Tropenmed Parasitol, 1984 Mar, 35(1), 47 - 49 The microfilaricidal activity of ivermectin in vitro and in vivo; Devaney E et al.; Ivermectin has been tested against the microfilariae of Onchocerca lienalis, Brugia pahangi and Dirofilaria immitis in vitro and in vivo . All in vitro tests were performed on larvae incubated for 48 hours at 37 degrees C in Hepes buffered medium 199 containing 20% serum, benzylpenicillin and streptomycin . In vivo tests were performed on larvae in female BALB/C mice dosed with ivermectin, 5 mg/kg, orally . The microfilariae of B . pahangi in vitro were insensitive to ivermectin at concentrations to 30 ng/ml . In vivo, an 87% reduction in the level of microfilaraemia was obtained by 24 hours after drugging but no reduction was observed in the numbers of peritoneal microfilariae . O . lienalis microfilariae in vitro were killed by ivermectin at 3 ng/ml and the larvae of this species within the subcutaneous and cutaneous tissues of the mouse were also eliminated by ivermectin at 5 mg/kg . D . immitis larvae within the bloodstream of the mouse were also sensitive to ivermectin at the dosage employed but were unaffected by ivermectin in vitro at concentrations up to 30 ng/ml. Can J Microbiol, 1984 Mar, 30(3), 353 - 9 Glutamine synthetase from Mycobacterium avium; Alvarez ME et al.; Mycobacterium avium was previously shown to be dependent upon ammonia or glutamine as a nitrogen source . In an effort to assess the physiology of ammonia assimilation by M . avium, a characterization of its glutamine synthetase was performed . The enzyme from M . avium was purified by streptomycin sulfate treatment, ammonium sulfate precipitation, and affinity chromatography . The enzyme was unusual in that it had a pH optimum of 6.4 and maximum enzyme activity was obtained between 50 and 60 degrees C as shown by the transferase assay . The glutamine synthetase activity from batch-cultured cells decreased with increasing concentration of ammonium chloride in the range of 0.25-5 mumol/mL of medium, which demonstrated a response to environmental supply of a nitrogen source . The mycobacterial enzyme was similar to the other bacterial glutamine synthetases in terms of molecular weight and sedimentation coefficient which were 600 000 and 19.5 S, respectively, and enzyme activity was lost by treatment with a glutamate analog, methionine sulfoximine . The isoelectric point was, however, pH 4.5 . Treatment of the enzyme with snake venom phosphodiesterase resulted in an increase in specific activity . AMP was released by the phosphodiesterase treatment, thus demonstrating that M . avium glutamine synthetase was regulated by adenylylation modification. Brain Res, 1984 Feb 6, 292(2), 382 - 6 Presynaptic effect of streptomycin on the insect neuromuscular junction; Washio H; The effect of streptomycin on the neuromuscular junction of the cockroach leg muscle was studied by means of intracellular electrodes . The miniature excitatory postsynaptic potential (MEPSP) frequency decreased in the presence of 1 mM streptomycin . Double logarithmic plots of the quantal content against the external calcium concentration in the absence and presence of streptomycin suggested the competition for a common site of presynaptic membrane at insect neuromuscular junctions. Acta Otolaryngol Suppl, 1984, 406, 263 - 70 Otoconia degradation; Yamane H et al.; During certain stages of mammalian inner ear development, small crystallized bodies which resemble otoconia may be found in the endolymphatic sac . In order to examine whether the endolymphatic sac plays any part in the process of degradation and dissolution of otoconia, we made an electron-microscopic examination on the endolymphatic sac of fetuses and adult guinea pigs injected with streptomycin sulfate (SM) . In 30-day-old fetal guinea pigs we found miniature otoconium-like bodies (OLBs) in the endolymphatic sac and a giant OLB in the endolymphatic duct . In adult animals we found no otoconia in the endolymphatic sac following SM intoxication . However, the results suggested that both the dark cells of the utricle, as well as the non-sensory epithelium of the saccule, may be engaged in the absorption and dissolution of otoconia. Mol Gen Genet, 1984, 197(3), 472 - 7 Mutagenicity of ozone in different repair-deficient strains of Escherichia coli; L'Herault P et al.; The mutagenic activity of ozone was investigated by the isolation of streptomycin-resistant mutants (Smr) in different strains of Escherichia coli . RecA, lexA, polA and parental strains were ozonated and streptomycin-resistant mutants were scored after a short or long phenotypic delay . Our results suggest that ozone is an active mutagen for forward mutation and that this oxidizing agent could be able to induce mutations via two mechanisms: directly and indirectly by the rec-lex error-prone repair system. Mol Gen Genet, 1984, 198(1), 90 - 9 Kinetic impairment of restrictive streptomycin-resistant ribosomes; Bohman K et al.; Comparisons in vivo and in vitro of wild-type and otherwise isogenic bacteria with five different mutant alleles of the gene (rpsL) specifying ribosomal protein S12, all resistant to high levels of streptomycin, show that the streptomycin-resistant (Smr) phenotype can be subdivided into major groups: restrictive and non-restrictive . The restrictive bacteria have a characteristically lower frequency of nonsense suppression in vivo, and are also slower than the wild type in their rate of protein synthesis . Non-restrictive Smr bacteria on the other hand do not differ significantly from the wild type either in nonsense suppression frequencies or in the rate of translation . A complementary pattern is seen in vitro, where ribosomes from the restrictive Smr bacteria translate poly(U) with a significantly lower missense error frequency than wild-type ribosomes, and also show an increased Michaelis constant (KM) with respect to their substrate, i.e . ternary complexes . Both effects are correlated with the more aggressive proofreading function that is characteristic of these restrictive ribosomes . In contrast, ribosomes isolated from the non-restrictive Smr bacteria do not show any major difference in either proofreading or missense error in vitro when compared to the wild type. Mol Gen Genet, 1984, 193(2), 255 - 62 Plasmid R46 provides a function that promotes recA-independent deletion, fusion and resolution of replicon; Yamamoto T et al.; We report that plasmid R46 provides a function which promotes recA-independent deletion, replicon fusion, and resolution of the fusion . R46 belongs to the incompatibility group N and specifies resistance to ampicillin, tetracycline, streptomycin and sulfonamide . Four kinds of deletion derivatives were observed by selection for susceptability to tetracycline from ampicillin-resistant clones . A common region, will be called alpha region thereafter, was postulated to be involved in these deletions . The replicon fusion occurred by a conjugative mobilization of each derivative with plasmid R388 . The fusion was suggested to contain both replicons linked at each junction by the sequence in the alpha region in direct orientation . The resolution of the replicon fusion was found between two alpha regions and a consequently generated, parental deletion derivative and an R388 derivative which gained one alpha region . It is possible that the alpha region contains one potential Insertion Sequence (IS) element . These events were also speculated to occur as a consequence of insertion of the potential IS onto the intramolecular or intermolecular target sequence, or reciprocal recombination between two potential IS elements. Teratog Carcinog Mutagen, 1984, 4(3), 261 - 72 Genetic effects of drug interaction in tuberculosis patients and their fate; Jaju M et al.; In this paper we will discuss the genetic consequences of drug interaction in tuberculosis patients . Blood from tuberculosis patients was cultured before, during, and after withdrawal of therapy involving five different drug combinations of isoniazid (INH), thiacetazone (TAZ), para-aminosalicylic acid (PAS), and streptomycin (SM) . The approaches used to detect DNA damage were chromosome aberrations and sister chromatid exchanges (SCEs) . A total of 179 subjects were analyzed . In combination these drugs showed synergistic, additive, and antagonistic effects, though they were found to be nonclastogenic individually . Four of the drug combinations, INH + TAZ, INH + PAS, INH + TAZ + SM, and INH + PAS + SM, induced a significant increase in the frequency of aberrations, whereas INH + SM did not induce aberrations . In fact, SM appeared to reduce the frequency of aberrations . SCEs were increased in only two patients: one treated with INH + TAZ and the other with INH + PAS . The frequency of aberrations after withdrawal of therapy was decreased; it was slightly higher than the controls, though it was insignificant . The return to normalcy could be due to elimination of damaged cells or the repair of DNA in lymphocytes . Though the drug-induced aberrations do not persist after withdrawal of therapy, the chromosome damaging combinations of drugs should be used with caution, because the possibility of meiotic chromosome damage in germ cells (during therapy), which might be passed on to the next generation, cannot be ruled out. Mol Gen Genet, 1984, 194(3), 534 - 8 Dissociation of peptidyl-tRNA from ribosomes is perturbed by streptomycin and by strA mutations; Caplan AB et al.; Peptidyl-tRNA may dissociate preferentially from ribosomes during protein synthesis when it is inappropriate to, does not correctly complement, the messenger RNA . To test this idea, growing cultures of Escherichia coli were treated with streptomycin to increase the frequency of errors during protein synthesis . Since the treated cells had a temperature-sensitive peptidyl-tRNA hydrolase and could not destroy dissociated peptidyl-tRNA, it was possible to measure the rate of its accumulation after raising the temperature to non-permissive conditions . Both low and high doses of streptomycin enhanced the rate of dissociation and accumulation of peptidyl-tRNA . The rank order of rates of dissociation/accumulation of various isoaccepting tRNA families was not significantly altered by the drug treatment . We concluded that streptomycin stimulated a normal pathway for dissociation of peptidyl-tRNA . Two streptomycin- resistant strains of E . coli had higher rates of dissociation of peptidyl-tRNA than did their sensitive parent strain . When treated with high doses of the drug, the resistant strains showed slightly reduced rates of dissociation of peptidyl-tRNA . These results were interpreted in terms of a two state, two site model for protein synthesis: streptomycin enhances the binding of aminoacyl-tRNA to a tight state of the ribosome A site; the strA mutation enhances translocation to a loose state of the ribosome P site. Braz J Med Biol Res, 1984, 17(3-4), 329 - 33 Effects of streptomycin and neomycin on the adrenal medulla of dogs; Corrado AP et al.; The blocking effects of streptomycin and neomycin upon adrenal neurotransmission were studied in dogs . The pressor responses to splanchnic nerve stimulation (SNS) or 50 micrograms/kg nicotine were both blocked by 100 mg/kg but not by 50 mg/kg of the antibiotics injected systemically through the femoral vein . The effect was reversed by intravenous infusion of calcium chloride . The pressor response to SNS, but not that to nicotine, was blocked by the antibiotics injected into the adrenal gland through the adrenolumbar vein at doses up to 10 mg/kg . This effect was reversed by 50 micrograms/kg calcium chloride . Higher doses of antibiotics blocked the response to both stimuli, with only the response to nicotine being reversed by calcium chloride . These data indicate that streptomycin and neomycin block adrenal neurotransmission by interfering with calcium ions at pre- or pre-plus postsynaptic levels depending on the dose and route of administration. Mol Gen Genet, 1984, 196(3), 513 - 20 Streptomycin-sensitivity in Streptomyces glaucescens is due to deletions comprising the structural gene coding for a specific phosphotransferase; Hintermann G et al.; The wild type strain of Streptomyces glaucescens produces hydroxystreptomycin and has a natural resistance towards the streptomycin group aminoglycoside antibiotics . The inherent resistance is a genetically unstable character and mutant strains sensitive to streptomycins arise spontaneously at unusually high frequencies . The gene conferring streptomycin resistance was cloned and characterised as a streptomycin specific phosphotransferase . Hybridisation experiments show that the mutational event leading to sensitivity is due to large deletions, most likely on the chromosome, comprehending the structural gene coding for a streptomycin phosphotransferase and its flanking regions . Interspecific expression of the S . glaucescens phosphotransferase was found in Streptomyces lividans as well as in Escherichia coli. Am Rev Respir Dis, 1983 Dec, 128(6), 1048 - 50 Short-course chemotherapy for pulmonary disease caused by Mycobacterium kansasii; Ahn CH et al.; Forty patients with pulmonary disease caused by Mycobacterium kansasii were treated initially with rifampin, isoniazid, and ethambutol daily for 12 months, and with streptomycin twice weekly for the first 3 months . Postchemotherapy follow-up examinations have ranged from 6 to 68 months, with an average of 31 months . One of the 40 patients (2.5%) relapsed 6 months after completion of chemotherapy . In vitro susceptibility of the mycobacteria to the drugs used, extent of