Cloning and nucleotide sequence of the gene responsible for chlorination of tetracycline.
(33/37)
Two cosmid clones containing distinct types of self-defense gene of a 6-demethylchlortetracycline producer, Streptomyces aureofaciens NRRL3203, were isolated. The gene responsible for chlorination of tetracycline (chl gene) was subcloned from one of the cosmid clones by complementation of a chlorination-deficient mutant, using a gene cloning system for strain NRRL3203 developed in this study. The nucleotide sequence analysis of a 4.4-kb SacI-BamHI fragment containing the chl gene showed that the predicted product of the chl gene is a polypeptide of 452 amino acids, and that the chl gene was preceded by two open reading frames, which could endode polypeptides of 50 kDa and 32 kDa, respectively. A search for sequences homologous to these ORFs found that the former product strongly resembles that of the 6-hydroxylation enzyme for oxytetracycline biosynthesis, and that the latter product has a weak but significant similarity to the hydroxyindole O-methyltransferase of bovine pineal gland. By Northern blot analysis, these three genes were suggested to be polycistronically transcribed. (+info)
Conserved organization of genes for biosynthesis of chlortetracycline in Streptomyces strains.
(34/37)
By genomic Southern blot analysis, the DNA sequences homologous to the gene cluster responsible for biosynthesis of 6-demethyl-chlortetracycline in Streptomyces aureofaciens NRRL3203 were shown to be highly conserved in independent chlortetracycline- or tetracycline producing Streptomyces strains. By contrast, oxytetracycline-producing Streptomyces strains had no hybridization with the cluster DNA. (+info)
Intensive and prolonged tetracycline therapy in non-specific urethritis.
(35/37)
Details are given of a double-blind trial involving 400 cases in which tetracycline 500 mg. four times a day for 7 days was compared with tetracycline 250 mg. four times a day for 14 days and also of the findings in 311 cases treated with Deteclo 300 mg. three times a day for 3 weeks. The treatment in the double-blind trial were equally effective and appeared to be as effective as the long-term Deteclo therapy. When the results of these treatments were compared with those obtained previously with tetracycline 250 mg. four times a day for 4 days and allowance was made for the time at which the latter results have been assessed, it was concluded that neither the treatment used in the double-blind trial nor Deteclo 300 mg. three times a day for 3 weeks offered any advantage over the customary treatment with tetracycline 250 mg, four times a day for 4 days. (+info)
Sensitivity of Brucella spp to tetracycline and its analogues.
(36/37)
The sensitivity to eight tetracyclines of 100 strains of brucellae, comprising strains of Brucella abortus, Br. melitensis, and Br. suis, was determined. Demethylchlortetracycline was the most effecitve against all the groups of brucellae, whereas oxytetracycline and chlortetracycline were the least effective. The mean MIC value for demethylchlortetracycline, doxycycline, lymecycline, and tetracycline was less than or equal to 1 mug/ml. Strains of Br. abortus biotype 2 and Br. suis were the most sensitive strains examined. (+info)
Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: a comparative histomorphometric study on the cancellous bone formed before, during, and after treatment.
(37/37)
To study the anti-resorptive effects of zoledronate and pamidronate on growing long bones we have performed a histomorphometric analysis of the three regions of the proximal tibial cancellous bone of bone formed before, during, and after drug treatment. Male rats (190-220 g) were treated subcutaneously for 10 days with zoledronate (0.028-2.8 microg/kg) or pamidronate (3.7-370 microg/kg) and sacrificed 5 days later. To delineate the three regions of cancellous bone, and for dynamic bone histomorphometry, calcein and demeclocycline were injected at various times. Both bisphosphonates caused a dose-dependent suppression of cancellous bone turnover and resorption to produce an increase in cancellous bone, but zoledronate was 100 times more potent than pamidronate. The increase in the bone amount and connectivity was more pronounced in the bone formed during treatment where transient bone resorption and normal bone formation led to a positive bone balance. In the bone formed before treatment, inhibition of bone resorption associated with reduced bone formation produced a net gain in amount of bone. Although both bone regions showed a positive bone balance, more bone accumulated in the bone formed during treatment probably because its trabecular bone surface was three times greater. In the primary spongiosa formed after treatment, a moderate increase in the bone amount and connectivity was observed only at the highest dose of both bisphosphonates. The bone formed before, during, and after treatment with bisphosphonates responds differently due to differences in bone architecture, rates of modeling and remodeling, and period of drug exposure. (+info)