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)

Three hundred and seventy-eight passengers reported gastroenteritis during four cruises in the western Mediterranean on consecutive weeks of 1995. The rate at which cases were reported each day increased on the fourth cruise. The ship's owner commissioned an epidemiological investigation from the PHLS Communicable Disease Surveillance Centre. Cases reported explosive vomiting and diarrhoea, which lasted from 24 hours to five days, and were suggestive of viral gastroenteritis. No food handlers reported illness, but enquiries suggested that some had been ill and treated themselves. No bacterial pathogens were isolated from faecal specimens provided by cases or from water, food, and environmental samples taken from the galley. Small round structured viruses (SRSV) were identified by reverse transcriptase polymerase chain reaction in two faecal specimens and one specimen of vomit from people who became ill during the fourth cruise. SRSV was also identified in one faecal specimen by electron microscopy. Environmental inspection revealed inappropriate food handling, hygiene, and storage. During one 24 hour period no chlorine was detectable in the water. A case control study conducted on the fourth cruise sought details of exposure to various foodstuffs, unbottled water, and various parts of the ship. No significant associations were found between illness and any exposures. The evidence strongly suggested a continuing outbreak of SRSV infection transmitted from person to person. Some passengers remained on board for a second week and could have transmitted their infection to new arrivals. The ship was cleared and disinfected at the end of the fourth cruise in order to interrupt transmission. Fewer than 10 cases presented in each of the fifth and sixth cruises.
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PMID:An outbreak of viral gastroenteritis on a cruise ship. 899 May 76

Retrovirally encoded proteases are responsible for the maturation of immature viral particles yielding mature, infectious virus. This is done by apparent (auto)-processing and self-activation of the protease (PR) from a larger viral gag-PR-(pol) protein (zymogen) precursor and subsequent processing of the viral reverse transcriptase (RT) and integrase (IN), and the gag protein precursor into mature gag proteins. Only the matured components are capable of forming capsids for intact, infectious viruses. Blocking this proteolytic process results in production of immature, non-infective virions. All retroviral proteases are aspartic-type proteases. Determination of the three-dimensional structure revealed retroviral proteases as small, nearly symmetric homodimers. This prompted de novo design of inhibitors for the HIV protease taking advantage of the unique symmetric structure of the active center, unparalleled by cellular proteases. The novel substances inhibit in vitro the HIV protease at nanomolar/subnanomolar concentrations and exhibit very low toxicity. They are inactive against human proteases such as renin or pepsin. The HIV protease inhibitors (PI) represent a promising alternative to the reverse transcriptase (RT) inhibitors (AZT, ddC, ddI) hitherto used with limited success for HIV chemotherapy. Clinical studies confirmed the low toxicity but revealed a pharmacological pattern typical for these hydrophobic compounds, such as low water solubility, poor oral bioavailibility, and short plasma half-life. Typical for antimicrobial agents, also a resistance phenomenon became evident. Latest clinical results show, however, promisingly that both problems might be overcome by application of the PI in combination with RT inhibitors (such as AZT, ddI or ddC) exerting a remarkable synergistic antiviral effect with lasting restoration of the CD4-T-cell level.
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PMID:Retroviral proteases: structure, function and inhibition from a non-anticipated viral enzyme to the target of a most promising HIV therapy. 899 87

Recent reports have demonstrated that prostaglandin F2alpha-induced generation of reactive oxygen species or their intermediates inhibits progesterone synthesis and may also serve as a trigger for apoptosis in the corpus luteum (CL). BCL-2, an inhibitor of apoptosis in a wide variety of cell types, has been reported to prevent oxidative stress-induced cell death. Thus, the present studies were conducted to determine whether levels of mRNA encoding BCL-2 and related members of this gene family (BAX and BCL-Xshort, which induce apoptosis; BCL-Xlong, a BCL-2 homologue that prevents apoptosis) differed in functional (Day 21 of pregnancy) versus regressed (Day 21 of the estrous cycle) CL in the bovine ovary. Levels of mRNAs encoding p53, a transcriptional regulator of the bcl-2 and bax genes, and interleukin-1beta-converting enzyme (ICE), a protein recently implicated in the induction of apoptosis whose expression may be enhanced by oxidative stress, were also assessed. Partial cDNA clones encoding bovine bax, bcl-x, p53, and Ice were isolated using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique with total RNA prepared from functional or regressed CL. A bovine bcl-2 cDNA could not be isolated from luteal tissue RNA despite the use of several primer pairs for amplification. Total RNA was then extracted from functional or regressed CL and analyzed by Northern blot analysis. The occurrence of apoptosis in regressed CL, as evidenced by the presence of internucleosomal DNA cleavage, was associated with a significant increase in both bax and Ice mRNA levels as compared with levels of bax and Ice expression in functional CL (p < 0.05, n = 3). There were no significant differences in bcl-x or p53 mRNA levels in functional versus regressed CL. Analysis of bcl-x mRNA by RT-PCR revealed that the long form was the primary, if not only, mRNA expressed in functional and regressed bovine luteal tissue. On the basis of data that increased expression of bax is associated with, and may be required for, apoptosis in ovarian granulosa cells and germ cells, we propose that BAX may play a similar role in apoptosis induction during luteal regression. Moreover, the increased Ice mRNA levels in regressed CL provides the first evidence that the ICE family of death proteases may be involved in luteolysis.
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PMID:Increased bax and interleukin-1beta-converting enzyme messenger ribonucleic acid levels coincide with apoptosis in the bovine corpus luteum during structural regression. 900 48

