Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Bacillus subtilis mutant cal1 carries a non-reverting mutation in ribosomal protein L17 (r-protein L17) that causes both resistance to the antibiotic chalcomycin (Calr) and temperature-sensitive sporulation (Spots). Second-site suppressor (rev) mutations that relieve the Spots phenotype have been isolated from cal1. Three suppressor mutations - rev4, rev10, rev11 - each increase the sporulation frequency of cal1 at the non-permissive temperature from 3% to 95% of the wild-type level. The cal1 rev strains remain resistant to chalcomycin and two-dimensional gel electrophoresis analysis indicates that they contain the same altered r-protein L17 as the original cal1 strain and no additional altered r-proteins. The three rev mutations have been mapped at a single locus between narA and sacA on the B. subtilis chromosome and recombination indexes for the rev mutations indicate that they are tightly linked to one another. Antibiotic resistance Spots mutations that cause temperature-sensitive sporulation have previously been isolated in RNA polymerase, in the 30S and 50S subunits of the ribosome, and in elongation factor G. The rev4, 10, and 11 suppressor mutations are non-specific in their action in that they restore significant levels of sporulation at the non-permissive temperature in all of the Spots strains that we have tested. This result suggests that Spots mutations in components of the B. subtilis transcription and translation systems share a common molecular basis for their sporulation-defective phenotypes.
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PMID:Intergenic suppressors of temperature-sensitive sporulation in Bacillus subtilis are allele non-specific. 680 27

Five hundred putative RNA polymerase mutants of Bacillus subtilis were isolated by selecting for resistance to the RNA polymerase inhibitors rifampin (Rifr), streptovaricin (Strr) or streptolydigan (Stdr). This collection was screened for mutants that were unable to sporulate at the non-permissive temperature of 46 degrees C, yet which sporulated well at 37 degrees C and had normal vegetative growth (Spots phenotype). Nearly one half of the Rifr and one quarter of the Stvr mutants were Spots, whereas none of the Stdr mutants had this phenotype. The streptovaricin resistant strain stv84 was studied in detail. The stv84 mutation maps between cysA14 and strA39 on the B. subtilis chromosome, and the Stvr and Spots phenotypes cotransform at a frequency of 100%. The Spots phenotype of stv84 could be physiologically corrected by supplementing the growth medium with inhibitors of RNA synthesis such as rifampin or azauracil, with carbohydrates such as ribose, mannose or glycerol, or with lipids such as Tween 40 or fatty acids native to Bacillus subtilis membranes. A Spots phenotype resembling that of stv84 was produced in wild type B. subtilis by adding cerulenin, an inhibitor of fatty acid biosynthesis, to the growth medium. This cerulenin-induced sporulation defect was reversed by the same treatments that correct the temperature-sensitive genetic defect of stv84. These data indicate that the Spots phenotype of strain stv84 is not due to an intrinsic inability of the mutant RNA polymerase to transcribe developmentally-specific genes at the nonpermissive temperature. Rather, the data suggest that the stv84 lesion causes a physiological imbalance which disrupts membrane structure or function in sporulating cells.
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PMID:Physiological suppression of the temperature-sensitive sporulation defect in a Bacillus subtilis RNA polymerase mutant. 680 29

The temperature-sensitive sporulation phenotype (Spots) of Bacillus subtilis RNA polymerase, ribosomal and protein synthesis elongation factor G mutations can be corrected by supplementing the growth medium with carbohydrates such as ribose or glycerol, or with synthetic lipids such as Tween 40. The data suggest that these mutations affect a single common aspect of developmental cell function. It is proposed that these lesions prevent sporulation by disturbing the regulation of sporulating cell metabolic balance.
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PMID:Physiological suppression of Bacillus subtilis conditioned sporulation phenotypes: RNA polymerase and ribosomal mutations. 680 30

