Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the agar dilution technique minimal inhibitory concentrations (MIC) with respect to spectinomycin were determined. 92 Neisseria gonorrhoeae isolates collected in a STD outpatient clinic and 160 Neisseria gonorrhoeae isolates collected from prostitutes were investigated. One isolate imported from Asia had a MIC of greater than 1024 micrograms/ml and was resistant. All other isolates, three penicillinase producing strains included, had MICs of 4-32 micrograms/ml and were sensitive to spectinomycin.
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PMID:[Spectinomycin sensitivity of Neisseria gonorrhoeae]. 296 57

From August of 1982 through February of 1983, the Sapporo Clinical Research Group for STD treated 131 cases of male gonorrheal urethritis at its affiliated clinical facilities in Sapporo City. The therapeutic efficacy of AT-2266 was investigated, together with an epidemiological study on the cases and bacteriological studies on the isolated strains of gonococcus. In addition, a few cases of female gonorrheal cervicitis were treated, and the therapeutic results for 3 of these cases evaluated. AT-2266 was administered at a daily dosage of 600 mg in one dose to 14 patients, 2 doses to 10 patients and 3 doses to 98 patients. At the end of 3 days of this therapy, the gonococci had been eliminated in all of the cases, but there was variation in the status of disappearance of the secretion. The "excellent" efficacy rates for these three regimens were thus 7.7%, 50% and 57%, respectively. These results showed that administration of the total dosage in two or more divided doses maintained higher minimum concentrations of the antibiotic in the blood and the urine, and were thus more clinically beneficial than when the dosage was given as one daily dose. Of the patients who were treated with 600 mg/day of AT-2266 in 3 divided doses, 93 were evaluated for the therapeutic efficacy. At the end of 3 days 57.0% were "excellent" cases, 39.8% were "good" cases and 3.2% were "fair" cases, and at the end of 7 days of therapy, 67 patients were 74.6% "excellent" cases, 23.9% were "good" cases and 1.5% were "fair" cases. The clinical efficacy rate was thus quite high. Those cases in which the secretion and leukocytes had not disappeared from the urine even at the end of the 7 days of therapy were probably cases of mixed infection involving Chlamydia, etc. Eight of the 77 gonococcal isolates (10.4%) were beta-lactamase producers. The MIC of AT-2266 hardly differed with the size of the bacterial inoculum. With an inoculum of 10(6)CFU/ml, the MIC distribution showed two peaks, i.e., at 0.05-0.2 micrograms/ml and 3.16-12.5 micrograms/ml. Only 11.7% of the strains were found to have high MICs. The distribution of these high MICs was found to be unrelated to the ability to produce beta-lactamase. Mild side effects of AT-2266 were seen in 2 out of 128 patients. (1.6%), an extremely low incidence.
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PMID:[Epidemiologic and therapeutic studies on gonorrheal infections--use of AT-2266--Sapporo Clinical Research Group for STD]. 346 20

287 strains of Neisseria gonorrhoeae isolated in Dakar during a 26 months period (April 1981-May 1983) were sent to Pasteur Institute of Paris for auxotyping. They are distributed in (+): 56%, (PRO-): 21%, (ARG-): 13%, and nine minor auxotypes to the exclusion of (AHU-). Auxotypes distribution according to the sex, the kind of samples and the race do not give proof of significant difference. Monthly distribution shows an endemic circulation of auxotypes (+) and (PRO-), as well as an unstability of auxotype (ARG-) that was prevailing in early months. 22 strains of penicillinase-producing Neisseria gonorrhoeae (among which the first strains isolated in Senegal) belong to auxotypes (+), (PRO-) and (PRO-, ARG-). This distribution does not differ from that of non-producer strains. Gonococcal auxotyping provides an useful epidemiologic marker in order to search after the source of a contamination, to discern a failure of the treatment from a later infection and, on a wide plan, to survey the resistant strains spreading.
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PMID:[Epidemiologic approach to gonococcal infections in Senegal through the study of auxotypes]. 644 54

