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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+ plays a key role in many pathological processes, including viral infections. Rotavirus, the major etiological agent of viral gastroenteritis in children and young animals, provides a useful model to study a number of Ca2+ dependent virus-cell interactions. Rotavirus entry, activation of transcription, morphogenesis, cell lysis, particle release, and the distant action of viral proteins are Ca2+ dependent processes. In the extracellular medium, Ca2+ stabilizes the structure of the viral capsid. During entry into the cell the low cytoplasmic Ca2+ concentration induced the solubilization of the outer protein layer of the capsid and transcriptase activation. Viral protein synthesis modifies Ca2+ homeostasis which, in turn, favours viral morphogenesis and induces cell death. The generation of diarrhea is a multifactorial process involving Ca2+ dependent secretory processes of mediators and water and electrolytes, as well as the induction of cell death in the different cell types that compose the intestinal epithelium. The discovery of the non-structural viral protein NSP4 as a viral enterotoxin and the possible participation of the enteric nervous system in the pathogenesis of diarrhea represent significant advances in its understanding. Ca2+ also plays a role in the replication cycles and pathogenesis of other viral diseases such as poliovirus, Coxsackie virus, cytomegalovirus, vaccinia and measles virus and HIV.
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PMID:Role of Ca2+in the replication and pathogenesis of rotavirus and other viral infections. 1102 Mar 76

A combined bio-analytical assay for abacavir, a reversed transcriptase inhibitor, and mycophenolic acid (MPA), based on reversed-phase liquid chromatography and both ultraviolet (UV) absorption and fluorescence detection, is reported. Both analytes are extracted from plasma with acetonitrile. After centrifugation, evaporation of the supernatant and reconstitution in water, the sample is injected into the chromatograph. Abacavir is detected using UV detection at 285 nm and MPA spectrofluorometrically at 345 and 430 nm for excitation and emission, respectively. The method has been validated in the 80-2000 ng/ml range for abacavir and in the 10-10,000 ng/ml range for MPA for 200-microl plasma samples. The lower limits of quantification are 80 and 10 ng/ml for abacavir and MPA, respectively. Precisions and accuracies are < or = 8% in the valid concentration ranges of both analytes.
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PMID:Liquid chromatographic assay for simultaneous determination of abacavir and mycophenolic acid in human plasma using dual spectrophotometric detection. 1120 16

DPC 961 and DPC 083 are investigational non-nucleoside reversed transcriptase inhibitors (NNRTI) being evaluated for the treatment of HIV infections (Corbett et al., Antimicrob Agents Chemother 1999;43:2893-2897). Both compounds are chiral and are synthesized as single enantiomers by an asymmetric synthetic pathway (Magnus et al., Tetrahedron Lett 2000;41:3015-3019). A chiral method was developed to control the enantiomeric purity of the drug substance and to monitor for any chiral inversion in the drug substance and in the tablet formulation during stability studies. Three columns were evaluated: Chiralpak AD, Chirobiotic V, and Whelk-O. All three columns have broad applicability and can resolve enantiomers of compounds of very diverse molecular structure and polarity. The three columns were evaluated with various mobile phase compositions for their ability to resolve the racemic mixtures of DPC 083, DPC 961, and their respective enantiomers and for their selectivity toward the synthetic impurities of the two drug substances. Nonaqueous mobile phases were selected because the two drugs are poorly water soluble. The separation between the unwanted enantiomer of DPC 083 and DPC 961, which is a major impurity of DPC 083, in particular, was closely monitored. The final method was fully validated and is used for the routine testing of the drug substance and tablets.
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PMID:Column selection and method development for the determination of the enantiomeric purity of investigational non-nucleoside reverse transcriptase inhibitors. 1128 24

Dysregulated renal water handling is a cardinal feature of nephrotic syndrome that has been shown in animal models of experimental nephrosis to mediate renal aquaporin (AQP) expression. However, data on the effect of proteinuria on the proximal tubule, which is heavily vested with AQP1 and therefore may participate in water homeostasis, are limited. To investigate this, we exposed primary human proximal tubular epithelial cells (PTECs) to two key proteinuric components shown to perturb tubule function: human serum albumin and transferrin. Using reverse-transcriptase polymerase chain reaction and immunocytochemical techniques, PTECs in the quiescent state were found to express AQP3 in addition to AQP1 gene and protein, which was also validated in a human proximal tubule cell line, HK-2. Immunohistochemical staining localized AQP1 synthesis to the apical and basolateral membranes and AQP3 synthesis to the basolateral membrane of proximal tubule epithelium. Transferrin in doses reaching nephrotic range upregulated PTEC transcription and translation of both AQP1 and AQP3 in a time- and dose-dependent manner. After 24 hours of stimulation, transferrin led to a 2.4- and 2.2-fold increase in AQP1 and APQ3 messenger RNA expression, whereas protein synthesis surged by 40.7% +/- 2.48% and 24.2% +/- 0.9% compared with control, respectively. These effects were not observed with albumin challenge and were not caused by osmolality fluctuation with transferrin treatment. In summary, our novel finding of AQP3 in PTECs indicates a role for AQP3 in proximal tubule water reabsorption. The pathophysiological significance of heightened AQP1 and AQP3 expression in PTECs on protein challenge as occurs in the nephrotic state requires further investigation.
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PMID:In vitro studies of aquaporins 1 and 3 expression in cultured human proximal tubular cells: upregulation by transferrin but not albumin. 1147 58