disease, and/or the coexistence of other diseases did not seem to influence the outcome . This 12-month chemotherapy regimen is considered to be sufficient for the initial treatment of pulmonary disease caused by M . kansasii. J Clin Microbiol, 1983 Dec, 18(6), 1335 - 9 Conventional and radiometric drug susceptibility testing of Mycobacterium tuberculosis complex; Laszlo A et al.; A recently developed method of drug susceptibility testing of Mycobacterium tuberculosis which measures the evolution of labeled CO2 from {1-14C}palmitic acid (BACTEC 460 system) was compared to three conventional methods . The proportion method of drug susceptibility testing was the standard against which all test results were compared . Indirect drug susceptibility to isoniazid, streptomycin, rifampin, and ethambutol of 245 isolates belonging to the M . tuberculosis complex was determined . In 95% of the cases, results obtained by the radiometric method were available within 1 week, as opposed to 3 to 6 weeks needed in conventional methodology . Overall agreement was 96.4% . Specificity values ranged from 0.98 to 1.0; sensitivity values of 1.0 for rifampin, 0.96 for streptomycin, 0.91 for isoniazid, and 0.18 for ethambutol were obtained . The specificity of the absolute concentration and resistance ratio drug susceptibility testing methods were 0.99 and 1.0, respectively . The sensitivity of the former was higher than that of the radiometric method (0.99 verus 0.92), whereas that of the latter was lower (0.88 verus 0.96) . Further testing indicated that the low sensitivity determined for ethambutol may be due to the choice of the critical concentration used, rather than to a shortcoming of the procedure . The radiometric method thus does not significantly differ in reliability from conventional methods of drug susceptibility testing of M . tuberculosis. Am Rev Respir Dis, 1983 Dec, 128(6), 1055 - 8 Antituberculosis drug resistance in south Texas; Carpenter JL et al.; The incidence of antituberculosis drug resistance in South Texas has been tabulated . Age, sex, and ethnic group were not found to significantly influence the incidence of resistance . The incidence of resistance to isoniazid (NH) was 16.4%, ethambutol, 3.9%, rifampin, 10.6%, and streptomycin, 7.8% . There was a 7.3% rate of resistance to INH and/or ethambutol or rifampin for any individual organism (i.e., to 2 of the 3 most commonly used antituberculosis drugs) . We conclude that the incidence of single and multiple antituberculosis drug resistance in South Texas is higher than previously reported. Infection, 1983 Nov-Dec, 11(6), 310 - 2 Brucellosis: difficulties in diagnosis and a report on 38 cases; Samra Y et al.; We have reviewed 38 patients with brucellosis who were admitted to the Chaim Sheba Medical Center between 1955 and 1977, i.e . during a 23-year period . The clinical manifestations varied greatly . Diagnosis was easy when brucellosis was suspected, as in cases presenting with fever of unknown origin . In nine of the 38 cases diagnosis was difficult and delayed for several weeks since brucellosis was not suspected . Some of these cases will be described in detail . The diagnosis was established in 16 patients by isolating Brucella melitensis and in the other 22 by serological tests . There were no relapses in the 26 patients treated with a combination of streptomycin and tetracycline; two of the 12 patients treated with tetracycline alone relapsed . Brucellosis should be considered when clinical manifestations are puzzling. Biochem Pharmacol, 1983 Nov 1, 32(21), 3213 - 20 Further studies of the response of kidney lysosomes to aminoglycosides and other cations; Powell JH et al.; Rat renal cortical lysosomes were isolated in 0.3 M sucrose containing 1 mM EDTA by differential centrifugation . Lysosomes were incubated in isotonic sucrose or isotonic glycine with various concentrations of endogenous and exogenous compounds at 37 degrees for 1 hr . Lysosomes were resedimented, and the N-acetyl-beta-glucosaminidase (NAG) activity was measured in the supernatant fraction and the disrupted pellet and the percentage of total NAG released was calculated . Gentamicin and its C1 and C2 components had similar potencies for inhibiting NAG release from lysosomes at low concentrations . The release of alpha-galactosidase and beta-galactosidase from lysosomes was also inhibited by streptomycin and gentamicin . Mepacrine at low concentrations stabilized lysosomes and at high concentrations disrupted lysosomes . This drug also enhanced the effect of low concentrations of gentamicin on lysosomes . Inositol hexaphosphoric acid was a potent antagonist of the effect of low concentrations of gentamicin and mepacrine on lysosomes . Rats were treated with gentamicin at doses of 40, 80 and 160 mg/kg for 1 and 3 days . NAG excretion in gentamicin-treated groups as compared to saline controls was unchanged at day 1 . Only the 160 mg/kg treatment group showed a tendency toward elevated renal cortical NAG at day 1 (P less than 0.06) . All treatment groups had elevated renal cortical NAG at day 3, while the 160 mg/kg group also had elevated NAG excretion . Lysine, arginine, L-canavanine and polymyxin B all affected NAG release from lysosomes in vitro . Lysine enhanced the disruptive effect of high gentamicin concentrations on lysosomes . Ferric and ferrous ions, tested over widely varied concentrations, inhibited NAG release at low concentrations while enhancing NAG release at high concentrations . We therefore conclude that the nephrotoxicity of aminoglycoside and other endogenous and exogenous renally excreted cationic compounds may be produced by their effects on lysosomes in the proximal renal tubule. Gene, 1983 Nov, 25(1), 155 - 9 Isolation and characterization of pock-forming plasmids for Streptomyces griseus from soil actinomycetes; Ohnuki T et al.; Thirty independent actinomycetes strains carrying plasmids were isolated from soil . These plasmids were purified as cccDNA by CsCl-EtBr equilibrium density-gradient centrifugation . Plasmids that induce "pocks", namely formation of circular zones of sporulation-inhibition, were selected by protoplast transformation of streptomycin-producing strain, Streptomyces griseus ATCC10137 . Six pock-forming plasmids, pOA7, pOA11, pOA15, pOA23, pOA29 and pOA30, were obtained, and their cleavage maps, transformation frequencies, and copy numbers, as well as their stability, are described. J Mol Biol, 1983 Oct 25, 170(2), 287 - 303 Plasmid pSC101 replication mutants generated by insertion of the transposon Tn1000; Linder P et al.; A derivative of pSC101, pLC709, was constructed by ligation of the HincII-A fragment of pSC101 to the mini-colEI plasmid pVH51 and to a DNA fragment encoding resistance to the antibiotics streptomycin and spectinomycin . Insertions of the transposon Tn1000 (gamma-delta) into the pSC101 replication region of pLC709 were isolated following cotransfer of the plasmid with the sex factor F . The sites of insertion of the transposon were determined by restriction enzyme analysis and the replication and incompatibility properties of the insertion plasmids and DNA fragments cloned from them were analysed . The insertion mutations defined a locus, inc, of approximately 200 base-pairs that is responsible for pSC101-specific incompatibility . Two mutations adjacent to this region inactivate pSC101 replication but can be complemented in trans by a wild-type pSC101 plasmid, and thus define a trans-acting replication function, rep . The inc locus is within a larger region of some 450 base-pairs that is essential for pSC101 replication and that includes the origin of replication . This 450 base-pair segment can replicate in the presence of a helper plasmid that supplies the rep function in trans. J Med Genet, 1983 Oct, 20(5), 357 - 60 Familial aggregation of streptomycin ototoxicity: autosomal dominant inheritance? Viljoen DL, Sellars SL, Beighton P. Eight members of a large kindred of mixed ancestry from a remote rural area of South Africa were investigated for deafness . In each, severe permanent perceptive hearing loss had developed during antituberculous therapy with streptomycin sulphate in conventional doses . Although unproven by the data available in this study, the familial aggregation and pattern of distribution of sensitivity to streptomycin suggested autosomal dominant inheritance. Br J Dis Chest, 1983 Oct, 77(4), 403 - 6 Hyperuricaemia induced by ethambutol; Narang RK et al.; Seventy patients with pulmonary tuberculosis and 12 healthy controls were included in a study to observe the effect of ethambutol on serum uric acid level . In ethambutol-treated cases a statistically significant increase in mean serum uric acid levels was observed in the second, third and fourth week of treatment . This increase was independent of dosage of ethambutol . However, 22 of the 52 (42%) ethambutol-treated cases showed no increase . Streptomycin was found not to potentiate the hyperuricaemic action of ethambutol . Hyperuricaemia due to ethambutol was reversed with probenicid but not by salicylates . No patient developed acute gouty arthritis although two developed arthralgia. Eur J Clin Microbiol, 1983 Oct, 2(5), 463 - 8 Dissemination of streptomycin and sulfonamide resistance by plasmid pBP1 in Escherichia coli; Korfmann G et al.; About one third of streptomycin resistance in Escherichia coli is mediated by APH-(3'') . This enzyme is encoded by the plasmid pBP1 in 80% of all streptomycin resistant strains tested . pBP1, which in addition mediates sulfonamide resistance, has been found to be disseminated in Escherichia coli strains all over the world . It has a molecular weight of 4.0 megadalton and does not seem to be disadvantageous for the metabolism of the bacterial cell . The reason for the slow decrease of resistance to streptomycin and sulfonamide in clinical isolates, despite the restricted use of these drugs, is presumably the survival of bacteria harbouring pBP1 which have been selected by streptomycin and sulfonamides in the early days of chemotherapy. Am Ind Hyg Assoc J, 1983 Sep, 44(9), 662 - 4 Sampling for airborne fungi: a statistical comparison of media; Morring KL et al.; Four broad spectrum media employed for enumeration of fungi from air were compared to determine which would yield the highest number of colony forming units when simultaneously sampling air from the same environment . The four media tested were: Inhibitory Mold Agar, Littman Oxgall Agar, Rose Bengal-Streptomycin Agar, and Sabouraud Dextrose Agar . The number of colony forming units produced on the media were compared by an incomplete four-factor factorial design (day, time, sampler and medium) . Analysis of variance of the data indicated that highly significant variation was associated with collection medium and different sampling days . Comparisons among the media were performed by Duncan's multiple range test which demonstrated significantly lower values on Littman Oxgall as compared to the other media . There was no significant difference in the number of colonies produced on Rose Bengal-Streptomycin Agar, Inhibitory Mold Agar, and Sabouraud Dextrose Agar . For a number of reasons, Rose Bengal-Streptomycin Agar is our medium of choice for broad spectrum aeromycological sampling. J Gen Microbiol, 1983 Sep, 129 (Pt 9), 2939 - 44 Genetic analysis of A-factor synthesis in Streptomyces coelicolor A3(2) and Streptomyces griseus; Hara O et al.; A-factor is a potent pleiotropic effector produced by Streptomyces griseus and is essential for streptomycin production and spore formation in this organism . Its production is widely distributed among various actinomycetes including Streptomyces coelicolor A3(2) . Genetic analysis of A-factor production was carried out with S . coelicolor A3(2), and two closely linked loci for A-factor mutations (afsA and B) were identified between cysD and leuB on the chromosomal linkage map . In contrast, genetic crosses of A-factor-negative mutants of S . griseus, using a protoplast fusion technique, failed to give a fixed locus for A-factor gene(s) and suggested involvement of an extrachromosomal or transposable genetic element in A-factor synthesis in this organism. Am Rev Respir Dis, 1983 Sep, 128(3), 425 - 8 A continuing study of primary drug-resistant tuberculosis among children observed at the Kings County Hospital Medical Center between the years 1961 and 1980; Steiner P et al.; A 20-yr prospective study of the incidence of primary drug-resistant tuberculosis among children treated at the Kings County Medical Center was undertaken in January 1961 and extended through December 1980 . There were 355 strains of Mycobacterium tuberculosis isolated during this time, 56 of which were found to be primarily resistant to one or more antituberculosis drugs, giving an overall resistance rate of 15.8% . The study was divided into five 4-yr periods . The resistance rate to isoniazid was 9.9%, varying from a peak of 15.2% in the third period of study (1969 to 1972) to 4.5% in the last period of study . The changes in the rate were not significant . The overall resistance rate for streptomycin was 9.2% . There were significant increases in the resistance rate in the second (1965 to 1968) and third (1969 to 1972) periods of study, but not in the last 2 periods . The rates for PAS (3.4%), rifampin (1%), and ethambutol (0.7%) were low . The type and severity of disease among those infected with a resistant strain were no different from those infected with a susceptible strain . Life-threatening disease was found in 10 of the 56 patients infected with a drug-resistant strain . There was one fatality in a child