Caliciviruses were isolated from feces of skunks imported from the north central United States to Canada. Virus isolation was accomplished using adenovirus-transformed human kidney (293) cells, swine testes and Vero cells. Plaque size variants were presented, but there was no apparent difference in virus morphology by negative stain or immune electron microscopy. Pigs infected with skunk calicivirus had a slightly elevated body temperature at 3 days postinfection. Although the infected animals seroconverted, no overt clinical signs were observed. Purified infectious genomic skunk calicivirus RNA behaved exactly as San Miguel sea lion virus (SMSV) 1 and 4 genomic RNA in cell culture transfection studies. Of the cell types examined, only primary porcine kidney, 293 and Vero cells supported viral replication. No viral replication was detected in cells of bovine, equine, ovine, caprine or feline origin. The skunk caliciviruses contained a single capsid protein with a relative mobility similar to SMSV virus 1 and 4 capsid proteins. The capsid protein was positive by Western blot analysis with SMSV and vesicular exanthema of swine virus (VESV) antisera. Purified RNA from skunk calicivirus infected cells was subjected to reverse transcription followed by polymerase chain reaction. Nucleotide sequences were identified that had greater than 85% similarity to the 2C and RNA polymerase gene regions of SMSV 1 and 4 and VESV A48. Predicted amino acid sequences of these regions were greater than 95% similar and the partial coding sequence of the polymerase gene contained the YGDD sequence common to positive-strand RNA virus polymerases.
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PMID:Isolation of caliciviruses from skunks that are antigenically and genotypically related to San Miguel sea lion virus. 748 17

The San Miguel sea lion viruses (SMSV) and vesicular exanthema of swine viruses (VESV) are related morphologically and antigenically, but little has been done to determine their genotypic relationship to each other and to other caliciviruses. To examine this relationship, reverse transcriptase PCRs were performed by using oligonucleotide primer sets designed to amplify portions of the 2C RNA helicase-like and RNA-dependent RNA polymerase regions with total cellular RNA purified from virus-infected cell cultures as a template. The 2C RNA helicase primers directed the amplification of this region from eight SMSV serotypes, five VESV serotypes, and four related viruses. The RNA polymerase primer sets amplified products from all these viruses except one. Phylogenetic comparison of the caliciviruses demonstrated that SMSV, VESV, and four related viruses are closely related while being distinct from feline calicivirus, the human caliciviruses (small, round-structured viruses), and rabbit hemorrhagic disease virus and that they should be classified as a single genotype within the Caliciviridae.
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PMID:Genetic relatedness of the caliciviruses: San Miguel sea lion and vesicular exanthema of swine viruses constitute a single genotype within the Caliciviridae. 776 8

Evidence suggests that nevirapine, a non-nucleoside reverse-transcriptase inhibitor, might be very effective in the prevention of HIV-1 integration and the reduction of risk of HIV-1 acquisition after exposure. We used a triple combination regimen, including nevirapine, for prophylaxis after occupational or sexual exposure to HIV-1 infection. Of 57 individuals who started therapy, only 41 returned for follow-up. Five had a grade three or four drug-induced hepatitis, two of whom also had a rash. This high rate of major adverse events raises concerns over the safety of such a regimen for its use in this population.
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PMID:Prophylaxis with a nevirapine-containing triple regimen after exposure to HIV-1. 1151 14

Expanded access programs (EAPs) provide medication to patients with life-threatening, treatment-refractory illnesses before regulatory approval and allow the acquisition of safety information. A 2-part, multisite EAP to evaluate abacavir, a carbocyclic nucleoside reverse-transcriptase inhibitor for use in combination antiretroviral therapy, was conducted. The EAP involved >13,000 adults infected with human immunodeficiency virus type 1 (HIV-1) who no longer responded to commercially available treatment regimens. Part A (open-label trials) examined the efficacy, safety, and tolerance of abacavir, and part B (provision of abacavir through expanded access) assessed only the occurrence of serious adverse events. By month 2 of abacavir-containing treatment, plasma HIV-1 RNA levels decreased by > or =0.5 log(10) in 31.4% of patients, and 5.6% of the patients had HIV-1 RNA levels decrease to <400 copies/mL. Drug-related serious adverse events were reported by 7.7% of patients, the most common of which were nausea, skin rash, diarrhea, malaise or fatigue, and fever. Approximately 4.6% of patients experienced a hypersensitivity reaction that was possibly drug related. Overall, the types and incidences of adverse events reported in the abacavir EAP were similar to those reported in phase 2 and 3 clinical trials evaluating abacavir.
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PMID:Abacavir expanded access program for adult patients infected with human immunodeficiency virus type 1. 1179 83

