Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reports of human immunodeficiency virus (HIV) infection in seronegative individuals prompted the authors to investigate subjects who are at very high risk of acquisition of HIV in San Francisco. Nine HIV seronegative subjects were evaluated extensively, eight of whom were drawn from a well-characterized cohort of seropositive and seronegative homosexual men who have been followed prospectively since 1983-1984. These men have calculated probabilities of infection based on a fitted model of between 0.22 and 0.94. One additional subject is an intravenous drug user who has shared needles with HIV-infected individuals extensively. Peripheral blood lymphocytes and monocytes were separately cultured from each subject and evidence of HIV infection was sought by a reverse transcriptase assay, enzyme immunoassay, and immunocytofluorographic analysis for HIV antigens, in situ hybridization, RNA slot blot analysis, and polymerase chain reaction amplification of HIV cDNA. Uncultured monocytes and lymphocytes from each donor were also examined by these techniques. Evidence of HIV infection was not found in the peripheral blood mononuclear cells of these high risk individuals.
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PMID:Lack of evidence of occult human immunodeficiency virus in seronegative individuals at very high risk of infection. 180 28

Sequences were determined of the coding regions of the M-protein genes of the Glasgow and Orsay strains of vesicular stomatitis virus (Indiana serotype) and of two group III (M-protein) mutants derived from each wild type. Synthetic primers were annealed with viral genomic RNA and extended with reverse transcriptase. The resulting high-molecular-weight cDNA was sequenced directly. Both Glasgow and Orsay wild types differed in 13 bases from a clone of the San Juan strain sequenced by J. K. Rose and C. J. Gallione (J. Virol. 39:519-528, 1981). Six of these base changes caused amino acid changes in each wild type, whereas seven were degenerate. The Orsay and Glasgow sequences resembled each other more closely than either resembled that of Rose and Gallione, differing in eight nucleotides and four amino acids. Each of the four mutants, however, differed from its parent wild type in only one or two point mutations. Every mutation caused a change either from or to a charged amino acid; the change for tsG31 was Lys (position 215) to Glu, the change for tsO23 was Gly (position 21) to Glu, the change for tsO89 was Ala (position 133) to Asp, the changes for tsG33 were Lys (position 204) to Thr and Glu (position 214) to Lys. The charge differences predicted from these amino acid changes was confirmed by nonequilibrium pH gradient electrophoresis for tsG31, tsG33, tsO23, and the two wild types. These mutations affect residues spanning nearly 85% of the linear sequence, although the mutants possess nearly identical phenotypic properties.
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PMID:Sequence alterations in temperature-sensitive M-protein mutants (complementation group III) of vesicular stomatitis virus. 299 21

Infectious retroviruses have been detected in 22 of 45 randomly selected patients with acquired immune deficiency syndrome (AIDS) and in other individuals from San Francisco. The AIDS-associated retroviruses (ARV) studied in detail had a type D morphology, Mg2+-dependent reverse transcriptase, and cytopathic effects on lymphocytes. The viruses can be propagated in an established adult human T cell line, HUT-78. They cross-react with antiserum to the lymphadenopathy-associated retrovirus isolated from AIDS patients in France. Antibodies to ARV were found in all 86 AIDS patients and in a high percentage of 88 other homosexual men in San Francisco. This observation indicates the widespread presence of these lymphocytopathic retroviruses and their close association with AIDS.
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PMID:Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. 620 63