with meningitis who was treated early in the study . Our experience suggests that rifampin and ethambutol be included in the initial treatment regimen of all children with a life-threatening form of tuberculosis until the susceptibility pattern of the infecting strain is determined, after which the drug regimen can be modified if necessary. Plasmid, 1983 Sep, 10(2), 156 - 63 A host-vector system for gene cloning in the cyanobacterium Anacystis nidulans R2; Kuhlemeier CJ et al.; We describe the construction of a series of vectors suitable for gene cloning in the cyanobacterium Anacystis nidulans R2 . From the indigenous plasmid pUH24, derivatives were constructed with streptomycin as the selective marker; one of these plasmids was used to construct pUC303, a shuttle vector capable of replication in A . nidulans R2 as well as in Escherichia coli K12 . It has two markers, streptomycin and chloramphenicol resistance, and three unique restriction sites . Instability of recombinant plasmids was overcome by using a derivative of A . nidulans R2 cured of the indigenous plasmid pUH24 . This strain, R2-SPc, can be transformed stably and at high frequency by the plasmids described in this paper . The combination of the cured strain R2-SPc and the new plasmid pUC303 serves as a suitable host-vector system for gene cloning in cyanobacteria. J Bacteriol, 1983 Sep, 155(3), 1238 - 48 Cloning of a pleiotropic gene that positively controls biosynthesis of A-factor, actinorhodin, and prodigiosin in Streptomyces coelicolor A3(2) and Streptomyces lividans; Horinouchi S et al.; A-factor (2S-isocapryloyl-3S-hydroxymethyl-gamma-butyrolactone), an autoregulating factor originally found in Streptomyces griseus, is involved in streptomycin biosynthesis and cell differentiation in this organism . A-factor production is widely distributed among actinomycetes, including Streptomyces coelicolor A3(2) and Streptomyces lividans . A chromosomal pleiotropic regulatory gene of S . coelicolor A3(2) controlling biosynthesis of A-factor and red pigments was cloned with a spontaneous A-factor-deficient strain of S . lividans HH21 and plasmid pIJ41 as a host-vector system . The restriction endonuclease KpnI-digested chromosomal fragments were ligated into the plasmid vector and introduced by transformation into the protoplasts of strain HH21 . Three red transformants thus selected were found to produce A-factor and to carry a plasmid with the same molecular weight, and a 6.4-megadalton fragment was inserted in the KpnI site of pIJ41 . By restriction endonuclease mapping and subcloning, a restriction fragment (1.2 megadaltons, approximately 2,000 base pairs) bearing the gene which causes concomitant production of A-factor and red pigments was determined . The red pigments were identified by thin-layer chromatography and spectroscopy to be actinorhodin and prodigiosin, both of which are the antibiotics produced by S . coelicolor A3(2) . The cloned fragment was introduced into the A-factor-negative mutants (afs) of S . coelicolor A3(2) by using pIJ702 as the vector, where it complemented one of these mutations, afsB, characterized by simultaneous loss of A-factor and red pigment production . We conclude that the cloned gene pleiotropically and positively controls the biosynthesis of A-factor, actinorhodin, and prodigiosin. Arch Histol Jpn, 1983 Sep, 46(4), 491 - 500 Quantitative changes of Holmes positive nucleolus-like inclusion bodies in the mouse locus coeruleus under various experimental conditions; Katoh Y et al.; The author demonstrated earlier that the nucleolus-like inclusion bodies in the central nervous system observed under an electron microscope are characteristically stained by the modified Holmes silver impregnation method . These inclusion bodies were then counted in the entire mouse brain; they numbered 1,547 +/- 144 on the unilateral side of the locus coeruleus . In the present experiment, mice were subjected to various experimental conditions or given several medicaments that might induce changes in body weight and in the number of inclusion bodies . Following dehydration, fasting, dehydration with fasting, induction of stress condition, reserpine, alpha-methyl-p-tyrosine, cycloheximide, cephalexin and puromycin administrations, body weight was decreased along with a decrease in the number of inclusion bodies in the locus coeruleus . After streptomycin sulfate injection, however, body weight was increased and inclusion bodies showed a moderate increase in number . Actinomycin D and mitomycin C, inhibitors of nucleic acid synthesis, brought about a definite decrease in body weight, but little if any changes in the number of inclusion bodies . Furthermore, after reserpine injection several small inclusion bodies were observed in the cytoplasm of locus coeruleus cells in a recovery stage and after inclusion bodies regained their normal number and size . The results suggested that the inclusion bodies might have some relation to body weight, as well as to monoamine of the brain and protein synthesis. J Biol Chem, 1983 Aug 25, 258(16), 10007 - 12 Codon usage and mistranslation . In vivo basal level misreading of the MS2 coat protein message; Parker J et al.; The coat protein of the small RNA virus MS2 shows charge heterogeneity in vivo . In most strains there is a basic satellite of the native protein . We have shown that this basic satellite is greatly diminished or absent in strains with the streptomycin-resistant allele, rpsL, a mutation which leads to increased translational accuracy . Further, the satellite is present in cells where the coat protein is encoded by duplex DNA . Tryptic digests of the satellite show that it contains new lysine-containing peptides which appear to be the same as those found in derivatives of coat protein which have a lysine for asparagine substitution . Sequencing of the NH2-terminal 19 amino acids of the satellite protein shows that the asparagine codon AAU at amino acid 12 is misread approximately 8 times more frequently than the AAC at amino acid 3 . We conclude that the satellite species is the result of basal level lysine for asparagine substitution . These substitutions are most likely caused by preferential misreading of AAU codons at a frequency of approximately 5 X 10(-3), 10-fold higher than the average error frequency. Antimicrob Agents Chemother, 1983 Aug, 24(2), 268 - 72 Rapid drug susceptibility testing of mycobacteria in tissue culture medium; Nozawa RT et al.; Mycobacteria grew rapidly in FST medium (tissue culture medium F12 supplemented with 5% serum and 0.05% Tween 80) . Growth of Mycobacterium tuberculosis and other niacin-negative mycobacteria in flat-bottomed, 96-well tissue culture plates was estimable by the naked eye within 3 to 5 days when mycobacteria were inoculated at 0.1 to 0.01 Klett units (5 X 10(4) to 0.5 X 10(4) CFU) per well . Spontaneous resistant variants of M . tuberculosis to isoniazid arose and grew in the medium within 2 weeks of culture . A total of 56 clinically isolated mycobacteria whose drug susceptibilities had been tested by a conventional method were tested in FST medium for minimal inhibitory concentrations of streptomycin, ethambutol, rifampin, and isoniazid . The minimal inhibitory concentrations of these drugs in FST medium strictly coincided with the drug susceptibility patterns obtained by a conventional method, except for 3 of 224 estimations. J Pharmacol Exp Ther, 1983 Aug, 226(2), 551 - 7 Pharmacology and regional variations of quinolinic acid-evoked excitations in the rat central nervous system; Perkins MN et al.; A physiological and pharmacological investigation of a novel endogenous excitant, quinolinic acid, was carried out in male rats using conventional iontophoretic techniques . It was established that quinolinic acid responses were preferentially reduced by antagonists acting at the N-methyl-D-aspartate (NMDA) preferring receptor, such as (+/-)-2-amino-7-phosphono-heptanoic acid and 1-hydroxy-3-amino-pyrrolidone-2 . Glutamic acid diethyl ester reduced responses to quinolinic acid, quisqualic acid and NMDA with no clear specificity . Streptomycin, thought to act at the quisqualic acid receptor, largely spared quinolinic acid responses, being more effective against quisqualic acid evoked excitations . It is therefore suggested that quinolinic acid acts primarily at the NMDA receptor . In addition, the sensitivity of various components of the neuraxis to quinolinic acid was assessed and compared with glutamate and NMDA . Neurons in the spinal cord and cerebellum were largely unresponsive to quinolinate, whereas cells in the neocortex, striatum and hippocampus responded to this agonist to a similar degree as glutamate . In the cortex quinolinate was about one-fifth as active as NMDA, which together with quinolinic acid was much less active in the spinal cord and cerebellum . It is concluded that the possibility that quinolinic acid has a neurotransmitter type function at central "amino acid" receptors merits further investigation. Acta Otolaryngol, 1983 Jul-Aug, 96(1-2), 21 - 30 Action of streptomycin and calcium on the apical membrane of hair cells of the frog isolated semicircular canal; Bernard C; An isolated frog posterior semicircular canal was placed in a two-compartment perspex chamber allowing separate perfusions of the peri- and endolymphatic space with adequate saline solutions . The ampullar receptors were mechanically stimulated with a hydraulic device which imposed sinusoidal movements to the cupulo-endolymphatic system at low frequency (0.10 Hz) . Slow potentials recorded with non-polarizable Ag/AgCl electrodes near the crista ampullaris (Adc) and on the ampullar nerve (Ndc) were displayed together with an analog signal of the mechanical stimulation and with the nerve spike frequency, on a strip chart . The streptomycin action or the high calcium concentration action (these two substances being administered together or separately into the ampullar space) indicated that the streptomycin seemed to block mechano-dependent channels (non-specific) assumed to be included into the hair cell apical membrane . The synaptic transmission process was altered by streptomycin but was improved by the high calcium concentration . Also, the mechanisms which would control the spontaneous release of a neurotransmitter, seemed, at least partly, different from those controlling the neurotransmitter release in response to a mechanical stimulation; these last ones were less sensitive to the calcium action. Plasmid, 1983 Jul, 10(1), 96 - 9 Restriction map of Tn7; Gosti-Testu F et al.; Tn7, a transposon of 14 kb, encodes resistance to trimethoprim (Tp) and streptomycin (Sm) . A cleavage site map of this transposon for twenty-two different restriction enzymes as determined by comparison of restriction enzyme cleavage patterns of the plasmids ColE1 and ColE1::Tn7 is presented . The precise localization of these sites was facilitated by the use of two deletion derivatives of ColE1::Tn7: pGB2 and ColE1::Tn7 delta 6, and by the use of pOB14 and pOB15 which contain a part of Tn7 cloned into the plasmid pBR322 . This map should aid in the study of the structural and genetic organization of this transposon. Biochim Biophys Acta, 1983 Jun 16, 752(1), 153 - 61 The effects of polyamines and aminoglycosides on phosphatidylinositol-specific phospholipase C from human amnion; Sagawa N et al.; The effects of polyvalent cations (polyamines and aminoglycoside antibiotics) on Ca2+-dependent phosphatidylinositol-specific phospholipase C activity of human amnion tissue were examined . In the presence of 1 mM Ca2+, the hydrolysis of phosphatidylinositol (2 mM) by phospholipase C was increased greatly (240-560% of control) by spermine (0.4 mM), spermidine (1 mM), neomycin (0.1 mM), gentamicin (0.2 mM), kanamycin (0.4 mM) and streptomycin (0.8 mM) . Putrescine and cadaverine (0.1-2.0 mM), however, stimulated phospholipase C activity only slightly . The effects of spermidine, spermine and gentamicin on phospholipase C activity were characterized and found to be dependent upon the concentrations of phosphatidylinositol, Ca2+ and the particular polyvalent cation . At low concentrations of phosphatidylinositol and Ca2+ the predominant effect of polyamines and aminoglycosides was to inhibit phospholipase C activity . When the concentrations of phosphatidylinositol and Ca2+ were increased, spermidine, spermine and gentamicin stimulated phospholipase C activity . In the presence of 16 mM Ca2+, however, phospholipase C activity was maximal and was unaffected by either polyamines or aminoglycosides . At all concentrations of Ca2+ examined, the maximal stimulation of phospholipase C activity by a given polyvalent cation occurred at a fixed molar ratio of the particular polyvalent cation to phosphatidylinositol . Polyamines and aminoglycosides appeared to modulate the Ca2+ requirement for phospholipase C activity, but could not substitute completely for Ca2+ . The activities of phospholipase A2, diacylglycerol lipase, monoacylglycerol lipase and diacylglycerol kinase in amnion tissue were unaffected by any of the polyvalent cations examined . It is proposed that any in vivo influences (stimulatory or inhibitory) of polyamines and aminoglycosides on amnion phospholipase C activity would depend upon the effective concentrations of Ca2+ and phosphatidylinositol. Acta Orthop Scand, 1983 Jun, 54(3), 449 - 51 Osteomyelitis caused by Mycobacterium avium; Collert S et al.; Osteomyelitis due to M . avium is extremely rare and frequently fatal . The successful cure of an 11-year-old patient with multiple mycobacterial lesions in the pelvis and right humerus