The subconfluent cultures demonstrated increased resistance to the toxic effects of streptomycin, again mimicking the clinical experience with aminoglycoside toxicity . Chamber analysis, at a streptomycin dose well below the toxic level, indicated changes in the transport activities of these cultured cells . It is proposed that the use of cultured proximal tubule cells could be a useful model system to extend current research avenues assessing the mechanism of aminoglycoside nephrotoxicity.

J Antibiot (Tokyo), 1988 May, 41(5), 675 - 83
Mode of action of deoxypheganomycin D on Mycobacterium smegmatis ATCC 607; Suzukake-Tsuchiya K et al.; Deoxypheganomycin D, a specific inhibitor of mycobacteria, inhibits the growth in vitro of Mycobacterium smegmatis ATCC 607 (M . 607) bacteriostatically at concentrations as high as 7 X 10(-5) M . It shows no cross-resistance to paromomycin, capreomycin, viomycin, streptothricin, kanamycin and streptomycin . Deoxypheganomycin D at 2.8 X 10(-7) M where the cell growth of M . 607 is only partially inhibited does not significantly inhibit DNA, RNA or protein synthesis but leads to marked decrease (13% of control) in {14C}glycerol-derived radioactivity in cell-walls . In the presence of 7 X 10(-6) M deoxypheganomycin D, the influx of leucine but not thymidine is affected while the reverse is true with efflux . The data suggest that the effect of deoxypheganomycin D on M . 607 may be related to both the cell membrane and specific mycobacterial lipid like components of the cell-wall.

J Thorac Cardiovasc Surg, 1988 May, 95(5), 862 - 7
Brucella infective endocarditis . Successful combined medical and surgical therapy; al-Kasab S et al.; Five cases of Brucella infective endocarditis are described involving a native aortic valve, two native mitral valves, a mitral valve bioprosthesis, and a ventricular septal defect patch . The diagnosis of Brucella infective endocarditis was established from the clinical features, with a high Brucella serologic titer in each case . Blood and tissue cultures were positive in four of five patients . Two-dimensional echocardiograms demonstrated moderately large vegetations on the three affected native valves and the patch and also revealed the development of vegetation on the mitral bioprosthesis as the disease progressed . All the patients were successfully treated by combined surgical and medical therapy, the latter consisting of co-trimoxazole, tetracycline, and streptomycin/gentamicin for 6 weeks; the affected valves and the ventricular septal defect patch were all replaced . There were no operative deaths and there has been no recurrence of infection to date . One patient died suddenly of an unknown cause 1 year after the operation.

Plasmid, 1988 May, 19(3), 175 - 88
A broad-host-range vector system for cloning and translational lacZ fusion analysis; Tai TN et al.; A broad-host-range vector system for studying translational fusions was constructed . The region that retains the origin of replication, nic, mob, and rep genes of the broad-host-range plasmid RSF1010 was isolated as either an HincII or a PstI-PvuII restriction fragment . These restriction fragments were ligated to tetracycline, kanamycin, or streptomycin/spectinomycin resistance genes to generate plasmids pUI501, pUI511, pUI504, and pUI506 . A functional lacZ gene lacking downstream lac operon sequences together with the lac promoter was constructed from plasmids pMC1871 and pUC18 . This lacZ gene was inserted into pUI501 and pUI511 to generate plasmids pUI502, pUI503, pUI512, and pUI513 . An oligodeoxynucleotide sequence that carries three unique blunt-end restriction sites was synthesized, annealed, and ligated in frame to the amino-terminal end of the lacZ gene in each of these plasmids . This multiple cloning sequence will allow translational fusions to the lacZ gene in all three reading frames . The stability of these plasmids and the expression of the lacZ gene in both Escherichia coli and Rhodobacter sphaeroides were studied.

Trop Geogr Med, 1988 Apr, 40(2), 151 - 2
Probable transmission of brucellosis from breast milk to a newborn; Lubani M et al.; The first case of neonatal brucellosis is described . The baby was fed breast milk only when the mother became acutely ill with fever, arthralgia and malaise . At the same time the baby was febrile . Blood cultures grew Brucella melitensis in both mother and child . The brucella agglutination titre in the breast milk was 1:2560 . Both mother and child recovered during treatment with streptomycin.

Chest, 1988 Apr, 93(4), 821 - 3
Comparison of antituberculosis drug regimens for lung disease caused by Mycobacterium avium complex; Tsukamura M et al.; A total of 123 patients with moderately advanced, cavitary lung disease caused by Mycobacterium avium complex untreated previously received different regimens of antituberculosis agents . The rate of sputum conversion (continuously negative cultures for six months or more) was compared among the regimens . It was shown that the regimens of rifampin + isoniazid + streptomycin and rifampin + isoniazid + enviomycin were superior to the regimens of streptomycin + isoniazid + p-aminosalicylate, isoniazid alone or isoniazid + p-aminosalicylate . This finding demonstrated that the regimens including rifampin, isoniazid and streptomycin or enviomycin were really effective in the initial treatment of lung disease caused by M avium complex.

Biochim Biophys Acta, 1988 Mar 2, 953(1), 106 - 13
Purification and properties of aspartate transcarbamylase from Mycobacterium smegmatis; Masood R et al.; Aspartate transcarbamylase (carbamoyl-phosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) has been purified from Mycobacterium smegmatis TMC 1546 using streptomycin sulphate precipitation, ammonium sulphate precipitation, DE-52 chromatography, second ammonium sulphate precipitation, Sephadex G-200 gel filtration, and aspartate-linked CNBr-activated Sepharose 4B affinity chromatography in successive order . The enzyme was purified 231.6-fold, and the preparation was found to be homogeneous on column chromatography and polyacrylamide gel electrophoresis . The purified enzyme had a molecular weight of 246,000 and was composed of two asymmetrical subunits . The kinetic and regulatory properties of aspartate transcarbamylase from M . smegmatis were also studied . The enzyme was found to be an allosteric in nature with carbamyl phosphate showing positive cooperativity and UMP exhibiting a negative cooperativity . CTP was found to be the most potent inhibitor among nucleotides . Phosphate acted as a non-competitive product inhibitor with respect to aspartate . Succinate and maleate exerted a competitive inhibition when aspartate was the variable substrate.

Tubercle, 1988 Mar, 69(1), 37 - 42
Primary antituberculosis drug resistance and acquired rifampicin resistance in Gujarat, India; Trivedi SS et al.; The prevalence of primary antituberculosis drug resistance in Gujarat, as studied between 1983 and 1986, was found to be significantly high, especially for isoniazid (13.9%) and streptomycin (7.4%) . Primary rifampicin and pyrazinamide resistance were not detected in any strain . The prevalence of rifampicin resistance among treatment failure and relapse cases of pulmonary tuberculosis increased significantly from 2.8% in 1980 to 37.3% in 1986 . In about 95% of the rifampicin resistant strains there was also resistance to isoniazid or streptomycin or both: resistance to isoniazid was detected in more than 90%.

Tubercle, 1988 Mar, 69(1), 5 - 14
Controlled clinical trial of a regimen of two durations for the treatment of isoniazid resistant pulmonary tuberculosis; Babu Swai O et al.; Patients with pulmonary tuberculosis who were failures of primary chemotherapy with strains resistant to isoniazid or to isoniazid and streptomycin were allocated at random to receive a regimen of rifampicin and ethambutol for 6 (4RE) or 9 months (7RE), supplemented in both treatment series by streptomycin plus pyrazinamide for the first 2 months . The patients were treated in hospital for the first 2 months and thereafter treatment was supervised on a daily basis in the nearest health institution by an appointed member of staff or at home by responsible members of the community . A total of 306 patients was admitted and 226 patients remained for analysis at the end of chemotherapy, 179 with a strain resistant to isoniazid alone and 47 with a strain resistant to isoniazid and streptomycin . There were only two failures at the end of chemotherapy, one in the 6-month series who had resistance to both isoniazid and streptomycin pretreatment, and one in the 9-month series who had resistance to isoniazid alone . For the 144 patients with initial resistance to isoniazid alone assessed up to 30 months, the relapse rates were low in both series: 4% for the 72 patients in the 6-month series and 3% for the 72 patients in the 9-month series . However, for the 34 patients with resistance to both drugs, three of the 14 in the 6-month but none of 20 in the 9-month series relapsed.

Sex Transm Dis, 1988 Jan-Mar, 15(1), 27 - 9
The treatment of donovanosis (granuloma inguinale); Latif AS et al.; Over a two-year period, 37 patients with genital ulcer disease attending a clinic for sexually transmitted diseases in Harare were found to have donovanosis . Of the 37 patients, 25 were male, and 12 were female; all presented with painless, indurated, granulating ulcers without lymph-node involvement . The lesions were more extensive in pregnant women . All patients responded well to either a combination of intramuscular streptomycin plus oral tetracycline given over 14 days, or a 14-day course of oral co-trimoxazole (trimethoprim-sulfamethoxazole) . No metastatic lesions were found.

Rev Infect Dis, 1988 Jan-Feb, 10(1), 211 - 7
The nature of human brucellosis in Kuwait: study of 379 cases; Mousa AR et al.; Three hundred seventy-nine Kuwaiti patients with brucellosis were admitted to Adan General Hospital, Kuwait, during the period 1984-1985 . Of these 231 were males and 148 were females . Diagnosis was based on symptoms and signs compatible with the disease and on the detection of significantly elevated antibody titer and/or positive blood culture . The primary means of exposure were the consumption of raw milk and contact with goats, sheep, or camels . Patients most frequently presented with fever (91%), chills (40%), sweats (39%), gastrointestinal symptoms (30%), headache (23%), respiratory symptoms (23%), and musculoskeletal symptoms (22%) . The major signs were osteoarticular involvement (37%), hepatosplenomegaly (27%), and lymphadenopathy (9%) . Different regimens of treatment were used, but the highest rate of cure was achieved with triple therapy--tetracycline, streptomycin, and rifampin.

Gut, 1988 Jan, 29(1), 62 - 9
Response of tuberculous stricture to antituberculous treatment; Anand BS et al.; Tuberculous infection of the gastrointestinal tract results in a variety of histopathological lesions . Some patients develop intestinal strictures and present with subacute intestinal obstruction . The treatment is controversial and vary from a trial of antituberculous drugs to early surgery:the response to medical therapy is not clear . To examine this issue the present prospective therapeutic trial was carried out on 39 patients with symptoms of bowel obstruction and radiological evidence of intestinal stricture . All patients were treated with conventional antituberculous drugs (streptomycin, rifampicin, and isoniazid) under close supervision . Thirty four (87%) patients completed the trial, five were lost to follow up . Thirty one (91%) of these showed significant clinical improvement:26 became completely symptom free, while the remaining five complained of only vague abdominal discomfort . Only three (8%) patients failed to respond to treatment and were subjected to surgery . Barium series were repeated in 23 of 31 who completed the treatment; the remaining eight refused further investigations . Complete resolution of the radiological abnormality was seen in 16 (70%) patients . In the remaining seven (30%) the stricture persisted; in two of these the treatment was continued for another year and both showed substantial radiological improvement . It is concluded that most patients with tuberculous strictures respond well to medical treatment and surgery should be resorted to only if drug therapy fails.

Eur J Clin Pharmacol, 1988, 33(6), 647 - 9
Pharmacokinetics of streptomycin in Ethiopian children with tuberculosis and of different nutritional status; Bolme P et al.; Fifty-six malnourished Ethiopian children with tuberculosis classified in four nutritional groups (normal, underweight, marasmus and kwashiorkor), were given streptomycin 20 or 30 mg.kg-1 i.m . The plasma concentration-time data revealed an increased apparent volume of distribution in children with kwashiorkor compared to normals . The total plasma clearance was low and did not differ between the nutritional groups . Thus, the half-life was prolonged only in kwashiorkor . The results could be explained by decreased protein binding in plasma and decreased renal clearance by glomerular filtration.

Exp Brain Res, 1988, 69(2), 260 - 71
Streptomycin in the chick embryo: post-hatching vestibular behavior and morphology; Kenyon RV et al.; Developing chick embryos were exposed to streptomycin injected on days 5 through 13 of the 21 day developmental period . Histological and behavioral abnormalities were found almost exclusively in chicks exposed after day 7 . The nature of the behavioral deficits included abnormal head posture, head tremor, and inability to compensate for applied vestibular stimuli . Head movement measurements showed that the head tremor had frequencies of oscillations from 10-35 Hz . The amplitude of the tremor was a large as 10 degrees . Histology showed damage to the secretory dark cells of the membranous labyrinth in those chicks that showed behavior changes . Even with increased dosages chicks exposed prior to day 7 rarely showed abnormal vestibular behavior but instead experienced increased mortality . Further tests examining tissue levels of streptomycin showed little or no streptomycin in embryos until day 10 . These results are discussed in terms of their utility as an alternative model to surgical manipulation of the vestibular system in developing embryos . Behavioral consequences are compared to other work with drugs and to the effects of weightlessness and unusual environments on vestibular orientation and behavior.

Microbiol Immunol, 1988, 32(6), 641 - 4
Mechanism of streptomycin resistance in Leptospira biflexa strain Urawa; Fukunaga M et al.; The mechanism of streptomycin resistance of Leptospira biflexa was investigated . A streptomycin-resistance mutant of Leptospira showed cross-resistance to dihydrostreptomycin but not to other antibiotics . Enzymatic inactivation of the drug could not be demonstrated in this mutant . Protein synthesis on the ribosomes from the mutant was insensitive to streptomycin . These results suggest that ribosomal resistance is the reason for streptomycin resistance in Leptospira biflexa.

Folia Microbiol (Praha), 1988, 33(4), 314 - 22
Effect of elevated temperature on genotoxicity of chemotherapeuticals toward Euglena gracilis; Macor M et al.; A collection of 20 compounds was tested for their ability to induce a permanent loss of chloroplasts from Euglena gracilis cells under conditions increasing the sensitivity of the flagellate to genotoxic compounds, viz . in the resting medium and at an elevated temperature . Streptomycin, dihydrostreptomycin, gentamicin, kanamycin and partially chloramphenicol exhibited mutagenic effects . Eight antibiotics eliminated chloroplasts only from growing cultures and seven antibiotics did not induce the mutation at all.

J Antibiot (Tokyo), 1988 Jan, 41(1), 94 - 103
Mechanism of increased kanamycin-resistance generated by protoplast regeneration of Streptomyces griseus . I . Cloning of a gene segment directing a high level of an aminoglycoside 3-N-acetyltransferase activity; Hotta K et al.; The genetic and biochemical basis of a 200-fold increase in kanamycin (KM)-resistance shown in Streptomyces griseus SS-1198PR generated by protoplast regeneration was investigated . A 15-kb Bcl I-DNA segment responsible for the KM-resistance was cloned into pIJ61 with Streptomyces lividans TK21 as host . The KM-resistance segment was then subcloned into pIJ702 as a 1.8-kb BamH I-Bgl II fragment with a BamH I site essential for the KM-resistance . Both S . lividans TK21 containing the cloned segments and S . griseus SS-1198PR showed multiple resistance to KM, dibekacin and gentamicin C complex . Cell free extracts from these strains inactivated the antibiotics in the presence of acetyl CoA in agreement with their resistance pattern . The structure of the inactivated KM-A was determined as 3-N-acetyl-KM-A indicating acetylation by an aminoglycoside acetyltransferase, AAC(3) . The substrate range of the enzyme was unique and was designated AAC(3)-V . No genetic linkage was found between the cloned 15 kb Bcl I segment and the separately cloned streptomycin resistance gene (str) segment (3.8 kb Sph I fragment) . The str genes cloned from both the parent (SS-1198) and the strain SS-1198PR were identical in their size, restriction site and function . In addition, these strains showed no significant difference in the total DNA digestion pattern . These results indicate that protoplast regeneration may cause a critical change in a specific region of DNA resulting in a high activity of an AAC(3) with a novel substrate range.

Rev Pneumol Clin, 1988, 44(6), 278 - 85
{Interactions of antitubercular drugs}; Hugues FC et al.; Antituberculous drugs are never used alone but are often given concomitantly with drugs prescribed for other diseases . We have therefore reviewed the potential interactions of antituberculous drugs between themselves and with other drugs . Rifampicin being a potent enzyme inducer will decrease the plasma levels of a wide range of drugs . This in turn will decrease the effectiveness of these drugs if they are unmetabolized and active, or increase drug toxicity if the metabolites are toxic . Within the first category are the oral contraceptives, steroids, oral antidiabetics, oral anticoagulants and digitalis . Within the second category is thought to be isoniazid on account of its hepatotoxicity . In contrast, isoniazid (INH) is an enzyme inhibitor . Drugs with hepatic metabolism will tend to accumulate, although this seems clinically relevant only with antiepileptic drugs, diazepam, triazolam and oral anticoagulants (with high INH doses) . Many other cases of drug interaction have been described, but they seem to be rare and may not be clinically relevant . INH and rifampicin do not seem to modify each other's metabolism consistently, but it may be wise to check the serum INH levels during coadministration . As said above, rifampicin does increase the hepatotoxicity of INH . INH also inhibits monoamine oxidase and will interact with other MAOI, as well as with fish, cheese or wine with high histamine or tyramine contents . The only interaction found with ethambutol is with diazepam: it increases its clearance and free fraction . Obviously, streptomycin potentiates the ototoxicity of other amino-glycosides, such as capreomycin, kanamycin or viomycin, so that combining them is strictly contra-indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Q J Med, 1988 Jan, 66(249), 39 - 54
Human brucellosis in Kuwait: a prospective study of 400 cases; Lulu AR et al.; The clinical pattern of 400 cases of brucellosis in Kuwait is presented . The disease was acute in 77 per cent, sub-acute in 12.5 per cent and chronic in 10.5 per cent of cases . Raw milk was the major source of infection . The major features on presentation, irrespective of the course of the disease, were fever, sweating, headache, rigors, arthralgia, myalgia, and low back pain . Hepatosplenomegaly was present in 41 per cent of cases and in 32 per cent neither liver nor spleen were palpable . The haematologic findings were not specific and hepatic dysfunction (shown by liver enzyme abnormalities) was common . Skeletal (26 per cent) and genital (8.5 per cent) changes and neurobrucellosis (7 per cent) were the major complications . The ELISA was the most sensitive and reliable diagnostic test especially in relation to chronic brucellosis and neurobrucellosis . ELISA allowed the determination of brucella-specific immunoglobulins (Ig)G, IgM and IgA in the CSF, and provided profiles of Ig, in sera, which were different in patients with chronic (elevated IgG and IgA) from those with acute (elevated IgM alone or IgG, IgM and IgA) brucellosis . Treatment with tetracycline, doxycycline or rifampicin gave a cure rate of over 91 per cent in acute and subacute brucellosis . Co-trimoxazole was associated with a relapse rate of 50 per cent . Two drug combinations of streptomycin and tetracycline, streptomycin and rifampicin or streptomycin and doxycycline were effective, but one of five patients with chronic brucellosis relapsed . A combination of streptomycin, tetracycline and rifampicin with or without steroids was used successfully in neurobrucellosis, septicaemic shock and subacute bacterial endocarditis.

Chemotherapy, 1988, 34(1), 56 - 60
Antimycobacterial drugs and the production of reactive oxidants by polymorphonuclear leucocytes in vitro; Zeis BM; The effect of five antimycobacterial drugs isoniazid, rifampicin, streptomycin, pyrazinamide and ethambutol on the generation of reactive oxidants by polymorphonuclear leucocytes was investigated in vitro, using N-formyl-L-methionyl-L-leucyl-phenylalanine (FMLP) activated and spontaneous luminol-enhanced chemiluminescence and myeloperoxidase-mediated iodination . Streptomycin, pyrazinamide and ethambutol had no effect on the assays at the concentrations investigated . Isoniazid as concentrations of 1.25 and 5 micrograms/ml and rifampicin at 100 micrograms/ml significantly inhibited iodination . Rifampicin also caused dose-dependent inhibition of chemiluminescence which was partly due to its light-absorbing activities . It is concluded that isoniazid, and to a lesser extent, rifampicin at therapeutic concentrations possess anti-oxidative properties.

Lancet, 1987 Dec 19, 2(8573), 1418 - 22
Controlled trial of prednisolone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei; Strang JI et al.; In Transkei, 143 patients with active tuberculous constrictive pericarditis without significant pericardial effusion all received the same daily 6-month antituberculosis regimen of streptomycin, isoniazid, rifampicin, and pyrazinamide for 14 weeks followed by isoniazid and rifampicin . They were randomly allocated to receive in addition either prednisolone or placebo for the first 11 weeks; the comparison was double-blind throughout treatment and follow-up . In the 114 patients assessable up to 24 months, improvement was significantly more rapid in the prednisolone group, as shown by the rate of fall in the mean pulse rate and the rate at which jugular venous pressure and level of physical activity became normal . During follow-up, 2 (4%) of the 53 prednisolone and 7 (11%) of the 61 placebo patients died from pericarditis, and 11 (21%) and 18 (30%), respectively, required pericardiectomy . By 24 months 50 (94%) prednisolone and 52 (85%) placebo patients had a favourable status . 3 patients (1 prednisolone, 2 placebo) were normally active but were classified as not having achieved a favourable status . It is recommended that, in the absence of a specific contraindication, antituberculosis chemotherapy should be initially supplemented by steroids.

Can J Microbiol, 1987 Dec, 33(12), 1064 - 8
Proficiency testing of conventional drug susceptibility tests of Mycobacterium tuberculosis; Laszlo A et al.; Proficiency testing of indirect drug susceptibility tests of Mycobacterium tuberculosis was begun in 1985 by the Laboratory Centre for Disease Control (LCDC) with the participation of Provincial Public Health Laboratories in Canada . Comparable sets of 60 cultures of Mycobacterium tuberculosis representing 30 strains were distributed by LCDC to the participating laboratories to be tested for drug susceptibility against isoniazid, streptomycin, rifampin, and ethambutol using conventional methodologies . Intralaboratory agreement values determined by comparing results obtained on sets of duplicate cultures were high and were found to vary little from drug to drug and from laboratory to laboratory . Interlaboratory agreement was determined by comparing results reported by participating laboratories to those obtained by the Reference Laboratory . Agreement percentages were found to be lower for drug-resistant cultures than for drug-susceptible cultures . The reliability of drug susceptibility testing results was higher for isoniazid and rifampin, than for ethambutol and streptomycin . This study shows that the higher subsidiary drug concentrations do not compare well with main drug concentrations, especially in the case of streptomycin and ethambutol . The significance of the higher subsidiary concentrations in in vitro susceptibility testing is therefore in need of clarification . The proficiency testing results obtained in this study compare favorably with those reported in other developed countries despite the fact that a variety of testing procedures are used throughout the country.

Mol Gen Mikrobiol Virusol, 1987 Dec, (12), 3 - 11
{Comparative analysis of the structure of incompatibility plasmids N, P and W}; Dobritsa AP et al.; Evolutionary relationships of the IncN plasmid R15 and other broad host range plasmids (IncN plasmids N3 and R46, IncP plasmids RP4 and R906, IncW plasmids Sa and R388) were studied by Southern blot hybridization technique . The IncN plasmids were shown to harbour homologous determinants for replication and conjugation . No homology was found between the rep and tra genes in R15 and in the IncW and IncP plasmids, respectively . The second rep region of the N3 plasmid is distinctive from the corresponding determinants in the IncN plasmids . Homology was demonstrated for the plasmid genes that mediate restriction and modification in R15 and N3, mercury resistance in R15 and R906, sulfanilamide resistance in R15, N3, R46, Sa, R388, and R906, streptomycin resistance in R15, R46 and Sa . The latter genes are different from the R906 SmR gene . In addition to the three known mobile elements in the plasmid R15, the fourth one (IS46) that is a part of the transposon Tn2353 was identified in this study . Besides, the third copy of this insertion sequence was found in the N3 plasmid.

Brain Res, 1987 Nov 3, 425(1), 120 - 7
Specific antagonism of excitotoxic action of 'uncommon' amino acids assayed in organotypic mouse cortical cultures; Ross SM et al.; Beta-N-Methylamino-L-alanine (BMAA) and beta-N-oxalylamino-L-alanine (BOAA) are chemically related excitant amino acids present in the seeds of Cycas circinalis and Lathyrus sativus, respectively . Consumption of these seeds has been linked to Guam amyotrophic lateral sclerosis (BMAA) and lathyrism (BOAA) (a form of primary lateral sclerosis) . We report that the acute neuronotoxic actions of these amino acids are blocked selectively by specific glutamate receptor antagonists . Administration of BOAA and BMAA to neonatal mouse cortex explants (EC100 = 28 microM and 1.6 mM, respectively) rapidly induces postsynaptic vacuolation (PSV) and neuronal degeneration characterized by dark/shrunken (D/S) cells . BOAA-mediated neuronotoxic effects are attenuated in a concentration-dependent manner by cis-2,3-piperidine dicarboxylic acid (PDA), an antagonist of quisqualate (QA)-preferring and kainate (KA)-preferring glutamate receptors . PDA maximally protected against BOAA-induced PSV by 84% at 1 mM and D/S cells by 80% at 0.5 mM . BMAA-induced cellular changes were antagonized selectively in a concentration-dependent manner by 2-amino-7-phosphono-heptanoic acid (AP7), an N-methyl-D-aspartate (NMDA) glutamate-receptor antagonist . AP7 maximally protected against BMAA-induced PSV and D/S by 88% at 1.0 and 0.5 mM, respectively . These protective actions were selective and specific since AP7 failed to attenuate BOAA-induced alterations, and PDA was ineffective in ameliorating BMAA-induced changes . Other glutamate receptor antagonists (glutamic diethyl ester and streptomycin) failed to protect the explants from the destructive action of either toxin . Taken collectively, our data indicate that the acute neuronotoxic actions of BOAA and BMAA (or a metabolite) operate through different glutamate receptor species.(ABSTRACT TRUNCATED AT 250 WORDS)

Thorax, 1987 Nov, 42(11), 838 - 42
Combined versus single antituberculosis drugs on the in vitro sensitivity patterns of non-tuberculous mycobacteria; Banks J et al.; Drug sensitivity tests were performed for ethambutol, rifampicin, streptomycin, and isoniazid both alone and in paired combinations, on 16 strains of Mycobacterium avium intracellulare, seven strains of Mycobacterium xenopi, and eight strains of Mycobacterium malmoense . Most strains were resistant to the individual drugs, but all strains of M malmoense, 86% of M xenopi, and 31% of M avium intracellulare were completely suppressed by the lowest concentrations of ethambutol and rifampicin when the two drugs were combined in vitro . Streptomycin combined with ethambutol or with rifampicin in the lowest combined concentrations suppressed 50% and 62% respectively of strains of M malmoense . All strains of M xenopi were suppressed by the lowest combined concentrations of streptomycin with rifampicin . Combinations with isoniazid were less effective . It is postulated that similar effects in vivo might account for the satisfactory clinical response seen in patients with disease caused by these mycobacteria who have received treatment with combinations of standard antituberculosis drugs despite in vitro resistance to the individual agents.