Maternal rubella is now rare in many developed countries that have rubella vaccination programmes. However, in many developing countries congenital rubella syndrome (CRS) remains a major cause of developmental anomalies, particularly blindness and deafness. WHO have provided recommendations for prevention of CRS, and, encouragingly, the number of countries introducing rubella vaccination programmes has risen. However, declining uptake rates due to concerns about the measles-mumps-rubella vaccine in the UK, and increasing numbers of cases in some European countries coupled with poor uptake rates might jeopardise this progress. Surveillance of postnatally and congenitally acquired infection is an essential component of CRS prevention since rubella is difficult to diagnose on clinical grounds alone. Laboratory differentiation of rubella from other rash-causing infections, such as measles, parvovirus B19, human herpesvirus 6, and enteroviruses in developed countries, and various endemic arboviruses is essential. Reverse transcriptase PCR and sequencing for diagnosis and molecular epidemiological investigation and detection of rubella-specific IgG and IgM salivary antibody responses in oral fluid are now available.
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PMID:Rubella. 1506 32

An epidemic of Chikungunya fever of unprecedented magnitude occurred in many parts of India in early 2006 after an interval of 33 years, and there has been a resurgence in some parts of South India since June 2007. The article highlights clinical manifestations of infection and various molecular tests that were used for diagnoses of Chikungunya virus infection. Of particular interest is the real-time loop-mediated isothermal amplification (RT LAMP) assay, which is rapid and cost-effective and can be adopted at ill-equipped laboratories. Clinical symptoms were characterized by a triad of fever, rash, and severe rheumatic manifestations. RT LAMP identified 20 additional Chikungunya virus-positive cases, compared with reverse-transcriptase polymerase chain reaction. Chikungunya virus was isolated from 20 randomly selected samples. Genotyping of the virus isolates revealed that the East Central South African genotype of Chikungunya virus was the etiologic agent of this epidemic. Molecular diagnosis is an important tool to identify such new vectorborne viral illnesses.
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PMID:Clinical features and molecular diagnosis of Chikungunya fever from South India. 1841 49

Different viruses belonging to the genus Vesivirus infect a broad range of animals, and cause gastroenteritis, vesicular skin lesions, hemorrhagic disease, respiratory diseases and other conditions. A recent report on Vesivirus viremia, as detected by PCR, in samples from patients with hepatitis of unknown etiology in the USA suggested a zoonotic potential for vesiviruses. These results have not been confirmed by another laboratory. In order to do so, a generic PCR assay on the RNA polymerase region was developed, and validated with RNA from 69 different Vesivirus species. Except SMSV serotype-8, all species tested were detected, including the ones that were suggested to be involved in zoonotic transmission in the USA (SMSV serotype-5). The generic Vesivirus assay was used on RNA extracted from serum samples from patients with hepatitis, stool samples from patients with gastroenteritis, throat-swab specimens of patients with rash illnesses, throat-swab and nose-swabs of patients with acute respiratory diseases, and cell cultures with cytopathologic effect from enterovirus surveillance in which no pathogen was found. None were found positive. In this study a generic Vesivirus assay was developed and it was concluded that vesiviruses are an unlikely cause of common illnesses in humans in the Netherlands.
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PMID:A new generic real-time reverse transcription polymerase chain reaction assay for vesiviruses; vesiviruses were not detected in human samples. 1913 80


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