The San Miguel sea-lion viruses (SMSV) and vesicular exanthema of swine viruses (VESV) are members of the calicivirus family and aetiologic agents of vesicular disease in susceptible hosts. These two virus groups have been shown by several serological methods to be closely related antigenically. To further examine their relatedness, two sets of non-degenerate oligonucleotide primers were designed for the specific amplification of two distinct regions of the SMSV and VESV genomes using a reverse transcriptase-polymerase chain reaction (RT-PCR) protocol. The sequence of the primers were based on the nucleotide sequence of SMSV serotypes 1 and 4. The RNAs from a number of SMSV serotypes and a single VESV isolate were used as template in this study. These included SMSV serotypes 1, 2, 4, 5, 6, 7, 13 and 14 and VESV serotype A48. Also included in this study were Tillamook calicivirus (Bos-1 calicivirus, BCV) and a recently isolated skunk calicivirus (SCV). The first primer set amplified a 357-bp fragment from the 2C-like or RNA-helicase-encoding region (11 of 11 viruses) and the second set amplified a fragment from the RNA-dependent RNA polymerase region (520 bp, 9 of 11 viruses). These primer sets did not amplify product from either feline calicivirus or mink calicivirus. The results of this study demonstrate the genetic relatedness of SMSV and VESV and the potential usefulness of RT-PCR to detect and identify these viruses in diagnostic and routine screening applications.
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PMID:Development of PCR primers for specific amplification of two distinct regions of the genomes of San Miguel sea-lion and vesicular exanthema of swine viruses. 776 Aug 57

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

Reverse transcription has been an important mediator of genomic change. This influence dates back more than three billion years, when the RNA genome was converted into the DNA genome. While the current cellular role(s) of reverse transcriptase are not yet completely understood, it has become clear over the last few years that this enzyme is still responsible for generating significant genomic change and that its activities are one of the driving forces of evolution. Reverse transcriptase generates, for example, extra gene copies (retrogenes), using as a template mature messenger RNAs. Such retrogenes do not always end up as nonfunctional pseudogenes but form, after reinsertion into the genome, new unions with resident promoter elements that may alter the gene's temporal and/or spatial expression levels. More frequently, reverse transcriptase produces copies of nonmessenger RNAs, such as small nuclear or cytoplasmic RNAs. Extremely high copy numbers can be generated by this process. The resulting reinserted DNA copies are therefore referred to as short interspersed repetitive elements (SINEs). SINEs have long been considered selfish DNA, littering the genome via exponential propagation but not contributing to the host's fitness. Many SINEs, however, can give rise to novel genes encoding small RNAs, and are the migrant carriers of numerous control elements and sequence motifs that can equip resident genes with novel regulatory elements [Brosius J. and Gould S.J., Proc Natl Acad Sci USA 89, 10706-10710, 1992]. Retrosequences, such as SINEs and portions of retroelements (e.g., long terminal repeats, LTRs), are capable of donating sequence motifs for nucleosome positioning, DNA methylation, transcriptional enhancers and silencers, poly(A) addition sequences, determinants of RNA stability or transport, splice sites, and even amino acid codons for incorporation into open reading frames as novel protein domains. Retroposition can therefore be considered as a major pacemaker for evolution (including speciation). Retroposons, with their unique properties and actions, form the molecular basis of important evolutionary concepts, such as exaptation [Gould S.J. and Vrba E., Paleobiology 8, 4-15, 1982] and punctuated equilibrium [Elredge N. and Gould S.J. in Schopf T.J.M. (ed). Models in Paleobiology. Freeman, Cooper, San Francisco, 1972, pp. 82-115].
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PMID:Reverse transcriptase: mediator of genomic plasticity. 882 43

We sought to determine the sensitivity and specificity of immunohistochemistry using the TORDJI-22 MoAb (BioGenex, San Ramon, Calif), which is specific for the C-100 protein of the hepatitis C virus, compared with reverse transcriptase-polymerase chain reaction (RT-PCR) of tissue for viral RNA. RT-PCR had been performed on 52 fixed tissue specimens. Immunohistochemistry was performed using prediluted antibody with the alkaline phosphatase/fast red (BioGenex) technique. Predigestion with Protease XXIV (BioGenex) and other procedures followed the manufacturer's protocols. Positive immunohistochemistry was narrowly defined as tightly clumped, perinuclear red granules in hepatocytes. Of the specimens, 28 were positive by RT-PCR. With RT-PCR as the standard of comparison, immunohistochemistry yielded a sensitivity of 70% and specificity of 84%. Positive cells, when present, were usually very rare. With stringent criteria, immunohistochemistry with the TORDJI-22 monoclonal antibody is a very specific, fairly sensitive diagnostic test for hepatitis C virus in fixed liver tissues.
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PMID:Immunohistochemical detection of hepatitis C antigen by monoclonal antibody TORDJI-22 compared with PCR viral detection. 966 20