J Gen Microbiol, 1987 Nov, 133 ( Pt 11), 3151 - 8
The synthesis of heat-shock proteins after a decrease in translational capacity in Escherichia coli; Schnier J; Various conditions which decrease translational capacity and enhance the synthesis of ribosomal components were analysed with respect to the synthesis of heat-shock proteins in Escherichia coli: (a) deprivation of streptomycin from a streptomycin-dependent mutant, (b) addition of tetracycline to a partially tetracycline-resistant strain, and (c) nutritional shift-up conditions . In all cases, the rate of synthesis of the heat-shock proteins DnaK, GroEL and C62.5 decreased while the synthesis of ribosomal components increased . Thus inhibition of ribosome formation or a decrease in translational capacity do not induce the stress proteins, but have the opposite effect.

Plasmid, 1987 Nov, 18(3), 246 - 9
Relationships among the streptothricin resistance transposons Tn1825 and Tn1826 and the trimethoprim resistance transposon Tn7; Tietze E et al.; The streptothricin resistance transposons Tn1825 and Tn1826 are closely related, based on physical and genetic characteristics, to the trimethoprim resistance transposon Tn7 . These transposons may be considered to be members of a transposon family sharing in common the transposition functions and a basic streptomycin/spectinomycin resistance determinant but differing from one another with respect to particular additional resistance genes inserted to the left of the aadA gene.

Nucleic Acids Res, 1987 Oct 12, 15(19), 8041 - 56
Gene cluster for streptomycin biosynthesis in Streptomyces griseus: nucleotide sequence of three genes and analysis of transcriptional activity; Distler J et al.; Three streptomycin (SM) production genes from Streptomyces griseus clustered around aphD, the major resistance gene, have been sequenced: strB, coding for an aminocyclitol amidinotransferase, ORF5 (strR), a putative regulatory gene, and ORF1 (strD), possibly coding for a hexose nucleotidylating enzyme . Three promoters and at least five, partially overlapping, transcripts have been identified by S1 mapping and Northern blot experiments . aphD, the resistance gene, is transcribed from two promoters . One of them, located inside the strR gene, seems to be constitutive and the other is switched on later in the growth phase . The late transcripts cover the resistance gene (aphD) and a regulatory gene (strR) which controls the expression of strB.

Eur J Clin Microbiol, 1987 Oct, 6(5), 530 - 5
Synergistic effects of antimycobacterial drug combinations on Mycobacterium avium complex determined radiometrically in liquid medium; Hoffner SE et al.; A technique to determine the effects of combining antimycobacterial drugs in liquid medium employing the radiometric growth readings in the Bactec system was tested using 20 Mycobacterium avium complex strains . Ten of the strains had been isolated from children with lymphadenopathy and ten from adults with pulmonary disease . All isolates were resistant to streptomycin, rifampicin, isoniazid and ethambutol when tested with a conventional resistant ratio technique on Lowenstein-Jensen medium . Synergistic interactions were shown for the two-drug combinations streptomycin + ethambutol and ethambutol + rifampicin against all 20 strains . Good efficacy was also found for all three-drug combinations containing ethambutol . Thus, although most isolates of the Mycobacterium avium complex are resistant to first-line antituberculous drugs when tested individually, they are susceptible in vitro to certain combinations of these drugs . This rapid radiometric assay is an efficient means for detecting such synergy.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Oct, 266(3-4), 359 - 69
Comparison of ribosomes and ribosomal proteins of sensitive and resistant mycobacteria; Medow I et al.; Ribosomal proteins from Mycobacterium tuberculosis H37 Rv were analyzed by polyacrylamide gel electrophoresis and 73 proteins were separated . The 30S subunit consists of 26 proteins, the 50S subunit of 41 proteins, 6 proteins of the ribosomes could not be shown in the subunits . The molecular weights for the proteins of the 30S subunit are 9100-43500, and for the proteins of the 50S subunit 8000-46000 . The sedimentation coefficient have values of 28.8S and 47.7S . It was demonstrated that streptomycin-resistant cells in comparison to sensitive cells have two additional 30S proteins . Moreover, the protein L34 has changed its position . Kanamycin- and capreomycin-resistant cells have also two additional proteins, but viomycin shows no changes.

Vet Microbiol, 1987 Oct, 15(1-2), 97 - 104
Probable transmission between animals of a plasmid encoding aminoglycoside 3-N-acetyltransferase IV and dihydrofolate reductase I; Chaslus-Dancla E et al.; Ten aminoglycoside-resistant Escherichia coli isolated from the faeces of healthy or diarrhoeic animals reared in the same herd were studied . These strains were resistant to high levels of apramycin and low levels of gentamicin . They were also resistant to streptomycin, tetracycline, trimethoprim and some to ampicillin, chloramphenicol, kanamycin or nalidixic acid . Two strains, isolated from a calf and a lamb, respectively, belonged to the same biotype . All the transconjugants resistant to gentamicin-apramycin were also resistant to streptomycin, tetracycline and trimethoprim . In all cases, these resistances were encoded by plasmids of 100 kb . Analysis of these plasmids by agarose gel electrophoresis after digestion by EcoRI or BamHI revealed their similarity . Hybridization with a 500-bp HpaI insert of plasmid pFE872 was observed with DNA from field strains and their transconjugants, demonstrating the presence on the 100-kb plasmids of the gene coding for a dihydrofolate reductase I . A single plasmid, designated pIP1831, could be observed in identical or different strains isolated from calves or lambs, suggesting the transmission of strains and plasmids between animals of different species.

Fortschr Neurol Psychiatr, 1987 Oct, 55(10), 291 - 3
{Primary chronic neurobrucellosis}; Omasits M et al.; Brucellosis involving the nervous system usually shows meningomyelitis and/or radiculoneuritis and can by their clinical appearance not be differentiated from other chronic proliferative diseases of the nervous system . Sporadic cases can only be suspected on clinical grounds if a previous exposition is known . The cerebrospinal fluid showing a proliferative or granulomatous cytological picture is strongly suggestive of the diagnosis, which is confirmed by two rising titer values in the complement binding reaction for Brucella-specific antigen . The agglutination method of Widal is not reliable due to blocking incomplete antibodies . A 46 year-old man developed a transverse myelitis within several months accompanied by fluctuating meningeal signs, segmental irritation and transient cranial nerve palsies . No involvement of other organs and no general symptoms of infectious diseases were seen throughout the clinical course . Most importantly, starting treatment as early as possible is decisive for the outcome using a combination of streptomycin, sulfonamides, gentamycin, rifampicin and tetracyclines.

Biochemistry, 1987 Sep 22, 26(19), 6227 - 32
Cross-linking of streptomycin to the 16S ribosomal RNA of Escherichia coli; Gravel M et al.; {3H}Dihydrostreptomycin was cross-linked to the 30S ribosomal subunit from Escherichia coli with the bifunctional reagent nitrogen mustard . The cross-linking primarily involved the 16S RNA . To localize the site of cross-linking of streptomycin to the 16S RNA, we hybridized RNA labeled with streptomycin to restriction fragments of the 16S RNA gene . Labeled RNA hybridized to DNA fragments corresponding to bases 892-917 and bases 1394-1415 . These two segments of the ribosomal RNA must be juxtaposed in the ribosome, since there is a single binding site for streptomycin . This region has been implicated both in the decoding site and in the binding of initiation factor IF-3, indicating its functional importance.

Ukr Biokhim Zh, 1987 Sep-Oct, 59(5), 90 - 3
{Changes in the fatty acid composition of pulmonary surfactant phospholipids after administration of antitubercular agents}; Protsiuk RG et al.; The prolonged inhalations of streptomycin sulphate and isoniazid in experiments on rats decrease the content of unsaturated fatty acids and increase that of saturated ones in the phospholipids composition of lungs surfactants.

Am Rev Respir Dis, 1987 Aug, 136(2), 325 - 8
The influence of epidemiologic factors on drug resistance rates in tuberculosis; Barnes PF; We evaluated the relationship between drug resistance rates and various epidemiologic factors in 376 hospitalized adults with culture-proved tuberculosis, studying 356 cases prospectively, 20 retrospectively . The patient was interviewed in 332 cases . Patients born in the United States, Canada, or Europe were considered to belong to Group I . Group II consisted of patients born in Latin America, Asia, or Africa and was subdivided into II(a), immigrants living in the United States for more than 10 yr, and II(b), those living here less than 10 yr . Of the 70 patients who had received antituberculosis therapy in the past, resistance rates in Group II (n = 31) to isoniazid (INH), streptomycin (SM), and rifampin (RIF) were extremely high: 39, 29, and 19%, respectively . Nineteen percent showed resistance to both INH and RIF . In Group I (n = 39), INH, SM, and RIF resistance rates were 8, 5, and 8%, respectively . Of 283 patients who gave no history of prior antituberculosis therapy, those in Groups I and II(a) (n = 170) rarely showed INH or RIF resistance . Among recent immigrants from Latin America or Asia {Group II(b), n = 113}, 11.5% showed INH or RIF resistance and 14% harbored organisms resistant to SM . Thus, the 3 variables that are most helpful in estimating the likelihood of drug resistance are a history of prior antituberculosis therapy, country of origin, and duration of residence in the United States.

J Bacteriol, 1987 Aug, 169(8), 3608 - 16
Metabolic initiation of differentiation and secondary metabolism by Streptomyces griseus: significance of the stringent response (ppGpp) and GTP content in relation to A factor; Ochi K; I investigated the significance of the intracellular accumulation of guanosine 5'-diphosphate 3'-diphosphate (ppGpp) and of the coordinated decrease in the GTP pool for initiating morphological and physiological differentiation of Streptomyces griseus, a streptomycin-producing strain . In solid cultures, aerial mycelium formation was severely suppressed by the presence of excess nutrients . However, decoyinine, a specific inhibitor of GMP synthetase, enabled the cells to develop aerial mycelia in the suppressed cultures at concentrations which only partially inhibited growth . A factor (2S-isocapryloyl-3S-hydroxymethyl-gamma-butyrolactone) added exogenously had no such effect . Decoyinine was also effective in initiating the formation of submerged spores in liquid culture . The ability to produce streptomycin did not increase but decreased drastically on the addition of decoyinine . This sharp decrease in streptomycin production was accompanied by a decrease in intracellular accumulation of ppGpp . A relaxed (rel) mutant was found among 25 thiopeptin-resistant isolates which developed spontaneously . The rel mutant had a severely reduced ability to accumulate ppGpp during a nutritional shift-down and also during postexponential growth and showed a less extensive decrease in the GTP pool than that in the rel+ parental strain . The rel mutant failed to induce the enzymes amidinotransferase and streptomycin kinase, which are essential for the biosynthesis of streptomycin . The abilities to form aerial mycelia and submerged spores were still retained, but the amounts were less, and for both the onset of development was markedly delayed . The decreased ability to produced submerged spores was largely restored by the addition of decoyinine . This was accompanied by an extensive GTP pool decrease . The rel mutant produced A factor normally, indicating that synthesis of A factor is controlled neither by ppGpp nor by GTP . Conversely, a mutant defective in A-factor synthesis accumulated as much ppGpp as did the parental strain . It was concluded that morphological differentiation of S . griseus results from a decrease in the pool of GTP, whereas physiological differentiation results from a more direct function of the rel gene product (ppGpp) . It is also suggested that A factor may render the cell sensitive to receive and respond to the specified signal molecules, presumably ppGpp (for physiological differentiation) or GTP (for morphological differentiation).

J Bacteriol, 1987 Aug, 169(8), 3400 - 8
Isolation and characterization of a new globomycin-resistant dnaE mutant of Escherichia coli; Sakka K et al.; We isolated a globomycin-resistant, temperature-sensitive mutant of Escherichia coli K-12 strain AB1157 . The mutation mapped in dnaE, the structural gene for the alpha-subunit of DNA polymerase III . The in vivo processing of lipid-modified prolipoprotein was more resistant to globomycin in the mutant strain 307 than in its parent . The prolipoprotein signal peptidase activity was also increased twofold in the mutant, and there was a threefold increase in the activity of isoleucyl-tRNA synthetase . The results suggest that a mutation in dnaE may affect the expression of the ileS-lsp operon in E . coli . In addition, strain 307 showed a reduced level of streptomycin resistance compared with its parental strain AB1157 (rpsL31) . Strain 307 was killed by streptomycin at a concentration of 200 micrograms/ml, which did not affect the rate of bulk protein synthesis in this mutant . A second mutation which was involved in the reduced streptomycin resistance in strain 307 was identified and found to be closely linked to or within the rpsD (ramA, ribosomal ambiguity) gene . Both dnaE and rpsD were required for the reduced streptomycin resistance in strain 307.

J Pharm Pharmacol, 1987 Aug, 39(8), 577 - 82
A comparative investigation of glycinebetaine and dimethylsulphoxide as liposome cryoprotectants; Higgins J et al.; The release of streptomycin from lecithin liposomes following a freeze-thaw cycle was used to measure the cryoprotective activities of glycinebetaine and dimethylsulphoxide (DMSO) . At concentrations between 4 and 8% w/v in the external solution, glycinebetaine was superior to DMSO at freezing rates faster than 50 degrees C min-1 . At lower rates their activities were similar, and drug loss ranged between 10 and 20% depending upon freezing rate and cryoprotectant concentration . The pattern of streptomycin loss when the concentrations of cryoprotectants inside and outside the liposome were varied indicated that glycinebetaine, in contrast to DMSO, does not diffuse across the liposome membrane . The activity of glycinebetaine was not impaired by the presence in the membrane of cholesterol or charged lipids.

Proc Natl Acad Sci U S A, 1987 Aug, 84(15), 5163 - 6
Active transport of messenger ribonucleoprotein particles in a reconstituted cell-free system; French BT et al.; The ability of a reconstituted cell-free system to transport mRNA as a ribonucleoprotein particle has been examined . Poly(A) messenger ribonucleoproteins (mRNPs), UV cross-linked after release from isolated liver nuclei in a cell-free system, exhibited a buoyant density of 1.33 g/cm3 in cesium sulfate and 1.47 g/cm3 in cesium chloride, values identical to those of poly(A) mRNP isolated directly from liver polysomes . Furthermore, the in vivo and in vitro transported mRNP showed a similar degree of resistance to RNase digestion and had sedimentation coefficients approximately 2.5 times that of the isolated mRNA . Release of both total mRNA and alpha 2 mu-globulin mRNA was proportional to the concentration of a specific cytoplasmic protein . Removal of the transport proteins from the cytosol with streptomycin sulfate provided a basal system incapable of supporting the active transport of alpha 2 mu-globulin mRNA . Hybridization of released RNA with a recombinant probe specific for intron 6 of alpha 2 mu-globulin showed that intron sequences were retained within the nucleus under optimal alpha 2 mu-globulin mRNA transport conditions and that the transported alpha 2 mu-globulin mRNA was of mature size.

Postgrad Med J, 1987 Jul, 63(741), 539 - 42
Abdominal tuberculosis in East Birmingham--a 16 year study; Sharp JF et al.; Abdominal tuberculosis, although rare, occurs mainly in immigrants from the Indian subcontinent . Such people comprise 13.5% of our local population and contributed 90% of a series of 72 patients presenting in the last 16 years; a local disease incidence of 1:6000 for Asian immigrants . Men and women were equally affected, but on average women were much younger . Diagnosis was made from one month to 10 years after immigration . No clinical feature was diagnostic, but abdominal pain, night sweats and weight loss occurred in more than half the patients . The erythrocyte sedimentation rate (ESR) was elevated in 95% and no patient tested had a negative Mantoux test . In 20 patients diagnosis was by clinical suspicion and response to therapeutic trial . In 52, including 39 who had a laparotomy, histological and culture material was obtained but these patients fared no better . Only one organism was resistant (to streptomycin) and rapid response to chemotherapy was the rule . Successful outcome was not related to the type of presentation, operative findings or specific chemotherapeutic agents . We would suggest that in Asians presenting with difficult-to-diagnose abdominal symptoms accompanied by malaise, raised ESR and a positive Mantoux test, a therapeutic trial of anti-tuberculous therapy should precede diagnostic laparotomy.

Rev Infect Dis, 1987 Jul-Aug, 9(4), 810 - 22
Brucellar meningitis; Bouza E et al.; Neurobrucellosis develops in less than 5% of cases of systemic brucellosis; however, most patients with neurobrucellosis have meningeal involvement . Seven new cases of brucellar meningitis and 17 cases from the Spanish- and English-language medical literature are analyzed in terms of epidemiologic data, clinical manifestations, laboratory results for cerebrospinal fluid and serum, treatment, and course of the disease . Brucellar meningitis mimics other neurologic and non-neurologic conditions, and its diagnosis is only suggested in the presence of adequate epidemiologic information . Isolation of Brucella from the cerebrospinal fluid is uncommon . Treatment is accomplished with the combination of tetracycline or doxycycline and streptomycin, rifampin, or both . Mean length of therapy in the seven new cases was 8.5 months . Brucellar meningitis has a better prognosis than other forms of chronic meningitis, and mortality is low for reasons that are not clear; however, the incidence of minor sequelae is high.

Mol Gen Genet, 1987 Jul, 208(3), 373 - 6
Effects of miaA on translation and growth rates; Diaz I et al.; We have measured the growth rates and elongation rates for different proteins in wild-type, miaA, rpsL, and miaA, rpsL double mutants of Escherichia coli in the presence as well as the absence of streptomycin . The data show that while miaA and rpsL mutants inhibit elongation rates to equivalent levels, miaA inhibits the growth rate twice as effectively as does rpsL . The double mutant is more effectively inhibited than either single mutant and Sm repairs in part the growth rate as well as protein elongation rates . The data suggest that the conditional streptomycin-dependent phenotype of the double mutant cannot be due simply to the depressed polypeptide elongation rates of the double mutant.

J Bacteriol, 1987 Jun, 169(6), 2548 - 54
Bradyrhizobium japonicum mutants defective in nitrogen fixation and molybdenum metabolism; Maier RJ et al.; Bradyrhizobium japonicum JH mutants deficient in molybdenum metabolism into the enzymes nitrogenase and nitrate reductase were isolated by using the vector pSUP1011, which carries transposon Tn5 (streptomycin and kanamycin resistance) . Mutants in Mo metabolism were obtained at a frequency of 3.6 X 10(-3) (per Kan Strr colony) . The mutants were detected by their poor ability to grow in nitrate-containing medium without added Mo . One of the mutant types required 10(5) times more molybdate than the wild type to obtain maximal nitrogen fixation activity . Double-reciprocal plots of Mo uptake versus concentration indicated that the wild-type strain had a high- and a lower-affinity component for Mo binding . Mutant strains JH-90 and JH-119 lacked the high-affinity Mo uptake component and were also clearly deficient in Mo accumulation into a nonexchangeable form . Nitrogenase activity as well as Mo uptake ability could be restored in strains JH-90 and JH-119 by the addition of the sterile supernatant fraction of the wild type . Therefore, mutant strains JH-90 and JH-119 appeared to be deficient in an extracellular Mo-binding factor produced by the wild type . Mutant strains JH-14 and JH-143 had Mo uptake kinetics like those of the wild type (both high- and low-affinity binding for Mo) and appeared to be deficient in intracellular Mo metabolism processes . The addition of the wild-type supernatant did not restore Mo uptake or nitrogenase activity in these strains.

Mol Gen Genet, 1987 Jun, 208(1-2), 195 - 203
Characterisation of the hydroxystreptomycin phosphotransferase gene (sph) of Streptomyces glaucescens: nucleotide sequence and promoter analysis; Vogtli M et al.; The nucleotide sequence of a 1384 bp fragment containing the coding and promoter sequences of the streptomycin phosphotransferase gene (sph) of the hydroxystreptomycin-producing Streptomyces glaucescens was determined . Evidence for an ATG as translation start codon for sph was derived from a comparison with the amino-terminal amino acid sequence of an aminoglycoside phosphotransferase (aphD gene product) of S . griseus, exhibiting a high degree of amino acid homology to the deduced amino acid sequence of the S . glaucescens sph gene product . Transcriptional start and termination sites for the sph gene were identified by primer extension and/or nuclease S1 mapping experiments . The promoter region of the sph gene appears to be complex since tandemly arranged promoters (orfIp1, orfIp2) initiating transcription of a likely coding region (ORFI) in the opposite direction overlap sph promoter sequences . The presumptive sphp and orfIp1 promoters show considerable sequence similarities in the -10 region to Escherichia coli consensus promoter sequences but no homology to E . coli or Streptomyces -35 regions.

J Biol Chem, 1987 May 5, 262(13), 6149 - 54
Drug-induced Ca2+ release from isolated sarcoplasmic reticulum . III . Block of Ca2+-induced Ca2+ release by organic polyamines; Palade P; Calcium ions that have been preloaded into isolated SR subfractions in the presence of ATP and pyrophosphate may be released upon addition of a large number of diverse pharmacologic substances in a manner that is effectively blocked by ruthenium red and other organic polyamines . Effective blocking substances include certain antibiotics (neomycin, gentamicin, streptomycin, clindamycin, kanamycin, and tobramycin), naturally occurring polyamines (spermine and spermidine), and a number of basic polypeptides and proteins (polylysine, polyarginine, certain histones, and protamine) . These agents have only one feature in common: the presence of several amino groups . Ruthenium red, neomycin, spermine, and protamine all appear to act by blocking SR Ca2+ channels since unidirectional 45Ca2+ efflux from the vesicles is strongly inhibited by these agents . Functions ascribable to the SR Ca2+ pump are largely unaffected by these agents . Since inositol 1,4,5-trisphosphate is ineffective at inducing Ca2+ release under these conditions, we conclude that these polyamines may directly block SR Ca2+ channels at very low concentrations by a mechanism unrelated to effects on inositol 1,4,5-trisphosphate production.

Rev Infect Dis, 1987 May-Jun, 9(3), 531 - 43
Osteoarticular complications of brucellosis: a study of 169 cases; Mousa AR et al.; Of 452 patients with brucellosis, 169 (111 male and 58 female) had osteoarticular complications . Brucella melitensis was isolated from the blood in 7.7% of the cases . Fever, chills, arthralgia, backache, high levels of C-reactive protein, positive rheumatoid factor, and splenomegaly were more frequent in osteoarticular brucellosis than in nonosteoarticular disease . Arthritis occurred in the hip joint in 90 cases (53%), knees in 61 (36%), sacroiliacs in 33 (20%), ankles in 25 (15%), elbows in nine (5.3%), shoulders in eight (5%), wrists in six (3.5%), and sternoclavicular arthritis occurred in three cases (1.8%) . Spondylitis occurred in 10 cases (6%), osteomyelitis in four (2.4%), and tendinitis or bursitis in two (1.2%) . Treatment with tetracycline or trimethoprim-sulfamethoxazole (TMP-SMZ) alone (four to eight weeks) or in combination with streptomycin (two to four weeks) resulted in a relapse rate of 16.6% . No relapses occurred in seven patients treated with repeated four- to six-weeks courses of rifampin plus tetracycline or TMP-SMZ plus streptomycin.

J Antibiot (Tokyo), 1987 May, 40(5), 685 - 91
Biological activity of nitroguaiacol ether derivatives of streptomycin; Abad JP et al.; The correlation between the "in vivo" and "in vitro" inhibitory properties of six nitroguaiacol ether derivatives of streptomycin is studied . The differential activity of the derivatives is more closely related to differences in efficiency in the transport of the drugs than to their capacity to inhibit poly(U) directed polyphenylalanine synthesis . The results obtained are discussed in relation to the characteristics of the different derivatives.

J Pharmacol Exp Ther, 1987 May, 241(2), 686 - 94
Potentiation of aminoglycoside-induced neuromuscular blockade by protons in vitro and in vivo; Talbot PA; pH-dependent effects of 100 microM streptomycin and various aminoglycosides were examined at frog (Rana pipiens pipiens) sciatic sartorii in vitro by using the intracellular microelectrode recording technique . pH-dependent effects of streptomycin were also examined on indirectly elicited (nerve-stimulated) and directly elicited sartorius muscle twitches in vitro . Furthermore, in vivo effects of systemic pH alterations on neomycin-induced mortality were examined in Sprague-Dawley rats . There was a direct correlation between aminoglycoside potency and the number of basic groups per drug molecule (r = 0.95) . At pH 7.2 and 9.0, the effect of pH on aminoglycoside potency correlated inversely with the pKa of the aminoglycoside (r = -0.98) . At 0.7 and 2.2 pH units below 7.2, however, aminoglycoside-induced inhibitions of quantal content, end-plate potential amplitude and the indirectly elicited muscle twitch were potentiated by a pH-dependent mechanism that was independent of the pKa of the aminoglycoside . At these pH values, qualitatively similar drug effects were not observed on miniature end-plate potential amplitude and frequency or the directly elicited muscle twitch . Potentiation of aminoglycoside action was observed on mortality of rats, however, when the pH was 0.1 pH unit below 7.4 . Thus, potentiation of aminoglycoside-induced neuromuscular blockade by protons in vitro and in vivo was demonstrated and appears to involve the pH-dependent activity of a prejunctional membrane component that regulates voltage-dependent, Ca++-mediated transmitter release.

J Gen Microbiol, 1987 May, 133 ( Pt 5), 1289 - 96
The nucleotide sequence of a streptomycin streptomycin phosphotransferase (streptomycin kinase) {corrected} gene from a streptomycin producer; Shinkawa H et al.; The nucleotide sequence of the DNA fragment containing the streptomycin phosphotransferase (streptomycin kinase) {corrected} gene from the streptomycin-producer Streptomyces griseus strain HUT 6037 was determined . Analysis of the sequence revealed an open reading frame which could encode 325 amino acid residues . A biased codon usage pattern, reflecting the high G + C composition (approximately 74%) of Streptomyces DNA, was observed in the gene.

Anal Biochem, 1987 Apr, 162(1), 219 - 23
Fluorometric determination of streptomycin in serum by high-performance liquid chromatography using mobile phase containing fluorogenic reagent; Kubo H et al.; A new postcolumn derivatization method for the fluorometric determination of streptomycin in serum by high-performance liquid chromatography is described . The serum was treated with 3.5% perchloric acid to precipitate proteins and the supernatant was directly injected into the chromatograph . Streptomycin was separated by reversed-phase, ion-pair chromatography with a mobile phase containing ninhydrin as a fluorogenic reagent, octanesulfonate, and 1,2-ethanedisulfonate as counterions, and was detected by fluorescence using continuous-flow, postcolumn derivatization in an alkaline stream with ninhydrin in the mobile phase . This method is sensitive to 1.0 microgram/ml using only 100 microliter of serum . Comparison with a fluorescence polarization immunoassay gave a good correlation coefficient of 0.976.

Mikrobiyol Bul, 1987 Apr, 21(2), 110 - 6
{Brucellosis: clinical and laboratory findings and treatment in 40 patients}; Colak H; Forty patients with brucellosis were hospitalized and clinical and laboratory findings of patients were recorded, treatment regimens were discussed . Twenty-five of the patients were males and 15 of the patients were females . Leukopenia 21.62%, anemia 27.02% and ESR elevation 83.87% were found . Fever and exhaustion were present all of the patients . Arthralgia, nonproductive cough, gastrointestinal symptoms, headache and night sweating were the other common symptoms . Hepatomegaly, splenomegaly, hepatosplenomegaly and ronchus were imported physical examination findings . First choice treatment solution was tetracycline-streptomycin combination and this combination succeed 89.19 in percent . Relapses were treated with rifampicin.