Using the molecular "cloud" of the HIV-1 reverse transcriptase (RT) as starting point, the peptide backbone of the polymerase subunit was visualized by molecular modelling. Then, the two subregions 98-106 and 179-190 of the allosteric area were "isolated". From the latter subregion, the Tyr181 to Tyr188 segment containing two amino acids (Asp185, Asp186) of the catalytic aspartyl triad and two amino acids (Tyr181, Tyr188) of the nonnucleoside RT inhibitor (NNRTI) binding sites, was excised. It was shown that the segment has a omega-like loop configuration which is highly hydrophilic. The two phenolic side chains of Tyr181 and Tyr188 represent the lipophilic "horizontal axes" of the omega-loop shape. The relative rigidity of the omega-loop is mainly based on a hydrogen bond between the peptide CO of Tyr181 and the peptide NH of Tyr188. Solvation in water increases the number of intramolecular hydrogen bonds. Therefore, desolvation is one of the conditions of binding with NNRTIs. Site-directed mutagenesis affects the hydrophilicity of the omega-loop while steric features are less influenced.
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PMID:A hydrophilic omega-loop (Tyr181 to Tyr188) in the nonsubstrate binding area of HIV-1 reverse transcriptase. 901 65

Angiotensinogen is the only known substrate for the enzyme renin. Angiotensin II, the end product of the reaction, is an extremely potent vasoconstrictor and a major determinant of salt and water homeostasis. It is also a growth factor. Angiotensinogen has been identified as a non-inhibitory member of the serine proteinase inhibitor family. Although the most abundant source of plasma angiotensinogen is the liver, the use of Northern blotting and reverse transcriptase PCR techniques has confirmed angiotensinogen mRNA expression in a wide range of tissues, including the kidney, brain, vascular tissue, adrenal gland, placenta and leucocytes. The sequencing of the rat and human angiotensinogen genes has increased our understanding of this protein and its role in physiology and the pathogenesis of human disease. Early observations on the regulation of angiotensinogen are now explicable at the molecular level, with the identification of the core promoter, hormone and acute phase responsive elements and tissue-specific enhancers. The role of angiotensinogen in the aetiology of hypertensive disorders has been tested in transgenic animals, and in case-controlled genetic association and linkage studies. This review examines our current understanding of angiotensinogen, in the light of recent advances.
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PMID:Angiotensinogen: molecular biology, biochemistry and physiology. 902 80

Somatostatin modulates important physiologic functions of the kidney, including mesangial cell contraction, glomerular prostaglandin synthesis, and phosphate, water and sodium excretion. In diabetic nephropathy, somatostatin inhibits renal hypertrophy. High affinity somatostatin receptors are expressed in the kidney. Circulating somatostatin concentrations, however, are generally well below the affinity constants of known somatostatin receptors. Thus, we hypothesized that somatostatin is produced in the kidney and released locally to act in an autocrine/paracrine manner. Using reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, we found that fresh human renal cortex and cultured human mesangial cells express somatostatin mRNA. Restriction enzyme and Southern blot analysis confirmed that RT-PCR cDNA products were derived from somatostatin mRNA. Radioimmunoassay of mesangial cell culture supernatants demonstrated SS-immunoreactive peptide (87 +/- 30 pg/ml compared to 19 +/- 9 pg/ml in medium not exposed to cells; P < 0.05). In contrast, renal cells did not transcribe detectable levels of vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY) mRNA, nor did they synthesize measurable peptide. Our results demonstrate that renal cells produce somatostatin and suggest that kidney-derived somatostatin may regulate renal function in an autocrine/paracrine manner. Characterization of this pathway may lead to novel methods to alter the course of diabetic nephropathy and other renal diseases.
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PMID:Somatostatin expression in human renal cortex and mesangial cells. 909 50