TEM beta-lactamase variants with the amino acid substitutions R164S, E104K, G238S, and E240K (ABL numbering) display increased activity toward extended-spectrum cephalosporins. The T265M substitution is frequently found to be associated with the above substitutions in extended-spectrum beta-lactamases. However, the residue is located away from the active site in the three-dimensional structure and has been assumed to have no effect on catalysis. To examine the effect of the substitution on the structure and function of TEM beta-lactamase we constructed the following mutants: G238S, T265M, T265M:G238S, and T265M:G238S:E240K. Each enzyme was purified to homogeneity and the kinetic parameters kcat, Km and kcat/Km were determined for cefotaxime, ceftazidime, cephaloridine, and ampicillin. The results indicate that the T265M mutation has little effect on hydrolysis. In addition, we used immunoblotting to show that the substitution has little or no effect on the in vivo steady-state levels of beta-lactamase.
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PMID:Effect of threonine-to-methionine substitution at position 265 on structure and function of TEM-1 beta-lactamase. 784 May 55

In China, staff at the National Center for STD Control and Research in Nanjing conducts surveillance of Neisseria gonorrhoeae to identify antibiotic-resistant strains, so health officials can control gonorrhea. Between 1987 and 1992, the center isolated 1529 strains from patients of clinics in the cities of Nanjing, Nanning, Harbin, Dalian, Shanghai, and Urumqi. Laboratory staff used the agar plate dilution test in the strains to determine the minimum inhibitory concentration (MIC) to penicillin, spectinomycin, and cephalosporins. They used the rapid idiometric method to examine the prevalence of penicillinase-producing N. gonorrhoeae (PPNG) strains. Most strains (57.5%) had MICs of = or 1 mcg/ml penicillin. The MIC50 values for penicillin increased each year (0.47, 0.45, 0.56, 0.79, 0.79, and 0.89 mcg/ml). PPNG strains comprised 18 (4.3%) of 419 strains isolated from Nanjing and Nanning. Resistant strains to spectinomycin (MIC 128 mcg/ml and the critical MIC values of 64 mcg/ml) made up 1.3% and 4% of all isolates, respectively. Few strains were resistant to ceftriaxone and cefotaxime (MIC = or 1 mcg/ml; 2.6% and 4.2%, respectively). These findings show considerable N. gonorrhoeae resistance to penicillin in China. They also demonstrate a need to adopt appropriate measures in the choice of drugs, follow-up of patients, and the surveillance of gonorrhea.
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PMID:Survey on antibiotic sensitivity of Neisseria gonorrhoeae strains isolated in China, 1987-1992. 797 78

Genital ulcerations typify one of the major reasons clients seek STD consultation in developing countries. The usual etiologies are syphilis, chancroid and herpes. The ideal diagnostic approach is to undertake complete laboratory examination that are rarely possible in structure destitute of laboratory analysis possibilities which is the case for most of the STD transmission agents. Chancroid is caused by Haemophilus ducreyi, a short Gram negative bacteria. The bacteriological diagnosis is based on direct examination, isolation and identification of the bacteria. The nutritive exigence of the bacteria required 3 medium of isolation (PPLO base Pasteur), GC base (GIBCO) and Muller Hinton base (Becton & Dickinson, with "chocolate" agar) have been tested from the chancre samples of 108 male patients who had a median age of 31 years. Direct exams were positive in 66 cases (61%) and culture exams positive in 53 cases (49%). The Muller Hinton base with "chocolate" agar produced the best results and seems to be the medium of choice for isolated strains in Senegal. The culture mediums currently used in Europe are apparently inappropriate for the germ culture in Senegal. We have also observed that all the isolated strains were producers of beta-lactamase. Antibiotic treatment before the sample swab is taken seems to have an inhibiting effect on the culture. Direct examination with a sensibility of 94.3% and a specificity of 70.9% remains sufficient in routine presumptive diagnosis in endemic areas.
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PMID:[Importance of culture media choice in the isolation of Haemophilus ducreyi. Experience in Senegal]. 800