Mol Gen Genet, 1987 Apr, 207(1), 15 - 23
Transposon-induced symbiotic mutants of Bradyrhizobium japonicum: isolation of two gene regions essential for nodulation; So JS et al.; Two strains of the soybean endosymbiont Bradyrhizobium japonicum, USDA 110 and 61 A101 C, were mutagenized with transposon Tn5 . After plant infection tests of a total of 6,926 kanamycin and streptomycin resistant transconjugants, 25 mutants were identified that are defective in nodule formation (Nod-) or nitrogen fixation (Fix-) . Seven Nod- mutants were isolated from strain USDA110 and from strain 61 A101 C, 4 Nod- mutants and 14 Fix- mutants were identified . Subsequent auxotrophic tests on these symbiotically defective mutants identified 4 His- Nod- mutants of USDA110 . Genomic Southern analysis of the 25 mutants revealed that each of them carried a single copy of Tn5 integrated in the genome . Three 61 A101 C Fix- mutants were found to have vector DNA co-integrated along with Tn5 in the genome . Two independent DNA regions flanking Tn5 were cloned from the three non-auxotrophic Nod- mutants and one His-Nod- mutant of USDA110 . Homogenotization of the cloned fragments into wild-type strain USDA110 and subsequent nodulation assay of the resulting homogenotes confirmed that the Tn5 insertion was responsible for the Nod- phenotype . Partial EcoR1 restriction enzyme maps around the Tn5 insertion sites were generated . Hybridization of these cloned regions to the previously cloned nod regions of R . meliloti and nif and nod regions of B . japonicum USDA110 showed no homology, suggesting that these regions represent new symbiotic clusters of B . japonicum.

Br J Ophthalmol, 1987 Mar, 71(3), 192 - 6
Use of contrast sensitivity measurement in the detection of subclinical ethambutol toxic optic neuropathy; Salmon JF et al.; Contrast sensitivity was measured by means of Arden grating plates in 100 patients on medication for pulmonary tuberculosis . The scores were abnormal in 38.2% of the patients whose therapy included ethambutol for three months, and 36.7% of the patients on similar treatment for six months . In comparison with age matched groups of patients on a regimen where streptomycin replaced ethambutol a statistically significant number of the patients on ethambutol had abnormal scores . This study suggests that Arden contrast sensitivity plates would be effective in detecting subclinical toxic optic neuropathy due to ethambutol and therefore could be used for routine monitoring of ocular function of patients on ethambutol . Loss of contrast sensitivity may explain why some patients on ethambutol with normal visual acuity and colour perception may still complain of visual disturbance.

Mutat Res, 1987 Mar, 183(2), 169 - 75
General characteristics, molecular and genetic analysis of two new UV-sensitive mutants of Chlamydomonas reinhardtii; Vlcek D et al.; Two new UV-sensitive mutants of Chlamydomonas, UVS10 and UVS11, were isolated . Both behave as single nuclear mutations . UVS10 was mapped to linkage group I . UVS11 is a separate, unlinked mutation but has not yet been located to a specific linkage group . Both mutants are proficient in the excision of pyrimidine dimers from nuclear DNA . The survival of UV-irradiated UVS11 is increased when plated in the presence of 1.5 mM caffeine, similar to wild-type . Caffeine has no effect on the survival of UV-irradiated UVS10 . UV-irradiated UVS11 frequently divides at least once before dying, in contrast to UVS10 or wild-type . UVS11 also exhibits a much increased frequency of mutation to streptomycin resistance after UV irradiation.

Q J Med, 1987 Mar, 62(239), 249 - 58
Treatment of tuberculous meningitis: role of short-course chemotherapy; Phuapradit P et al.; Twenty-eight adult patients admitted consecutively with tuberculous meningitis were treated with pyrazinamide, isoniazid, rifampicin and streptomycin daily during the first two months, followed by isoniazid and rifampicin daily for seven months with intensive management of the complications during the active stage of the meningitis . Twenty-two patients completed the course of treatment and recovered with minimal morbidity in three patients . Two patients died in a vegetative state from other causes seven and nine months after the start of treatment . No evidence of recurrence of meningitis was observed in the 21 patients who were regularly observed for 12 to 29 months after completing treatment . Four patients dropped out during the early stage of treatment . Intensive chemotherapy of tuberculous meningitis with this regimen before the development of serious neurological damage can shorten the duration of treatment to nine months with a favourable outcome.

Early Hum Dev, 1987 Mar, 15(2), 61 - 74
Teratology of the antituberculosis drugs; Holdiness MR; The teratogenic effects of twelve antituberculosis drugs in animal models and man are reviewed . A number of congenital malformations have been associated with the use of these agents; however, for the most part, the birth defect rate is not above that expected for the normal population . Isoniazid and ethambutol are considered the safest for maternal use . Although rifampicin appears to be more problematic, if the disease is severe or extensive, it may be added, preferably after the first trimester . Streptomycin and kanamycin are associated with eighth cranial nerve damage and should be avoided if possible during cyesis . At least five of these compounds have documented evidence of transplacental passage . In consideration of the number of drugs that are available for treatment, routine therapeutic abortions in pregnant females with tuberculosis is not medically indicated.

Otolaryngol Head Neck Surg, 1987 Mar, 96(3), 256 - 9
Streptomycin treatment in Menière's disease; Moretz WH Jr et al.; Streptomycin treatment in Meniere's disease has traditionally been used for control of vertigo in patients with severe bilateral involvement or unilateral involvement in the only hearing ear . Guidelines for use that have worked at the Shea Clinic are presented . In addition, a special case is discussed in which this form of therapy has been used for treatment of fluctuant hearing loss in a patient with Meniere's disease.

Nucleic Acids Res, 1987 Feb 25, 15(4), 1819 - 33
Nucleotide sequence of the streptomycinphosphotransferase and amidinotransferase genes from Streptomyces griseus; Tohyama H et al.; Genes for streptomycin phosphotransferase and inosamine-P-amidinotransferase from a streptomycin-producing Streptomyces griseus were cloned on a 3.8kb BamHI-SphI fragment in S . lividans using the multicopy cloning vector pIJ702 . The nucleotide sequence of this 3.8kb fragment was determined and the coding sequences for the two genes were identified by comparison with the amino-terminal sequences of the two enzymes purified from S . lividans clones.

Neurochem Res, 1987 Feb, 12(2), 179 - 88
Translational regulation in rat brain hemispheres; Tewari S et al.; Present studies on the sensitivity of the transcription process in rat cerebral hemispheres showed that the relative abundance and translation of free and bound poly (A)+ mRNAs in a reticulocyte mRNA-dependent system were reduced following 1 h and 4 h of ethanol or pentobarbital administration with free being affected to a greater extent than the bound poly (A)+ mRNAs . In addition, the energy-dependent nucleocytoplasmic transport of in vivo {3H}labeled nuclear RNA to surrogate cytoplasm was modified in response to ethanol exposure . The translocation of the labeled nuclear RNA fraction occurred only to the microsomal/ribosomal fractions of the cytoplasm, was stimulated by cyclic cAMP and abolished when the cytoplasm was depleted of its protein factors following streptomycin treatment, thereby establishing the translocated RNA as messenger RNA . It is concluded that the neural cell, in response to ethanol exposure, modifies the efficiency of nuclear processing and transport of mRNA . This nuclear restriction probably occurs at multi-levels during the post-transcriptional modification of mRNAs.

Vet Res Commun, 1987, 11(4), 353 - 8
Pharmacokinetics of streptomycin with particular reference to its distribution in plasma, milk and uterine fluid of she-buffaloes; Jayachandran C et al.; The study elucidated the pharmacokinetics of streptomycin in healthy lactating she-buffaloes after a single intramuscular (IM) injection (10 mg/kg) . The drug attained its peak concentrations of 24.39 +/- 2.67, 0.45 +/- 0.05 and 5.06 +/- 0.18 micrograms/ml at 1, 4 and 1 hour in plasma, milk and uterine fluid respectively . Calculations based on the assumption of a 2-compartment model gave a plasma t1/2 (beta) of 4.01 +/- 0.44 h and an apparent volume of distribution {Vd(area)} of 0.47 +/- 0.06 1/kg . The drug was detectable in the plasma, milk and uterine fluid for 30, 8 and 12 hours, respectively . A therapeutic concentration of the drug was maintained for 6 to 7 hours in the plasma and for around 1 hour only in the uterine fluid . However, a therapeutic level could not be achieved in milk at any time . The results suggest that the drug can be used clinically by the IM route against streptomycin susceptible systemic infections but not those in the uterus and mammary gland.

Ter Arkh, 1987, 59(7), 75 - 7
{Pharmacokinetic bases for the drug-free prevention of drug-induced hepatitis in pulmonary tuberculosis patients}; Koriakin VA et al.; The causes and frequency of occurrence of toxic hepatitides determined by isoniazid and rifampicin, were analysed in 551 patients with primary tuberculosis detected by clinical pharmacological methods . The intravenous mode of drug administration was shown to be indicated for prevention of isoniazid hepatitides in patients with a fast type of acetylation . Doses and methods of therapy with isoniazid and streptomycin leading to their high concentrations in the patients' body should be avoided to prevent liver affection with rifampicin . Since rifampicin hepatitides develop in persons with a slow type of acetylation, rifampicin and isoniazid with streptomycin should be injected with a 6-hour interval to prevent them.

Nephron, 1987, 46(4), 373 - 6
Rapidly progressive glomerulonephritis associated with rifampicin therapy for pulmonary tuberculosis; Murray AN et al.; Two months after commencing continuous treatment with rifampicin, isoniazid, streptomycin and pyrazinamide for pulmonary tuberculosis a patient developed a nephrotic syndrome, acute nonoliguric renal failure and evidence of intravascular hemolysis . Renal biopsy revealed a severe crescentic nephritis with mild interstitial changes . The use of rifampicin has been associated with various renal abnormalities and this report documents the occurrence of a rapidly progressive crescentic glomerulonephritis presenting as nephrotic syndrome in a patient receiving continuous treatment with rifampicin.

Pediatr Med Chir, 1987 Jan-Feb, 9(1), 57 - 61
{Osteomyelitis caused by atypical mycobacteria in multiple colonies}; Zammarchi E et al.; The authors describe a seven months and a half little girl, A.B., affected by multiple localization osteomyelitis caused by an Atypical Mycobacterium, with the culture identifies as M . Avium, belonging to the third group of Runjon classification . The radiographic tests show a primary pulmonary complex and some osteolytic areas of the seventh right rib and of the bones of the lower legs (femur and tibia) . From the beginning a multiple antituberculous chemotherapy against non tuberculous mycobacterial disease has initiated: Streptomycin (for two months) associated with Rifampicin, Isoniazid and Pyridoxine . The patient responds very slowly to the treatment and only three years later the whole radiologic regression of the lesions occurs . The interest of the case comes from the extreme rarity of disseminated bone localization during an atypical mycobacterial infection, and also from the early beginning of the clinical and radiologic manifestations.

Audiology, 1987, 26(2), 103 - 10
Diagnostic value of extratympanic electrocochleography in Menière's disease; Mori N et al.; In order to examine the usefulness of the noninvasive extratympanic electrocochleography (ECochG) in the diagnosis of Meniere's disease, the results of extratympanic ECochG, performed on 28 normally hearing ears, 3 ears with otosclerosis and 325 ears with sensorineural hearing loss of various origins including 56 Meniere ears, were analyzed . The characteristics of summating potential (SP) parameters in Meniere ears were different from those of ears with hair cell loss due to streptomycin and kanamycin ototoxicity and noise, while there was no difference between the action potential (AP) of the cochlear nerve parameters of Meniere ears and ears with hair cell loss . A much higher incidence of increased-SP/AP amplitude ratios in Meniere's disease was observed than in hearing loss of other origins . The results demonstrate the usefulness of noninvasive extratympanic ECochG in the diagnosis of Meniere's disease.

Med Toxicol, 1987 Jan-Feb, 2(1), 33 - 51
Neurological manifestations and toxicities of the antituberculosis drugs . A review; Holdiness MR; The neurological manifestations and toxicities of 12 antituberculosis drugs {isoniazid, rifampicin (rifampin), ethambutol, p-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin, ethionamide, cycloserine, capreomycin, viomycin and thiacetazone} are reviewed . Their effects upon the central nervous system, cranial nerves, peripheral nerves and the neuromuscular junction are examined, and drug interactions of neurological concern are briefly discussed . Isoniazid is well known to increase the concentrations of gamma-aminobutyric acid in neural tissues . Although conflicting data have been published, isoniazid may play a limited future role in reducing the degree of adventitious movements noted in certain neurological diseases such as multiple sclerosis, spasmodic torticollis, and other segmental dystonic syndromes . With rifampicin neurological complications have been observed infrequently . Rifampicin penetrates into the CSF and has been shown to have useful activity against various micro-organisms in the CSF, including certain viruses; however, contrary to earlier suggestions, it appears to have no role in the treatment of subacute sclerosing panencephalitis . A number of studies have indicated that isoniazid is associated with a large number of accidental and intentional poisonings . The highest incidence has been observed with Southwestern American Indians in which this agent was involved in 7% of all suicide attempts and 19% of the suicide deaths . Degeneration of the optic chiasma and nerve is a well-known adverse effect of ethambutol; toxicity is manifested by impairment of visual acuity, marked loss of colour discrimination, constricted visual fields, and central and peripheral scotoma . Ototoxicity is a well known problem caused by streptomycin, kanamycin, capreomycin and viomycin . The use of streptomycin in pregnant mothers is associated with congenital deafness in newborns in certain cases . The aminoglycoside antibiotics are also associated with flaccid paralysis following neuromuscular blockade . Adverse reactions to cycloserine are mainly dose-related with neurological and psychiatric syndromes noted in up to 50% of patients . Recent data indicate that isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, kanamycin, ethionamide, and cycloserine appear in measurable quantities in the cerebrospinal fluid . Five of these compounds (isoniazid, rifampicin, ethambutol, kanamycin, cycloserine) pass to some degree through non-inflamed meninges . Other than discontinuation of the therapeutic regimen and general supportive measures, very few methods are described in the literature for treatment of acute intoxications with antituberculosis drugs.

Pol Arch Weter, 1987, 27(2-3), 75 - 87
{Biological properties of Mycoplasma isolated from bulls' semen}; Marciszewska M et al.; The occurrence of Mycoplasma in bulls' semen obtained from different Artificial Insemination Centers in Poland was studied . Out of 380 semen samples 234 mycoplasma strains were isolated (61%) . Nutritional requirements and biochemical properties of the isolated strains were studied . On the basis of the results of catabolism of glucose and arginine three different groups of isolates were found . The final identification was determined by growth inhibition test and indirect antibody fluorescent technique . 98% of the isolated strains were classified . In Acholeplasma genus two species were found: A . laidlawii and A . modicum . In the genus of Mycoplasma the majority of isolates were identified as M . bovigenitalium (76%) . The remaining strains belonged to three other species: M . bovis, M . bovirhinis, M . arginini and to serological group number 7 . The sensitivity of isolates to streptomycin and their viability at different temperature were examined . The occurrence of the pathogenic Mycoplasma strains in the examined bulls' semen, their long survival time at -196 degrees C (24 months) and the resistance of some strains to streptomycin indicate the necessity to examine the semen before it is used in artificial insemination.

Ter Arkh, 1987, 59(11), 96 - 8
{Use of inhalation of ultrasonic aerosols and galvanic current in the treatment of patients with pulmonary tuberculosis}; Kim ACh et al.; Multimodality treatment of 83 patients with newly detected destructive forms of pulmonary tuberculosis included the use of inhalation of isoniazid and streptomycin in ultrasonic aerosols in combination with galvanic current . This method was well tolerated by the patients, inhalation agents showed high efficacy: elimination of bacteria and disintegration cavity closing in most of the patients occurred in the first 4 months, i . e . by the end of a course of inhalation therapy . The incorporation of rifampicin in the therapeutic scheme did not result in the improvement of therapeutic results but increased the frequency of side effects (toxic and hepatotoxic) . The time course of radionuclide scanning showed that the improvement of the capillary blood flow was more frequently observed in therapy with galvanic current.

Chemotherapy, 1987, 33(3), 204 - 10
Effects of anti-tuberculosis drugs on the production of prostaglandin E2 and on mononuclear leucocyte transformation; Zeis BM; The effects of the anti-tuberculosis (TB) drugs isoniazid, rifampicin, streptomycin, pyrazinamide and ethambutol on the synthesis of prostaglandin E2 (PGE2) by polymorphonuclear leucocytes were investigated . Only rifampicin at a concentration of 100 micrograms/ml caused statistically significant stimulation of PGE2 production whereas the other compounds had no effect . Immunomodulatory properties of the compounds individually and in combination were investigated using phytohaemagglutinin-stimulated mononuclear leucocyte transformations . Rifampicin caused dose-dependent inhibition of blastogenesis and combinations containing this agent also had an inhibitory effect . The prostaglandin synthesis inhibitor indomethacin caused stimulation of phytohaemagglutinin responsiveness and this effect was not influenced by the presence of the anti-TB drugs.

Acta Microbiol Hung, 1987, 34(2), 165 - 71
Protective value of the plasmid-coded outer membrane protein of enteroinvasive Escherichia coli; Ketyi I et al.; O-antigenically not related enteroinvasive Escherichia coli strains and rabbit sera prepared with them were used to study the role of plasmid-coded outer membrane proteins in protective immunity . Active immunization experiments were performed using a mouse model based on a long-lasting symptomless carriership after elimination of the bowel flora by streptomycin . Preliminary histological studies showed adhesion, penetration, intraepithelial multiplication, and epithelial desquamation after infection . In active immunization experiments only massive oral doses evoked protective immunity . Seroconversion against the plasmid-coded antigens was not observed in mice . Passive immunization was carried out in chick embryos with unabsorbed sera . A high level of protectivity was reached by serogroup-specific sera and a very low but significant protection was yielded by antibodies against the plasmid-coded protein antigens.

Otolaryngol Head Neck Surg, 1987 Jan, 96(1), 39 - 42
The treatment of acoustic neuroma and Menière's disease in the same patient; McDaniel AB et al.; Although total excision is accepted as the standard of care in the treatment of acoustic neuromas, for the elderly patient this approach is modified . Small tumors which cause only eighth nerve symptoms of hearing loss and tinnitus can be followed radiologically while larger tumors with brain stem compression may be subtotally excised through the translabyrinthine route . Our standard treatment for Meniere's disease--that is refractory to medical management--has been vestibular nerve section through a retrolabyrinthine approach . In the event of bilateral Meniere's disease or Meniere's disease in an only hearing ear, treatment with low-dose intramuscular injections of streptomycin sulfate is preferred . Two elderly patients are discussed, each of whom has an acoustic neuroma in one ear and Meniere's disease in the other . These patients' histories, diagnostic evaluations, treatment rationale, and follow-up data are presented to illustrate the decision-making process and the management of complicated and unusual cases.

Hear Res, 1987, 26(2), 139 - 44
Prostaglandins in the semicircular canal of the frog; Ferrary E et al.; The synthesis of prostaglandins by ampulla and duct tissue isolated from the frog posterior semicircular canal was investigated in vitro . Ampulla and duct produced PGE2 (9 and 6 pg/structure, respectively) and prostacyclin (26 and 12 pg/structure) . In the ampulla, prostaglandins mostly originated from the part containing dark and sensory cells and was not altered by 10(-3) M streptomycin . Prostaglandin levels were time-dependent and temperature-dependent . Arachidonic acid (3 X 10(-5) M) stimulated PGI2 synthesis by ampulla and duct (by 11.4 and 17 times) and PGE2 synthesis by 50 times in both structures . Ionophore A23187 stimulated ampulla and duct PGI2 synthesis (by 4.8 and 5.6 times) and PGE2 synthesis (by 2.4 and 1.8 times) . Subcutaneous 100 mg/kg aspirin reduced PGI2 and PGE2 synthesis (ampulla: -87%, -33%; duct: -100%, -33%) . Indomethacin (10(-6) M), in vitro, decreased PGI2 and PGE2 synthesis (ampulla: -47%, -47%; duct; -22%, -77%) . Within 3 h, aspirin (5 X 10(-6) M) or arachidonic acid (2 X 10(-5) M) did not change Na and K concentrations in endolymph . It is concluded that frog inner ear produces PGI2 and PGE2, mostly from the part containing the dark cells, and that prostaglandins could be involved in the physiology of inner ear.

Vet Med Nauki, 1987, 24(8), 9 - 12
{Localization of the genes coding for the specific modification-restriction system in the E . coli tF strain}; Popovski B; The recombinant Escherichia coli tF strain has been shown to have its own specific modificational and restrictional system . In order to establish the location of genes, coding this system a plasmid has been isolated from the investigated strain, which substantiates the resistance to streptomycin . The plasmid DNA has been transformed into a recipient strain, E . coli O, which has no modificational and restrictional system of its own . The newly obtained E . coli O (ptF) transformants also have proved negative with regard to their testing for the presence of a specific modificational and restrictional system . The conclusion follows that the genes, coding the modificational and restrictional system of the E . coli tF strain are not located in the plasmid isolated from it.

Gene, 1987, 56(2-3), 283 - 8
A series of Tn5 variants with various drug-resistance markers and suicide vector for transposon mutagenesis; Sasakawa C et al.; A series of variants of transposon Tn5 were constructed by replacement of the 2.7-kb central segment which encodes kanamycin resistance with various other resistance-coding genes: tetracycline, chloramphenicol, gentamicin, trimethoprim, streptomycin or ampicillin . A thermosensitive replication mutant of the broad-host-range transmissible plasmid R388 was also constructed for use as a suicide vector for the delivery of transposable elements.

Biochim Biophys Acta, 1987, 895(1), 11 - 23
On the mechanism of translocation of dihydrostreptomycin across the bacterial cytoplasmic membrane; Nichols WW; This review examines two mechanisms, the channel and the uniport, proposed to explain the rapid, energy-dependent (EDP-II) phase of transport of dihydrostreptomycin (and streptomycin) across the bacterial cytoplasmic membrane . Bioenergetic and kinetic predictions are made from these two mechanisms and compared with available experimental data . Both the above mechanisms would be expected to lead to reversible transport kinetics, and to observable uptake of dihydrostreptomycin by respiring cytoplasmic membrane vesicles . However, transport is kinetically irreversible and is not observed in membrane vesicles (although the membrane vesicle findings need further confirmation), so the author rejects the proposed channel and uniport mechanisms . A possible mechanism of dihydrostreptomycin transport that would be consistent with the above experimental data, would be one in which a chemical reaction occurred as an obligatory part of the translocation cycle . Such a mechanism could be classified as primary translocation . The author emphasizes that this hypothesis is put forward to stimulate further experimental testing; it is not proposed to be a definitive explanation of the mechanism of energy-dependent dihydrostreptomycin transport.

Neurotoxicology, 1987 Spring, 8(1), 33 - 44
The species-specific nature of the ototoxicity of dihydrostreptomycin in the patas monkey; Stebbins WC et al.; The remarkable susceptibility of the inner ear of the patas monkey (Erythrocebus patas) to the ototoxic action of dihydrostreptomycin (DHSM) (and streptomycin (SM)) is well established in this paper and affords a rare example of a species-specific reaction to a restricted class of compounds within the aminoglycoside group of antibiotics . In a series of experiments, behavioral and morphological observations together provided the following profile of DHSM ototoxicity in the patas monkey: Sudden onset of hearing loss beginning after 7-9 weeks of treatment; Substantial, though often partial, hearing impairment beginning at the high frequencies and progressing with or without continued treatment to the low frequencies; In the inner ear, a corresponding and selective loss of nerve fibers and of outer hair cells, relative to inner hair cells, beginning in the base of the cochlea and proceeding toward the apex; Continued and progressive loss of hearing for several months after cessation of drug treatment; and Non-auditory effects in some animals on the kidney and vestibular system . Results from control experiments confirmed this special relationship between the patas monkey and DHSM: Other nonhuman primates (macaques and vervet monkeys) were essentially unaffected by DHSM; The patas showed no equivalent sensitivity to other aminoglycosides such as kanamycin or to other forms of ototraumatic insult such as intense noise.

EMBO J, 1986 Dec 20, 5(13), 3705 - 8
E . coli ribosomes with a C912 to U base change in the 16S rRNA are streptomycin resistant; Montandon PE et al.; Resistance to streptomycin (Sm) of Euglena gracilis chloroplasts can be due to a single C to T transition of the 16S rRNA gene in an invariant position which is equivalent to C912 of the Escherichia coli 16S rRNA . Since Euglena chloroplasts cannot be transformed we introduced, by site-directed mutagenesis, a C912 to T transition in the cloned rrnB operon (pKK3535) of E . coli and used this new construct (pEM109) in transformation experiments . Transformed E . coli cells were selected for Sm resistance by colony plating and stepwise increase of Sm up to 25 micrograms/ml of culture medium . Several Sm-resistant colonies were obtained . Ribosomes were isolated from pEM109-transformed Sm-resistant and pKK3535-transformed Sm-sensitive cells . The ribosomes were assayed in vitro for Sm-induced misreading of poly(U) mRNA . We isolated 16S rRNA and sequenced the crucial RNA region by reverse transcription . The results clearly show that ribosomes from Sm-resistant cells correctly read the poly(U) mRNA in the presence of 25 micrograms Sm/ml of reaction mixture and the 16S rRNA contains the C912 to U transition . We conclude that C912 is involved in a translation step(s) which is (are) sensitive to streptomycin.

J Vasc Surg, 1986 Dec, 4(6), 612 - 5
Tuberculous aortitis with associated necrosis and perforation: treatment and options; Cargile JS 3rd et al.; Tuberculous aortitis is a rare entity and its association with necrosis and perforation is even more unusual . Our pulmonary medicine service originally evaluated an elderly woman with a right pleural effusion and upper lobe infiltrate thought to be tuberculosis . An abdominal CT scan performed at that time showed extensive periaortic adenopathy . Isoniazid and rifampin were started, but both were stopped by the patient after less than 6 months of therapy . The patient later had night sweats, a left pleural effusion, and a tender abdominal mass thought to be a symptomatic aneurysm . At operation, the aorta was necrotic and had an inflammatory mass and perforation on the left side . Infrarenal aortic ligation and resection were performed to control infection . A previously placed axillofemoral graft obviated the need for concomitant revascularization . The patient was treated postoperatively with isoniazid and rifampin until hyperbilirubinemia developed, which necessitated alternate therapy with ethambutol and streptomycin . The patient died one month after operation of a presumed pulmonary embolus.