is reported . Although the mycobacteria were in vitro resistant to most antituberculous drugs a five-drug regimen was given over a total of 2 1/2 years . The accumulated streptomycin dose was 160 g but no adverse effects were noted . Streptomycin therapy was judged of major importance for the favourable outcome. J Gen Microbiol, 1983 Jun, 129 (Pt 6), 1683 - 7 Purification and characterization of streptomycin 6-kinase, an enzyme implicated in self-protection of a streptomycin-producing micro-organism; Sugiyama M et al.; Streptomycin 6-kinase of the streptomycin-producing strain Streptomyces griseus HUT 6037 was purified by fractionation with (NH4)2SO4 and chromatography on DEAE-Sephadex A-25, hydroxyapatite and Sephadex G-100 . After PAGE of the final fraction, a protein band corresponding to streptomycin 6-kinase was detected, together with a less intense band having no enzyme activity . Molecular weights determined by SDS-PAGE and by Sephadex G-100 chromatography were about 36000 and 38000, respectively, suggesting that the enzyme was a monomer . The isoelectric point of the enzyme was pH 6.6 . Among the nucleoside 5'-triphosphates tested, ATP was the preferred phosphoryl donor . The Km values for streptomycin and ATP were 3.5 mM and 0.4 mM, respectively . The enzyme activity was strongly inhibited by EDTA and AgNO3 . It was shown by using an in vitro protein-synthesizing system that purified streptomycin 6-kinase could protect polyphenylalanine synthesis of the streptomycin-susceptible S . griseus strain KSN from inhibition by streptomycin. An Esp Pediatr, 1983 May, 18(5), 377 - 83 {Brucellosis in children}; Armas H et al.; It has been studied in a series of 30 children affected of brucellosis, the most important epidemiologic, clinical and biologic characteristics . It has been emphasized the good response to the combined treatment of tetracycline and streptomycin. Prikl Biokhim Mikrobiol, 1983 May-Jun, 19(3), 356 - 61 {Effect of the A-factor on the adenylate level in Streptomyces griseus}; Vasilenko TI et al.; The adenylate content of various strains of Streptomyces griseus was measured . With respect to the ATP and ADP content the strains capable of spore formation, streptomycin synthesis and A-factor (2-isocapryloyl-3-hydroxymethyl-4-hydroxybutyrolactone) synthesis differed from the A-factor deficient mutants . The addition of the A-factor to the recipient strains decreased the intracellular content of ATP and the ATP/ADP ratio . The strain which is not an A-factor recipient did not modify the ATP content when the A-factor was added to the medium. Pathol Biol (Paris), 1983 May, 31(5), 446 - 50 {Activity of rifampicin administered daily and intermittently on experimental tuberculosis in mice}; Grosset J et al.; Intermittent regimens with rifampicin (RMP) for chemotherapy of pulmonary tuberculosis are cheaper and can be usually supervised more easily than daily regimens . They are recommended, specially, in developing countries . The present study is designed to evaluate the reduction of RMP activity as the interval between doses is increased in experimental mouse tuberculosis . The mice are given 10 mg/kg oral doses of RMP once, twice, three times or six times a week . The RMP activity is measured as the decrease of viable counts (cfu) in the spleen of mice . RMP given once a week has no activity neither in combination with isoniazid and streptomycin on a large population of organisms nor alone on a small population . RMP given alone twice a week has an activity slightly better than RMP given once a week . RMP given alone three times a week has a weak but not worthy activity: the mean number of cfu after a three times weekly treatment is significantly lower than the mean number of cfu in control (p less than 0.001) but significantly higher than the mean number of cfu after a six times weekly treatment (p less than 0.001) . These experimental results are consistent with the experimental data on the effects of RMP on the RNA polymerase . They are not favourable to the intermittent administration of RMP in the chemotherapy of tuberculosis. Brain Res, 1983 Apr 18, 265(2), 241 - 7 The effect of streptomycin on the neuromuscular junction of the frog; Tamaki M; The neuromuscular block produced by streptomycin was studied in the frog sartorius muscle by means of intracellular recording and iontophoretic application of acetylcholine . Decreases of the end-plate potentials (e.p.p.s) and acetylcholine potentials (ACh potentials) were observed following the application of streptomycin . At a concentration of 10(-4) M, the e.p.p . was 36.8 +/- 5.5% (mean +/- S.E.) (n = 12), and the ACh potential was 53.7 +/- 3.8% (n = 12) of the control size . The resting membrane potential and membrane conductance of the muscle fibers were not affected by streptomycin . Streptomycin did not significantly alter the spontaneous prejunctional activity, but the amplitude of the miniature end-plate potentials (m.e.p.p.s) was decreased . After the application of higher concentrations of streptomycin, the quantum content decreased from the control value . It is suggested that the reduction of the e.p.p . amplitude produced by streptomycin is mainly due to a decrease in the sensitivity of the end-plate membrane . In addition, at higher concentrations, streptomycin reduced the amount of transmitter released from the motor nerve in response to a nerve volley. Virologie, 1983 Apr-Jun, 34(2), 103 - 11 RNA--streptomycin interaction on cellulose; Horer OL et al.; Bichromatic paper disk spectrophotometry allowed the demonstration of an analogy between the increase in the solubility of highly polymerized RNA complexed with streptomycin cations (which accounts for the preservation in vivo of the infectivity of a viral RNA--streptomycin complex) and the effect of a cellulose/solution interface on the distribution of the highly polymerized RNA. J Mol Biol, 1983 Mar 15, 164(4), 529 - 60 Genetic characterization of early amber mutations in the Escherichia coli polA gene and purification of the amber peptides; Kelley WS et al.; The polA1 mutation of Escherichia coli K12 and two further mutations, resA1 and resA2, characterized in E . coli B have been shown to produce enzymatically active nonsense (amber) peptides . These enzymes can be purified to virtual homogeneity by use of the lambda polA transducing phage system . The peptides are immunologically related and react weakly but specifically with antibody to whole DNA polymerase I . In their purified form the peptides are less heat-labile than the whole enzyme or the Klenow fragment produced by proteolysis . Physiological studies indicate that all three alleles are compatible with a number of different streptomycin resistance mutations (rpsL alleles) in a variety of genetic backgrounds . There is, however, clear evidence for slight amounts of "read-through" of these mutations under these conditions . DNA sequence studies have indicated the exact nucleotides that have been mutated to produce the amber alleles . The resA1 and resA2 alleles appear to be independent isolates of the same mutation both resulting in CAG (Gln) leads to TAG (amber) at amino acid residue 298 . The polA1 mutation results in TGC (Trp) leads to TAG (amber) at amino acid residue 342 . The significance of these findings is discussed with reference to the structure of the whole enzyme as shown by the DNA sequence data of Joyce et al . (1982) and protein chemistry of Brown et al . (1982). Biochim Biophys Acta, 1983 Mar 10, 739(2), 244 - 8 Effect of hydrostatic pressure on translational fidelity; McMahon G et al.; We have used the application of hydrostatic pressure to modify the misreading of polyuridylate template . Pressure was used to test ribosomes isolated from Escherichia coli strains containing mutations in the S12 ribosomal protein which lead to streptomycin-resistance and -dependence . The incorporation of phenylalanine into polypeptide, at a given pressure, was found to vary with the source of ribosomes and was found to correlate with S12-dependent changes in rates of incorporation suggesting a role of the S12 ribosomal protein in the pressure effect . Streptomycin partially alleviated the increased pressure-resistance in those cases where control rates of incorporation were found to be stimulated by the addition of streptomycin . In contrast, the misincorporation of isoleucine was substantially more sensitive to pressure application, regardless of ribosome source or the presence of streptomycin . These results suggest that the application of hydrostatic pressure affects at least two distinct ribosomal reactions important to the discrimination of these two amino acids. Ann R Coll Surg Engl, 1983 Mar, 65(2), 105 - 11 Abdominal tuberculosis--a disease revived; Addison NV; Abdominal tuberculosis was common in the United Kingdom in the 18th and 19th centuries and in the first half of the 20th century . During the 1950's the recognition of Crohn's disease, the use of streptomycin and other drugs, and the pasteurisation of milk led to the virtual disappearance of abdominal tuberculosis in the western world . During the last two decades a new type, mycobacterium tuberculosis hominis, has appeared mainly in the immigrant population, especially in those from the Indian subcontinent . A retrospective review of 68 patients with abdominal tuberculosis is presented . The pathology, diagnosis and management of these cases is discussed, together with the differential diagnosis of Crohn's disease . It is suggested that the immigrant brings the disease into the United Kingdom in his mesenteric glands and that the disease is reactivated or 'revived' at some later date due to some modification of the immune process. Arch Surg, 1983 Mar, 118(3), 356 - 9 Mycobacterial infections in renal allograft recipients; Spence RK et al.; Primary mycobacterial infections developed in five of 565 patients who had transplants during a 15-year period . All had negative PPDs and normal chest roentgenograms; none had tuberculosis before transplantation . Atypical mycobacteria were cultured in three of five infections . All were treated with a multiple-drug regimen, including isoniazid, rifampin, ethambutol, and streptomycin sulfate . In four of five patients, there were serious drug-related complications . No major initial alteration of immunosuppressive therapy was necessary in any of the patients . During the study, a treatment policy was followed that included one year of isoniazid treatment of all recipients with a positive PPD, history of tuberculosis, chest x-ray film suggestive of tuberculosis, or PPD-positive donor . An additional 14 transplant recipients were treated in accordance with this policy without complications or subsequent mycobacterial infections (32-month average follow-up) . Despite the low incidence of mycobacterial infection in this series, the potential lethality and morbidity mandate constant vigilance. Brain Res, 1983 Feb 7, 260(2), 347 - 9 Quisqualic acid excitation of cortical neurones is selectively antagonized by streptomycin; Stone TW et al.; Although evidence exists for at least 3 kinds of excitatory amino acid receptor in the CNS, responding to N-methyl-D-aspartic acid, kainic acid and quisqualic acid, respectively, only antagonists at the former two sites are currently available . It is now reported that when applied by microiontophoresis to neurones in the rat cerebral cortex, excitatory responses to quisqualic acid can be selectively reduced by streptomycin. Pharmazie, 1983 Feb, 38(2), 98 - 100 Effect of certain additives on stability of streptomycin sulphate; Kassem AA et al.; The effect of certain additives on the stability of streptomycin sulphate at 37 and 60 degrees C, for one month was studied . In pure distilled water, streptomycin sulphate was stable for 21 d at 37 degrees C, while at 60 degrees C a significant loss occurred after only three d . The effect of McIlvain buffer at different pH values showed maximum stability at pH values of 6.5 and 7 . The stability was altered when Sorensen buffer at pH = 6.5 was used . On the other hand, the effect of other commonly used additives demonstrated that at 37 degrees C Aerosil 200, kaolin and pectin did not cause any significant loss, while bentonite caused significant decrease in the activity after 15 d . In contrast, activated charcoal and veegum reduced the activity to 54.5% and 57.5%, after just 1 d and to zero after 4 d, respectively . At 60 degrees C, the rate of decomposition of streptomycin sulphate was highly accelerated. Biull Eksp Biol Med, 1983 Feb, 95(2), 44 - 6 {Effect of antitubercular preparations on the isoform composition of cytochrome P-450 of rat liver microsomes}; Dzhuzenova ChS et al.; The effects of the antituberculous drugs, isoniazide, phthivazide, streptomycin and PAS, on the isoform content of rat liver microsomal cytochrome P-450 was studied by electrophoresis in acrylamide concentration gradient (5-15%) in the presence of sodium dodecyl sulphate . It was discovered that administration of the antituberculous drugs did not increase the specific content of cytochrome P-450 in rat liver microsomes . At the same time isoniazide had an inducing effect on isoforms of cytochrome P-450, with molecular weights of subunits varying within the range of 49000 to 50000 dalton . Phthivazide induced subfractions with molecular weights of subunits being equal to 50000, 49000 and 47500 dalton . PAS induced subfractions with molecular weights of subunits being equal to 54000, 50000, 49000, and 47500 dalton . Administration of streptomycin did not affect the isoform content of rat liver microsomal cytochrome P-450 . For comparison purposes, a study was made of the generally recognized cytochrome P-450 inductors, phenobarbital and 3-methylcholanthrene . It is suggested that the changes in the isoform content of rat liver microsomal cytochrome P-450 might be of importance for understanding the mechanism of drug tolerance induction in the treatment of tuberculosis, since the changes discovered are likely to lead to the increased metabolic rate of the antituberculous drugs at the cytochrome P-450 level and to the accelerated excretion from the body. J Gen Microbiol, 1983 Feb, 129 (Pt 2), 519 - 27 Chromosomal instability in Streptomyces glaucescens: mapping of streptomycin-sensitive mutants; Crameri R et al.; Streptomyces glaucescens strain GLAO (=ETH 22794) produces hydroxystreptomycin and has a high natural resistance to hydroxystreptomycin, dihydrostreptomycin and streptomycin . The wild-type strain gives rise spontaneously to streptomycin-sensitive (StrS-) variants at a frequency of 0 . 