HIV-protease inhibitors demonstrated such high efficacy in short-term studies that they have been approved by the FDA, even though possible toxicity still needs further investigation. In the period between January 1997 and August 1998, 101 patients, staying at San Patrignano Medical Centre (Italy), received an HIV protease inhibitor (indinavir) plus two nucleoside reverse transcriptase inhibitors (NRTI's) selected from the following: AZT, didanosine, zalcitabine, lamivudine or stavudine. Seventy-three patients were male, 28 female and their ages ranged from 25 to 60 years, with an average of 34. At the end of the study, 84 patients were suitable for evaluation, as the other 17 dropped out for various reasons. Forty-eight patients (57.1%) developed cheilitis, 34 (40.5%) experienced diffuse cutaneous dryness and pruritus, 10 (11.9%) developed asteatotic dermatitis on the trunk, arms and thighs and another 10 (11.9%) complained of scalp defluvium. A severe alopecia was observed in only 1 patient (1.2%), while 6 reported that their body hair had become fairer, thinner and shed considerably. Multiple pyogenic granulomas were observed in the toenails of 5 patients (5. 9%). Softening of the nail plate was noted in 5 subjects as well. A peripheral lipodystrophy syndrome was noted in 12 patients (14.3%). Among these, one patient only developed a "buffalo hump" and another had diffused lipomatosis. The temporal relationship between the taking of indinavir and the onset of such cutaneous effects was striking. This was confirmed by the regression of symptoms in those patients who later discontinued indinavir. The emerging side effects of protease inhibitors require a multidisciplinary team for adequate diagnosis and treatment. Cutaneous toxicity involving the patient's own body image has a peculiar influence on compliance to the treatment and the patient's quality of life.
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PMID:Cutaneous side effects induced by indinavir. 1084 57

Recently, some Alzheimer-associated genes have been found: amyloid precursor protein (APP), apolipoprotein E (apoE), presenilin 1 (PS-1) and presenilin 2 (PS-2). First, we examined mutations of APP, PS-1, and PS-2 genes in familiar Alzheimer's disease (FAD) (7 cases) found in San-in district by single-strand conformation polymorphism and sequence analysis. These seven cases with FAD did not show any mutations of APP, PS-1, and PS-2 genes. Other susceptibility genes of FAD still remain to be not identified. Many reports have established that apoE genotype distribution for the epsilon 4 allele is a susceptibility factor for the earlier onset and more rapid progression of Alzheier's disease (AD). However, the cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors may be associated with development of SAD. Second, we investigated the association between polymorphisms of the estrogen receptor (ER) alpha gene and SAD. The frequencies of P and X alleles in SAD were significantly higher than those in the control group (p < 0.05). Polymorphisms of the ER alpha gene may be a genetic risk factor for SAD. The apoE genotype is a genetic factor closely related SAD, but it is not full by appreciated how apoE has an effect on developing AD. There are few reports on the quantitative change of apoE, namely the expression of apoE mRNA. Third, ApoE mRNA level in the brains of patients with Alzheimer's disease (27 cases) and Down's syndrome (11 cases) was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ApoE mRNA level in the DS as well as AD was significantly higher than that in control group (p < 0.05, p < 0.05, respectively). High levels of apoE mRNA in AD and DS may play an important role in the development of Alzheimer pathology.
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PMID:[Causative genes in Alzheimer's disease]. 1130 15

A three-month human trial will be conducted in Los Angeles, New York, and San Francisco, to test a new drug, HBY 097. In laboratory tests, HBY 097 has weakened HIV. Volunteers will begin a regimen of either HBY 097, AZT, or the combination. The study will measure all mutations that develop in the HIV reverse transcriptase enzyme. Participants must have a CD4 count between 200 and 500, and have not received any approved HIV treatment before.
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PMID:Los Angeles, New York, Stanford University: HBY 097, new drug may weaken HIV. 1136 77


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