Clin Pharm, 1986 Dec, 5(12), 977 - 87
Short-course drug therapy for tuberculosis; Stratton MA et al.; The cost, patient compliance considerations, and toxicity of short-course chemotherapy (SCC) and conventional 18- to 24-month treatment regimens for pulmonary tuberculosis are compared; studies of the efficacy of SCC regimens are evaluated; and the future of SCC in the United States is examined . SCC is defined as treatment for nine months or less . A definite advantage of SCC over conventional therapy in terms of cost, patient compliance, or adverse effects has not been established . A series of studies conducted by the East African-British Medical Research Council documented the efficacy of various six-month, multiple-drug regimens that contain rifampin and verified the sterilizing activity of pyrazinamide during the first two months of therapy . The studies of the Hong Kong Chest Service and British Medical Research Council documented the efficacy of several intermittent drug regimens . Acceptable relapse rates were achieved with streptomycin, isoniazid, and pyrazinamide given two or three times a week for four or six months, preceded by a two-month, multiple-drug, daily regimen, and various four-drug, pyrazinamide-containing intermittent regimens . The benefit of pyrazinamide in reducing the relapse rate with SCC was confirmed by studies of the British Thoracic and Tuberculosis Association . Few studies of SCC have been conducted in the United States . Treatment practices in the United States are becoming more uniform, and SCC is being used more frequently for uncomplicated pulmonary tuberculosis . SCC will probably be used more widely in the future . Current guidelines of the Centers for Disease Control recommend treatment for nine months with isoniazid and rifampin, plus ethambutol in areas where resistance to isoniazid is common . In vitro data suggest that the addition of pyrazinamide may be more effective, but clinical experience with this drug in the United States is limited.

Mutat Res, 1986 Dec, 175(4), 199 - 204
Study of MFD-type repair in locus determining resistance of Escherichia coli to streptomycin; Filippov VD; The yield of induced mutations to streptomycin resistance (Str) in E . coli, UV-irradiated and temporarily incubated in liquid medium not permitting protein synthesis, depends upon the conditions of preirradiation growth and preirradiation treatment of the bacteria, i.e . on their physiological state at the moment of irradiation . This fact is not readily reconciled with a model postulating mutation production in the structural genes of E . coli during excision repair . A preferred explanation is offered, based on the assumption that the efficiency of mutagenesis at the rpsL (strA) locus is determined by interference of antimutagenic (generalized excision repair and MFD) and promutagenic (mutation fixation of excision repair) events . The participation of macromolecular syntheses in Str mutation fixation is suggested.

Am J Vet Res, 1986 Dec, 47(12), 2612 - 3
Comparison of the susceptibility of Brucella abortus isolates obtained before and after cows were treated with oxytetracycline and streptomycin; Guerra MA et al.; Eight isolates of Brucella abortus were obtained from cows before and after they were treated with oxytetracycline and streptomycin . The susceptibility to these antibiotics was determined by broth-dilution minimal inhibitory and minimal lethal concentrations . Differences were not found in the minimal lethal concentrations of oxytetracycline or streptomycin in isolates obtained from cows before and after they were treated . This indicates that treatment failures in the cows were not the result of development of resistance to the antibiotics by B abortus.

Mol Gen Mikrobiol Virusol, 1986 Dec, (12), 10 - 5
{Molecular-genetic organization of plasmid R89S of the incompatibility group Q}; Zinchenko VV et al.; A new IncQ plasmid R89S has been analysed by molecular-genetic methods . A restriction map of this plasmid has been constructed and regions of homology with the plasmid RSF1010 have been identified . A genetic map of the plasmid R89S has been prepared based on the deletion and insertion plasmid derivatives . The phenotypic analysis of the derivatives has identified the location of genes coding for replication, incompatibility, mobilization for genetic transfer and resistance to streptomycin in the genome of R89S.

Tubercle, 1986 Dec, 67(4), 243 - 59
A controlled trial of six-month and nine-month regimens of chemotherapy in patients undergoing radical surgery for tuberculosis of the spine in Hong Kong . Tenth report of the Medical Research Council Working Party on Tuberculosis of the Spine; Chemotherapy of field cases of East Coast fever using halofuginone lactate; The chemotherapeutic effect of halofuginone lactate (Terit, Hoechst) was tested against natural pathogenic Theileria parva infections (East Coast fever, ECF) in 24 cattle . Halofuginone lactate, administered per os, 1.2 mg per kg b.wt and repeated after 48 h manifested a potent schizonticidal effect, observed between 5 and 11 days post treatment . Disappearance of erythrocytic forms (EF) took long, ranging from 6 to 34 days post treatment . Differences on efficacy between halofuginone lactate tablets and solution were not observed . The use of furosemide (Dimazon, Hoechst) to promote diuresis in pulmonary oedema and streptomycin sulphate for control of secondary pulmonary infections, as supportive therapy measures, enhanced recovery from ECF . A recovery rate of 96% was recorded . Relapses were not observed.

Contact Dermatitis, 1986 Nov, 15(5), 282 - 8
Contact dermatitis to antituberculosis drugs; Holdiness MR; The literature has been reviewed for contact dermatitis occurring to antituberculosis agents . Of the 12 known drugs, 6 (isoniazid, rifampicin, ethambutol, para-aminosalicylic acid, streptomycin and kanamycin) have been documented by patch test to cause this type of dermatitis in certain individuals . Cross sensitization has been observed to contribute significantly to the allergic reactions noted from isoniazid, streptomycin, and kanamycin . Hyposensitization has also been discussed in this review.

Am Rev Respir Dis, 1986 Nov, 134(5), 1056 - 61
Clinical trial of two short-course (6-month) regimens and a standard regimen (12-month) chemotherapy in retreatment of pulmonary tuberculosis in Pakistan . Results 18 months after completion of treatment (Lahore Tuberculosis Study); Aziz A et al.; This study compared the efficacy and tolerability of two 6-month daily regimens of isoniazid and rifampin in combination with either pyrazinamide or ethambutol (RHZ and RHE regimens) against a standard daily regimen of streptomycin, isoniazid, and ethambutol (SHE regimen) given for 6 months followed by isoniazid and ethambutol for an additional 6 months . Only previously treated sputum positive patients suffering from active pulmonary tuberculosis were entered into the study . Three hundred and fifty-eight patients were admitted to the study and 267 (75%) completed chemotherapy . Eighty-five percent of RHZ-regimen and 82% of RHE-regimen patients achieved sputum culture negativity compared to 55% of patients in SHE regimen . Successfully treated patients were followed up for 18 months, and among these, all 3 treatment regimens showed broadly similar levels of culture negativity at the end of the follow-up period . Final therapeutic outcome was based on sputum culture results obtained throughout the follow-up period, and no statistically significant difference in relapse rate was noticed in the 3 regimens . Severe drug intolerance necessitated discontinuation of therapy in only 2 patients.

Ukr Biokhim Zh, 1986 Nov-Dec, 58(6), 27 - 34
{Isolation of the proteolytic complex from industrial waste waters from streptomycin production}; Mishunin IF et al.; Dynamics of industrial biosynthesis of polyenzymic Streptomyces griseus system proteases and changes in their activities are studied in the process of streptomycin production . The method to isolate protease preparations is developed with optimization of production cycles of the stabilization, vacuum-concentration, ballast protein salting-out and lyophilization stages . The preparation is low toxic, retains 98% of the proteolytic activity at the temperature of 60 degrees C, 30 and 80%--under the effect of EDTA and urea, the activity maximum is at pH 7.0-8.0 . The production technique of the preparation is estimated for its economic efficiency.

Plasmid, 1986 Nov, 16(3), 161 - 7
Broad host range vectors derived from an RSF1010::Tn1 plasmid; Chistoserdov AY et al.; Plasmid vector derivatives of the IncQ/P4 plasmid RSF1010 available for cloning DNA into a broad range of bacterial species were constructed . The plasmid pAYC31 constructed for the positive selection of inserted fragments contains part of transposon Tn1 inserted into the sequence of the gene sul . Gene aph transcription in pAYC31 can be initiated from the promoter for the transposase gene tnpA which is under the negative control of the gene tnpR product (Heffron, 1983) . The insertion of a BamHI fragment, or of fragments generated by Sau3A, BclI, BglII, or XhoII digestion into the unique BamHI site within the gene tnpR sequence, leads to initiation of transcription from the promoter of the tnpA gene toward the aph gene . Expression of the aph gene upon insertion of a BamHI restriction fragment provides a positive selection for hybrid plasmids by plating the transformed bacteria on media with streptomycin . Versatile cloning vectors pAYC32 of 9.7 kb in length and pAYC39 of 11.3 kb in length were also constructed . Insertion into the BamHI site of vector pAYC32 of a 1.6-kb BglII fragment that contains the lambda cos site produced cosmid vectors pAYC51 and pAYC52 . The two 11.3-kb cosmids differ only by the orientation of the 1.6-kb BglII fragment . By insertion into the BamHI site of pAYC32 of a BglII-BamHI fragment of plasmid pHC79 that contains the gene tet and lambda cos site cosmid vector pAYC53 was constructed . Vector pAYC31 was used to construct a gene bank from the chromosomal DNA of an obligate methylotrophic strain Methylomicrobium flagellatum KT.

Prikl Biokhim Mikrobiol, 1986 Nov-Dec, 22(6), 736 - 41
{Study of restrictase Sal GI biosynthesis and optimum conditions for its isolation}; Ren LS et al.; The effect of the growing phase of Streptomyces albus G . and the components of the culture medium on the biosynthesis of restriction endonuclease Sal GI was studied . The conditions of DNA sedimentation with streptomycin sulfate and polyethylenimine and separation of proteins with ammonium sulfate were investigated as well . A maximal quantity of the enzyme was observed in the cells in 18-20 h of cultivation in flasks on a shaker . The optimal concentrations of the medium components (g/l) were found by mathematical methods of the experiment planning: glucose--19,0; pepton--5.2; K2HPO4 X 3H2O - 5.0 . The optimal concentrations for DNA sedimentation with streptomycin sulfate and polyethylenimine were found to be 1.8-2.0% and 0.2-0.3%, respectively . The optimal concentration of ammonium sulfate for protein separation is 70% of saturation.

Dtsch Med Wochenschr, 1986 Oct 17, 111(42), 1603 - 5
{Tuberculostatics-induced systemic lupus erythematosus}; Layer P et al.; Clinical manifestations including rheumatoid changes, lymph node swelling, fever, butterfly rash, anaemia and leukopenia had developed gradually over a period of years in a 46-year-old female patient . Due to these findings systemic lupus erythematosus (SLE) was suspected . Further diagnostic procedures revealed concomitant pulmonary tuberculosis . In the course of the tuberculostatic therapy, there occurred six episodes of marked exacerbation of drug-induced SLE signs and symptoms including fever, myalgia, swelling of joints, butterfly rash and high titers of antinuclear antibodies . These exacerbations were induced by single-agent or combination therapy with ethambutol, pyrazinamide, streptomycin and/or prothionamide and resolved readily after discontinuation of the drug(s) . With concomitant use of hydroxychloroquine sulfate, a combination therapy with rifampicin and cycloserine did not give rise to further complications although the autoantibodies persisted . This treatment regimen was given until clinical cure was achieved.

J Antimicrob Chemother, 1986 Oct, 18 Suppl C, 85 - 92
Insertions of resistance genes into Tn21-like transposons; Wiedemann B et al.; The evolution of Tn21 and related multiresistance transposons of natural and artificial origin is described . Variations resulting from insertions and deletions in these transposons indicate the presence of specific recombination sites . There is evidence that these 'hot spots' are flanking several resistance genes . We examined these structures on the basis of the aadA gene, mediating resistance to spectinomycin and streptomycin . Comparison of the DNA sequences of Tn21, Tn7 and pSa indicate the wide spread of these recombination sites.

Mutat Res, 1986 Oct, 163(1), 15 - 22
Mutagenic and cytotoxic effects of oxygen free radicals generated by methylviologen (paraquat) on Escherichia coli with different DNA-repair capacities; Yonei S et al.; Investigations were carried out to examine the mutagenic and cytotoxic effects of oxygen free radicals on E . coli . E . coli B strains with different DNA-repair capacities were exposed to methyl viologen, commonly called paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride, MV), which has been shown to act as an intracellular generator of superoxide radicals . The results obtained were as follows: The cytotoxicity of MV in E . coli was dioxygen-dependent and due to the extent of intracellular generation of superoxide radicals . Cells containing higher levels of superoxide dismutase were more resistant to the toxic effect of MV . The cytotoxicity of MV was greater in DNA repair-deficient E . coli, Bs-1(exrA uvrB), NG30(recA) and R15(polA), than in DNA-repair-proficient strains (B/r and H/r30) and Hs30 (uvrB) . MV was found to be mutagenic to E . coli H/r30 and Hs30 under aerobic conditions . The mutation frequencies to streptomycin resistance and to arginine prototrophy increased with the dose of MV in both strains . However, E . coli NG30 was unmutable by MV . The mutation induction did not occur under anaerobic conditions . The expression of the umu operon in E . coli was induced by MV under aerobic conditions . From these results, it was concluded that superoxide radicals intracellularly generated by MV include DNA damage, which causes cytotoxicity and mutation induction in E . coli, and that DNA damage induced by oxygen radicals is repairable by at least recA, polA and exrA(lexA) gene-controlled mechanisms.

J Bacteriol, 1986 Oct, 168(1), 257 - 69
Nucleotide sequence of afsB, a pleiotropic gene involved in secondary metabolism in Streptomyces coelicolor A3(2) and "Streptomyces lividans"; Horinouchi S et al.; The nucleotide sequence of afsB from Streptomyces coelicolor A3(2), a pleiotropic gene which positively controls the biosynthesis of A-factor and the pigmented antibiotics actinorhodin and undecylprodigiosin in S . coelicolor A3(2) and "Streptomyces lividans," was determined . The determinant of the afsB gene, which includes the putative AfsB protein consisting of 243 amino acids, was mapped functionally by tests for A-factor and pigment production in "S . lividans" and S . coelicolor A3(2) after introduction of recombinant plasmids containing various restriction endonuclease fragments on the vector plasmids pIJ41 and pIJ702 . The putative AfsB protein contains two regions separated by 167 residues which resemble conserved domains of known DNA-binding proteins . High-resolution nuclease S1 protection mapping revealed that the afsB mRNA, approximately 1,300 base pairs (bp) long, which was determined by Northern blot hybridization, had its start point 340 bp upstream of the putative methionine start codon . The Northern hybridization experiment also suggested that the afsB gene was constitutively transcribed throughout growth . Also shown by the Northern hybridization was the presence of an unidentified gene with an extraordinary amount of 880-bp mRNA located downstream from afsB . Dot hybridization with the brown pigment production genes, possibly involved in polyketide biosynthesis, as the probe suggested that the afsB gene did not stimulate transcription of the pigment production genes . In Southern blot DNA-DNA hybridization analysis with the afsB sequence as the probe, sequences exhibiting various degrees of homology were found in several Streptomyces spp . A DNA sequence showing strong homology to the afsB in Streptomyces griseus FT-1, a high streptomycin producer, behaved like an extrachromosomal element, homologous to the afsA gene, a structural gene for A-factor biosynthesis.

Infection, 1986 Sep-Oct, 14(5), 233 - 6
Brucella arthritis in children; Lubani M et al.; A study in 50 children suffering from acute brucellosis demonstrated that acute arthritis is a common and often predominant manifestation of the disease . The patients lived in an area where brucellosis is endemic: their ages ranged from six months to 12 years . All patients had a brucella agglutination titer of greater than or equal to 1:320 on admission . The knee and hip joints were most commonly affected with symptoms and findings from only one joint predominating . Associated findings of only moderately elevated ESR and normal leucocyte counts with relative lymphocytosis in the vast majority of the cases made it fairly easy to distinguish acute brucella arthritis from septic arthritis of other origin . A positive blood culture for Brucella melitensis was obtained in 35 of the patients . Treatment with tetracyclines, trimethoprim-sulphamethoxazole, with or without combination with streptomycin, resulted in a prompt recovery in all patients . No mortality was seen . Seven patients were readmitted with reinfections during a mean follow-up period of 13 months . Two patients with a history of prolonged fever, malaise and arthralgia were found to have osteomyelitis of the adjacent bone tissue . They also recovered without sequelae.

Q J Med, 1986 Sep, 60(233), 873 - 85
Brucella meningitis: presentation, diagnosis and treatment--a prospective study of ten cases; Mousa AR et al.; Diagnosis of brucella meningitis was made in 10 patients by serological tests on blood and cerebrospinal fluid using Rose Bengal, standard agglutination, indirect immunofluorescent and enzyme-linked immunosorbent assay (ELISA) tests and by blood and CSF culture . All patients had significantly elevated antibody titres . In three Br . melitensis was isolated both from blood and CSF and in a further three from blood only . Eight patients were 30 years old or less and seven were female . Seven patients had a history of contact with livestock and had consumed raw milk . Meningitis occurred in five, meningoencephalitis with hemiplegia in one, paraplegia and cranial nerve palsies in one and psychosis and/or nightmares in three . Transient Parkinsonism was seen in one patient and generalized rigidity and non-Parkinsonian tremors in another . Computerized tomography revealed ventricular dilation in one patient and punctate hyperdense, non-enhancing shadows in the lentiform nuclei in two others . Treatment with a combination of tetracycline, rifampicin and streptomycin was successful.

Tubercle, 1986 Sep, 67(3), 189 - 95
Controlled clinical trial of three short-course regimens of chemotherapy for pulmonary tuberculosis in Nigeria--a preliminary report; Onadeko BO et al.; A controlled clinical trial of daily short course (6-month) chemotherapy in newly diagnosed cases of pulmonary tuberculosis in Nigerians was carried out . The three regimens used contained streptomycin, isoniazid, rifampicin and pyrazinamide in the initial phase; and isoniazid plus rifampicin or isoniazid plus rifampicin and/or pyrazinamide in the continuation phase . Sputum culture conversion was satisfactory after 2 and 6 months of treatment and no positive cultures were found one year after treatment had been completed . Side effects were few and consisted mainly of arthralgia, possibly associated with pyrazinamide.

Am Rev Respir Dis, 1986 Sep, 134(3), 438 - 41
A four-drug regimen for initial treatment of cavitary disease caused by Mycobacterium avium complex; Ahn CH et al.; Forty-six patients with positive sputum cultures for Mycobacterium avium complex and cavitary disease were placed on a 4-drug regimen consisting of isoniazid, rifampin, and ethambutol daily and streptomycin twice weekly . Forty-two (91.3%) converted their sputum to negative and 4 (8.7%) failed to convert . All of the 4 nonconverters had prior subtotal gastrectomy . Twenty-two patients were available for long-term follow-up: 12 patients completed 24 months of chemotherapy, all experienced sputum conversion, but 2 reactivated, 1 at 9 and the other at 27 months after termination of chemotherapy . These 2 patients had prior subtotal gastrectomy . Ten patients completed 18 months of chemotherapy with sputum conversion, 2 of these reactivated but had not had prior subtotal gastrectomy . In this group of patients, subtotal gastrectomy appeared to be an adverse risk factor for both initial treatment response and reactivation in pulmonary disease caused by Mycobacterium avium complex.

Public Health Rep, 1986 Sep-Oct, 101(5), 487 - 94
Tuberculosis screening in Boston's homeless shelters; Barry MA et al.; From February 1984, through March 1985, a total of 26 cases of tuberculosis (TB) were verified in homeless persons in Boston . Fifteen cases were resistant to isoniazid (INH) and streptomycin (SM) and were most likely the result of a common source exposure to one or possibly two highly infectious persons . Five cases without multiple drug resistant organisms occurred in persons with previous positive tuberculin tests who had not received adequate therapy for prophylaxis of infection or treatment of disease . The remaining cases were in persons with a previous negative skin test or no history of ever receiving a skin test . A screening program using chest roentgenograms (CXR), skin tests, and sputum smears led to the identification of several cases . CXR, the most readily accepted test, was the mechanism by which all cases detected through screening were identified . Detection and therapy of TB in the homeless, a group at particular risk for disease, required intensive intervention and outreach efforts.

Am Rev Respir Dis, 1986 Sep, 134(3), 446 - 8
Primary drug-resistant tuberculosis in children . Emergence of primary drug-resistant strains of M . tuberculosis to rifampin; Steiner P et al.; A prospective study of primary drug-resistant strains of Mycobacterium tuberculosis among children was begun at the Kings County Hospital Medical Center of Brooklyn in 1961 and reported at 5 4-yr periods through 1980 . The present report extends our observations of primary drug-resistant tuberculosis in children through 1984 . The salient finding in the present report was the increase in primary drug resistance to rifampin, 3 of 19 strains resistant in the last period of study (1981 to 1984) as compared with 1 of 96 strains isolated in the previous 3 periods of study (1969 to 1980) . This increase was significant (p less than 0.02) even though the number of strains isolated was small . There were continued low resistance rates to ethambutol and para-aminosalicylic acid and stable resistance rates for isoniazid and streptomycin.

Mol Gen Genet, 1986 Sep, 204(3), 404 - 9
Expression of Tn5-encoded streptomycin resistance in E . coli; Mazodier P et al.; Four Tn5 mutations able to express streptomycin resistance in E . coli were obtained independently . These mutations (called Tn5) were localized and sequenced . All of them consist of a 6 bp deletion in the str gene near the 3' end . The mutation affects a region peculiar for its repetition of an identical 6 bp sequence . The mutation does not affect the level of transcription of the kan, ble, str operon of Tn5, neither does it increase the level of translation of str . The mutation seems to interfere with a post-translational event.

Ann Intern Med, 1986 Aug, 105(2), 210 - 3
Central nervous system tuberculosis with the acquired immunodeficiency syndrome and its related complex; Bishburg E et al.; Central nervous system tuberculosis occurred in three patients with the acquired immunodeficiency syndrome (AIDS) and seven patients with AIDS-related complex who were evaluated for 48 months . Nine patients were intravenous drug abusers and one was Haitian . Five patients had cerebral-ring-enhancing lesions and three had hypodense areas . The clinical spectrum included meningitis in two patients, multiple cerebral abscesses in one, and tuberculomas in four . All Mycobacterium tuberculosis isolates were sensitive to standard antituberculous drugs . All patients received treatment with isoniazid, rifampin, and pyrazinamide; six patients also received streptomycin . Three patients with AIDS died of opportunistic infection preceded by central nervous system tuberculosis . Among the patients with the AIDS-related complex, three improved with treatment, three were lost to follow-up, and one died . Tuberculosis should be considered in the differential diagnosis of central nervous system mass lesions in intravenous drug abusers with AIDS or AIDS-related complex . Because patients with tuberculosis can be cured, biopsy of accessible brain mass lesions should be mandatory . Preventive therapy may be indicated in drug abusers without disease.

Chest, 1986 Aug, 90(2), 247 - 50
Tuberculosis in Korea . The relationship between prior therapy and drug resistance; Etzkorn ET et al.; A review of 121 culture-positive cases of pulmonary tuberculosis from 1979 to 1984, including both Korean and American patients, at the major US military hospital in Korea indicated that most antituberculosis drug resistance occurred in patients with a history of previous antituberculosis therapy . The 98 patients without previous therapy who were not household contacts of a known resistant case had low rates of drug resistance (7 percent to isoniazid, 5 percent to streptomycin, 2 percent to p-aminosalicylic acid, and none to rifampin or ethambutol) . All were sensitive to at least two of the drugs in the commonly prescribed regimen of isoniazid, rifampin, and ethambutol . In contrast, both patients who were household contacts of a known resistant case and 11 (52 percent) of the 21 patients with previous therapy had drug-resistant organisms . Our data support the use of isoniazid as preventive therapy for those who develop tuberculin reactivity while in Korea, in the absence of close contact with a known resistant case . Our data also suggest that the regimen of isoniazid, rifampin, and ethambutol is appropriate initial therapy for active disease acquired in Korea, provided that an adequate history excluding these risk factors can be obtained.

J Laryngol Otol, 1986 Jul, 100(7), 809 - 15
The effect of streptomycin and irradiation on rhinoscleroma (electron microscopic study); Toppozada HH et al.; Irradiation of scleromatous lesions produces its effect by destroying the organisms, whereas Streptomycin improves the mucosal defence mechanisms . A combination of both lines of treatment seems to be indicated for the arrest of the pathological process.

Int J Clin Pharmacol Ther Toxicol, 1986 Jul, 24(7), 344 - 8
Hepatic mixed function oxidase induction during rifampicin/isoniazid therapy in Indian vegetarians; Perry W et al.; To determine the effect of rifampicin therapy on hepatic oxidase activity in animal protein deficient patients antipyrine and quinine t 1/2 and 6B-hydroxycortisol (6B-OHF) excretion was studied in 8 Indian vegetarians during treatment for tuberculosis . In 4 patients at the start of treatment rifampicin/streptomycin caused a steady decline in by time antipyrine t 1/2 which was complete in 3 weeks, in one patient introduction of isoniazid produced a temporary reversal . After 4 months rifampicin/isoniazid 6B-OHF excretion was increased 2 to 10 fold in all patients although one followed serially showed a marked fall when isoniazid was begun . Decline in antipyrine t 1/2 persisted in 4 patients at the end of 18 months therapy and in one of these concurrent quinine t 1/2 confirmed partial isoniazid reversal of this decline . Rifampicin-mediated mixed function oxidase induction appeared similar to that reported for non-vegetarians and largely persists with combination therapy throughout treatment . Isoniazid can act as a competitive inhibitor of hepatic oxidase activity in some patients.

Am Rev Respir Dis, 1986 Jul, 134(1), 39 - 43
Epidemiology of infection by nontuberculous mycobacteria . VI . Identification and use of epidemiologic markers for studies of Mycobacterium avium, M . intracellulare, and M . scrofulaceum; Fry KL et al.; A comparison of clinical and environmental (e.g., soil, dust, water, and aerosol) isolates of the Mycobacterium avium-intracellulare and M . scrofulaceum (MAIS) group has been made . The frequency of M . avium-intracellulare clinical isolates able to grow without OADC enrichment, able to grow at 43 degrees C, or express resistance to streptomycin or cadmium was significantly higher than those among environmental isolates . Only the frequency of clinical M . scrofulaceum isolates able to grow at 43 degrees C and without OADC enrichment was significantly higher than that of environmental isolates . Because of the high frequency of clinical M . avium-intracellulare isolates able to grow without OADC, grow at 43 degrees C, and resistant to streptomycin, these 3 characteristics are suggested for use as epidemiologic markers for MAIS . There were no significant differences between clinical M . avium-intracellulare isolates from 3 widely separated geographic regions . Among M . avium-intracellulare environmental isolates, only those collected in droplets above bodies of water (i.e., aerosols) shared those characteristics unique to clinical MAIS . That observation suggests that these aerosols are a likely source of human MAIS infection . The ability of isolates to grow at 43 degrees C and without OADC enrichment was highly correlated . Gentamicin-, streptomycin-, and D-cycloserine-resistances were also frequently found together . Isolates carrying plasmids and either able to grow at 43 degrees C, without OADC enrichment, or mercury-resistant were found more frequently than expected as well . This suggests their genetic determinants are plasmid-encoded.

Tubercle, 1986 Jun, 67(2), 99 - 108
Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide; Parthasarathy R et al.; Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide . The incidence was high in patients treated with daily regimens of isoniazid and rifampicin: 16-39% in children with tuberculous meningitis, 10% in patients with spinal tuberculosis (non-surgical cases), and 2-8% in those with pulmonary tuberculosis . Hepatitis, in those receiving rifampicin occurred more often in slow than in rapid acetylators of isoniazid, the proportions amongst those whose acetylator phenotype had been determined being 11% of 317 slow acetylators and 1% of 244 rapid acetylators . In children with tuberculous meningitis, the risk of hepatitis with isoniazid 20 mg/kg (39%) was higher than that with 12 mg/kg (16%), and appreciably lower in patients given rifampicin twice-weekly (5%) rather than daily (21%) . There was no indication that pyrazinamide contributed to the hepatic toxicity.