The viral reverse transcriptase (RT) provides an attractive target in the search for anti-HIV therapies. The nonnucleoside inhibitors (NNIs) are a diverse set of compounds (usually HIV-1 specific) that function by distorting the polymerase active site upon binding in a nearby pocket. Despite being potent and of generally low toxicity, their clinical use has been limited by rapid selection for resistant viral populations. The 2.65-A resolution structure of the complex between HIV-1 RT and the bis(heteroaryl)piperazine (BHAP) NNI, 1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4- [3-(1-methyl-ethylamino) pyridinyl] piperazine (U-90152), reveals the inhibitor conformation and bound water molecules. The bulky U-90152 molecule occupies the same pocket as other NNIs, but the complex is stabilized quite differently, in particular by hydrogen bonding to the main chain of Lys-103 and extensive hydrophobic contacts with Pro-236. These interactions rationalize observed resistance mutations, notably Pro-236-Leu, which occurs characteristically for BHAPs. When bound, part of U-90152 protrudes into the solvent creating a channel between Pro-236 and the polypeptide segments 225-226 and 105-106, giving the first clear evidence of the entry mode for NNIs. The structure allows prediction of binding modes for related inhibitors [(altrylamino)piperidine-BHAPs] and suggests changes to U-90152, such as the addition of a 6 amino group to the pyridine ring, which may make binding more resilient to mutations in the RT. The observation of novel hydrogen bonding to the protein main chain may provide lessons for the improvement of quite different inhibitors.
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PMID:Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor. 910 91

This study describes a competitive reverse transcriptase polymerase chain reaction (RT-PCR) method for assaying the amounts of vasopressin (AVP) and ocytocin (OT) mRNAs in the rat hypothalamus and uterus. Despite the low concentrations of these mRNAs, the RT-PCR method readily measured both AVP and OT mRNAs in the same sample. A common internal standard for both reactions was designed to quantify the reaction. Both AVP and OT mRNAs were readily quantified in a 75 ng sample of total RNA from the hypothalamus. Water deprivation stimulated AVP mRNA production 3-fold and OT mRNA production 1.7-fold in the hypothalamus. Gestation only influenced the amount of OT mRNA in the hypothalamus (3-fold increase) and uterus (38-fold increase). The amount of AVP mRNA in the hypothalamus remained unchanged and no AVP mRNA was detected in the uteri of either non-pregnant or pregnant rats. This competitive RT-PCR is a powerful tool that provides rapid and precise assays of AVP and OT mRNAs.
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PMID:A sensitive reverse transcriptase polymerase chain reaction assay for measuring the effects of dehydration and gestation on rat amounts of vasopressin and ocytocin mRNAs. 914 86

The presence of Cryptosporidium in drinking water supplies is a significant problem faced by the water industry. Although a variety of methods exist for the detection of waterborne oocysts, water utilities currently have no way of assessing the infectivity of detected oocysts and consequently are unable to accurately determine the risks posed to public health by waterborne Cryptosporidium. In this paper, the development of an infectivity assay for waterborne Cryptosporidium parvum is described. Oocysts were inoculated onto monolayers of Caco-2 cells and grown on microscope slides, and infections were detected by C. parvum specific reverse transcriptase PCR of extracted mRNA, targeting the heat shock protein 70 (hsp70) gene. A single infectious oocyst was detected by this experimental procedure. The use of concentrated samples obtained from 250 liters of finished water had no observable effect on the integrity of cell monolayers or on the infectivity of oocysts seeded into the concentrate. Intracellular developmental stages of the parasite were also detected by using fluorescently labeled antibodies. One pair of PCR primers targeting the hsp70 gene was specific for C. parvum, while a second pair recognized all species of Cryptosporidium tested. The C. parvum-specific primers amplified DNA from 1 to 10 oocysts used to seed 65 to 100 liters of concentrated environmental water samples and were compatible with multiplex PCR for the simultaneous detection of C. parvum and Giardia lambia. This paper confirms the utility of PCR for the detection of waterborne C. parvum and, most importantly, demonstrates the potential of an in vitro infectivity assay.
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PMID:An assay combining cell culture with reverse transcriptase PCR to detect and determine the infectivity of waterborne Cryptosporidium parvum. 914 32

Polysaccharopeptide (PSP) isolated from the edible mushroom Coriolus versicolor was tested for its potential as an anti-human immunodeficiency virus type 1 (HIV-1) compound in a series of in vitro assays. It demonstrated inhibition of the interaction between HIV-1 gp 120 and immobilized CD4 receptor (IC50 = 150 microg/ml), potent inhibition of recombinant HIV-1 reverse transcriptase (IC50 = 6.25 microg/ml), and inhibited a glycohydrolase enzyme associated with viral glycosylation. These properties, coupled with its high solubility in water, heat-stability and low cytotoxicity, make it a useful compound for further studies on its possible use as an anti-viral agent in vivo.
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PMID:Polysaccharopeptide from Coriolus versicolor has potential for use against human immunodeficiency virus type 1 infection. 919 94


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