2 to 1 . 4% . These mutants lack streptomycin phosphotransferase activity responsible for the wild-type resistance to streptomycin group antibiotics and are unable to produce detectable amounts of hydroxystreptomycin . Mapping experiments showed that the strS marker lies between the chromosomal markers lys-2 and ura-3 on the linkage map of S . glaucescens . The molecular basis for instability of this marker is as yet unknown. J Gen Microbiol, 1983 Feb, 129 (Pt 2), 529 - 37 Hydroxystreptomycin production and resistance in Streptomyces glaucescens; Ono H et al.; The wild-type strain of Streptomyces glaucescens produces hydroxystreptomycin and shows an inherent natural resistance to streptomycin group aminoglycoside antibiotics . Cell free extracts of the wild-type strain were able to inactivate streptomycin, hydroxystreptomycin and dihydrostreptomycin in the presence of ATP . The phosphotransferase did not inactivate other aminoglycoside antibiotics, including spectinomycin . Mutant strains were isolated, which were highly sensitive to streptomycin group aminoglycosides, had no measurable phosphotransferase activity and were unable to form detectable amounts of hydroxystreptomycin . This suggests either a correlation between phosphotransferase activity, streptomycin resistance and hydroxystreptomycin formation or defects in more than one gene in the strS mutant strains tested. Mutat Res, 1983 Feb, 112(1), 3 - 16 Mutagenic repair in Escherichia coli . VIII . Effect of gyrB mutations on ultraviolet light mutagenesis; Bridges BA et al.; Introduction into Escherichia coli WP2 bacteria of a mutation in the gyrB locus previously shown to reduce the degree of chromosomal superhelicity caused a small decrease in the frequency of UV-induced mutations to streptomycin resistance (but not significantly) and to tryptophan independence (mostly ochre suppressors) in excision repair-proficient bacteria . It did not influence the 'broth effect' or the rate or extent of 'mutation frequency decline' of suppressor mutations . In an excision-deficient (uvrA 155) background the yield of UV-induced streptomycin-resistant mutations was lower in gyrB bacteria at all doses; the yield of tryptophan-independent mutations was slightly lower at low doses and slightly higher at high doses . In both excision-proficient and -deficient bacteria the yield of UV-induced mutations to rifampicin resistance was apparently lower in gyrB mutants but this could be due at least in part to a hypersensitivity of some Rifr gyrB bacteria to UV . The number of spontaneous tryptophan-independent mutations was lower in gyrB bacteria but this was almost certainly due to their poorer viability on tryptophan-limiting plates and not to a lower spontaneous mutation rate . In a temperature-sensitive presumed gyrase-deficient strain a small decrease in mutant yield at low doses was observed following incubation at restrictive temperature before UV . This was ascribed to an enhancement of excision repair . Our failure to find any significant effect of gyrB mutations does not support the hypothesis that hairpin formation (which should be dependent on a high degree of superhelicity) is involved in determining the 'broth effect', 'mutation frequency decline' or the probability that a mutation will occur spontaneously . Dramatic effects of superhelicity on UV mutagenesis also seem to be unlikely. Arch Gynecol, 1983, 234(2), 95 - 101 The changing pattern of tuberculosis of the female genital tract . A thirty year survey; Sutherland AM; Between 1st January, 1951 and 31st December, 1980, 704 women with proven tuberculosis of the genital tract were investigated . The previous obstetrical history, age incidence, presenting symptoms, and pelvic findings have been reviewed in 10-year periods . The incidence of previous pregnancies rose in successive periods and the average age increased . The main differences in the presenting symptoms were a lessening in the frequency of amenorrhoea and vaginal discharge and an increase in postmenopausal bleeding . The incidence of palpable adnexal masses decreased in successive 10-year periods . Short drug courses were mainly employed in the earlier years and longer courses in the later years . The drugs used initially were streptomycin, PAS and isoniazid, ethambutol and rifampicin being introduced later . The incidence of surgical treatment following failure of drug therapy was much higher in those who had received short drug courses than in those who had received longer ones. Trans R Soc Trop Med Hyg, 1983, 77(5), 658 - 9 The use of dexamethasone in preventing ocular complications in tuberculous meningitis; Girgis NI et al.; Twenty-seven patients with tuberculous meningitis (TBM) were treated with ethambutol, isonicotinic acid hydrazide, streptomycin and dexamethasone and 28 were treated with triple anti-tuberculous drugs only . Only two of the patients to whom steroids were given developed ocular complications as compared to seven of those not receiving dexamethasone . High dose dexamethasone apparently prevents optic atrophy in TBM . Controlled double-blind studies with and without dexamethasone are needed to confirm this postulation. Z Allg Mikrobiol, 1983, 23(6), 351 - 8 Relation of anabolic-catabolic glucose utilization in growth-limited cultures of Streptomyces griseus; Christner A et al.; Phenotypically different submerged mycelium conserves had been produced from a spore conserve of the HP-strain Streptomyces griseus and proofed in a product formation culture as a test system . The phenotypical characters induced on the base of the genotype proved in a cultivation cycle during 30-34 reduplications of the biomass constant . Employing the HP phenotype we investigated the possibility of economizing the substrate turnover by utilizing the anabolic potential for the synthesis of secondary substances and/or reducing the conservation catabolism during the stationary growth stage . As criteria for that served the stoichiometric turnover equation of the streptomycin biosynthesis and the quotient qO2/qGluc taking at full substrate oxidation the numerical value 6 . During the stationary growth stage the relation of maintenance anabolism to maintenance catabolism in addition to the formation as secondary substances is not fixed in the tested HP phenotypes, but in a striking manner variable . The relation of by-product synthesis to secondary metabolism synthesis, too, is variable in the stationary growth stage with constant maintenance catabolism . Due to those response reactions on phenotypical manipulations an economization of the substrate turnover during the product formation stage with stationary growth is not possible in the streptomycin producer Streptomyces griseus. Mol Gen Genet, 1983, 190(2), 289 - 94 The role of 2-methylthio-N6-isopentenyladenosine in readthrough and suppression of nonsense codons in Escherichia coli; Petrullo LA et al.; Readthrough and suppression of nonsense codons was compared in Escherichia coli strains with and without a miaA mutation, which confers a loss of the isopentenyladenosine modification in transfer RNA . Generally speaking, our results conform to predictions based on previous literature . In addition, we showed that the miaA mutation in strain TRPX is itself a UAA mutation . An antagonism between miaA and rpsL mutations, which confer streptomycin resistance, was also discovered . Our data further suggest that slight alterations of the translation apparatus are easily detectable by monitoring readthrough and suppression of nonsense codons . Our findings are discussed in the context of old and recent reports. Microbiol Immunol, 1983, 27(6), 471 - 8 Drug resistance and R plasmids in Escherichia coli strains isolated from broilers; Kanai H et al.; In 1978, 1,021 Escherichia coli strains were isolated from 105 field broilers (F) and 1,058 strains from 106 broilers in a zootechnical experiment station (Z), and their drug-resistance patterns and the presence of conjugative R plasmids were compared . The resistance markers examined were tetracycline (TC), chloramphenicol (CM), streptomycin (SM), sulfonamides (SA), kanamycin (KM), and ampicillin (APC) . The populations of individuals that excreted resistant strains were 100% in F and 58% in Z . Frequencies of isolation of drug-resistant strains among the total isolates were 93% in F and 36% in Z, indicating that the resistant strains are a rather high proportion of the intestinal flora in F but are slightly less prevalent in Z . The resistance pattern to (TC.SM.SA.KM) was seen at the highest frequency in both groups . Conjugative R plasmids were demonstrated more frequently in field broilers (F) . The results reflect the wide use of antibiotics in the livestock industry, resulting in the appearance of drug-resistant strains mostly due to the presence of R plasmids. Mol Gen Genet, 1983, 191(2), 207 - 12 The frequency of transcriptional and translational errors at nonsense codons in the lacZ gene of Escherichia coli; Rosenberger RF et al.; Nonsense alleles in the lacZ gene of E . coli do not completely eliminate enzyme activity as errors during protein synthesis allow some chains to be completed . The relative contributions of transcriptional and translational errors to this leakiness were investigated by two methods: the introduction of rho- alleles into extreme-polar mutants and the kinetics of beta-galactosidase induction . Virtually all the errors appeared to be transcriptional in the case of two extreme-polar and one non-polar mutation . These alleles should prove useful for further in vivo investigations of RNA polymerase accuracy . With two other non-polar alleles, transcriptional mistakes were low and translational ones high . The frequency of RNA polymerase errors was context-dependent and varied for different nonsense codons in the same position and for the same codon in different positions . The reasons why some alleles showed no activity due to translational errors could not be clearly established . However, increasing the rates of ribosomal errors from one such allele with streptomycin raised the contribution of ribosomal errors to activity markedly and non-linearly . Translational mistakes may give rise to active enzyme only if the monomers are formed at a rate sufficient for effective aggregation to the normal tetramer. Intervirology, 1983, 19(2), 77 - 84 Adenosine- and ADP-phosphorylating capacity of herpes simplex virus-induced thymidine kinase enzyme complex; Labenz J et al.; The herpes simplex virus(HSV)-coded thymidine kinase (TK) enzyme complex was isolated from HSV type 1 strain Lennette(TK+)-infected CLID (TK-) cells and was enriched by streptomycin sulfate and ammonium sulfate fractionation . This enzyme preparation was tested for dTMP:Ado (adenosine) and for dTMP:ADP phosphotransferase activities . The presence of dTMP:Ado phosphotransferase activity was proven by time-course studies with cells infected for 0-18 h, by biophysical studies in polyacrylamide gels, by affinity chromatography studies using AMP- and dTMP-Sepharose, and by immuno-neutralization experiments . The presence of dTMP:ADP phosphotransferase activity was demonstrated by kinetic experiments . These results were taken as evidence that the two functional subunits of the HSV-TK enzyme complex, AMP:dThd (deoxythymidine) phosphotransferase and ATP: dThd kinase, catalyze highly reversible enzyme reactions . New data are presented indicating that the ATP:dThd kinase is a nonspecific enzyme with respect to the nucleoside acceptor. Hum Genet, 1983, 64(1), 42 - 9 Cytogenetic effects of chemotherapy with three combinations of anti-tubercular drugs involving isoniazid, thiacetazone, para-aminosalicylic acid and streptomycin on human lymphocytes: chromosome aberrations, sister chromatid exchanges and mitotic index; Jaju M et al.; Cytogenetic effects of three combinations of anti-tubercular drugs were evaluated on human lymphocytes in vivo and were compared with controls of two types: (1) newly diagnosed tuberculosis patients before starting therapy and (2) individuals from the general population . The drugs used were: isoniazid (INH), thiacetazone (TAZ), para-aminosalicylic acid (PAS), and streptomycin (SM) . These drugs were tested in the following combinations: (a) INH + TAZ + SM, (b) INH + PAS + SM, (c) INH + SM . The frequency of chromosome aberrations was significantly increased in patients treated with both the triple drug combinations, i.e., with INH + TAZ + SM and INH + PAS + SM, whereas patients treated with INH + SM did not exhibit an increase in the frequency of chromosome aberrations as compared to the controls . Although both the triple drug combinations were clastogenic, none