Arch Dis Child, 1986 Jun, 61(6), 569 - 72
Cardiac manifestations in brucellosis; Lubani M et al.; Cardiac involvement in childhood brucellosis is rare and when present mimics findings usually noted in acute rheumatic fever with carditis . We report five children aged 6 to 11 years . Echocardiography showed mitral valve vegetations in one, functional mitral valve incompetence in two, and sluggish myocardial function in one . All the patients presented with fever, arthralgia, and malaise, four of them had leucopenia, and all five showed relative lymphocytosis . Blood cultures grew Brucella melitensis, biotype 1 in four cases and type 2 in one . Treatment with oral tetracyclines over three weeks together with streptomycin over the first two weeks was successful in all the patients, including one in whom oral trimethoprim/sulphamethoxazole was first tried but was unsuccessful as the patient developed a relapse after two months.

Am Fam Physician, 1986 Jun, 33(6), 159 - 64
Plague; Welty TK; Successful treatment of plaque depends on early diagnosis, institution of effective antibiotics (streptomycin, chloramphenicol, tetracycline or gentamicin) and adequate supportive care . To reduce mortality, therapy should be started in patients suspected of having plague while diagnostic procedures are under way . If persons with acute febrile illness (especially regional lymphadenitis) have been in plague-endemic areas within the week preceding the onset of illness, the diagnosis of plague should be considered.

Mol Cell Biochem, 1986 Jun, 71(1), 87 - 93
Purification and properties of dipeptidase from Escherichia coli AJ005; Ota A; A Co2+-dependent dipeptidase from E . coli strain AJ005, a peptidase-deficient mutant, was purified with streptomycin sulfate, ammonium sulfate and DEAE-cellulose . The purified dipeptidase increased by about 106-fold in specific activity, with dilysine as a substrate . The dipeptidase cleaved dilysine to two lysines among the lysine homopolymers, the possibility remaining that it is active toward peptides other than dilysine, since it was investigated in the present study only for activity toward lysine homopolymers . Activity was inhibited 54% by 10(-3) M KCN and completely by 10(-3) M PCMB, EDTA and benzethonium chloride, but not at all by soybean trypsin inhibitors . 78% and 95% of its activity was lost with 30 minutes' treatment at 45 degrees C and 50 degrees C, respectively . The apparent Km value was 6.7 X 10(-4) M for dilysine . It is probable that the dipeptidase differs from dipeptidase DP.

J Comp Physiol {A}, 1986 May, 158(5), 681 - 8
The Ca++ permeability of the apical membrane in neuromast hair cells; Baumann M et al.; The mechanosensitivity of eel (Anguilla anguilla) neuromasts was measured by the impulse responses of single afferent nerve fibers to mechanical stimuli . It is dependent on the potential across the skin and on the ions in the water outside the apical membrane of the sensory cells . The mechanosensitivity decreases to zero when the skin is polarized by 10-100 mV cathodal DC (skin surface negative); it increases with increasing (10-60 mV) anodal DC and remains remarkably constant with higher polarization (Fig . 1) . The mechanosensitivity increases with increasing concentrations of Ca++ outside the apical membrane of the sensory cells . Na+ and K+ have no influence . Addition of La , Co++, Mg++, D 600 and A-QA 39 inhibits the mechanosensitivity; the degree of inhibition varies with the inhibitor and the ratio {Ca++}/{inhibitor}, indicating that the inhibition is competitive (Figs . 2, 3) . We conclude that the apical membrane is specifically permeable to Ca++ ('late Ca channel') and that the inward receptor current through the apical membrane is carried by Ca++ . Streptomycin also inhibits mechanosensitivity by competing with Ca++ . With streptomycin, however, anodal polarization reduces, rather than increases, the mechanosensitivity (Fig . 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Biochimie, 1986 May, 68(5), 705 - 13
Functional interactions between mutated forms of ribosomal proteins S4, S5 and S12; Andersson DI et al.; Here we show that ram mutations, either in ribosomal protein S4 or S5, decrease the proofreading flows for both cognate and noncognate ternary complexes bound by streptomycin-dependent (SmD) ribosomes . This effect is accompanied by a slight increase in the overall error frequency . More important, however, is the decreased proofreading of the cognate species which is almost reduced to wild-type levels . The data suggest that it may be the reduction of the proofreading of the cognate substrate that is important for suppressing streptomycin dependence . Furthermore, we show that rpsE mutants, selected from streptomycin-dependent strains, behave kinetically very similarly to the previously described rpsD mutants.

J Clin Microbiol, 1986 May, 23(5), 934 - 7
Nonweekend schedule for BACTEC drug susceptibility testing of Mycobacterium tuberculosis; Hawkins JE; Determination of the drug susceptibility of Mycobacterium tuberculosis by conventional methods using an agar-based medium may take 3 weeks or more to complete . On the other hand, results on positive cultures are generally available in 4 to 7 days with the radiometric (BACTEC, Johnston Laboratories, Towson, Md.) procedure . One disadvantage to the latter is the requirement to determine the quantity of 14CO2 in each test vial on a daily basis from the day of inoculation . Growth index readings often must be made over weekends, adding to the work load of clinical laboratories during periods of reduced staff or necessitating compensatory pay or time . Susceptibility tests with streptomycin, isoniazid, ethambutol, and rifampin against 104 M . tuberculosis strains were performed by the submerged disk method, the recommended BACTEC method with daily growth index readings, and the radiometric procedure with readings delayed for 2 days after inoculation . Criteria for interpretation of "delayed" tests were established . Drug concentrations tested included some modifications of those available commercially . Overall agreement for the four drugs by the three methods was greater than 90% . We conclude that under our test conditions a schedule of inoculation of radiometric test vials on Friday with growth index readings commencing on Monday gives susceptibility results that correlate well with the daily BACTEC method and with a conventional 7H10 agar method.

Biochem Pharmacol, 1986 May 1, 35(9), 1539 - 45
Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone; Turk SR et al.; The effects of thiosemicarbazone derivatives of 2-acetylpyridine on mammalian and viral ribonucleoside diphosphate reductases were investigated . The enzymes were partially purified from uninfected and herpes simplex virus type-1 (HSV-1)-infected KB cells by sequential salt fractionation with streptomycin sulfate and ammonium sulfate and by affinity chromatography on ATP-agarose . The five thiosemicarbazone derivatives investigated were all potent inhibitors of the virus-induced reductase . Fifty percent inhibitory concentrations (IC50 values) range from 2 to 13 microM . Four of the five derivatives also were inhibitors of the host cell reductase (IC50 values = 7-34 microM) . A semicarbazone was inactive against the cellular enzyme and relatively weak as an inhibitor of the viral enzyme (IC50 = 340 microM) . Four of six compounds were preferential inhibitors of the viral reductase based on a comparison of IC50 values (5- to greater than 85-fold difference) . Kinetic experiments revealed that inhibition of the HSV-1 reductase by the thiosemicarbazones was noncompetitive with respect to CDP and dithiothreitol . A comparison of the inhibitory effects of 2-acetylpyridine thiosemicarbazone itself on viral reductase and on virus replication in vitro demonstrated a similarity in the dose-response relationships for the two parameters . This observation supports the hypothesis that the HSV-induced ribonucleoside diphosphate reductase is an important target for the design of antiviral drugs.

J Microencapsul, 1986 Apr-Jun, 3(2), 101 - 8
Streptomycin sulphate microspheres: formulation and in vivo distribution; Gurkan H et al.; Albumin and gelatin microspheres of streptomycin sulphate were formulated and their potential as a drug delivery system for a tuberculostatic agent in vivo was evaluated . Biodistribution was determined by i.v . administration of a 99mTc-labelled microsphere suspension to mice . The radioactivity of the lungs was compared with the radioactivity of the liver, spleen, kidney and heart at 10 min, 60 min, 4 h and 24 h post-injection . The percentage accumulated was higher in the lungs than in the other organs for both albumin and gelatin microspheres.

J Pharm Pharmacol, 1986 Apr, 38(4), 259 - 63
Factors influencing cryoprotective activity and drug leakage from liposomes after freezing; Higgins J et al.; The effects of freezing and thawing conditions and cryoprotective additives on release of streptomycin from lecithin liposomes following freeze-thaw cycles have been investigated . Drug retention was maximized by slow cooling (approx . 1 degree C min-1) . At temperatures between 0 degree and -20 degrees C, the extent of drug loss was time-dependent indicating incomplete freezing; below -45 degrees C this effect was abolished and the system was stable . Osmotic gradients across the liposome membrane during freezing were found to have little effect on drug loss . Marked cryoprotective activity was shown by dimethylsulphoxide, glycerol, alanine and glycinebetaine at concentrations of 3% w/v or less . At this concentration sucrose and mannitol had little activity.

Mutagenesis, 1986 Mar, 1(2), 111 - 7
Mutagenic DNA repair in Escherichia coli . XII . Ultraviolet mutagenesis in excision-proficient umuC and lexA (ind-) bacteria as revealed by delayed photoreversal; Bridges BA et al.; Streptomycin-resistant mutations are induced in excision-proficient umuC122::Tn5 bacteria given delayed photoreversal after u.v . light . The mutations occur after much earlier photoreversal than is found with the similar induction of tryptophan-independent mutations in excision-deficient umuC bacteria and the process is not markedly influenced by the presence of Casamino acids . The yield of mutants is between 25 and 40% of that found immediately after u.v . irradiation of isogenic umu+ bacteria . Mutagenesis is not inhibited by the presence of chloramphenicol after u.v . and before photoreversal when the bacteria have also been pretreated with chloramphenicol . Loss of photoreversibility of streptomycin-resistant mutations in umu+ excision-proficient bacteria also occurs during a similar period after u.v . and is similarly unaffected by Casamino acids and chloramphenicol . The results are interpreted on a 2-step model of error-prone repair in which a misincorporation step is followed by a lesion bypass step which requires induced levels of umuC gene product, the latter step being unnecessary when the pyrimidine dimer is removed by photoreversal after the misincorporation has taken place . Differences from the same phenomenon in excision-deficient bacteria are accounted for by the fact that in excision-proficient bacteria the mutation process is initiated by excision repair rather than during normal chromosomal replication . It is suggested that loss of photoreversibility in excision-proficient umu+ bacteria may reflect the misincorporation step only, thus explaining the apparent non-inducible nature of loss of photoreversibility previously reported . The bypass step alone requires induced levels of umuD,C gene products as is evidenced by the u.v.-induction of mutations in lexA102(ind-) bacteria after delayed photoreversal.(ABSTRACT TRUNCATED AT 250 WORDS)

Mol Gen Genet, 1986 Feb, 202(2), 207 - 11
How do combinations of rpsL- and miaA- generate streptomycin dependence?
Diaz I, Ehrenberg M, Kurland CG.
Petrullo et al . (1983) have studied the consequences of combining a mutation (rpsL-) that normally generates streptomycin resistant (Smr) ribosomes with a mutation (miaA-) that leads to loss of a tRNA hypermodification . They found surprisingly that such doubly mutant bacteria become streptomycin dependent (Smd) . Here, we show in vitro that ribosomes purified from an Smr mutant behave very like Smd ribosomes when they are combined with tRNA from an miaA- mutant . Our analysis suggests that proofreading becomes excessively intense when the mutant components are combined, and that this reduces the efficiency of translation to the very low levels characteristic of Smd ribosomes . We show that Sm increases the efficiency of translation in vitro by suppressing the proofreading flows . We suggest that this will explain the growth stimulatory effect of Sm on the rpsL-, miaA- double mutants.

J Maxillofac Surg, 1986 Feb, 14(1), 8 - 9
Peripheral streptomycin/lidocaine injections in the treatment of idiopathic trigeminal neuralgia . A preliminary report; Sokolovic M et al.; Streptomycin sulphate dissolved in 2% lidocaine solution was deposited adjacent to peripheral branches of maxillary or mandibular nerves in 20 patients with idiopathic trigeminal neuralgia . The patients were given five injections at approximately one week intervals . In the postinjection period, once the local anaesthetic had worn off, apparently normal sensation returned . All patients obtained pain relief, only four having a recurrence of symptoms . The remaining 16 patients remained free of pain after periods of up to 30 months.

J Clin Microbiol, 1986 Feb, 23(2), 385 - 6
Evaluation of streptomycin and ethambutol concentrations for susceptibility testing of Mycobacterium tuberculosis by radiometric and conventional procedures; Woodley CL; Clinical isolates of Mycobacterium tuberculosis were used to compare various concentrations of streptomycin and ethambutol in the BACTEC 460 (Johnston Laboratories, Inc., Towson, Md.) radiometric method for drug susceptibility testing with those in the conventional method . Streptomycin used at 2.0 micrograms/ml for both methods showed a 0.99 agreement with susceptible strains and a 0.97 agreement with resistant strains . Ethambutol used at 2.5 micrograms/ml for the radiometric method showed 1.00 agreement with both susceptible and resistant strains when compared with ethambutol at 5.0 micrograms/ml for the conventional method.

Nucleic Acids Res, 1986 Jan 24, 14(2), 883 - 98
The enigma of the gene coding for ribosomal protein S12 in the chloroplasts of Nicotiana; Fromm H et al.; A 2.9 kbp region from within the inverted repeat of Nicotiana chloroplast DNA hybridized with a chloroplast DNA fragment from Euglena containing the complete rps12 gene coding for ribosomal protein S12 . Nucleotide sequencing within this region revealed the existance of two rps12 coding stretches interrupted by 540 bp having class II intron structure . Joining and decoding the exon regions produced a sequence of 85 amino acids colinear and 81% homologous to the S12 protein of Euglena chloroplasts and E . coli, starting from amino acid residue 38 to the stop codon . Immediately upstream of codon 38, conserved intron sequences were located . However, the 5' 37 codon of Nicotiana chloroplast rps12 could not be identified by electron microscopy of RNA-DNA hybrids within a DNA region extending 4000 bp upstream of codon 38, nor by computer search of a completely sequenced region extending for more than 9000 bp upstream of this codon . In E . coli, alteration in rps12 codons 42 or 87 causes streptomycin resistance . However, the nucleotide sequence of the identified rps12 exons in two Nicotiana chloroplast mutants resistant to streptomycin were found to be identical to that of wild type.

Dtsch Med Wochenschr, 1986 Jan 3, 111(1), 20 - 2
{Brucella canis infection in man}; Schoenemann J et al.; A Brucella canis infection, causing recurrent fever with so-called granulomatous hepatitis and splenomegaly, was detected serologically in a 30-year-old female patient . The disease originated in an infected dog from Greece which also showed a high titre . Following successful initial treatment with cotrimoxazole and streptomycin the disease broke out again on two further occasions . The infection was finally cured by 4-months continuous cotrimoxazole treatment after which the Brucella canis titre dropped from 1:1280 to 1:40 and then to zero . The patient has been symptom-free for the last two years.

Eur J Respir Dis, 1986 Jan, 68(1), 12 - 8
Short-course tuberculosis chemotherapy studies conducted in Poland during the past decade; Snider DE Jr et al.; During the past decade, six short-course (6-month) chemotherapy regimens were studied in which drugs were given daily and intermittently . Four regimens containing isoniazid, rifampin, and ethambutol caused little toxicity but yielded relapse rates (8-21%) which were unacceptably high . The safety of giving rifampin (450 or 600 mg) twice weekly was confirmed, however, and there was evidence that daily therapy during the 4-month continuation phase was no more effective than twice weekly isoniazid and rifampin . Once weekly therapy during the continuation phase was clearly inadequate . The use of four drugs (isoniazid, rifampin, pyrazinamide, and streptomycin) given daily during the initial 2 months of therapy followed by 4 months of twice weekly isoniazid and rifampin resulted in a nearly 100% cure rate . However, this regimen was not well tolerated by patients . Deleting streptomycin improved the tolerability of the regimen but appears to have slightly increased the frequency of treatment failure and relapse . A suggested model for choosing treatment regimens is presented.

Radiat Res, 1986 Jan, 105(1), 8 - 17
Mutation induction in Escherichia coli WP2 uvrA by Cerenkov emission associated with 137Cs gamma irradiation; Redpath JL et al.; Evidence is presented for the mutation of the tryptophan-requiring bacterial strain Escherichia coli WP2 uvrA from auxotrophy to prototrophy, and from streptomycin sensitivity to resistance, by Cerenkov emission associated with 137Cs gamma irradiation . Furthermore, the data strongly suggest a more than additive interaction between the gamma-induced damage and that induced by Cerenkov emission for both mutations scored . An additional observation is that mutant yields (expressed as mutants/10(7) survivors) show a dependence on the number of viable cells plated for both uv (254 nm) and Cerenkov-induced mutations, but not for those induced by gamma irradiation . This demonstrates another similarity between uv- and Cerenkov-induced damage.

Auris Nasus Larynx, 1986, 13 Suppl 2, S181 - 92
Clinical investigation of vestibular damage by antituberculous drugs; Nakayama M et al.; Vestibular function testing was done regularly on the cases given streptomycin, kanamycin, or enviomycin and a method to detect the cases of vestibular dysfunction at an early stage was discussed, as well as the time these drugs should be discontinued . Subjects were 85 cases of tuberculosis treated with streptomycin, kanamycin, or enviomycin who were admitted to our hospital from December 1984 to May 1986 . The method of equilibrium examination performed at regular intervals is as follows: standing test (Romberg test), stepping test, and Meyer zum Gottesberge's head-shaking test were done once a week for a month after starting antituberculous injections and they were re-examined once every 2 weeks for at least 3 months after beginning the injections . After the 3 months these tests were done once a month . Eight cases of vestibular damage due to streptomycin or enviomycin could be easily detected at an early stage by performing Meyer zum Gottesberge's head-shaking test, together with the standing test and the stepping test . Vestibular dysfunction is apt to occur after about 1 month or within a month from the start of daily injections especially with streptomycin . Therefore, the method of equilibrium examination, we suggest, is that the Meyer zum Gottesberge's head-shaking test, the standing test (Romberg test), and the stepping test should be performed once a week during the first month after the start of this drug . When the result of the Meyer zum Gottesberge's head-shaking test is less than 50% and swaying and/or rotation occur in the stepping test, the drugs being given should be discontinued.

Hear Res, 1986, 22, 297 - 304
Molecular mechanisms of drug-induced hearing loss; Schacht J; Although the ototoxic actions of a variety of drugs have long been documented, the biochemical mechanisms underlying such toxicity largely remain to be established . For example, recent advances have provided us with information about the actions of salicylates (aspirin) and diuretics (furosemide) but we are not yet able to specify the mechanisms by which these drugs damage the cochlea . On the other hand, the considerable amount of biochemical and pharmacological data on the effects of aminoglycosides (streptomycin, neomycin, gentamicin and related compounds) has enabled us to formulate a rational hypothesis of their mechanism of action . We have previously presented evidence for an involvement of polyphosphoinositides in the ototoxic actions of aminoglycosides . Recent electrophysiological and pharmacokinetic studies have shown in addition that aminoglycosides occupy at least two distinct compartments in the course of their actions . Further studies of drug uptake in vitro and of drug toxicity in cochlear perfusions suggested the involvement of an active (energy-requiring) aminoglycoside transport system . These and other data are compatible with the following multi-step model of aminoglycoside toxicity: The initial step in the reaction sequence is an electrostatic interaction of aminoglycosides with the plasma membrane . The resulting displacement of calcium accounts for acute effects but the action is reversible and antagonized by divalent cations . An energy-dependent uptake process is required for the expression of toxicity . It can be prevented by select metabolic blockers . A crucial step in subsequent intracellular drug actions is the binding of aminoglycosides to phosphatidylinositol bisphosphate inhibiting its hydrolysis and preventing its physiological function.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene, 1986, 42(2), 221 - 4
Cloning of a streptomycin-production gene directing synthesis of N-methyl-L-glucosamine; Kumada Y et al.; A Streptomyces bikiniensis DNA fragment complementing a deficiency in streptomycin (Sm) production was cloned on the plasmid vector pIJ385 . Host strain S . bikiniensis SD 1 used as the recipient in cloning displayed deficiency in biosynthesis of N-methyl-L-glucosamine, one of the moieties of Sm . The cloned fragment on the multicopy plasmid pIJ385 conferred sevenfold increase in Sm production in comparison with the wild-type parental strain . By subcloning, the region complementing the Sm deficiency of SD 1 was narrowed to a 3.0-kb fragment.

Histochemistry, 1986, 84(3), 237 - 40
Localization of an aminoglycoside (streptomycin) in the inner ear after its systemic administration . A histochemical study using fluorescence microscopy; Bareggi R et al.; We used the simple method of direct cytofluorescence to detect the presence of the aminoglycoside, streptomycin, in the inner ear after its systemic administration . In the cochlea, fluorescence was observed in the organ of Corti, the spiral ganglion, the nerve fibres, the vascular stria and Reissner's membrane; in the vestibulum, fluorescence was seen in the crista ampullaris and the planum semilunatum . The localization of the drug was related to the distribution of its specific receptor, triphosphoinositide (TPI); therefore, it is reasonable to assume that aminoglycosides exert their toxic effects by binding to TPI.

Gene, 1986, 41(2-3), 145 - 52
Tn1721 derivatives for transposon mutagenesis, restriction mapping and nucleotide sequence analysis; Ubben D et al.; New derivatives of the tetracycline-resistance transposon Tn1721 that carry resistances to chloramphenicol, tetracycline, kanamycin and streptomycin are described . These elements are provided on various plasmid vehicles and as chromosomal insertions to extend the range of targets for Tn mutagenesis . Single EcoRI sites at the ends of these transposons proved most useful for physical mapping, for the generation of new EcoRI sites in cloning experiments, for end-labelling and for sequencing of DNA adjacent to an insertion.

Gene, 1986, 41(1), 125 - 8
Improved vector, pHSG664, for direct streptomycin-resistance selection: cDNA cloning with G:C-tailing procedure and subcloning of double-digest DNA fragments; Hashimoto-Gotoh T et al.; A plasmid cloning vector, pHSG664, has been constructed which is suitable for the direct-selection of transformed cells with recombinant DNAs . The plasmid contains the replicon and ApR-gene region of pUC9 ligated to the strA+ (rpsL+) gene derived from pNO1523 {Dean, Gene 15 (1981) 99-102} . The vector contains ten unique restriction sites: EcoRI, HpaI, PvuII, SphI, PstI, SmaI(XmaI), BamHI, SalI(AccI, HincII), XbaI and HindIII . Five sites (bold-face lettering) are located within the coding region of the strA+ gene . Any insertion at the five bold-faced sites or any nucleotide replacement involving the strA+ gene region and the other unique sites can be selected by Ap and Sm double selection in a strA- (SmR) strain such as E . coli HB101 . Thus, this vector is useful for cDNA cloning at either the SphI or the PstI site with the G:C-tailing procedure, as well as for the cloning of double-digest DNA segments.

Mol Gen Genet, 1986 Jan, 202(1), 143 - 51
The nucleotide sequence of the mercuric resistance operons of plasmid R100 and transposon Tn501: further evidence for mer genes which enhance the activity of the mercuric ion detoxification system; Brown NL et al.; The DNA sequences of the mercuric resistance determinants of plasmid R100 and transposon Tn501 distal to the gene (merA) coding for mercuric reductase have been determined . These 1.4 kilobase (kb) regions show 79% identity in their nucleotide sequence, and in both sequences two common potential coding sequences have been identified . In R100, the end of the homologous sequence is disrupted by an 11.2 kb segment of DNA which encodes the sulfonamide and streptomycin resistance determinants of Tn21 . This insert contains terminal inverted repeat sequences and is flanked by a 5 base pair (bp) direct repeat . The first of the common potential coding sequences is likely to be that of the merD gene . Induction experiments and mercury volatilization studies demonstrate an enhancing but non-essential role for these merA-distal coding sequences in mercury resistance and volatilization . The potential coding sequences have predicted codon usages similar to those found in other Tn501 and R100 mer genes.

Gene, 1986, 50(1-3), 133 - 40
The construction of a cloning vector designed for gene replacement in Bordetella pertussis; Stibitz S et al.; We report here the construction of a plasmid cloning vector, pRTP1, designed to facilitate exchange of cloned and chromosomal alleles of the human bacterial pathogen Bordetella pertussis . pRTP1 provides the ability to successively select two homologous recombination events within the cloned sequences . The first is by selection for maintenance of the ampicillin-resistance gene on the plasmid which is unable to replicate autonomously after transfer via conjugation . The second selection, via streptomycin (Sm) selection, is against the maintenance of vector sequences which contain a gene encoding the Sm-sensitive allele of the gene for ribosomal protein S12 thus rendering an otherwise Sm-resistant strain Sm-sensitive . We demonstrate the use of this vector to introduce an unmarked mutation, constructed in vitro, into the chromosomal locus encoding pertussis toxin.

Nippon Yakurigaku Zasshi, 1985 Dec, 86(6), 377 - 83
{Measurement of an auditory impairment induced by aminoglycosides using a shuttle box method in newborn rats}; Kameyama T et al.; To investigate the auditory impairment induced by the administration of aminoglycosides in the newborn, the shuttle box method was employed to measure the auditory threshold of rats . Five groups of newborn rats were administered kanamycin sulfate, 250 and 500 mg/kg, streptomycin sulfate, 250 and 500 mg/kg, or 1 ml/kg saline, subcutaneously, from the 10th to the 15th day of birth . The auditory threshold of the control group could be measured by the shuttle box method at the age of 100 days . The auditory threshold of the control group was 52.1 +/- 1.0 dB (N = 14) . The auditory thresholds of the animals treated with kanamycin 250 mg/kg and streptomycin 250 mg/kg groups were measured in only 1 (61.0 dB) and 4 (64.8 +/- 4.6 dB), respectively, since the auditory toxicity of these drugs in newborn rats was stronger than adult rats . Auditory threshold of the 250 mg/kg streptomycin group was significantly higher than that of the control group . The animals which could not be measured for the auditory threshold had the ability to acquire conditioned avoidance response when both conditioned stimuli (tone and light) were presented . However, after differentiation of the stimuli, the percent avoidance to tone in these animals was significantly decreased and did not recover by the following trainings, while the percent avoidance to light was similar to that before the differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Can J Genet Cytol, 1985 Dec, 27(6), 776 - 9
Neomycin is more efficient than streptomycin in suppressing frameshift mutations; Phoenix P et al.; The effects of streptomycin and neomycin on the phenotypic suppression of frameshift mutations in the lacZ gene of Escherichia coli and on the efficiency of suppression of amber mutations in T4 phage by the informational supE tRNA nonsense suppressor were compared . Neomycin stimulated much more efficiently than streptomycin the phenotypic suppression of frameshift mutations . Because neomycin favors mismatches of the central codon base whereas streptomycin favors mismatches of the first codon base, this result suggests that mismatching of the central codon base pair and shifting of the reading frame are two correlated phenomena . In contrast, both streptomycin and neomycin stimulated about equally the efficiency of the tRNA nonsense suppressor, an effect probably related to their interference with the proofreading control in tRNA selection.