We previously reported increased aortic reactive oxygen species (ROS) production in mineralocorticoid (deoxycorticosterone acetate [DOCA]-salt) hypertensive rats. In the present study, we tested the hypothesis that NADH/NADPH oxidase is responsible for increased ROS production, namely superoxide (O(2-)), in aorta from the DOCA-salt rat. Treatment of aortic rings from DOCA-salt rats with the NO synthase inhibitor N-nitro-L-arginine and the xanthine oxidase inhibitor allopurinol did not significantly change O(2-) production. Furthermore, de-endothelialization of aorta from DOCA-salt rats did not affect O(2-) production compared with that of sham-operated rats. Thus, xanthine oxidase and uncoupled endothelial NO synthase were not responsible for increased O(2-) production in the DOCA-salt rats. In contrast, treatment with the NADPH oxidase inhibitor apocynin significantly decreased O(2-) production in aortic rings from DOCA-salt rats compared with sham-operated rats. Moreover, long-term administration of apocynin (in drinking water, 1.5 mmol/L, 28 days) to DOCA-salt rats significantly decreased systolic blood pressure compared with that of rats treated with DOCA-salt alone. Furthermore, O(2-) production in aortic rings from DOCA-salt rats treated with apocynin for 28 days was reduced compared with that of untreated DOCA-salt rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that DOCA-salt rats have significantly greater mRNA levels of the NADPH oxidase subunit p22phox than do sham-operated rats. These findings suggest that NADPH oxidase is increased and is responsible for increased O(2-) production and possibly contributes to increased blood pressure in the DOCA-salt hypertensive rat.
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PMID:NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat. 1171 6

The expression, localization, and regulation of aquaporin 5 (AQP5), a member of the water channel family of proteins, was investigated in tissues of the rat gastrointestinal tract. Reverse transcriptase--polymerase chain reaction (RT--PCR) detected AQP5 mRNA in the lower stomach and duodenum. DNA sequencing confirmed that the cDNA fragment amplified had the complete sequence of the AQP5 cDNA fragment. Western blot analysis indicated the expression of a 27 kDa molecular mass AQP5 protein in the lower stomach and duodenum, which size was the same as that found for the protein in the submandibular gland and lungs. By immunohistochemistry using the IgG affinity-purified AQP5 antibody, the pyloric gland and Brunner's gland were primarily stained in the lower stomach and duodenum, respectively; a strong staining appeared in the apical and lateral membranes in both glands. These results indicate that AQP5 is present in the rat lower stomach and duodenum where it may be involved in a water transport mechanism. These results also support the idea that AQP5, and probably other aquaporins, are involved in water secretion in the stomach and duodenum although the volume of water transported via AQPs is unclear.
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PMID:Expression and localization of AQP5 in the stomach and duodenum of the rat. 1185 85

This study demonstrated that a galactose-binding protein (GBP) produced by a fish pathogenic water mold, Aphanomyces piscicida, activates carp leukocytes. Leukocytes were separated from the head kidney and peripheral blood using Percoll density centrifugation. A flow cytometric analysis revealed that GBP binds with many cells and a variety of cell types including lymphocytes, granulocytes and thrombocytes. Intracellular calcium flux of the peripheral blood leukocytes induced by stimulation with GBP was confirmed by counting the fluo-3 loaded cells whose fluorescence increased after the stimulation using flow cytometry. The percentage of cells in which a calcium flux was induced peaked 1 min after the stimulation. Approximately 6% of the cells specifically responded 1 min after the stimulation. The proliferation response was determined by the level of BrdU uptake by the leukocytes after the stimulation. Cell proliferation was observed 2, 4 and 6 days after stimulation with GBP. The expression of cytokines IL-1beta and TGF-beta1 in the peripheral blood leukocytes, after the stimulation was evaluated by a semi-quantitative reverse-transcriptase polymerase chain reaction. Increased expression of IL-1beta was observed 4h after stimulation with GBP. Variation of TGF-beta1 expression under the same conditions was not observed. The kinetics of intracellular calcium flux and the level of IL-1beta expression induced by GBP stimulation were different from those induced by phytohemagglutinin stimulation. These results confirmed that GBP is a pathogenic microbial component that can induce cell activation. GBP seems to induce the inflammatory response observed in the Aphanomyces infection.
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PMID:Activation of carp leukocytes by a galactose-binding protein from Aphanomyces piscicida. 1190 25