of the three drug combinations tested induced an increase in the frequency of sister chromatid exchanges (SCEs) . In other words, the mechanisms leading to SCEs and chromosome aberrations may be different . SM appeared to depress the mitotic index in patients treated with INH + SM and INH + PAS + SM, though it was found to possess a mild anti-clastogenic effect . INH + TAZ + SM, on the other hand, enhanced the mitotic index . This enhanced mitotic index was probably due to the presence of TAZ. Microbiol Immunol, 1983, 27(8), 695 - 708 Purification and characterization of beta-glucuronidase inhibitor from Mycobacterium tuberculosis; Kiyotani K et al.; Factors inhibitory to beta-glucuronidase were found in the culture filtrate and in a bacillary extract of Mycobacterium tuberculosis H37Rv grown for 6 weeks on Sauton medium . The inhibitors were purified by ammonium sulfate fractionation, treatment with n-butanol and streptomycin, and chromatography on DEAE-Sepharose CL-6B . Two inhibitors were obtained from the culture filtrate . The molecular weights were estimated to be 25,500 and 15,500 by gel filtration on a Sephadex G-75 column . Three inhibitors were purified from the bacillary extract, two of which were similar to those from the culture filtrate . The molecular weight of the third inhibitor was 21,000 . However, the molecular weight of all the denatured inhibitors was 8,600 in the presence of sodium dodecyl sulfate . The inhibitors contained extremely high amounts of glutamic and aspartic acids and had a highly acidic isoelectric point of pH 2.5 . The inhibitors acted noncompetitively against beta-glucuronidase of guinea pig origin at an optimal pH 4.5 . beta-Glucuronidases from human peripheral leukocytes and beef liver were partially sensitive to the inhibitors; all the other enzymes tested for sensitivity were unaffected by the inhibitors. J Am Vet Med Assoc, 1982 Dec 1, 181(11), 1358 - 62 Nontuberculous mycobacterial infection attributable to Mycobacterium intracellulare serotype 10 in two rhesus monkeys; Fleischman RW et al.; Infection with Mycobacterium intracellulare serotype 10 was diagnosed in 2 rhesus monkeys (Macaca mulatta) in a closed colony of 90 animals . The clinicopathologic presentation in 1 animal with advanced disease was characterized by a precipitous weight loss, therapeutically unresponsive diarrhea, anemia, weakness, prostration, refractory tuberculin tests (using mammalian old tuberculin and M bovis purified protein derivative tuberculin), and disseminated granulomas in the lungs, spleen, liver, kidneys, lymph nodes, salivary glands, and intestines . The lamina propria throughout the large and small intestines was infiltrated with mycobacteria-laden macrophages . Severe hypoproteinemia, hypoalbuminemia, hypoglobulinemia, mild hypocalcemia, and edema were compatible with a malabsorption-like syndrome . The 2nd animal was clinically normal, but a weak positive tuberculin reaction to M bovis purified protein derivative at 72 hours necessitated euthanasia . This animal's disease was characterized by microgranulomas in the lungs, bronchial lymph nodes, liver, and pancreas, without involvement of the gastrointestinal tract . There was no evidence of M intracellulare infection in the remaining 88 animals in the colony, as determined by mycobacterial cultures of tracheobronchial washings, additional tuberculin testing, thoracic radiography, and mycobacterial culture of the drinking water . Tuberculin testing and thoracic radiographs of personnel working with the nonhuman primates were also negative . These cases were considered to be important because both animals were infected with the same serotype and because there has been an increasing number of isolations of this organism in human infections throughout Massachusetts . Drug-sensitivity testing revealed the organism to be sensitive to cycloserine and resistant to isoniazid, rifampin, ethambutol, streptomycin, kanamycin, and pyrazinamide. Antibiotiki, 1982 Dec, 27(12), 53 - 6 {Concentration of streptomycin and isoniazid in the blood of patients over 50 with pulmonary tuberculosis after administration of the drugs in ultrasonic aerosols}; Korablev VN; Patients aged over 50 with pulmonary tuberculosis were treated with streptomycin and isoniazid administered by the routine routes and in the form of ultrasound aerosols . The drug levels in the blood of the patients were studied comparatively . It was shown that administration of the drugs in the form of aerosols provided their sufficiently high blood levels for a long time in patients with a primary diagnosis of the disease . Such levels did not depend on the patients' age and the state of the lung ventilation. Vet Rec, 1982 Nov 20, 111(21), 478 - 82 Isolation of the contagious equine metritis organism from colts and fillies in the United Kingdom and Ireland; Timoney PJ et al.; Between January 1978 and August 1982 the streptomycin resistant strain of the contagious equine metritis organism (CEMO) was isolated from 15 colts and two fillies in the United Kingdom and Ireland . A first season stallion was also suspected of having initiated an outbreak of contagious equine metritis (CEM) at the beginning of the 1982 breeding season . A detailed investigation of the breeding history of the dams and sires of each positive individual indicated that in a number of cases the CEMO was acquired either in utero or following transmission at the time of parturition . In several other cases the retrospective evidence suggested that the genital tract of colt foals became contaminated with vaginal discharge from mares showing clinical signs of the disease during the nursing period . The findings emphasise the need for a thorough examination of the genital tract of colts and fillies as recommended in the code of practice for the control of CEM when they begin their breeding career. J Antibiot (Tokyo), 1982 Nov, 35(11), 1571 - 7 UDP-N-methyl-D-glucosamine-phosphate--a possible intermediate of N-methyl-L-glucosamine moiety of streptomycin; Hirose-Kumagai A et al.; The formation of N-methyl-L-glucosamine moiety of streptomycin from D-glucosamine by Streptomyces griseus was studied . The addition of thymine to the culture medium stimulated the formation of streptomycin and the incorporation of D-glucosamine into N-methyl-L-glucosamine moiety . During a study of sugar nucleotides in the mycelia, a novel UDP-amino sugar was isolated . The compound was formed before the maximum production of streptomycin . It was UDP-N-methyl-D-glucosamine-phosphate. Am J Trop Med Hyg, 1982 Nov, 31(6), 1216 - 21 Identification of an isolate of Rickettsia canada from California; Philip RN et al.; A strain of Rickettsia canada was recovered in 1980 an adult rabbit tick, Haemaphysalis leporispalustris, taken from a black-tailed jack rabbit, Lepus californicus, in Mendocino County, California . In all examined biologic characteristics, this isolate, CA410, is indistinguishable from the prototype, strain 2678, isolated in Ontario, Canada, in 1963 . These similarities include serologic and immunologic reactivity in laboratory mice and guinea pigs, cultural characteristics in Vero cells, chick embryo cells and embryonated eggs, low pathogenicity for mice, meadow voles and guinea pigs, unusual resistance to streptomycin, morphology by electron microscopy, and molar percentages of guanine plus cytosine of the deoxyribonucleic acids . Recovery of this second strain in the same species of tick, but far removed in time and place from the origin of the prototype, provides evidence that R . canada is an established, ecologically stable, rickettsia in North America. Neurotoxicology, 1982 Nov, 3(3), 13 - 9 Alteration of high-affinity binding sites of neurotransmitter receptors in rats after neonatal exposure to streptomycin; Seth PK et al.; Central neurotransmitter functions were analyzed in dyskinetic rats that were treated subacutely with streptomycin as neonates . Data indicated that the treatment caused an increase in the binding of {3H}spiroperidol in striatum and of {3H}serotonin in frontal cortex, but no significant changes were observed in the binding of {3H}quinuclidinyl benzilate and {3H}muscimol to cerebellum and of {3H}diazepam to frontal cortex . The increase in the binding of {3H}spiroperidol and {3H}serotonin was evident in both sexes; however, the increase of {3H}spiroperidol binding was statistically significant only in females . Kinetic studies as revealed by Scatchard plots show that the increase in the binding of the two ligands is due to an increase in the number of the receptors . These results support the concept of a central mechanism of action for the streptomycin-induced dyskinesias. Semin Arthritis Rheum, 1982 Nov, 12(2), 245 - 55 Articular involvement in human brucellosis: a retrospective analysis of 304 cases; Gotuzzo E et al.; Brucellosis is a zoonosis which in humans is caused by one of four species of the Brucella genus: B . melitensis, B . abortus, B . suis and B . canis . B . abortus is the species prevalent in North America and Europe and B . melitensis in most developing countries . Differences in disease manifestations may be accounted for either by differences in the species or by differences in the host . Articular involvement in brucellosis, although recognized since 1904, has been variably emphasized . Three hundred and four cases of human Brucellosis caused by B . melitensis, the prevalent species in Peru, were seen during a 12-yr period in one Lima hospital . Fever, malaise and hepatomegaly were the most frequent findings . Diagnosis was greatly improved when cultures were done in the biphasic Ruiz-Castaneda medium, rather than in trypticase soy broth . Serologic diagnosis is still important, and it should include standard tube testing, detection of IgG blocking antibodies and fractionation with 2-ME in chronic cases . The disease may take one of three courses: acute, (< 8 wk), chronic (> 8 wk) or undulant (periods of remissions and exacerbations) . Four syndromes were recognized in a total of 33.8% of patients with Brucellosis . The most frequent pattern (in approximately 46.6% of patients with arthritis) was sacroiliitis, usually non-destructive and either uni- or bilateral . The second most frequent articular syndrome was peripheral arthritis (38.8%), manifested either as a single large lower extremity joint or as an asymmetric pauciarthritis . Rarely patients presented with a rheumatoid-like arthritis . Mixed arthritis (7.8%) was a combination of the first two . The above forms occurred in patients with an acute or undulant course . Spondylitis was the least common form of arthritis (6.8%), and differed significantly from the other forms of arthritis in the duration of symptoms (chronic course), age of patients (older individuals) and the paucity of fever and malaise . It also tended to be destructive . The arthritis usually resolved with the combined regimen of tetracycline (2 g p.o . for 21 days) and streptomycin (1 g i.m . for 21 days) without sequelae . Illustrative cases of these syndromes are presented . The relatively benign nature of most of the patients with bruccellar arthritis lead us to postulate that they are for the most part reactive arthritides . Host factors are thought to be important in determining the response to the infection, but they are yet to be identified . Our own genetic studies have failed to identify an increased frequency of B27 or CREG antigens in the patients with sacroiliitis.(ABSTRACT TRUNCATED AT 400 WORDS) HNO, 1982 Oct, 30(10), 375 - 80 {Vitamin A concentration in plasma and ability to hear in patients with chronic alcoholic liver diseases}; Lohle E et al.; 59 patients with chronic alcoholic liver disease and with negative history of ear infection, noise exposure, head injury, use of streptomycin and without hereditary deafness underwent a basic audiologic examination . In all age groups we found a depression of the pure tone threshold on from 2,000 Hz and compared to a control group and to the norm curves (Spoor 1966) . Following the Carhart-test and the acoustic facial reflex there were always signs of cochlear lesions . Fifty per cent of the alcoholics in the Carhart tone decay test showed a depression of the threshold between 10 and 30 dB . The concentration of vitamin A, RBP, beta-Carotin and zinc in the blood measured at the same time were diminished . Considering recent electron microscopic findings on the pattern of the inner ear of young rats following vitamin A deficit we suppose that the vitamin A deficit in the alcoholics leads to poor hearing. Am J Vet Res, 1982 Oct, 43(10), 1852 - 5 Occurrence and characterization of plasmids in field isolates of Bordetella bronchiseptica; Graham AC et al.; Twenty-seven isolates of Bordetella bronchiseptica were examined for the presence of plasmid DNA . Eleven of the isolates contained plasmids . An attempt was made to correlate the presence of plasmids with resistance to a number of antibiotics or heavy metals or with production of bacteriocins . Eight of the isolates contained a plasmid of approximately 35 megadaltons molecular weight; these isolates were all resistant to 1 mM mercuric chloride . There were no other correlations between plasmid content and any of the phenotypes tested . The plasmids conferring resistance to mercuric chloride were transferred by conjugation to Escherichia coli K-12 . The plasmid-bearing isolates were then compared with their isogenic plasmidless parent for resistance to a number of antibiotics . Isolates acquiring the plasmids demonstrated increased resistance to streptomycin and ampicillin, as well as to mercuric chloride . The 8 plasmids were also analyzed by restriction endonuclease digestion. Am Rev Respir Dis, 1982 Sep, 126(3), 460 - 2 A controlled trial of six months chemotherapy in pulmonary tuberculosis . Second report: results during the 24 months after the end of chemotherapy . British Thoracic Association; Induction of streptomycin-inactivating enzyme by A-factor in Streptomyces griseus; The effect of A-factor on streptomycin resistance and productivity in Streptomyces griseus and S . bikiniensis was studied using A-factor-negative mutants . Resistance of several of these mutants was markedly increased by adding A-factor to the growing medium, as also was their streptomycin productivity . The A-factor induced resistance was due to inactivation by streptomycin-6-phosphotransferase, and enzyme synthesis in these mutants was completely dependent on the presence of A-factor . In the case of S . griseus 2247 where streptomycin productivity was independent of A-factor, resistance and synthesis of the inactivating enzyme were also independent of A-factor . A-Factor-negative mutants of S . griseus showed a decreased level of NADP-glycohydrolase and an increased level of several NADP-linked dehydrogenases, but these enzymes did not return to parental levels in cultures supplemented with A-factor . A-Factor seems to regulate streptomycin biosynthesis, not through an indirect metabolic sequence involving these enzymes but, more likely, by directly stimulating synthesis of enzyme(s) in the biosynthetic pathway. Laryngol Rhinol Otol (Stuttg), 1982 Aug, 61(8), 477 - 80 {What effect does ligation of the large neck arteries have on cochlear potentials?