FEBS Lett, 1985 Nov 11, 192(1), 165 - 9
Effect of streptomycin on the stoichiometry of GTP hydrolysis in a poly(U)-dependent cell-free translation system; Smailov SK et al.; The technique of Sepharose-bound template translation has been used to estimate the stoichiometry of GTP hydrolysis during peptide elongation in the presence of streptomycin . The presence of streptomycin has been shown to have no great effect on the elongation rate and the stoichiometry of GTP hydrolysis during codon-specific peptide elongation in the poly(U)-directed translation system: the molar ratio of hydrolysed GTP to incorporated phenylalanine was about 2 . At the same time streptomycin exerted a significant effect during misreading when a ribosome-bound peptide in the poly(U)-programmed system was elongated by leucine or isoleucine residues: the miselongation was stimulated and hence the ratio of hydrolysed GTP per peptide bond was strongly reduced, as compared with the excessive GTP hydrolysis which is characteristic of the misreading system in the absence of streptomycin {(1984) FEBS Lett . 178, 283-287} . The conclusion has been made that streptomycin blocks the stage of correction ('proof-reading') following GTP hydrolysis during EF-Tu-dependent aminoacyl-tRNA binding.

Nucleic Acids Res, 1985 Oct 11, 13(19), 7095 - 106
Nucleotide sequence of the transposon Tn7 gene encoding an aminoglycoside-modifying enzyme, 3"(9)-O-nucleotidyltransferase; Fling ME et al.; The nucleotide sequence of a transposon Tn7 DNA fragment encoding a 3"(9)-O-nucleotidyltransferase, an aminoglycoside-modifying enzyme, which mediates bacterial resistance to spectinomycin and streptomycin, was determined . The aadA structural gene was 786 bases long and predicted a polypeptide of 262 amino acids with a calculated molecular weight of 29,207 . Comparison of the DNA sequences of Tn7 and plasmid R538-1 indicated that their aadA genes were nearly identical . Comparison of the polypeptides predicted by the aadA genes of Tn7 and Tn554 indicated that the genes were related.

J Chromatogr, 1985 Oct 11, 343(2), 379 - 85
Determination of streptomycin in serum by high-performance liquid chromatography; Kurosawa N et al.; A high-performance liquid chromatographic method was developed for monitoring the serum concentration of streptomycin . The method includes clean-up using a Sep-Pak C18 cartridge and quantitation using dihydrostreptomycin as an internal standard . Streptomycin and dihydrostreptomycin were separated by reversed-phase ion-pair chromatography on LiChrosorb RP-18 and detected by UV absorption (195 nm) . The calibration graph of serum streptomycin concentration was linear over the range 5-50 micrograms/ml . Streptomycin was added to serum at the level of 20.0 micrograms/ml and its concentration was determined to be 18.9 micrograms/ml with a coefficient of variation of 2.07% (n = 5) . The clinical application of this method was confirmed by comparison with fluorescence polarization immunoassay.

Postgrad Med, 1985 Oct, 78(5), 249, 253 - 4, 257
Brucella canis infection in a woman with fever of unknown origin; Rousseau P; A 58-year-old woman with prolonged febrile illness was found to have brucellosis caused by Brucella canis, presumably acquired through contact with infected dogs . After initial laboratory tests failed to yield a diagnosis, the disease was confirmed by the Brucella agglutination test . A combination of tetracycline and streptomycin therapy was begun, and the illness resolved . B canis, a recently recognized cause of human brucellosis, must now be considered in patients with fever of unknown origin . With adequate medical therapy, rapid and complete recovery can be expected.

Can J Microbiol, 1985 Oct, 31(10), 957 - 60
Intralaboratory comparison of drug susceptibility testing of Mycobacterium tuberculosis by BACTEC and conventional methodology; Laszlo A; The BACTEC radiometric method of drug susceptibility testing of Mycobacterium tuberculosis is a reliable and rapid diagnostic tool in clinical mycobacteriology . However, large scale comparative studies have also shown that the level of agreement with standard methodology was less satisfactory with strains resistant to ethambutol and streptomycin than with strains resistant to rifampin and to isoniazid . Since disagreement with drug resistance strains is far more frequent than with drug susceptible strains, it was felt that only the comparison of a large number of resistant strains would be needed to further refine this new technique . The analysis of BACTEC-derived data for isoniazid and rifampin shows that the level of agreement with conventional methodology falls well within accepted limits . Statistical analysis of the radiometric versus conventional comparisons shows no significant differences between the two methods in the case of isoniazid, rifampin, and ethambutol (3 mg/L) . Streptomycin and two other ethambutol concentrations tested showed lower levels of agreement and significant statistical differences with conventional methodology.

Am Rev Respir Dis, 1985 Oct, 132(4), 737 - 41
Operational evaluation of treatment for tuberculosis . Results of 8- and 12-month regimens in Peru; Hopewell PC et al.; To measure the effectiveness of treatment for pulmonary tuberculosis in Peru we evaluated the fate of 2,669 patients who had tuberculosis diagnosed in 1981 . Two regimens were used: (1) isoniazid, rifampin, pyrazinamide, and streptomycin daily for 2 months, then either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily for 6 months; and (2) isoniazid, streptomycin, and thiacetazone daily for 2 months, then either isoniazid and streptomycin twice weekly or isoniazid and thiacetazone daily for 10 months . Patients were not assigned at random to the 2 treatment regimens; thus, the results cannot be directly compared . In the 8-month group, 70% had a favorable outcome, 14% abandoned, 9% failed, 3% died, and 3% relapsed . In the 12-month group, 53% had a favorable outcome, 34% abandoned, 6% failed, 4% died, and 2% relapsed . In patients who did not abandon treatment, the results of both regimens were nearly identical . Patients in both groups who had been treated previously had significantly lower rates of cure than those not treated previously.

Avian Dis, 1985 Oct-Dec, 29(4), 1239 - 51
Investigations of toxicity episodes involving chemotherapeutic agents in Victorian poultry and pigeons; Reece RL et al.; This series of case reports details observations on toxicity episodes in poultry due to a variety of chemotherapeutic agents . These problems arose owing to overdosage, variation in species susceptibility, potentiation of the toxic effects of one substance by the presence of another substance, and particular disease or other on-farm factors . Ignorance and accident were responsible for some of these situations . The episodes involved monensin, salinomycin, nicarbazin, sulphaquinoxaline, dinitolmide, dimetridazole, nitrofurans, streptomycin, and 3-nitro-4-hydroxyphenylarsonic acid.

J Bacteriol, 1985 Oct, 164(1), 85 - 94
Self-cloning in Streptomyces griseus of an str gene cluster for streptomycin biosynthesis and streptomycin resistance; Ohnuki T et al.; An str gene cluster containing at least four genes (strR, strA, strB, and strC) involved in streptomycin biosynthesis or streptomycin resistance or both was self-cloned in Streptomyces griseus by using plasmid pOA154 . The strA gene was verified to encode streptomycin 6-phosphotransferase, a streptomycin resistance factor in S . griseus, by examining the gene product expressed in Escherichia coli . The other three genes were determined by complementation tests with streptomycin-nonproducing mutants whose biochemical lesions were clearly identified . strR complemented streptomycin-sensitive mutant SM196 which exhibited impaired activity of both streptomycin 6-phosphotransferase and amidinotransferase (one of the streptomycin biosynthetic enzymes) due to a regulatory mutation; strB complemented strain SD141, which was specifically deficient in amidinotransferase; and strC complemented strain SD245, which was deficient in linkage between streptidine 6-phosphate and dihydrostreptose . By deletion analysis of plasmids with appropriate restriction endonucleases, the order of the four genes was determined to be strR-strA-strB-strC . Transformation of S . griseus with plasmids carrying both strR and strB genes enhanced amidinotransferase activity in the transformed cells . Based on the gene dosage effect and the biological characteristics of the mutants complemented by strR and strB, it was concluded that strB encodes amidinotransferase and strR encodes a positive effector required for the full expression of strA and strB genes . Furthermore, it was found that amplification of a specific 0.7-kilobase region of the cloned DNA on a plasmid inhibited streptomycin biosynthesis of the transformants . This DNA region might contain a regulatory apparatus that participates in the control of streptomycin biosynthesis.

Am Rev Respir Dis, 1985 Sep, 132(3), 510 - 5
Pharmacokinetic studies on antituberculosis regimens in humans . I . Absorption and metabolism of the compounds used in the initial intensive phase of the short-course regimens: single administration study; Acocella G et al.; The absorption and metabolism of streptomycin, isoniazid, rifampicin, and pyrazinamide were evaluated after administration of each drug alone and in combination . In the combination sessions, isoniazid, rifampicin, and pyrazinamide were administered orally, either individually or in a single fixed-ratio triple preparation . The results have shown that the pattern of absorption and metabolism (acetyl-isoniazid, desacetyl-rifampicin, and pyrazinoic acid) found after administration of each drug alone did not differ from that found after administration of the drugs in free and fixed combination . The 3 orally administered drugs given in a fixed combination resulted in a reduction of the order of 50% of the total number of tablets to be ingested.

J Am Vet Med Assoc, 1985 Sep 1, 187(5), 493 - 5
Efficacy of long-acting oxytetracycline alone or combined with streptomycin in the treatment of bovine brucellosis; Nicoletti P et al.; Twenty-nine Brucella abortus culture-positive cows were treated with a long-acting oxytetracycline (20 mg/kg of body weight, IM) alone or combined with streptomycin (25 mg/kg, IM or IV) or were re-treated with the same product . There appeared to be a synergism by the 2 drugs . Of 21 courses of treatment with the combined antibiotics, 14 (67%) were considered successful . Only 3 of 14 (21%) were successful using oxytetracycline alone . The period from onset of therapy to cessation of shedding in udder secretions was variable . Four cows that ceased shedding were culture-positive in tissues taken at slaughter . The titers on tube agglutination and complement-fixation tests were of limited value in short-term evaluations of therapeutic regimens.

Mol Gen Mikrobiol Virusol, 1985 Sep, (9), 19 - 22
{The use of transposons for the mutagenesis of R . phaseoli and R . japonicum}; Ivashina TV et al.; Plasmid pSUp2011 has been used to transfer transposon Tn5 into the cells of R . japonicum 110 and R . phaseoli 693 . Transposition of Tn5 into the chromosomes of R . japonicum and R . phaseoli has been demonstrated,resulting in isolation of auxotrophic and symbiotic mutants of both strains . The frequencies of selected auxotrophic mutations have reached 4% in R . japonicum 110 and 0.6% in R . phaseoli 693 . Streptomycin resistance gene locating on Tn5 has been found to be phenotypically expressed in R . japonicum 110 and R . phaseoli 693 cells.

Neuroscience, 1985 Sep, 16(1), 171 - 9
Non-N-methyl-D-aspartate receptors mediating synaptic transmission in the avian cochlear nucleus: effects of kynurenic acid, dipicolinic acid and streptomycin; Jackson H et al.; We have examined the effects of a number of excitatory amino acid antagonists on transmission at the cochlear nerve-nucleus magnocellularis synapse in the chicken . Using an in vitro preparation and bath application of drugs, we studied the effects of kynurenic acid and several related substances, streptomycin and a selective N-methyl-D-aspartate receptor antagonist, DL-alpha-aminosuberate . The last compound had no effect on evoked transmission . Of the various kynurenic acid-related compounds tested, only kynurenic and dipicolinic acid selectively altered responses in nucleus magnocellularis . Quinolinic acid, a kynurenic acid analogue that is structurally akin to dipicolinic acid but which acts selectively at N-methyl-D-aspartate receptors, was without effect . The effect of kynurenic acid was solely inhibitory, completely blocking postsynaptic responses with a potency dependent on the frequency of nerve stimulation . No such frequency dependence was seen with dipicolinic acid although this compound also completely suppressed evoked responses . In addition dipicolinic acid potentiated postsynaptic responses at concentrations only slightly lower than those causing inhibition . Streptomycin inhibited responses in nucleus magnocellularis but this effect seems to result partially from the ability of the drug to inhibit presynaptic calcium influx . Our finding that selective antagonists of N-methyl-D-aspartate receptors were ineffective while antagonists of both receptor types, such as kynurenic and dipicolinic acids, inhibited evoked responses reinforces the conclusion that postsynaptic receptors mediating transmission at this synapse are of the non-N-methyl-D-aspartate type {Nemeth et al . (1983) Neurosci . Lett . 40, 39-44}.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasmid, 1985 Sep, 14(2), 99 - 105
Physical and genetic structure of the IncN plasmid R15; Dobritsa AP et al.; Restriction sites for seven hexanucleotide-specific endonucleases were located on the map of the conjugative IncN plasmid R15 (SmrSurHgr, 62.3 kb) . The distribution of the cleavage sites is strongly asymmetric . Twenty-eight of thirty-four sites for BamHI, EcoRI, HindIII, SalI, SmaI, and PstI were located close to or within the sequences of an IS5-like element and the transposons Tn2353 and Tn2354 . By analysis of R15::Tn1756 deletion derivatives and recombinant plasmids harboring R15 fragments, the genetic determinants for the streptomycin, sulfonamide, and mercury resistances were mapped, as well as the regions necessary for EcoRII restriction-modification and for plasmid replication and conjugation . The features of physical and genetic structures of the plasmid R15 and other IncN plasmids are discussed.

Schweiz Med Wochenschr, 1985 Aug 24, 115(34), 1160 - 5
{Brucella spondylodiskitis}; Bodmer K; In the light of two personal observations some epidemiological, radiological and serological aspects of brucellar spondylodiscitis are discussed . In Switzerland livestock is considered brucellosis-free, and hence spondylodiscitis has become an infectious disease imported from well known endemic brucellosis regions . The clinical picture is not very typical, except for circumscript vertebral pathology, and frequently the disease process lacks the humoral signs of inflammation and infection . Radiologically, early osseous reparative processes are characteristic, frequently with only minor destructive lesions . A tendency to spontaneous recovery is not uncommon and in fact is suggested by one of our own observations . The disease is, therefore, essentially different from tuberculous spondylitis . In only 20% of all cases can the presence of germs be shown in abscess or granulation tissue . Serologic tests provide valuable information but always point to a generic and not a specific diagnosis . Good therapeutic effects are obtained with trimethoprim-sulfamethoxazole which are possibly better than with combined therapy using tetracycline and streptomycin.

Lab Anim Sci, 1985 Aug, 35(4), 395 - 9
Use of streptomycin and isoniazid during a tuberculosis epizootic in a rhesus and cynomolgus breeding colony; Ward GS et al.; An epizootic of tuberculosis occurred following the addition of new cynomolgus monkeys to a nonhuman primate breeding colony . A total of 5/47 cynomolgus and 51/148 rhesus became tuberculin positive (reactors) . Mycobacterium tuberculosis was cultured from reactors which were euthanatized and monkeys which died spontaneously . The isolates were sensitive to the standard antitubercular agents . Rhesus reactors and their unweaned infants were quarantined and given streptomycin and isoniazid by intramuscular injection . Isoniazid was added to the drinking water quarantined and given streptomycin and isoniazid by intramuscular injection . Isoniazid was added to the drinking water of the remainder of the breeding colony to curtail the outbreak . Isoniazid toxicity was observed in both infants and adults with an overall incidence of 3% . Forty-eight rhesus reactors and their infants born before the outbreak were alive and healthy at the end of the treatment period . In addition, nine surviving infants were born during the 6 month treatment period . Tuberculin tests were still positive in many of the treated reactors following treatment . In this epizootic, the institution of quarantine and chemotherapy instead of euthanasia resulted in significant savings.

Am J Dis Child, 1985 Aug, 139(8), 780 - 2
Primary drug-resistant tuberculosis in children . Correlation of drug-susceptibility patterns of matched patient and source case strains of Mycobacterium tuberculosis; Steiner P et al.; The purpose of this study is to compare the drug-susceptibility patterns of Mycobacterium tuberculosis isolated from patients (children) and from their corresponding adult contacts . We wished to ascertain if the susceptibility pattern of the isolate from the adult contact could be used as a guide in the initial selection of the antituberculous drug regimen in the child . Strains resistant to one or more antituberculous drugs were emphasized in our study . For 120 children with positive cultures, adults were identified who had positive cultures and who were the source of the children's infections . All strains had susceptibility tests for isoniazid, streptomycin, aminosalicylic acid, ethionamide, and, when they became available, ethambutol and rifampin . There were 29 instances in which either the adult's and/or the child's strain were resistant to one or more antituberculous drugs . In 111 (92.5%) instances the organism isolated from the child and that from the adult contact had identical drug-susceptibility patterns . Fourteen (93%) of 15 of the adult/child pairs were both resistant to isoniazid . The drug-susceptibility pattern of isolates obtained from the source of a child's illness is useful as a guide in planning initial drug therapy . In addition, knowledge of isoniazid-resistant strains in adult contacts may alert the physician to the potential failure of isoniazid prophylaxis.

Minerva Med, 1985 Jul 31, 76(30-31), 1407 - 10
{Therapy of brucellosis: clinical experience with a rifampicin- doxycycline combination}; Montanari M et al.; After an examination of the data on brucellosis treatment in the literature, it is concluded that short-term courses of cotrimoxazole and tetracyclines give largely unsatisfactory results . In view of the synergism noted between rifampicin and doxycycline against in vitro and animal brucella, the association was given to 19 clinical cases and was found to be effective and easily handled . It is therefore concluded that this treatment is currently the best alternative to the classic streptomycin-doxycycline association.

Vet Rec, 1985 Jul 6, 117(1), 11 - 2
Comparative bacterial drug resistance in modern battery and free-range poultry in a tropical environment; Ojeniyi AA; A correlation between the use of antibiotics and drug resistance was found among Escherichia coli strains isolated from modern battery poultry at the University of Ibadan, Nigeria . All 1248 E coli strains from university poultry and 2196 strains from a commercial poultry farm in Ibadan were resistant to tetracycline, streptomycin and sulphonamide, the minimal inhibitory concentrations of these drugs being found to be several times those of the control E coli NCTC 10418 . In contrast, all 2284 strains isolated from free-range town and village poultry were sensitive to these drugs . In the tropical developing countries with poor environmental sanitation and low personal hygiene, this situation has public health implications.

Vopr Virusol, 1985 Jul-Aug, 30(4), 427 - 33
{Characteristics of tick-borne encephalitis virus strains isolated from patients with chronic diseases of the central nervous system}; Pogodina VV et al.; Two groups of tick-borne encephalitis (TBE) virus strains were studied: Group 1, 5 strains isolated from patients with chronic TBE with progressive course, Group 2, 13 strains isolated from residents of an endemic locality, with chronic diseases of the CNS (amiotrophic lateral sclerosis, epidemic encephalitis, polyoencephalomyelitis, syringomyelia, etc.) . Strains of both groups belong to two serotypes of TBE virus: mid-Siberian and Transbaikal (synonym Aina/1448) and eastern . Group 1 strains were heterogeneous in their virulence, immunogenic and surface properties of the virions . The latter characteristic was demonstrated in studies of elution from macropore glass and sensitivity of hemagglutinin to the effect of detergents (Bridge-96, Tween-80) . Eight of 13 Group 2 patients had concurrent diseases (tuberculosis, toxoplasmosis, tumors, etc.) . Streptomycin was demonstrated to activate asymptomatic infection with TBE virus in hamsters . It is assumed that isolation of TBE virus from Group 2 patients could be due to activation of persistent infection under the effect of concurrent diseases and drugs.

J Gen Microbiol, 1985 Jul, 131 ( Pt 7), 1657 - 69
Cloning of a DNA fragment from Streptomyces griseus which directs streptomycin phosphotransferase activity; Vallins WJ et al.; DNA from Streptomyces griseus ATCC 12475 was partially digested with Sau3A and fragments were ligated into BglII-cleaved pIJ702 . When the ligation mixture was used to transform protoplasts of Streptomyces lividans TK54, two transformants resistant to both thiostrepton and streptomycin were isolated . The hybrid plasmids pBV3 and pBV4 which they contained, carrying inserts of sizes 4.45 and 11.55 kbp respectively, each retransformed S . lividans to streptomycin resistance at high efficiency . Both plasmids hybridized to restriction digests of S . griseus chromosomal DNA in Southern blot experiments . In vitro deletion and sub-cloning experiments showed the sequence conferring streptomycin resistance to lie within a segment of 1.95 kbp . Extracts of TK54(pBV3) and TK54(pBV4) contained a streptomycin phosphotransferase similar to that in extracts of S . griseus . Streptomycin phosphotransferase activity appeared in extracts of S . griseus, TK54(pBV3) and TK54(pBV4) within 2 d of inoculation . When pBV3 and pBV4 were retransformed into S . griseus with selection for thiostrepton resistance, plasmid DNA of sizes corresponding to the incoming plasmids was found in the transformants . In these transformants the phosphotransferase appeared at 1.5 rather than 2 d, and reached a level over twice that of the original S . griseus strain.

Nucleic Acids Res, 1985 Jun 25, 13(12), 4299 - 310
Streptomycin-resistance of Euglena gracilis chloroplasts: identification of a point mutation in the 16S rRNA gene in an invariant position; Montandon PE et al.; We sequenced the chloroplast 16S rRNA gene of two Euglena gracilis mutants which contain streptomycin-resistant chloroplasts (Smr 139.12/4 and Smr 139.20/2) . These mutants are known to contain a single intact rrn operon per circular chloroplast genome . Nucleotide sequence comparison between a 16S rRNA gene of wild type Euglena gracilis, strain Z, with streptomycin-sensitive chloroplasts, and the 16S rRNA gene of both Smr-strains reveals a single base change (C to T) at position 876 . This position is equivalent to the invariant position 912 of the E . coli 16S rRNA gene . The analogous position is also conserved in all chloroplast small subunit RNA genes from lower and higher plants sequenced so far . Light dependent protein synthesis with purified chloroplasts from streptomycin-resistant cells is not inhibited by streptomycin . Based on the results reported here we postulate linkage between the observed point mutation on the 16S rRNA gene and streptomycin-resistance of chloroplast 70S ribosomes.

Am Rev Respir Dis, 1985 Jun, 131(6), 944 - 6
Dosage of antituberculous drugs in obese patients; Geiseler PJ et al.; There are no published data defining efficacious drug therapy for obese patients with active tuberculosis . Current dosage recommendations are based on total body weight (TBW); drug toxicity might result in obese patients receiving TBW doses . Peak and trough serum levels were measured for rifampin, streptomycin, ethambutol, and pyrazinamide in an obese patient (166 kg TBW, 87 kg ideal body weight (IBW} with miliary and meningeal tuberculosis . The observed drug levels and the calculated serum half-lives of these drugs were compared with the expected serum levels and serum half-lives in lean patients treated with literature-recommended doses . The observed serum levels in our obese patients were within the expected range for lean patients when dosage was based on IBW rather than on TBW . The observed cerebrospinal fluid penetrations of the drugs studied in our obese patient were similar to those reported in lean patients.

Cell, 1985 Jun, 41(2), 587 - 95
Production of abnormal proteins in E . coli stimulates transcription of lon and other heat shock genes; Goff SA et al.; The product of the lon gene in Escherichia coli, protease La, plays an important role in the degradation of abnormal proteins . To determine whether the presence of abnormal proteins stimulates expression of this gene, we examined its transcription using a lon-lacZ operon fusion . After the cells synthesized large amounts of aberrant polypeptides (e.g . following incorporation of the arginine analog, canavanine, or production of incomplete proteins with puromycin, or induction of translational errors with streptomycin), these cells showed a two- to threefold increase in lon--lacZ expression . Furthermore, synthesis of a single cloned protein, e.g . human tissue plasminogen activator, caused a similar increase in lon transcription . This induction of lon by abnormal proteins requires the heat shock regulatory gene htpR and was not seen in htpR- cells . Under these various conditions, other heat shock proteins were also induced . Thus, the appearance of aberrant cell proteins may be a common signal under many adverse conditions for the induction of cell protease (or proteases) and other heat shock proteins.

J Bacteriol, 1985 Jun, 162(3), 1332 - 5
Broad-host-range plasmid pRK340 delivers Tn5 into the Legionella pneumophila chromosome; Keen MG et al.; Transposon Tn5 was introduced into Legionella pneumophila on plasmid pRK340, which is temperature sensitive for plasmid maintenance . The presence of plasmid DNA was confirmed by agarose gel electrophoresis and by conjugal transfer of the plasmid to Escherichia coli . Tn5 insertions were obtained by culturing L . pneumophila at the nonpermissive temperature (43 degrees C) on buffered charcoal-yeast extract agar containing kanamycin . Of the 260 kanamycin-resistant colonies picked, 220 failed to conjugate pRK340 to E . coli . Plasmid DNA was not visualized from eight randomly picked Tn5-containing strains, and Southern hybridizations indicated that Tn5, but not pRK340, inserted into multiple sites in the Legionella chromosome . In addition, the streptomycin resistance determinant on Tn5 was expressed in L . pneumophila.

Arch Int Pharmacodyn Ther, 1985 Jun, 275(2), 259 - 66
The rat isolated mast cell as a model for the study of calcium antagonists; Wenzel AM et al.; EDTA-treated rat isolated mast cells were used to study the influence of Ca2+-antagonists on stimulus-secretion coupling . The concentration of Ca2+-effect curves for histamine release were parallelly shifted to the right when the cells were in the presence of Mg2+, La3+, verapamil or aminoglycoside antibiotics such as streptomycin, neomycin or gentamicin . The relative potency among the aminoglycoside was similar to that described in the literature for their action on the excitation-contraction coupling . The employed isolated mast cells preparation presented basic properties required for the study of coupled stimulus-secretion and represent an optimal model for the study of drugs which interfere with Ca2+ passage across cell membranes.

J Antibiot (Tokyo), 1985 May, 38(5), 636 - 41
The cloned Streptomyces bikiniensis A-factor determinant; Horinouchi S et al.; By cleavage with restriction endonucleases and cloning the resultant fragments, the A-factor determinant cloned from streptomycin-producing Streptomyces bikiniensis (Horinouchi et al., J . Bacteriol . 158: 481 approximately 487, 1984) was narrowed down to a 1.1-kilobase (kb) fragment . A hybrid multicopy plasmid (pAFB15) carrying the 1.1-kb fragment conferred A-factor production in a large quantity to A-factor-deficient mutants of S . bikiniensis and Streptomyces griseus as well as afsA mutants of Streptomyces coelicolor A3(2) . A transcriptional control signal in the 1.1-kb fragment was identified by using a promoter-probe vector pARC 1 . Plasmid pAFB15 also caused A-factor production with a marked gene dosage effect in four different Streptomyces strains which originally had no ability to produce A-factor and no DNA sequence homologous to the S . bikiniensis A-factor determinant, suggesting that precursors of A-factor are common metabolites in streptomycetes and that acquisition of only a single key enzyme encoded by the 1.1-kb fragment is sufficient for Streptomyces strains to synthesize A-factor.