The clinical isolate Escherichia coli PEY was highly resistant to amoxycillin, ticarcillin and piperacillin associated to beta-lactamase inhibitors such as clavulanic acid, sulbactam, tazobactam and brobactam but susceptible to cephalosporins, aztreonam and imipenem. The susceptibility to mecillinam indicated that this phenotype was not related to hyperproduction of the TEM-1 beta-lactamase. E. coli PEY produced a new plasmid-mediated inhibitor-resistant beta-lactamase of pI 5.2, which was named IRT-4. The determination of the amino acid sequence (Swiss-Prot accession number, P00810) of the purified protein indicated that IRT-4 differed from TEM-1 by two substitutions: Leu for Met-69 (ABL numbering) and Asp for Asn-276. A Met-69-Leu variant of TEM-1, obtained by site-directed mutagenesis, has been described as resistant to clavulanate. The Asp for Asn-276 substitution has not been reported previously. The side chains of Asp-276 and Arg-244 were expected to interact. Determinations of 50% inhibitory concentrations of beta-lactamase inhibitors and substrate profile of IRT-4 suggested that such an ionic bond was implicated in the alteration of the mechanistic process of TEM-1 beta-lactamase.
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PMID:Characterization and amino acid sequence of IRT-4, a novel TEM-type enzyme with a decreased susceptibility to beta-lactamase inhibitors. 805 82

Treatment regimens for sexually transmitted infections continue to evolve. The natural history of syphilis in HIV-infected patients is leading to more aggressive policies in terms of both investigation and treatment. In particular, treatment protocols for late syphilis, especially neurosyphilis, are under scrutiny. Epidemiological change typified by the spread of penicillinase-producing Neisseria gonorrhoeae (PPNG) has led to a search for new agents to treat gonorrhoea, with a more extensive use of cephalosporin and quinolone antibiotics emerging. The problem of compliance with the antibiotic courses presently required for chlamydial infection may be close to being solved with the development of newer macrolide agents. Single dose azithromycin, although expensive, seems to be as effective as longer courses with other agents. Furthermore, its efficacy in gonococcal infection is also encouraging. Increased understanding of the pathogenesis and natural history of pelvic inflammatory disease (PID) and bacterial vaginosis (BV) has led to rationalization of treatment policies for these conditions.
Int J STD AIDS
PMID:Antibiotic chemotherapy of bacterial sexually transmitted diseases in adults: a review. 806 Oct 86

Recently, TEM beta-lactamase variants with amino acid substitutions in the active-site pocket of the enzyme have been identified in natural isolates with increased resistance to extended-spectrum cephalosporins such as cefotaxime and ceftazidime. To identify other amino acid substitutions that alter the activity of TEM-1 toward extended-spectrum cephalosporins, a random library was constructed that contained all possible amino acid substitutions over the 3-residue window of 238-241 (ABL numbering). Mutants were selected for 100-fold greater ceftazidime resistance than wild-type. All mutants had a serine substitution at position 238, a lysine or arginine at position 240, and a small amino acid at position 241. The role of each substitution was investigated by constructing individual G238S, E240K, and R241G substitutions as well as the G238S:E240K double mutant. Each enzyme was purified to homogeneity and the kinetic parameters kcat and Km were determined using several substrates. The G238S substitution increases catalytic efficiency for both ceftazidime and cefotaxime. However, to achieve large increases in catalytic efficiency, both G238S and the E240K substitutions are required. The R241G substitution results in a small increase in catalytic efficiency for only ceftazidime. The contribution of each residue to the transition-state stabilization energy was found to be additive indicating that the substitutions act independently to change the catalytic properties of the enzyme.
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PMID:Characterization of TEM-1 beta-lactamase mutants from positions 238 to 241 with increased catalytic efficiency for ceftazidime. 808 10

The main pathogens of gram-negative infections are Neisseria gonorrhoeae, Neisseria meningitidis and Moraxella catarrhalis infection. N. Gonorrhoeae infection is one of the STD, but the chemotherapy for this infection is very easy because this pathogen is very susceptible to new quinolones. Meningococcal infection is very rare in Japan. Since 1980, M. catarrhalis is one of the important pathogen of respiratory infections such as acute bronchitis, pneumonia, chronic bronchitis. This pathogen also causes acute sinusitis and otitis. Most pathogenic strains of M. catarrhalis are beta-lactamase producing.
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PMID:[Gram-negative coccus infection]. 812 87


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