}; Steinert R et al.; In guinea-pigs the course of summating potentials (SP) is observed . After the potentials have been identified by their typical form, their sensitivity to a reduction of oxygen, damage by streptomycin and adaptation to excessive noise, the quantity of the SP after ligature of the main neck arteries is recorded . After ligature of the external carotid arteries, the internal carotid arteries and the vertebral arteries on both sides, the SP remain active . This is presumably caused by anastomoses between the external carotid and subclavian arteries, the subclavian and spinal arteries, the external carotid and basilar arteries, and the double origin of the vertebral arteries on both sides . The subclavian arteries and the common carotid arteries can be ligated on both sides in random order . The SP remain almost unchanged as long as one vessel is open. J Pharmacol Exp Ther, 1982 Aug, 222(2), 488 - 93 Mechanism of neuromuscular block by streptomycin: a voltage clamp analysis; Farley JM et al.; The effects of streptomycin on neuromuscular transmission were investigated on frog cutaneous pectoris muscles . The half-inhibition doses of peak end-plate current amplitude are 3 x 10(-5) and 8.5 x 10(-5) M in the presence of 0.9 and 1.8 mM extracellular calcium, respectively . The quantal content of the end-plate current was reduced by 50% in the presence of 3 x 10(-5) M streptomycin in Ringer's solution containing 0.35 mM Ca and 2 mM Mg . Miniature end-plate currents under these conditions were reduced by only 20%, suggesting that the presynaptic blocking action predominates over the postsynaptic action . A much higher concentration of streptomycin (3.5 x 10(-4) M) was required to achieve 50% block of peak transient depolarizations induced by iontophoretic application of acetylcholine . The postsynaptic action involves primarily a blocking action on acetylcholine receptors since the drug did not alter the linearity of current-voltage relationship for end-plate currents at membrane potentials more positive than -50 mV . An additional weak blocking action on the acetylcholine-activated channels exhibited a slight voltage and concentration dependence, giving rise to a slight prolongation of the end-plate current and curvature of the current-voltage relation at membrane potentials more negative than -50 mV . Thus, under normal conditions the predominant action of streptomycin at the neuromuscular junction is to reduce transmitter release . A secondary competitive inhibition on the acetylcholine receptor and a weak blocking action on the ionic channels may also contribute to the overall block. Biochimie, 1982 Aug-Sep, 64(8-9), 655 - 9 Constitutive error-prone repair at sites of excision repair in Escherichia coli: a re-examination; Bridges BA et al.; No evidence was found for production during incubation in chloramphenicol of a signal capable of inducing a rec-lex function (lysogenic induction) when protein synthesis was restored . The majority of UV-induced mutations to streptomycin resistance require lesions in the DNA and cannot be attributed to untargeted mutator activity . Therefore the loss of photoreversibility of these mutations occurring in the absence of protein synthesis and DNA replication cannot be attributed to the production of a signal for the induction of subsequent rec-lex dependent mutator activity . The simplest interpretation is that they arise as errors at excision sites by the operation of a constitutive pathway. J Bacteriol, 1982 Aug, 151(2), 723 - 8 A gene and its product required for transposition of resistance transposon Tn2603; Tanaka M et al.; Tn2603 is a multiple-resistance transposon encoding resistance to ampicillin, streptomycin, sulfonamide, and mercury and having a molecular size of 20 kilobase pairs, with 200-base-pair inverted repeats at both ends . The essential sites and functions of Tn2603 which are required for its transposition were determined through construction and characterization of various deletion mutants affecting the efficiency of transposition . Deletions were introduced in plasmid pMK1::Tn2603 by partial digestion with restriction endonuclease EcoRI in vitro . Analysis of deletion mutants showed that the inverted repeat segments at both ends of the trans-acting diffusible product(s) encoded in the right-hand side of the central portion were required for the transposition of Tn2603 . An essential gene product was revealed as a protein having a molecular weight of 110,000 by analysis of polypeptides synthesized in Escherichia coli minicells . This protein was assumed to be the so-called transposase. Antimicrob Agents Chemother, 1982 Jul, 22(1), 148 - 50 In vitro synergistic activity of ethambutol, isoniazid, kanamycin, rifampin, and streptomycin against Mycobacterium avium-intracellulare complex; Zimmer BL et al.; Strains of Mycobacterium avium-intracellulare complex often exhibit in vitro resistance to common antimycobacterial agents . Combinations of etambutol, isoniazid, kanamycin, rifampin, and streptomycin were tested to determine if synergism occurred . Ninety-six percent of the strains were susceptible to a combination of ethambutol and rifampin at concentrations attainable clinically . Other combinations of antimycobacterial agents inhibited 4 to 82% of the isolates tested. J Bacteriol, 1982 Jul, 151(1), 516 - 20 Effect of S12 ribosomal mutations on peptide chain elongation in Escherichia coli: a hydrostatic pressure study; McMahon G et al.; Protein synthesis in Escherichia coli mutants that differ from one another in mutations which impart streptomycin resistance was investigated by the application of hydrostatic pressure . Increased pressure resistance was only observed in mutants which exhibited reduced rates of peptide chain elongation . These findings indicate that the major effect of pressure on protein synthesis in E . coli may involve the S12 ribosomal protein. Ann Acad Med Singapore, 1982 Jul, 11(3), 366 - 9 Tuberculosis chemotherapy--developments in Singapore from 1957-1982; Teo SK et al.; The last 25 years have seen many important developments in tuberculosis chemotherapy in Singapore . Beginning in the 1950s, chemotherapy consisting of streptomycin (S), isoniazid (H) and p-aminosalicylic acid (PAS) was introduced at first with 2-drug and later 3-drug combinations (i.e., SPH/PH for a total of 18 to 24 months) . In the 1960s, 2 early studies showed that thiacetazone (T) could not be substituted for PAS in standard chemotherapy as it was a more toxic and less potent drug . Routine tuberculosis treatment achieved good results for patients followed up for 5 years after completing treatment . A fully supervised regimen of streptomycin and isoniazid (S2H2) given twice weekly proved to be as effective as a largely self administered regimen of PAS/INH . Ethambutol (EMB) was shown to be effective in the initial treatment of pulmonary tuberculosis when combined with isoniazid . In the 1970s, rifampicin (R) was first investigated starting with an intermittent regimen of isoniazid and rifampicin given once or twice weekly . The success of this regimen led to 2 short course studies of 6-month regimens . Rifampicin was given daily for the full duration of 6 months (2SHRZ/HR; 2SHRZ/HRZ; Z = pyrazinamide) or intermittently 3 times a week in the continuation phase (2SHRZ/H3R3; 2HRZ/H3R3; 1SHRZ/H3R3) . All the 6 months regimens were highly effective. Acta Virol, 1982 Jul, 26(4), 241 - 6 Effect of kanamycin on the reproduction of orthomyxoviruses; Ghendon YuZ et al.; Kanamycin sulphate at a concentration of 8 mmol/l had no effect on the protein synthesis in uninfected chick embryo cell (CEC) cultures, but caused a 2-fold decrease of virus-specific protein synthesis in CEC infected with fowl plague virus (FPV) . Kanamycin at a concentration of 2 mmol/l decreased the yield of infectious FPV in one growth cycle experiments on CEC culture by 1.5 log10 units and when added into the agar overlay it decreased the plaque number by nearly 1 log10 unit . Inoculation of 10 mg of kanamycin into a chick embryo decreased the yield of virus by 1.0 log10 . Administration of kanamycin to mice (5-10 mg for three days post infection) reduced mortality of the animals 2--3-fold . Antibiotics of the streptomycin group presumably may penetrate into orthomyxovirus-infected cells due to virus-induced impairment of leakiness of the cell membrane and inhibit both the virus protein synthesis and formation of infectious virions. Pathol Biol (Paris), 1982 Jun, 30(6), 444 - 8 {Sterilizing activity of the main drugs on the mouse experimental tuberculosis (author's transl)}; Grosset J et al.; In a first experiment mice infected intravenously with 10(6) Mycobacterium tuberculosis were randomly treated either with isoniazid (INH) + rifampicin (RMP) 25 mg/kg or with INH + RMP + pyrazinamide (PZA) or with INH + RMP + PZA + streptomycin (SM) . The decrease of the viable counts (CFU) in the lungs was similar with all three regimens . In a second experiment, mice were treated for six months either with INH + RMP 25 mg/kg or INH + RMP 10 mg/kg . After a follow-up of six months, mice were killed and their lungs and spleen cultivated . Positive cultures were obtained in 7.5 p . cent of the mice treated with the high dose of RMP and 36.5 p . cent in the mice treated with the low dose (p less than 0.05) . A third experiment demonstrated that, during the first two months of treatment, adding PZA to INH + RMP 10 mg/kg increased significantly the overall effectiveness of INH + RMP 10 mg/kg combination . A fourth experiment demonstrated that after three initial months of INH + RMP 10 mg/kg, RMP alone was as effective as RMP + INH or RMP + INH + PZA . It may be concluded that RMP and PZA are both active on the intracellular population of Mycobacterium tuberculosis and that RMP is the only drug to act on persisting Mycobacterium tuberculosis in extracellular lesions. Am J Vet Res, 1982 May, 43(5), 796 - 800 Observation on the morphology of contagious equine metritis bacterial colonies isolated from infected pony mares; Sahu SP et al.; In uterine or cervical specimens obtained from pony mares infected with streptomycin-resistant contagious equine metritis bacteria, several colonies of the bacteria which differed in morphologic characteristics were recognized during their primary isolation on Eugon chocolate agar and tryptose chocolate agar plates . The differences were usually not observed until plates were incubated 10 to 15 days . On Eugon chocolate agar plates, smooth colony, sandy colony with rings, and colony with blebs were recognized . On tryptose chocolate agar plates, only a round smooth convex colony was observed . By scanning electron microscopy, colonies consisted of coccal, coccobacillary, and bacillary forms . Only one type of colony was isolated from any mare. Biochim Biophys Acta, 1982 Apr 3, 702(2), 204 - 11 Chorismate mutase-prephenate dehydrogenase from Escherichia coli . Purification and properties of the bifunctional enzyme; Sampathkumar P et al.; A pure, stable preparation of chorismate mutase-prephenate dehydrogenase (chorismate pyruvatemutase, EC 5.4.99.5-prephenate:NAD+ oxidoreductase (decarboxylating), EC 1.3.1.12) has been obtained in good yield from a regulatory mutant of Escherichia coli . The enzyme was purified from extracts of the organism by treatment with streptomycin sulfate and fractionation with ammonium sulfate followed by chromatography on columns of Sepharose-AMP, DEAE-cellulose and hydroxyapatite . The native enzyme has a molecular weight of 88,000 and is made up of two identical subunits as indicated by the results of amino acid composition, peptide mapping and electrophoresis in the presence of sodium dodecyl sulfate . The enzyme has a sedimentation coefficient of 4.85 S as determined in the ultracentrifuge and an isoelectric point of pH 5.3 . Preliminary studies on the kinetic properties of the enzyme indicated that both the mutase and the dehydrogenase reactions catalyzed by the enzyme conform to Michaelis-Menten