Mutat Res, 1985 May, 149(3), 321 - 6
Mutation induction in Escherichia coli incubated in the reaction mixture of NADPH-dependent lipid peroxidation of rat-liver microsomes; Akasaka S et al.; Experiments were carried out to examine mutation induction in E . coli cells incubated in the reaction mixture of NADPH-dependent lipid peroxidation of microsomes isolated from rat liver . The results obtained were as follows: (1) Lipid peroxidation of microsomes occurred extensively on incubation with NADPH and Fe2+ . In the E . coli WP2uvrA(pKM101) system, the mutation frequency to streptomycin resistance increased markedly when the cells were incubated in the reaction mixture of microsomal lipid peroxidation . The induced mutation frequencies were dependent on the extent of the lipid peroxidation . (2) It was also found that the mutations were induced at the same rate as in the case of (1) when the cells were added to the microsomal suspensions after the reactions due to the short-lived free radicals had terminated . (3) The cytotoxicity of the lipid peroxidation products was larger in the DNA repair-defective mutant, E . coli SR18 (uvrArecA) than the wild-type strain, SR749 . From these results it is concluded that some DNA-damaging and mutagenic substances are indeed produced in the degradation process of peroxidized polyunsaturated fatty acids in liver microsomal lipids.

J Theor Biol, 1985 Apr 7, 113(3), 407 - 23
Error propagation in E . coli protein synthesis; Blomberg C et al.; A new approach to the error catastrophe theory, proposed by Leslie Orgel, is presented here . Our model is a development of previous models, but differs in several respects: the overall activity is assumed to be dependent on the error level, the effect of errors in the translating system, giving rise to additional errors in the succeeding generation of products, is explicitly included as a special term in our model, and scavenging enzymes are assumed to break down and eliminate products with a loose structure . Their efficiency is dependent on the error level . The model also takes into account the dilution of incorrect ribosomes and enzymes, and is described by a time-dependence in terms of ribosome/enzyme generations . The model and the contribution to the time development are discussed in the light of experiments on E . coli treated with streptomycin.

Avian Dis, 1985 Apr-Jun, 29(2), 341 - 6
Production of H2S by Escherichia coli isolated from poultry: an unusual character useful for epidemiology of colisepticemia; Barbour EK et al.; Eleven isolates of H2S-producing Escherichia coli were recovered from necropsy materials of chickens with symptoms and lesions of colisepticemia on Saudi Arabian broiler farms . Results of 19 out of 20 biochemical reactions studied were typical for E . coli . Hydrogen sulfide production by the E . coli isolates was used as an epidemiological marker to pinpoint a breeding farm as the probable source of these strains, which were then transferred to progeny farms, where colisepticemia occurred . This finding was confirmed by the presence of the same antigenic structure (O78:H-) and by the same drug-resistance pattern (a multiple resistance to streptomycin, sulfathiazole, and tetracycline) in the isolates.

Antimicrob Agents Chemother, 1985 Mar, 27(3), 367 - 74
Isolation of streptomycin-nonproducing mutants deficient in biosynthesis of the streptidine moiety or linkage between streptidine 6-phosphate and dihydrostreptose; Ohnuki T et al.; Eight streptidine idiotrophic mutants (SD20, SD81, SD141, SD189, SD245, SD261, SD263, and SD274) which required streptidine to produce streptomycin were derived from Streptomyces griseus ATCC 10137 by UV mutagenesis . By both the characterization of intermediates accumulated by the idiotrophs and the assay of enzymes involved in streptidine biosynthesis, the biochemical lesions of the mutants were deduced as follows: SD20 and SD263, transamination; SD81, SD261, and SD274, phosphorylation; SD141, transamidination; SD189, dehydrogenation; SD245, linkage between streptidine 6-phosphate and dihydrostreptose . An accumulation of streptidine 6-phosphate was found in SD245 to impair its aminotransferase activity . This finding suggests that aminotransferase activity might have been negatively controlled by the end product, streptidine 6-phosphate, of the streptidine biosynthetic pathway.

J Mol Biol, 1985 Jan 20, 181(2), 313 - 5
Streptomycin-induced, third-position misreading of the genetic code; Johnston TC et al.; Streptomycin was used to increase the frequency of errors in protein synthesis in vivo . In the system under study two misreading errors were observed . Both involved the erroneous insertion of lysine at asparagine codons, because of misreading of a pyrimidine as a purine at the 3' position of the codon . Streptomycin increased the errors at the two codons AAU and AAC to the same extent, thereby maintaining the error ratio found for basal level mistranslation.

Scand J Infect Dis, 1985, 17(4), 371 - 5
Airborne transmission of tularemia in farmers; Syrjala H et al.; In a tularemia epidemic during 1982 in northern Finland, 53 patients showed no peripheral portal of entry for infection or associated lymphadenopathy . Respiratory symptoms were observed in 72% of the patients . 26/38 cases had abnormal chest films . Hilar adenopathy was the most common finding (36%) . Four patients did not receive antibiotics; 43 received tetracyclines, 5 streptomycin and 1 cefuroxime and amoxycillin . All patients recovered . 50 patients acquired the infection during common farming activities, such as making fresh hay with a hay-cutter, handling dry hay, threshing, etc . Thus, airborne transmission may be an important source of infection in normal farming activities in endemic areas of tularemia.

ORL J Otorhinolaryngol Relat Spec, 1985, 47(5), 242 - 8
Statoconia displacement in squirrel monkey ears; Ohashi K et al.; When findings in squirrel monkey temporal bones after streptomycin sulfate intoxication were compared with those after application of intense linear acceleration, the dislocated utricular statoconia were more frequently found around the cupula of the crista ampullaris posterior in the latter group, whereas statoconia were rather widely disseminated within three semicircular canals (cupula, ampulla, and duct) after streptomycin intoxication . This difference is most probably due to the fact that, in the linear acceleration group, normal statoconia were instantaneously dislodged in a block (or forming a large-sized mass) and thereafter moved in the gravity direction, whereas in the streptomycin group, degenerated statoconia formed smaller groups and were more freely disseminated . In the endolymphatic sac, dislocated statoconia were readily phagocytosed by the epithelium of the intermediate portion and rugous portion (and transitory portion) . The incidence of phagocytosis was found more in the streptomycin group, compared to the linear acceleration group.

Toxicol Appl Pharmacol, 1985 Jan, 77(1), 108 - 15
Ototoxicity of subcutaneously administered aztreonam in neonatal rats; Myhre JL et al.; Aztreonam (SQ 26,776) was given subcutaneously to three groups of neonatal rats at daily doses of 150, 600, and 2400 mg/kg from postnatal Days 10 through 16 . Two similar groups given 400 mg of streptomycin kg-1 day-1 or 12 ml of 0.9% sodium chloride kg-1 day-1 on the same schedule served as a positive and negative control group, respectively . On postnatal Days 28 and 56, the neonates were evaluated for level of spontaneous activity and auditory and vestibular function . Half of the neonates in each group were necropsied on postnatal Day 29, and the other half on postnatal Day 57 . The inner ears of all neonates were evaluated for histopathologic evidence of ototoxicity . No functional or histopathologic evidence of ototoxicity was found in any neonatal rat dosed with aztreonam or saline . However, neonates given streptomycin were hyperactive, had severely impaired hearing and vestibular function, and had morphologic changes in the sensory nerve endings of the semicircular canals, utriculus, sacculus, and cochlea . The histopathologic evidence of the ototoxic effects of streptomycin correlated highly with the functional data . Thus, under these conditions, aztreonam demonstrated no ototoxic effects in neonatal rats.

Auris Nasus Larynx, 1985, 12(1), 5 - 14
A study of the nerve endings of the outer hair cells in the organ of Corti--using scanning electron microscopy; Harada Y et al.; The nerve endings on the outer hair cells of the guinea pig organ of Corti were studied using a scanning electron microscope . The nerve endings in the basal turn were entirely exposed in the space of Nuel, whereas in the upper turns almost all nerve endings were covered by the Deiters' cell bulge . The number and the size of the nerve endings gradually decreased from the basal turn toward the apical turn . The shape of the nerve endings was spindle-shaped in the basal turn, while it was round in the upper turn . Some nerve endings were found to locate close to the outer hair cell surface . No pathological change was observed in the nerve endings 25 hr after completion of series treatments of streptomycin or kanamycin . However, the outer hair cells consistently showed shrinkage, especially in the basal turn.

J Assoc Off Anal Chem, 1985 Jan-Feb, 68(1), 29 - 36
Determination of neomycin in animal tissues, using ion-pair liquid chromatography with fluorometric detection; Shaikh B et al.; A liquid chromatographic (LC) method is described for the determination of neomycin in animal tissues . Tissues are homogenized in 0.2M potassium phosphate buffer (pH 8.0); the homogenate is centrifuged, and the supernate is heated to precipitate the protein . The heat-deproteinated extract is acidified to pH 3.5-4 and directly analyzed by LC . The LC method consists of an ion-pairing mobile phase, a reverse phase ODS column, post-column derivatization with o-phthalaldehyde reagent, and fluorometric detection . The LC method uses paromomycin as an internal standard, and separates neomycin from streptomycin or dihydrostreptomycin because they have different retention times . The LC column separates neomycin in 25 min; the detection limit is about 3.5 ng neomycin . The overall recovery of neomycin from kidney tissues spiked at 1-30 ppm was 96% with a 9.0% coefficient of variation . The method was also applied to muscle tissue.

Acta Med Scand, 1985, 217(1), 139 - 40
A case of brucellosis complicated by endocarditis and disseminated intravascular coagulation; Almer LO; Brucellosis, being eradicated among domestic animals in some countries, is still prevalent in some others where it poses a potential threat to the consumers of milk and cheese and those working with animals and meat . The patient presented below had contracted a severe and long-standing Brucella abortus infection by ingesting raw camel milk . She had signs of endocarditis and disseminated intravascular coagulation, but recovered when treated with tetracyclin and streptomycin.

Mol Gen Genet, 1985, 201(1), 129 - 32
Stimulation of recombination between homologous sequences on carcinogen-treated plasmid DNA and chromosomal DNA by induction of the SOS response in Escherichia coli K12; Abbott PJ; Previous studies have shown that transformation of Escherichia coli by plasmid DNA modified in vitro by carcinogens leads to RecA-dependant recombination between homologous plasmid and chromosomal DNA sequences . The mechanism of this recombination has now been studied using recombination-deficient mutants, and the influence of induction of the SOS response on the level of recombination investigated . Plasmid pNO1523, containing the str+ operon (Sms), has been modified in vitro by either irradiation with UV light, or by reaction with (+/-) trans-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) and used to transform streptomycin-resistant hosts . The formation of Ampr transformants which also carry streptomycin resistance was used as a measure of the level of recombination between plasmid and chromosomal DNA . Transformation of recB and recC mutants produced no change in the level of recombination while in the recF mutant a significant decrease was observed compared to the wild type host . Thermal induction of the SOS response in tif-1 and tif-1 umuC mutants followed by transformation led to a four-fold increase in recombination in both cases . The results suggest that the streptomycin-resistant transformants arise exclusively via a recombinational pathway which is largely dependant on the recF gene product, and that this pathway is influenced by induction of the SOS response . These results are discussed in terms of the mechanism of this recombination.

J Bacteriol, 1985 Jan, 161(1), 377 - 84
Isolation and characterization of antisuppressor mutations in Escherichia coli; Sullivan MA et al.; Nonsense mutations in lacI have been shown to be useful as indicators of the efficiency of nonsense suppression . From strains containing supE and a lacI nonsense mutation, selection for LacI- mutants has resulted in the isolation of four antisuppressor mutations . Tn10 insertions linked to these mutations were isolated and used to group the four mutations into three loci . The asuA1 and asuA2 mutations are linked to trp, reduce suppression by supE approximately twofold, and affect a variety of suppressors . The asuB3 mutation was mapped by P1 cotransduction to rpsL but does not confer resistance to streptomycin . The asuC4 mutation reduced suppression by supE by 95% and was shown biochemically to result in the loss of two pseudouridine modifications from the 3' side of the anticodon stem and loop of tRNA2Gln . This mutation is linked to purF, suggesting that it is a new allele of hisT.

Z Erkr Atmungsorgane, 1985, 164(2), 150 - 4
{Current status of tuberculosis in children and adolescents of East Germany}; Weiland P; The morbidity from juvenile tuberculosis in the GDR amounts presently to 0.6 per 100.000 in the age group 0 to 15 years . The GDR's centre for treating children affected by tuberculosis is the above hospital for lung diseases in the town of Harzgerode . Between 1980 and 1983 a total of 89 children (48 boys and 41 girls) with various forms of tuberculosis have been treated there . The anamnesis of the children with lung tuberculosis was largely unspecific, only 6 from 29 had pneumonia or pneumonia was suspected respectively . All patients with abdominal tuberculosis had pains in the peritoneal cavity, whereas 26 from 31 children with cervico-glandular tuberculosis developed local lymphatic nodes . The family anamnesis showed primary tuberculous infections, lung tuberculosis and other forms of tuberculosis in the respiratory system among the patient's parents, grandparents and other relatives . The cases were initially registered mainly with the special outpatients' departments for lung diseases and tuberculosis or with other surgically orientated departments . Whilst tuberculin tests with 2 TE on children with lung tuberculosis gave a clear diagnosis, the same tests proved to be negative in nearly all cases with histologically confirmed lymphatic tuberculosis . Tuberculous bacteria could be detected in only 15 from 29 cases of lung tuberculosis . A strict initial therapy with three antituberculous drugs, usually Streptomycin, INH and Ethambutol, is decisive for the successful treatment . In the following intermittent period Streptomycin and INH are preferred . The total duration of chemotherapy of all forms of juvenile tuberculosis is at present 9 months.

ORL J Otorhinolaryngol Relat Spec, 1985, 47(5), 236 - 41
Impairment of the chick's grip and balance by streptomycin . A preliminary study; Cohen GM et al.; Chicks were injected daily with streptomycin (400 or 1,200 mg/kg) . Damage to the vestibular apparatus was accompanied by steadily impaired abilities of chicks to tighten their grips as evidenced by reduced torque and by slippage of their feet on the perch . As compensation, intoxicated chicks adjusted their footing with cautious, deliberate movements . They always stood erectly and stiffly on the perch; they were unable to roost . They also experienced difficulties in balancing . While symptoms were qualitatively similar at both dosages, their onset came earlier and with greater severity at 1,200 mg/kg . Control chicks steadily increased their torque and displayed normal balance during the course of the experiment.

ORL J Otorhinolaryngol Relat Spec, 1985, 47(2), 76 - 83
Vestibular training after sudden loss of vestibular functions; Takemori S et al.; 12 cases of unilateral labyrinthectomy, 3 cases of VIIIth nerve section, 22 cases of streptomycin sulfate infusion into the middle ear cavity and 8 cases of bilateral vestibular a-functions underwent vestibular training . Our training is very useful for regaining equilibrium and for evaluating the effects of training on equilibrium by recording the gravity center movements.

Mol Gen Genet, 1985, 201(2), 258 - 64
Tn7-encoded proteins; Brevet J et al.; Proteins encoded by Tn7 have been studied in Escherichia coli maxicells harbouring either various deleted ColE1::Tn7 plasmids or Tn7 fragments cloned in pBR322 . Six Tn7-encoded proteins were detected and named p18, p32, p40, p54, p85-a and p85-b according to their apparent molecular weight . Protein p18 is dihydrofolate reductase type I and p32 is probably the protein conferring resistance to streptomycin/spectinomycin . Both genes map on the left-hand part of Tn7 . The genes for the four other proteins are located on the right-hand part of Tn7 . We propose that they fully cover a 6.9 kb DNA fragment without any overlapping . Starting from the right-hand end towards the middle of the transposon, these four genes are in the following order: p85-a, p54, p40 and p85-b . Transposition of Tn7 onto E . coli plasmids requires the proteins p85-a, p85-b, p54 and p40 . However, transposition onto the chromosome does not require the p85-b and p40 products.

Gene, 1985, 36(1-2), 97 - 104
The aminoglycoside-resistance operon of the plasmid pSa: nucleotide sequence of the streptomycin-spectinomycin resistance gene; Tait RC et al.; The nucleotide sequence of the probable C terminus of the kanamycin-resistance gene (KmR) and the probable complete sequence of the streptomycin-spectinomycin-resistance gene (SpR) of the IncW plasmid pSa have been determined . The two genes appear to be oriented in the same direction and separated by a spacer region of 53 bp, with transcription proceeding from the KmR gene into the SpR gene . An RNA transcript encompassing the C terminus of the KmR gene, the 53-base spacer, and the N terminus of the SpR gene has the potential to form a stem-loop structure with a free energy value of -68 kcal/mol . The SpR gene of pSa has extensive sequence homology with the aadA gene of the plasmid R538-1 . Comparison of the proposed amino acid sequence of the KmR protein of pSa with those of two aminoglycoside phosphotransferases revealed a region of potential homology with those proteins.

Mol Gen Genet, 1985, 200(3), 375 - 84
Certain chromosomal regions in Streptomyces glaucescens tend to carry amplifications and deletions; Hasegawa M et al.; Streptomycetes are subject to a high degree of genetic instability . One manifestation of this phenomenon is the occurrence of tandemly reiterated DNA stretches within the chromosome . We describe the analysis of ten reiterated sequences observed in various ethidium bromide-treated streptomycin-sensitive and melanin-negative mutant strains of Streptomyces glaucescens . The repeated DNA units were 2.9 to 35 kb in length . No two sequences were identical . The amplified sequences occupied up to 45% of the total genomic DNA . Structural analysis of the cloned repeated DNA stretches by means of restriction enzymes and by cross hybridization revealed the presence of two chromosomal areas rich in DNA reiterations . In some cases reiterated regions were accompanied by nearby rearrangements.

Plasmid, 1985 Jan, 13(1), 17 - 30
Nucleotide sequence analysis of a gene encoding a streptomycin/spectinomycin adenylyltransferase; Hollingshead S et al.; The nucleotide sequence of 1400 bp from R-plasmid R538-1 containing the streptomycin/spectinomycin adenyltransferase gene (aadA) was determined, and the location of the aadA gene was identified by a combination of insertion and deletion mutants . Its gene product, aminoglycoside 3"-adenylyltransferase (AAD(3")(9), has a Mr of 31,600.

J Bone Joint Surg Br, 1985 Jan, 67(1), 103 - 10
A 10-year assessment of controlled trials of inpatient and outpatient treatment and of plaster-of-Paris jackets for tuberculosis of the spine in children on standard chemotherapy . Studies in Masan and Pusan, Korea . Ninth report of the Medical Research Council Working Party on Tuberculosis of the Spine; UV-repair and mutagenesis in Azotobacter vinelandii . I . Repair of UV-induced damages; UV-irradiated Azotobacter vinelandii OP cells were found to be sensitive to dark repair-inhibitors, like caffeine and acriflavine . Sensitivity to both the inhibitors started to decrease at a fast rate immediately following UV-irradiation, when incubated in Burk's broth in dark . Total insensitivity to caffeine was attained at a time that was approximately double the time of the corresponding ribonucleic acid synthesis-inhibition and less than one generation time of the unirradiated cells . Nearly at the same time the rate of loss of sensitivity to acriflavine became much slower and total insensitivity to acriflavine occurred after relatively prolonged incubation . The protein synthesis inhibitor, streptomycin, reduced UV-survival, but after a time lag . The organism did not show liquid holding recovery and its UV-survival was not affected by components of complex medium . It is proposed that A . vinelandii OP possesses at least two dark-repair pathways: pre replication (acts immediately after UV exposure and is faster) and post replication (delayed and slower) repair . The first one is inhibited by caffeine and acriflavine and the second by acriflavine and streptomycin . The latter therefore requires de novo protein synthesis after UV-irradiation and may be inducible.

Schweiz Med Wochenschr, 1984 Dec 22, 114(51), 1906 - 9
{Brucellosis: a varied clinical presentation in 9 patients}; Vogt P et al.; From 1973 to 1983 nine cases of Brucella melitensis infection were hospitalised at the Centre hospitalier universitaire vaudois (CHUV), Lausanne . In each case, the infection was acquired in a Mediterranean country (4 cases in Italy, 2 in Spain, 2 in Portugal and 1 in Greece) . In 6 of the cases the disease was acquired by ingestion of dairy products and in 2 cases by direct animal contact . Despite classical initial symptomatology (fever, rigors, weakness), the time from first symptoms to diagnosis varied between 10 days and 5 months . This delay probably explains why 6 of 9 patients were admitted because of septic complications: orchi-epididymitis, arthritis, meningitis and endocarditis . With prolonged antibiotherapy, the evolution was favourable in all cases . The patient who presented with endocarditis required emergency aortic valve replacement . Culture of the valve showed the presence of 10(9) B . melitensis/g of tissue . Cure was achieved by the administration of streptomycin and tetracycline for 6 weeks, followed by cotrimoxazole for one year . These cases show that the diagnosis of Brucella infection is becoming rare in Switzerland . It is often not suspected, and prompt diagnosis is delayed until further complications occur . Serology and blood cultures should be done in every patient presenting with fever after a stay in endemic countries.

Nucleic Acids Res, 1984 Dec 21, 12(24), 9551 - 65
Nucleotide sequence of Marchantia polymorpha chloroplast DNA: a region possibly encoding three tRNAs and three proteins including a homologue of E . coli ribosomal protein S14; Umesono K et al.; The nucleotide sequence of a region of Marchantia polymorpha chloroplast DNA was determined . On this DNA sequence (3.38kb), three open reading frames (ORFs) and three putative tRNA genes were detected in the following order: -ORF701-tRNASer(UGA)-ORF702-tRNAGly(GCC)-initiator tRNAMet(CAU)-ORF703- . The ORF703 is composed of 100 codons in which those for lysine (15%) and arginine (11%) are abundant, and could be accounted for as a counterpart of E . coli ribosomal protein S14 since they share 45% homology in the amino acid sequences . The ORF701 appears to code for a membrane protein, showing a periodic appearance of seven clusters of hydrophobic amino acids . Although the mechanisms remain unknown, the ORF701 causes a streptomycin-sensitive phenotype in resistant mutants of E . coli . The ORFs and tRNA genes are separated from each other by extremely AT-rich spacers containing sequences of dyad symmetry . The third letter positions of the codons in the ORFs are also rich in A and T residues.

Am Rev Respir Dis, 1984 Dec, 130(6), 1091 - 4
Supervised six-months treatment of newly diagnosed pulmonary tuberculosis using isoniazid, rifampin, and pyrazinamide with and without streptomycin; Snider DE et al.; In a previous study, we have shown that a 6-month regimen consisting of 2 months of isoniazid, rifampin, pyrazinamide, and streptomycin administered daily (2IRSZ) followed by 4 months of isoniazid and rifampin administered twice weekly (4I2R2) yielded no relapses after 30 months of follow-up . In order to assess the contribution of streptomycin to this treatment regimen, 213 patients with newly detected smear-positive pulmonary tuberculosis were randomly assigned to the following two 6-month treatment regimens: 2IRZ/4I2R2 and 2IRSZ/4I2R2 . One hundred seventy-two of the 213 patients (81%) completed therapy, i.e., 116 of 135 patients (86%) treated with 2IRZ/4I2R2 and 56 of 78 patients (72%) treated with 2IRSZ/4I2R2 . Adverse reactions requiring withdrawal of drugs for 7 days or longer were observed in 4.2% of patients (3.7% receiving the 2IRZ/4I2R2 regimen and 5.1% receiving the 2IRSZ/4I2R2 regimen) . At the end of treatment, all patients in the 2IRZ/I2R2 series had negative smears and cultures . Two of the 116 patients (1.7%) in the 2IRZ/I2R2 series developed isoniazid resistance in the fourth month of treatment and remained sputum positive at the end of treatment . In the follow-up period, 4 patients (3.4%) treated with 2IRZ/4I2R2 relapsed and 1 (1.8%) treated with 2IRSZ/4I2R2 relapsed . The only significant difference between the 2 regimens was the higher dropout rate among those assigned to the 2IRSZ/4I2R2 regimen.

Can J Microbiol, 1984 Dec, 30(12), 1448 - 52
The effects of chlorate- and streptomycin-resistance mutations on nitrofurantoin resistance in Escherichia coli K-12; Obaseiki-Ebor EE et al.; Chlorate-resistant mutants with none of the usual pleiotropic effects such as defective nitrate reductase activity were isolated from Escherichia coli K-12 . These chlorate-resistant mutants (designated chlHW) did not yield strains with a high level of nitrofurantoin resistance following selection with nitrofurantoin . The chlorate-resistance mutation reduced the nitrofurantoin resistance of high-level mutants to an intermediate level . Further mutation to resistance to streptomycin and other aminoglycoside antibiotics suppressed the effect of chlHW on the level of nitrofurantoin resistance . Other chlorate-resistance genes examined did not have the same effect on nitrofurantoin resistance as chlHW . The gene was cotransducible (Pl) with intermediate-level nitrofurantoin resistance and proC . It is suggested that the chlHW mutation may enhance the accumulation of nitrofurantoin inside the cell since it is known that a multiple aminoglycoside-resistance mutation with pleiotropic effects on the cell membrane can also confer high-level resistance to nitrofurantoin.

Gene, 1984 Dec, 32(1-2), 225 - 33
The transposon Tn5 carries a bleomycin-resistance determinant; Genilloud O et al.; Transposon Tn5 carries a determinant for resistance to bleomycin (Bm) . Deletion mapping and cloning experiments have shown that this determinant, gene ble, is located between the determinant for kanamycin (Km) and neomycin resistance (gene neo) and the determinant for streptomycin resistance (gene str) . Genes neo, ble, and str belong to an operon controlled by the common promoter . The Mr of the ble product, as determined by polyacrylamide gel electrophoresis, is 12000 to 13000.

J Clin Microbiol, 1984 Nov, 20(5), 966 - 71
Characteristics of an unclassified Mycobacterium species isolated from patients with Crohn's disease; Chiodini RJ et al.; The characteristics of an unclassified Mycobacterium sp . isolated from three patients with Crohn's disease are presented . The organism is extremely fastidious and mycobactin dependent and may require up to 18 months of incubation for primary isolation . Colony morphology is rough . Characteristics are unlike those of any presently defined species . The isolates produced postive niacin, catalase, and 2-week arylsulfatase reactions and were susceptible to neotetrazolium chloride (1:40,000), streptomycin (2 micrograms/ml), and rifampin (0.25 micrograms/ml) . Chromogenicity, nitrate reduction, quantitative catalase, Tween hydrolysis, urease, tellurite reduction, pyrazinamidase, and 3-day arylsulfatase tests were negative, and the isolates were resistant to thiophene-2-carboxylic acid hydrazide (10 micrograms/ml) and isoniazid (10 micrograms/ml) . Optimum growth in broth was determined to be in 7H9 medium with Dubos oleic albumin complex, Tween 80, and mycobactin J at 37 degrees C without CO2 or agitation and in low medium depth . This Mycobacterium sp . may be a subspecies or biovariant of Mycobacterium paratuberculosis, or it may represent a new species of Mycobacterium . It is suggested that this Mycobacterium sp . may play an etiological role in some cases of Crohn's disease.