To determine whether calcium polyvalent cation-sensing receptors (CaRs) are salinity sensors in fish, we used a homology-based cloning strategy to isolate a 4.1-kb cDNA encoding a 1,027-aa dogfish shark (Squalus acanthias) kidney CaR. Expression studies in human embryonic kidney cells reveal that shark kidney senses combinations of Ca(2+), Mg(2+), and Na(+) ions at concentrations present in seawater and kidney tubules. Shark kidney is expressed in multiple shark osmoregulatory organs, including specific tubules of the kidney, rectal gland, stomach, intestine, olfactory lamellae, gill, and brain. Reverse transcriptase-PCR amplification using specific primers in two teleost fish, winter flounder (Pleuronectes americanus) and Atlantic salmon (Salmo salar), reveals a similar pattern of CaR tissue expression. Exposure of the lumen of winter flounder urinary bladder to the CaR agonists, Gd(3+) and neomycin, reversibly inhibit volume transport, which is important for euryhaline teleost survival in seawater. Within 24-72 hr after transfer of freshwater-adapted Atlantic salmon to seawater, there are increases in their plasma Ca(2+), Mg(2+), and Na(+) that likely serve as a signal for internal CaRs, i.e., brain, to sense alterations in salinity in the surrounding water. We conclude that CaRs act as salinity sensors in both teleost and elasmobranch fish. Their tissue expression patterns in fish provide insights into CaR functions in terrestrial animals including humans.
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PMID:Polyvalent cation receptor proteins (CaRs) are salinity sensors in fish. 1209 23

At the beginning of the 20th century malaria was a major problem of tropical medicine until eradication campaigns succeeded in reducing its occurrence. Its recent epidemic resurgence in Madagascar, Namibia, Sao Tome and Principe, and Sudan shows the vulnerability of populations. The World Health Organization estimates that 110 million cases of malaria occur annually, most of them in Africa (90 million cases in sub-Saharan Africa). 1-2 million people die because of malaria. The matter is complicated by the resistance of Plasmodium falciparum to chloroquine and other drugs. In some parts of the world the mosquitos have developed resistance to insecticides, which makes vector control more difficult. This serious situation prompted a ministerial conference on malaria in Amsterdam in 1992, which resulted in the declaration that the fight against malaria necessitates the participation of the community concerning water resources, sanitation, and general development. The transmission of AIDS is connected to sexuality having social, behavioral, and ethical aspects. The first cases occurred among hemophiliacs, homosexuals, and intravenous drug addicts. HIV-1 was identified in 1983 and HIV-2 in 1987. In June 1994 the number of AIDS cases were approximately 4 million in the world, more than 2.5 million of them in sub-Saharan Africa. In Mozambique, in June 1993, a total of 826 cases had been diagnosed. In the area of treatment, inverse transcriptase inhibitors and the use of azidothimidine (AZT) are promising, the latter having prevented maternal-fetal transmission during pregnancy and labor. The toxicity of AZT is a major drawback. There is hope that eventually a vaccine can be developed. WHO developed a global strategy for the prevention and fight against AIDS in 1985, which was revised and adopted in 1987 by the World Health Assembly. The strategy aims to prevent HIV infection, to reduce its social and individual impact, and to gather national and international forces.
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PMID:[Malaria and AIDS: the great genocides]. 1229 61

In the Netherlands about 4 million people (283/1000) suffer from gastroenteritis every year, of which 500,000 cases are caused by 'Norwalk-like viruses' (NLVs), formerly known as 'small round-structured viruses'. The reports of two outbreaks illustrate the difficulties in determining the cause and source of the infection. The course is usually mild, but complications may be serious and ought to be documented. Vomiting and diarrhoea are the prominent signs and dehydration is the most common complication. Strict hygiene is warranted to prevent spreading of the disease. NLVs are highly infectious, notably via the faecal-oral route or by aerosols generated by vomiting. Fecally contaminated seafood and other food components that are not heated are an important source of infection, the main vehicle being sewage water. The microbiological quality control of food is often still based on bacteriological contamination, and therefore viral contamination may remain unnoticed. Reverse transcriptase PCR is a recent diagnostic tool.
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PMID:[Outbreaks of viral gastroenteritis, in particular due to the Norwalk virus: an underestimated problem]. 1281 28


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