kinetics. J Antibiot (Tokyo), 1982 Apr, 35(4), 507 - 16 Genetic and biochemical features of spiramycin biosynthesis in Streptomyces ambofaciens--curing, protoplast regeneration and plasmid transfer; Ikeda H et al.; Spiramycin-producing Streptomyces ambofaciens KA-1028 harboring the pSA1 plasmid gave rise to spiramycin non-producing variants at high frequencies by various curing treatments . However, a number of the spiramycin non-producing progeny obtained by treatment with acridine dyes, still harbored plasmid DNAs which could not be differentiated from plasmid pSA1 by contour length, cleavage patterns and heteroduplex analysis . By treatment with mitomycin C, plasmid pSA1 was cured at high efficiency and spiramycin non-producing strains were obtained . Strain U-1717R obtained by regeneration of protoplasts of plasmid-cured strain U-1717 regained spiramycin production on growth on solid medium only . Furthermore, transconjugants obtained by mating between strain KA-1028 and U-1717R-24 (streptomycin-resistant) regained spiramycin production in both liquid and solid media . We conclude that the genes for the biosynthesis of spiramycin are encoded in a replicon other than plasmid pSA1 but that this plasmid plays a role in the regulation of spiramycin production. Eur J Biochem, 1982 Apr, 123(3), 643 - 6 Effect of neomycin and protein S1 on the binding of streptomycin to the ribosome; Grise-Miron L et al.; The binding of {3H}dihydrostreptomycin to the 70-S ribosome or to the 30-S subunit has been investigated in the presence of neomycin by the Millipore filtration or the equilibrium dialysis procedure . It was observed that dihydrostreptomycin binds equally well to the 30-S subunit and the 70-S ribosome, and that neomycin stimulates the binding of dihydrostreptomycin to the ribosome by increasing the association constant and not by creating new binding sites . Specific removal of protein S1 from the 30-S subunit neither affected the binding of dihydrostreptomycin to the ribosome nor the stimulation of dihydrostreptomycin binding by neomycin. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1982 Mar, 251(3), 402 - 12 {Photometry of Mycobacteria and its application in sensitivity-testing of chemotherapeutic agents (author's transl)}; Hussels H et al.; Using photometry in measuring the growth of mycobacteria in liquid medium 7 H 9 Middlebrook slightly modified, we could achieve a 5 to 8 fold increase of extinction values within 8 days . The reproducibility of these results were investigated by tenfold assay of the laboratory mycobacterial strain H37Rv and about 10 strains recently isolated from patients . As antituberculous chemotherapeutic agents require different pH for their optimal activity, the experiments were performed at pH 5.5, pH 6.8 and pH 7.3 . By daily measuring the extinction values of all strains showed less growth at pH 5.5 compared to their behaviour at pH 6.8 and 7.3 . Yet growth at pH 5.5 was sufficient to estimate the inhibitory effect of Pyrazinamide as later experiments could show . The variation coefficient at pH 5.5 revealed to be significantly lower than at pH 6.8 and pH 7.3 . Isoniazid, Prothionamid and Rifampicin were tested at pH 6.8, Streptomycin, Ethambutol and Tetracyclin at pH 7.3 and Pyrazinamide at pH 5.5 . The results of our calculations were expressed as growth percentages in relation to growth in the control tubes . Usually the measurements of the last day of incubation were chosen for this evaluation . Inhibition of growth in 50% or more of the extinction values of the control tubes was the criterion for regarding a strain as sensitive to a given drug . All drugs were tested in two concentrations . In case of only one concentration effecting inhibition of growth in 50% ore more, the strain was reported to give a borderline result . Sensitivity testing with photometry was compared to conventionally performed tests on Loewenstein-Jensen-Medium which were in good agreement between 80 and 100% . Results being available within 8 days in an advantage of the photometric method of sensitivity testing . Furthermore Pyrazinamide and Tetracyclin can be tested without difficulties while these drugs give unsatisfactory results when tested on Loewenstein-Jensen-medium. Am J Otolaryngol, 1982 Mar-Apr, 3(2), 117 - 27 Vestibular ototoxicity in the chick: effects of streptomycin on equilibrium and on ampullary dark cells; Park JC et al.; Starting a week after they were hatched, chicks received daily subcutaneous injections of streptomycin sulfate for 15 or 30 days at one of three dosages: 400, 800, or 1,200 mg/kg body weight . During the period of administration, the chicks were weighed, examined for signs of systemic intoxication, and tested for impairment of equilibrium . At intervals some birds from each group were sacrificed and the end-organs of the semicircular canals were examined for damage . After the fifteenth injection, the weights of the control and experimental chicks were similar . By comparison, the chicks that received streptomycin injections showed varying degrees of impairment of equilibrium . First, some birds in the three experimental groups began to tremble at least slightly by the third injections, but others, particularly at the highest dosage (1,200 mg/kg body weight), trembled severely by the fifth injections . However, trembling began to subside in the lowest-dosage (400 mg/kg body weight) group by the fourteenth injection . Second, the chicks' ability to perch on dowels, either hooded or unhooded, and their ability to perch on the investigator's fingers in the dark deteriorated . Perching performances on the dowel deteriorated conspicuously only at higher dosages, while changes in perching on the finger were detected earlier and at lower dosages . Streptomycin damaged dark cells before other cell types . The cuboidal dark cells were most sensitive, followed by the pyriform cells . The eminential cells were least sensitive . Although the hair cells were functionally damaged by either the primary or the secondary actions of streptomycin, as evidenced by the chicks' early impairment of equilibrium, they showed distinct cytologic lesions later than did the dark cells. J Antibiot (Tokyo), 1982 Mar, 35(3), 349 - 58 Mutants blocked in streptomycin production in Streptomyces griseus - the role of A-factor; Hara O et al.; Ninety-five streptomycin-nonproducing mutants derived from Streptomyces griseus FT-1 by UV-irradiation could be classified into major two classes by cosynthesis tests . Class I mutants (42 strains) were mutants blocked in the pathway of streptomycin biosynthesis while class II mutants (49 strains) required a factor for streptomycin biosynthesis which was excreted by the parental or class I mutant strains . The factor could be replaced by synthetic A-factor (2S-isocapryloyl-3-S-hydroxymethyl-gamma-butyrolactone) which restored both streptomycin biosynthesis and spore formation in the class II mutants . A-Factor deficient mutants were obtained from several strains of S . griseus and S . bikiniensis at high frequency by treatment with acridine orange or incubation at high temperature . A mutant whose streptomycin biosynthesis was independent of A-factor deficiency was found . The production of A-factor was distributed among various species of actinomycetes. Acta Otolaryngol, 1982 Mar-Apr, 93(3-4), 211 - 7 The ototoxic interaction of viomycin, capreomycin and polymyxin B with ethacrynic acid; Davis RR et al.; The ototoxic interaction between the aminoglycoside antibiotics (streptomycin, kanamycin, etc.) and the loop-inhibiting diuretics (ethacrynic acid, furosemide and bumetanide) has been well documented . This interaction causes extensive destruction of the hair cells of the cochlea . Brummett et al . (1974) demonstrated that this interaction did not occur with the non-loop-inhibiting diuretics and kanamycin . The present study was undertaken to determine if antibiotics other than the aminoglycosides could produce the ototoxic interaction when combined with a loop-inhibiting diuretic . Three antibiotics-viomycin, capreomycin, and polymyxin B- when given with ethacrynic acid were found to produce cochlear hair cell damage that was similar to that produced by aminoglycoside antibiotics administered with ethacrynic acid . Therefore, the interaction appears to be specific to the loop-inhibiting diuretics but not specific for the aminoglycoside antibiotics. Nouv Presse Med, 1982 Feb 27, 11(9), 655 - 6 {An epidemic of chancroid . 587 cases (author's transl)}; Morel P et al.; Between 1973 and 1979, 673 cases of chancroid were diagnosed in the authors' Department at the hopital Saint-Louis, Paris . Therapeutic results could be assessed in 587 patients of whom 297 were treated with daily intramuscular injections of 1 g streptomycin sulphate and 290 with co-trimoxazole, 4 tablets per day . All patients were completely cured within 10 to 20 days, irrespective of the therapeutic regimen . Needle aspiration, repeated if necessary, of purulent lymph nodes is recommended, as it prevents surgical drainage which would delay healing. Am Rev Respir Dis, 1982 Feb, 125(2), 265 - 7 Successful intermittent treatment of smear-positive pulmonary tuberculosis in six months: a cooperative study in Poland; Snider DE Jr et al.; One hundred nineteen patients 15 to 70 yr of age, all with smear-positive, previously untreated, pulmonary tuberculosis, were treated with a 6-month regimen containing isoniazid and rifampin, supplemented during the initial 2 months with streptomycin and pyrazinamide . The 4 drugs were administered daily in the hospital during the initial 2 months, followed by isoniazid and rifampin administered twice weekly on an outpatient basis during the next 4 months . Adverse reactions to the drugs were seen in 19 patients, but only 6 had toxic reactions requiring withdrawal of drugs for 7 days or more . Three of the toxic reactions were attributed to streptomycin, 2 to rifampin, 1 to isoniazid, and none to pyrazinamide . Eighty-five (71%) of the 119 eligible patients completed treatment . After the first 2 months of therapy, 91% of these patients had negative sputum cultures, and all of them had negative cultures by the end of the third month of treatment . No relapses have occurred among the 84 patients observed for 18 months after therapy was completed. Antimicrob Agents Chemother, 1982 Feb, 21(2), 336 - 8 Occurrence of transposable trimethoprim resistance in clinical isolates of Escherichia coli devoid of self-transmissible resistance plasmids; Towner KJ et al.; Fifty trimethoprim-resistant clinical isolates of Escherichia coli, devoid of self transmissible trimethoprim resistance plasmids, were examined for the presence of trimethoprim resistance transposons . Trimethoprim resistance was mobilized from 12 strains by transposition onto plasmid RP4 . The trimethoprim resistance transposons isolated comprised two groups: those with and without linked streptomycin resistance. Microbios, 1982, 35(140), 71 - 8 In vitro drug sensitivity of M . avium-intracellulare complex in the presence and absence of dimethyl sulphoxide; Nash DR et al.; In vitro growth inhibition of 27 drug resistant isolates of M . avium-intracellulare was compared following continuous culture in the presence of single drugs alone and in combination with 2.5% dimethyl sulphoxide . In the absence of DMSO, 63% of the isolates were inhibited by rifampin and streptomycin, 19% by isoniazid and ethambutol and 4% by ethionamide . Addition of DMSO increased the number of isolates demonstrating growth inhibition by 26-30% for all drugs except ethionamide (11%) . The growth inhibitory effect of each drug, whether assayed alone or in combination with DMSO, varied considerably for each strain . Three isolates were inhibited only in the presence of DMSO plus a drug, six isolates demonstrated growth inhibition without any enhanced effect due to DMSO, while the remaining eighteen isolates were sensitive to at least one drug in the presence of DMSO and to different drugs in the absence of DMSO. Arch Otorhinolaryngol, 1982, 234(2), 167 - 73 The influence of chronic vitamin A deficiency on human and animal ears; Lohle E; After feeding young rats a diet deficient in vitamin A, we examined the inner ear with the electron microscope . There were changes in the cuticle of the outer and inner hair cells . Furthermore, there were changes in the reticular system of the intermediate zone and massive degenerative changes in the ganglion cells of the VIII nerve . In a second experiment with older animals we found no significant changes in the sensory cells, though there was new bone formation in Rosenthal's canal and damage to the ganglion cells, of a lesser extent than was evident in the first experiment, however . In a further clinical study, we carefully chose human subjects suffering from alcoholic liver disease who also had a negative history of ear infection, noise exposure, head injury and use of streptomycin . Normal auditory function in the family was also a criterion . A decreased auditory function associated with low vitamin A levels was found in these patients . Those with liver disease showed not only a significant auditory dysfunction in the higher frequencies, but as well a poorer performance in the tone decay test . They were compared to a control group with normal hepatic, renal and thyroid status. Am Rev Respir Dis, 1982 Jan, 125(1), 43 - 8 Synergistic effect of rifampin, streptomycin, ethionamide, and ethambutol on Mycobacterium intracellulare; Heifets LB; A method of quantitative estimation to determine the interaction of antituberculosis drugs is suggested . The desi