Am Rev Respir Dis, 1984 Nov, 130(5), 827 - 30
A successful supervised outpatient short-course tuberculosis treatment program in an open refugee camp on the Thai-Cambodian border; Miles SH et al.; The operation of a tuberculosis treatment program in an open refugee camp of 45,000 refugees on the Thai-Cambodian border is described . Fifty-eight patients received 6 months of supervised daily, outpatient therapy with a protocol employing isoniazid, rifampin, streptomycin, and pyrazinamide . Patient compliance was high, with only 15 of 10,209 patient days being missed, despite a high incidence of minor side effects . Three patients died, 4 defaulted, and 1 moved to another camp for treatment . The therapies of 4 patients were extended because of the need for reduced doses of medications, the development of extrapulmonary disease, treatment failure, and slow resolution of infiltrates on radiographs . There was 1 late relapse . This report demonstrates the feasibility in integrating short-course therapies with program designs to produce high compliance under difficult field conditions.

Mikrobiologiia, 1984 Nov-Dec, 53(6), 890 - 5
{Regulators of differentiation in Streptomyces cyaneofuscatus}; Anisova LN et al.; Streptomyces cyaneofuscatus PRL 1642 producing valinomycin was shown to synthesize bioregulators of differentiation similar to A factor . The regulators stimulate spore formation and streptomycin synthesis in a Streptomyces griseus 1439 mutant deficient in A factor . Some S . cyaneofuscatus mutants respond to A factor addition into the medium by an increase in valinomycin synthesis and a change in morphological properties . The regulators from S . cyaneofuscatus are more effective toward mutants of this species than toward S . griseus mutants.

Am J Otolaryngol, 1984 Nov-Dec, 5(6), 387 - 93
Further observations of vestibular ototoxicity in the chick: effects of streptomycin on the ampullary sensory epithelium; Park JC et al.; Starting eight days after hatching, chicks received daily subcutaneous injections of streptomycin sulfate, either 400 mg/kg for 30 days or 1,200 mg/kg for 15 days . Randomly selected chicks from each group were killed at intervals during the injection period, and the ampullae were examined for signs of vestibulotoxicity . Ampullary cell types differed in sensitivity to streptomycin . First, dark cell processes withered . Second, vacuoles formed in the apices of the light cells of the planum semilunatum . Third, nerve terminals swelled, and their organelles and ground substance clumped together, creating cleared areas . Last, hair cells and supporting cells became slightly vacuolated . However, these cells showed less overt damage than the other cell types . The onset of damage was earlier and the damage more severe with the 1,200-mg than with the 400-mg dosage . There was no evidence of hair cell loss during the experiment.

Gene, 1984 Nov, 31(1-3), 165 - 71
A pSC101-derived plasmid which shows no sequence homology to other commonly used cloning vectors; Churchward G et al.; We have constructed a plasmid cloning vector, pGB2, which is derived from the Escherichia coli plasmid pSC101 . The plasmid, which specifies resistance to spectinomycin and streptomycin, contains unique restriction sites for the enzymes HindIII, PstI, SalI, BamHI, SmaI and EcoRI . pGB2 shows no sequence homology, as detected by DNA-DNA hybridization, to several widely used vectors such as pBR322, pUC8 and phage lambda L47.1 . Amongst other applications, DNA fragments can be cloned into the plasmid and then radioactive plasmid DNA can be used as a probe to screen recombinant DNA libraries.

Mutat Res, 1984 Oct, 138(1), 39 - 46
Powerful mutagenicity of a bipyridylium herbicide in a nitrogen-fixing blue-green alga Nostoc muscorum; Vaishampayan A; The herbicide, paraquat (1,1'-dimethyl-4,4'-bipyridylium ion), was found to be toxic and lytic to Nostoc muscorum in N2 (at the expense of elemental nitrogen, i.e . unsupplemented with any combined nitrogen source) and NO-3 media, without any apparent inhibitory or stimulatory effect on its nitrogen-fixing apparatus, i.e . heterocyst formation . At a dose of paraquat resulting in 20, 50 and 75% survival, induction of reverse mutations (from het- nif- auxotrophy to het+ nif+ prototrophy), forward mutations (for streptomycin {St}-resistance), and auxotrophic mutations (carbon-auxotrophy through methylamine {MA}-resistance) were observed with frequencies comparable to those obtained through induction with the well known mutagen MNNG (N-methyl-N'-nitro-N-nitrosoguanidine).

Br J Dis Chest, 1984 Oct, 78(4), 330 - 6
A controlled trial of 6 months' chemotherapy in pulmonary tuberculosis . Final report: results during the 36 months after the end of chemotherapy and beyond . British Thoracic Society; Anaphylaxis presumed to be caused by beef containing streptomycin; Most adverse reactions to foods have been blamed on proteins derived from the ingested substance . Reports in the literature document that adverse reactions to foods can be caused by contaminants . The youngster reported here had anaphylaxis on four occasions, likely caused by the presence of streptomycin.

Genetika, 1984 Sep, 20(9), 1457 - 62
{Selection, analysis and mapping of mutations in the gene for resistance to kanamycin in plasmid RP4}; Mironov VN et al.; We have tested possibilities of Escherichia coli strains dependent on drugs streptomycin and paromomycin for selection of spontaneous mutations in the RP4 kan gene specifying resistance to aminoglycosids--kanamycin, neomycin and paromycin . A set of kan gene mutations were obtained, classified ad mapped.

Am J Vet Res, 1984 Sep, 45(9), 1825 - 8
Effectiveness of various therapeutic regimens for bovine brucellosis; Milward FW et al.; Various chemotherapeutic regimens were evaluated in 48 culture-positive dairy cows . Cessation of shedding of Brucella abortus from udder secretions and absence in selected tissues at necropsy were criteria of success . A combination of a long-acting oxytetracycline and streptomycin eliminated Brucella in 10 of 14 (71.4%) cows . Two cows that were retreated with the same regimen also became culture-negative . Other treatment regimens, including the use of liposome-encapsulated antibiotics, were less successful . Serotests were a poor criterion of effectiveness.

Tubercle, 1984 Sep, 65(3), 195 - 9
Ethambutol-induced hyperuricaemia; Khanna BK et al.; A prospective study involving 134 cases of pulmonary tuberculosis was conducted to determine the incidence and severity of ethambutol-induced hyperuricaemia . The cases were randomly allocated to two groups: one group (71 cases) received ethambutol (20 mg/kg bodyweight/day) streptomycin and isoniazid (SHE), the other group (60 cases) received streptomycin, isoniazid and thioacetazone (SHT) . All the cases were hospitalized . A significant rise in serum uric acid levels was found in 66% of SHE patients during the first 60-90 days of treatment, but there was no such change in the SHT patients . In one patient who received ethambutol generalized arthralgia developed and in another acute gouty arthritis was observed . In both cases, symptoms abated when ethambutol was withdrawn and reappeared when it was resumed.

Arch Otolaryngol, 1984 Aug, 110(8), 538 - 9
Streptomycin drug fever during treatment of bilateral Meniere's disease; Feldbaum JS et al.; The use of intramuscular injections of streptomycin sulfate for the ablation of vestibular function in patients with bilateral Meniere's disease is well established . Although hypersensitivity reactions to streptomycin are documented, frank drug fevers are rare . Our patient, with no previous history of drug allergies, was treated with parenteral streptomycin for disabling bilateral Meniere's disease . The patient's hospital course was complicated by severe hypotension and spiking fevers, which were temporally related to the streptomycin injections, and which resolved on cessation of the drug therapy . A challenge dose of a new batch of streptomycin resulted in renewed rigors, fever, and hypotension . The necessity of early recognition of this uncommon, life-threatening drug fever with streptomycin is emphasized by our experience.

Genetics, 1984 Aug, 107(4), 563 - 76
Genetics of Chlamydomonas reinhardtii diploids . II . The effects of diploidy and aneuploidy on the transmission of non-Mendelian markers; Eves EM et al.; The transmission of two non-Mendelian drug resistance markers has been studied in crosses of Chlamydomonas reinhardtii involving diploids and aneuploids with different mating type genotypes . Under normal laboratory conditions for gametogenesis, mating and zygote maturation, the transmission pattern of the non-Mendelian markers sr-u-1 (resistance to streptomycin) and spr-u-1-27-3 (resistance to spectinomycin) is primarily determined by the mating type genotypes of the parental cells . Our results confirm and expand an earlier observation suggesting that an apparent codominant function of the female (mt+) allele in regulating chloroplast gene transmission in meiosis appears to be distinct and separate from its recessive function in regulating mating behavior . The chloroplast DNA complement (as indexed by the number of extranuclear DNA-containing bodies) may exert a secondary effect on the transmission of these markers . Within a mating type group (mt+/mt- or mt-/mt-) a cell line with more chloroplast DNA tended to transmit its non-Mendelian markers more frequently than a cell line with less chloroplast DNA.

Pharmacol Res Commun, 1984 Aug, 16(8), 831 - 44
Antitubercular and CNS activities of some 2-aryl-3-{N-(2/3/4-benzimidazol-2-yl)phenyl}iminomethylenyl indoles; Agarwal R et al.; The title 2-aryl-3-{N-(2/3/4-benzimidazol 2yl)phenyl}iminomethylenyl indoles were synthesised by condensing 2-aryl-indol-3-aldehydes with 2-(2/3/4-aminophenyl)benzimidazoles in isopropanol and characterised by elemental and spectral (IR, PMR) studies . Compounds were screened in vivo for toxicity and gross CNS effects on albino mice and in vitro for antitubercular activity against human tuberculosis bacteria, Mycobacterium tuberculosis, H37RV . The tested compounds were nontoxic and CNS depressant . Some of them have been found to possess significant antitubercular activity, comparable with streptomycin.

Can J Microbiol, 1984 Aug, 30(8), 1058 - 67
Tyrosinase activity in Streptomyces glaucescens is controlled by three chromosomal loci; Crameri R et al.; In Streptomyces glaucescens the production of the enzyme tyrosinase (EC 1.14.18.1) is controlled by at least three loci: MELA, MELB, and MELC . Mutations in MELA and MELB are rare . They both map on the S . glaucescens chromosome in the interval between the markers leu-2 and ura-3 . MELC, however, shows an exceptionally high mutation rate . MelC strains arise spontaneously with a frequency of about 0.1%, and they can be specifically induced with ethidium bromide, acridine orange, or by prolonged storage of spores or mycelium at 4 degrees C . Ultraviolet (UV) irradiation or treatment with N-methyl-N'-nitro-N-nitrosoguanidine under conditions which induce auxotrophic mutations, however, do not specifically induce the appearance of tyrosinase-negative strains . Most, but not all, of the melC strains acquire additional mutations which make them sensitive to streptomycin (strS) and unable to produce hydroxystreptomycin . Mapping of the mutations classified as melC proves to be difficult . Some of the matings indicate a map position between his-2 and pro-1, while others, all highly unbalanced crosses, can not be analyzed in a meaningful way because of abnormal segregation of the reference markers . This is probably due to some of the additional mutations which occur frequently with the melC mutations and not to extrachromosomal inheritance of MELC.

Otolaryngol Head Neck Surg, 1984 Aug, 92(4), 440 - 7
Titration streptomycin therapy for bilateral Meniere's disease: a preliminary report; Graham MD et al.; Intramuscular dosages of streptomycin sulfate were titrated in eight patients with bilateral Meniere's disease in an attempt to alleviate disabling vertigo and hearing loss . It appears possible to eliminate the vertiginous episodes, preserve or improve hearing, and avoid ataxia and oscillopsia in most of these individuals . At present we consider this treatment regimen our first choice of therapy in people with bilateral active Meniere's disease or in patients whose only hearing ear is actively fluctuating and in whom associated disabling vertigo is present . Great caution and supervision should be exercised in the use of streptomycin titration therapy in the individual with bilateral Meniere's disease, as further experience is required to determine the efficacy of this form of management.

Ann Otol Rhinol Laryngol Suppl, 1984 Jul-Aug, 112, 44 - 8
Streptomycin treatment for Meniere's disease; Silverstein H; This paper describes the author's 10-year experience using streptomycin sulfate in the treatment of Meniere's disease in the following: the classical Schuknecht ablation of the vestibular system in bilateral Meniere's disease (eight patients); the classical Schuknecht ablation of the vestibular system in unilateral Meniere's disease in the only hearing ear (five patients); the intratympanic treatment of unilateral Meniere's disease (four patients); and low dose intramuscular outpatient treatment in unilateral Meniere's disease (five patients) . The results of bilateral vestibular ablation were similar to those obtained previously by Schuknecht and others: patients developed profound ataxia with a wide-based gait and oscillopsia, which improved rapidly over a period of months; approximately 30% of patients experienced significant improvement in hearing, which usually deteriorated again after several months; and all patients were relieved of vertigo . Patients with unilateral Meniere's disease in the only hearing ear responded similarly, and hearing was preserved in all cases . Intramuscular streptomycin ablation of the vestibular system is strongly recommended in place of surgery in the only hearing ear in Meniere's disease . Controlled intratympanic injection of streptomycin is not successful as yet because of difficulty in controlling the dose . Low dose subototoxic streptomycin treatment on an outpatient basis offers promise for relief of Meniere's attacks, and may improve hearing in some cases without producing the temporary disabling effects of ataxia and oscillopsia . Streptomycin and similar drugs which may reduce endolymph production may eventually be the treatment of choice for Meniere's disease.

Biochem Biophys Res Commun, 1984 Jun 15, 121(2), 487 - 92
Control of basal-level codon misreading in Escherichia coli; Parker J et al.; Basal-level misreading of asparagine codons was examined in a number of Escherichia coli strains . Lysine substitutions were measured by quantitating the amount of charge heterogeneity in MS2 coat protein . In most strains the heterogeneity was consistent with misreading of AAU codons at a frequency of 3-6 X 10(-3) . Strains with streptomycin resistance mutations (rpsL) have reduced levels of misreading . There is no significant difference in the frequency of basal-level errors in stringent (relA+) and relaxed (relA) strains, even during starvation for amino acids unrelated to the substitution being studied.

Am Rev Respir Dis, 1984 Jun, 129(6), 921 - 8
Controlled clinical trial comparing a 6-month and a 12-month regimen in the treatment of pulmonary tuberculosis in the Algerian Sahara . Algerian working group/British Medical Research Council cooperative study; Physical and genetic analyses of the Inc-I alpha plasmid R64; A 126-kilobase (kb) physical and genetic map of the Inc-I alpha plasmid R64 was constructed by using the restriction enzymes, BamHI, SalI, XhoI, HindIII, and EcoRI . The replication (Rep) and incompatability (Inc) functions of this plasmid were located in a 1.75-kb segment of an EcoRI fragment, E10 (3.3 kb) . In addition, the genes determining growth inhibition of phage BF23 (Ibf), suppression of dnaG ( Sog ), resistance to tetracycline (Tetr), and resistance to streptomycin ( Strr ) were located on the 5.5-kb HindIII-XhoI fragment, the 8.1-kb EcoRI fragment (E5), the 4.6-kb HindIII fragment (H8), and the 4.1-kb HindIII fragment (H10), respectively . The map of R64 was compared with that of ColIb, which belongs to the Inc-I alpha group.

Mutat Res, 1984 Jun-Jul, 140(2-3), 67 - 9
Influence of recF on spontaneous mutation in Escherichia coli; Southworth MW et al.; A recF mutation increased the spontaneous mutation rate for mutations to histidine and tryptophan independence, and to streptomycin resistance but not significantly to rifampicin resistance . The results suggest the recF gene may have a role in maintaining DNA replication fidelity.

J Biol Chem, 1984 May 10, 259(9), 5932 - 6
A hybrid superoxide dismutase containing both functional iron and manganese; Clare DA et al.; A hybrid superoxide dismutase containing functional Mn and Fe has been isolated from Escherichia coli . Streptomycin, which binds tightly to both the Mn- and the Fe-containing superoxide dismutases, had the expected effect on the electrophoretic and chromatographic behavior of the hybrid . Treatment of the hybrid with H2O2, which selectively inactivates the Fe-containing enzyme, resulted in partial inactivation accompanied by a resegregation of subunits, with the formation of active Mn-enzyme and inactive Fe-enzyme . A similar resegregation of subunits was observed when the hybrid was exposed to 2.5 M guanidinium chloride . Hybrids containing Mn or Fe could be generated in vitro by mixing the Mn-enzyme with the Fe-enzyme, removing metals with 8-hydroxyquinoline in the presence of 2.5 M guanidinium chloride, and then dialyzing against Mn(II) or Fe(II) salts . Ten per cent of the activity of the Fe-superoxide dismutases is resistant to H2O2, which correlates with its content of Mn . Since the activity remaining after exhaustive treatment with H2O2 exhibited the electrophoretic mobility of the Fe-enzyme, we concluded that some of the active sites of the Fe-enzyme were actually occupied by Mn . It should be noted, however, that for purposes of metal reconstitution experiments, a definite specificity was demonstrated . The Mn-enzyme was reconstituted with Mn(II), whereas the Fe-enzyme activity was recovered using only Fe(II) . We propose that the Fe-superoxide dismutase may be heterogeneous and that 10% of its activity is actually due to a Mn-containing variant with the same electrophoretic mobility . Only the apohybrid enzyme regained enzymatic activity using both Mn(II) and Fe(II).

Thorax, 1984 May, 39(5), 376 - 82
Pulmonary infection with mycobacterium xenopi: review of treatment and response; Banks J et al.; Forty seven patients (82% male) with pulmonary infection caused by Mycobacterium xenopi have been reviewed . Pre-existing lung disease was present in 35 (75%) . In 21 patients the disease was characterised by a subacute illness developing over a period of two to four months, while in another 20 patients there was a longer history of chronic respiratory problems often associated with slowly progressive changes evident from chest radiographs . Response to treatment was poor and unpredictable, and was not related to the results of in vitro sensitivity tests, pre-existing lung disease, or mode of onset of symptoms . Eleven patients (23%) were cured with chemotherapy . The best drug regimen appeared to be rifampicin and isoniazid combined with either streptomycin or ethambutol . Another 12 (26%) showed favourable responses to drug treatment initially, but eventually relapsed . Four patients had progressive disease while receiving prolonged courses of chemotherapy . Resection was performed in five patients with resultant cure in four . Since the prognosis with drug treatment alone is so unpredictable it is suggested that resection might be part of first line treatment, and that it should usually be performed if patients fail to respond to initial chemotherapy or if they relapse.

Infection, 1984 May-Jun, 12(3), 205 - 7
Brucella arthritis of the sacro-iliac joint; Porat S et al.; We are reporting a case of culture-proven brucella sacro-iliitis . The treatment included surgical drainage and curettage together with tetracycline and streptomycin . A five-year follow-up showed complete cure: the patient was free of symptoms, the sacro-iliac joint was normal and a serologic test negative . The diagnostic difficulties, the differential diagnosis and the appropriate treatment are also discussed in this paper.

Zh Mikrobiol Epidemiol Immunobiol, 1984 May, (5), 67 - 70
{Multiplication of Mycobacterium tuberculosis in the organs of mice with a single exposure to cyclophosphamide}; Vladimirskii MA et al.; The injection of cyclophosphamide, used as an immunomodulating agent in a dose of 100 mg/kg, into mice infected with M . tuberculosis induced an increase (a virulent culture) or a decrease (a culture with low virulence) in the multiplication of mycobacteria in the spleen . In mice infected with a virulent culture and protected from infection with streptomycin for 1 week cyclophosphamide induced a considerable decrease in the number of viable mycobacteria in the lungs by days 18-20 after infection.

J Bacteriol, 1984 May, 158(2), 481 - 7
Unstable genetic determinant of A-factor biosynthesis in streptomycin-producing organisms: cloning and characterization; Horinouchi S et al.; We cloned a DNA fragment directing synthesis of A-factor from the total cellular DNA of streptomycin-producing Streptomyces bikiniensis on the plasmid vector pIJ385 . Introduction of the recombinant plasmid ( pAFB1 ) into A-factor-deficient S . bikiniensis and Streptomyces griseus mutants led to A-factor production in the host cells, as a result of which streptomycin production, streptomycin resistance, and spore formation of these mutants were simultaneously restored . The plasmid pAFB1 also complemented both afsA and afsB mutations of Streptomyces coelicolor A3(2) . These results indicated that the cloned DNA fragment contained the genetic determinant of A-factor biosynthesis . The cloned fragment, when carried on a multicopy vector plasmid, induced production of a large amount of A-factor in several Streptomyces hosts . In Southern blot DNA/DNA hybridization analyses with a trimmed 5-kilobase fragment containing the intact A-factor determinant as probe, total cellular DNA from A-factor-deficient mutants gave no positive hybridization . The DNA blot experiment also showed a wide distribution of sequences homologous to the S . bikiniensis A-factor determinant among most, but not all, A-factor-producing actinomycetes with a varying extent of homology and the absence of these sequences from most A-factor nonproducers .

Can J Biochem Cell Biol, 1984 May, 62(5), 231 - 44
The control of accuracy during protein synthesis in Escherichia coli and perturbations of this control by streptomycin, neomycin, or ribosomal mutations; Brakier-Gingras L et al.; This review surveys the different experimental approaches which describe the binding of tRNA to mRNA-programmed ribosomes and the control of tRNA selection . This selection is best described by the two-step model proposed by Hopfield and demonstrated by Thompson and his collaborators . The model involves a first control at the initial reversible binding of tRNA to the ribosome and a second control, the proofreading control, which promotes rejection of the incorrect tRNA from a high-energy intermediate during the transition from the initial to the final binding state . Streptomycin, neomycin, and ribosomal fidelity mutations appear to affect both control steps . Their effect can be related to the location of the mutated ribosomal proteins and to the conformational changes induced in the ribosome by the misreading agents . An alteration of the first control probably results from a distortion of the codon-anticodon interaction, while an alteration of the second control may be caused by a change in the association between ribosomal subunits.

J Clin Microbiol, 1984 Apr, 19(4), 546 - 7
Mycobacterium thermoresistibile infection in an immunocompromised host; Liu F et al.; This is the second report of Mycobacterium thermoresistibile as the etiological agent of a pulmonary granuloma and the first occurrence of this organism in a patient who has not been outside the continental United States . The organism is susceptible to rifampin, ethambutol, and streptomycin but resistant to isoniazid and p-aminosalicylic acid.

Otolaryngol Head Neck Surg, 1984 Apr, 92(2), 229 - 32
Use of streptomycin sulfate in the treatment of Meniere's disease; Silverstein H et al.; Streptomycin sulfate has been known to be ototoxic since its use in the treatment of tuberculosis . This report describes 10 years of experience in the treatment of Meniere's disease with streptomycin . Streptomycin has been used in classical Schuknecht ablation of the vestibular system in bilateral Meniere's disease; classical Schuknecht ablation of the vestibular system in unilateral Meniere's disease in the only hearing ear; intratympanic streptomycin in the treatment of unilateral Meniere's disease; and low-dose intramuscular streptomycin as outpatient treatment in unilateral Meniere's disease . The results of bilateral vestibular ablation were similar to Schuknecht's and others . Patients developed profound ataxia with a wide-based gait and oscillopsia, which improved rapidly over a period of months . Approximately 30% experienced significant improvement in hearing, which usually deteriorated again after several months . All patients were relieved of vertigo . Patients with unilateral Meniere's disease in the only hearing ear responded as did the bilateral cases . Hearing in the only hearing ear was preserved in all cases . Low-dose subototoxic streptomycin as outpatient treatment offers promise in some cases for relieving attacks of Meniere's disease while improving hearing without producing the temporary disabling effects of ataxia and oscillopsia . Streptomycin and similar drugs that may reduce the production of endolymph may eventually be the treatment of choice in Meniere's disease.

Int J Radiat Biol Relat Stud Phys Chem Med, 1984 Apr, 45(4), 389 - 97
Error-free uvr+-dependent inducible DNA repair in Escherichia coli B/r Hcr+ cells; Pirsel M et al.; The frequency of suppressor (tryptophan reversions) and of true (streptomycin-resistant and dependent) mutations has been followed in E . coli cells irradiated with a single dose or two separate doses of ultraviolet (U.V.) radiation . Under these conditions dimers were efficiently excised after a single dose, while about 40 per cent of the dimers remained unexcised after two doses . Although the level of unexcised dimers in the latter case increased proportionally with the second U.V . dose, the mutation frequency increased by 1.5-2-fold, but did not continue to increase with the level of unexcised dimers . A comparison of excision-proficient and excision-deficient cells containing similar amounts of persisting dimers has shown that proficient cells can tolerate a high level of dimers without an adequate increase in mutation frequency . Our results suggest the existence of an error-free uvr+-dependent inducible repair in E . coli B/r Hcr+ cells.

Minerva Med, 1984 Mar 17, 75(11), 569 - 72
{Evolution of the treatment of tuberculosis}; Grassi C; An evolution analysis of tuberculosis management includes four essential times . The first time coincides with the streptomycin therapeutic employment; the second develops with isoniazid disposing; the third time takes in the period of identification of several drugs a long time called "minor", but very important to formulate some "ad personam" therapeutic patterns . At last, the fourth time is characterized by formulation of short-course chemotherapy . Now the suggested protocol is a regimen of short-course chemotherapy with daily administration of INH and RIF for six-nine months with an initial supplement of ethambutol, or streptomycin or pyrazinamide for the first two months.

Minerva Med, 1984 Mar 17, 75(11), 561 - 3
{Pharmacokinetics of antitubercular agents in man}; Acocella G; The good results gotten employing short-term (6 months) medication regimes with rifampin, isoniazid and an initial supplement (2 months) of streptomycin and pyrazinamide, gave an impulse to pharmacodynamic research . Some recent studies divided bacterial population into four groups, according to bacterial growth time and they showed that rifampin, isoniazid and streptomycin act on mycobacterial groups continuously or intermittently growing . This fact confirms the validity of employed therapeutic regimens . An other paper considered the trend of hematic levels of streptomycin, isoniazid, rifampin and pyrazinamide . The results of this study showed that the variations observed in hematic peaks were independent from the administered doses and from the administration way . These researches help in solving the most important problems of present tubercular chemotherapy, such the use of a single drug or the therapy interruption.

Vopr Virusol, 1984 Mar-Apr, 29(2), 217 - 23
{Streptomycin--an activator of persisting tick-borne encephalitis virus}; Malenko GV et al.; The effect of streptomycin (C) on persistence of tick-borne encephalitis (TBE) virus in Syrian hamsters infected with 3 strains of the virus (41/65, Aina/1448, Vasilchenko ) intracerebrally or subcutaneously was studied . In the animals not given C the infectious virus could be detected in the brain for 8-14 days but not later although their organs (mostly brains and spleens) contained the hemagglutinating antigen and viral antigen detectable by immunofluorescence . Intramuscularly C was given twice daily for 13-35 days in a daily dose of 200 mg/kg . The C-treated hamsters yielded 7 virulent TBE virus strains: 3 from the brain, 3 from the spleen, and one from the blood . No virus could be isolated from the liver, kidneys, or lungs despite the use of various methods for isolation including tissue explantation . The activating effect of C was observed against the background of 4-fold decrease in the titre of complement-fixing and antihemagglutinating antibodies . C exerted its activating effect both at early (70 days) and late (9 months) stages of TBE virus persistence . The activating effect of C appears to be due to its immunosuppressive properties and neurotoxic action on the CNS.

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