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)

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor and is shown to be allelic with the white-spotting locus (W) of the mouse. In order to elucidate the role of c-kit protein during placental development, we have examined the expression of c-kit protein in the uterus and placenta of mice at pre- and post-implantation stages by the avidin-biotin-peroxidase (ABC) method using rat anti-mouse c-kit monoclonal antibody. At Days 3 and 5 of pregnancy and pseudo-pregnancy, c-kit protein was detected in the glandular epithelium, but little expression was observed in the luminal epithelium. At Day 7 of pregnancy, expression was detected in the stromal cells around the uterine crypts of the mesometrial portion, but not in the vigorously proliferating decidual cells around the developing embryo. At Days 9 and 10 of pregnancy, the decidua basalis facing invading trophoblasts gradually expressed c-kit protein. In the mature placenta, c-kit protein was detected in the labyrinthine and decidual layers, but in neither the giant trophoblastic nor the spongiotrophoblastic layer. By Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), c-kit mRNA was detected at the stages of periimplantation and placental development. These results suggested that the c-kit protein might be involved in the proliferation and differentiation of placenta.
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PMID:Expression of c-kit protein during placental development. 138 31

cDNA encoding the core protein of rat syndecan was cloned from a neonatal rat aortic cDNA library by polymerase chain reaction amplification. Expression of syndecan mRNA in rat aortic vascular smooth muscle (VSM) cells was demonstrated by reverse transcriptase-linked polymerase chain reaction amplification of syndecan sequences using total RNA from rat aortic VSM cells as templates. Polyclonal antibodies against rat syndecan core protein were produced by immunizing rabbits with a recombinant fusion protein containing a fragment of the extracellular domain. The anti-syndecan antibodies immunoprecipitated a large 35SO4-labeled molecule synthesized by cultured rat aortic VSM cells. The immunoprecipitated molecule was identified as a hybrid proteoglycan, based on results of alkaline, nitrous acid, and chondroitinase ABC digestions. On immunoblots the antibodies recognized a proteoglycan of greater than 200 kDa, with a core protein size after deglycosylation of approximately 50 kDa. The anti-syndecan antibodies stained cultured rat aortic VSM cells as well as tissue sections of neonatal and adult rat aortas in the medial, smooth muscle layer. On Northern blots of RNA isolated from cultured VSM cells, a syndecan cDNA probe hybridized to a major RNA species of 2.6 kilobases. Quantitative Northern blot analysis of total RNA isolated from VSM cells harvested at different cell densities revealed a decrease in syndecan mRNA levels with increased cell density. These results demonstrate the regulated synthesis of syndecan by rat VSM cells.
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PMID:Regulated expression of syndecan in vascular smooth muscle cells and cloning of rat syndecan core protein cDNA. 163 9

Proteoglycans metabolically labelled with [35S]sulphate and [3H]glucosamine or [3H]leucine were isolated from the incubation medium and cell layer of human adult mesangial cells and glomerular visceral epithelial cells using sequential DEAE chromatography purification steps followed by gel-filtration chromatography. The proteoglycan composition of each peak was analysed by treatment with HNO2, chondroitinase ABC or chondroitinase AC followed by chromatography on Sephadex G-50 columns. Heparan sulphate proteoglycan (HSPG) and dermatan sulphate proteoglycan were detected in both the culture medium and cell layer of mesangial cells. Culture medium of glomerular visceral epithelial cells contained HSPG and a second proteoglycan with the properties of a hybrid molecule containing HS and chondroitin sulphate (CS). The cell layer contained HSPG and CSPG. Detailed analysis of the hybrid molecule revealed that it had an apparent molecular mass of 400 kDa. SDS/PAGE of hybrid molecules, after treatment with heparitinase and chondroitinase ABC, revealed a core protein of 80 kDa. Using 1.8% polyacrylamide/0.6% agarose-gel electrophoresis, we deduced that the HS and CS were independently attached to one core protein. Because glomerular-basement-membrane HSPG is thought to be derived from mesangial cells and glomerular visceral epithelial cells and this molecule is involved in several kidney diseases, we investigated its synthesis in more detail. Anti-(rat glomerular-basement-membrane HSPG) monoclonal antibodies (JM403) and anti-(human glomerular-basement-membrane HSPG) polyclonal antibodies (both antibodies known to react with the large basement-membrane HSPG, perlecan) reacted strongly with HSPG obtained from both mesangial cells and glomerular visceral epithelial cells. However, the hybrid molecule did not react with these antibodies, suggesting that the HS side chain and the core protein were different from glomerular-basement-membrane HSPG. To quantify HS we performed an inhibition ELISA using mouse antibodies specific for glomerular-basement-membrane HS glycosaminoglycan side chains. Glomerular visceral epithelial cells produced significantly higher levels of HS (between 197.56 and 269.40 micrograms/72 h per 10(6) cells) than mesangial cells (between 29.8 and 45.5 micrograms/72 h per 10(6) cells) (three different cell lines; n = 3; P < 0.001). HS production by these cells was inhibited by cycloheximide, revealing that it was synthesized de novo. Expression of perlecan mRNA, demonstrated using reverse transcriptase PCR, was different in the two cell types. We conclude that glomerular visceral epithelial cells and mesangial cells have characteristic patterns of proteoglycan production. Glomerular visceral epithelial cells produced a hybrid proteoglycan containing CS and HS independently attached to its core protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteoglycan production by human glomerular visceral epithelial cells and mesangial cells in vitro. 753 59

Our aim was to investigate the collagenolytic potential and localization of matrix metalloproteinase-2 (MMP-2) in relation to its regulatory proteins membrane type MT1-MMP and tissue inhibitor of metalloproteinases-2 (TIMP-2) in rheumatoid arthritis (RA). For this purpose, we have used purification of MMP-2, MMP-8, MMP-9 and interstitial type I, II and III collagens; SDS-PAGE/densitometric collagenase activity assay; zymography; Western blotting; reverse transcriptase polymerase chain reaction; in situ hybridization; and immunofluorescence, ABC, ABC-APAAP double immunostainings. MMP-2 degraded human type II collagen almost as effectively as MMP-8, whereas MMP-9 did not cleave type II collagen. In synovial tissue, MT1-MMP, TIMP-2 and MMP-2 were found in synovial lining in fibroblast- and macrophage-like cells, in stromal cells and in vascular endothelium. MT1-MMP, TIMP-2 and MMP-2 were strongly expressed in the pannocytes of the invasive pannus at the interface, but staining was weak and/or there were few positive cells both "above" and "below" the soft-to-hard tissue (cartilage and/or bone) interface. Rheumatoid synovial tissue extract contained proteolytically active 62/59 kDa MMP-2 and 43 kDa MT1-MMP, but no free TIMP-2. These results indicate that components of the ternary MT1-MMP/TIMP-2/MMP-2 complex are coexpressed in the normal synovial lining and in its pathological extension on the hyaline articular cartilage. MMP-2 may participate in the remodeling of the normal lining and also seems to be localized/focalized to pannocytes at a site critical for tissue destruction in arthritis.
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PMID:New collagenolytic enzymes/cascade identified at the pannus-hard tissue junction in rheumatoid arthritis: destruction from above. 992 52

Treatment activists are circulating a letter opposing drug-pricing strategies for abacavir (Ziagen) and efavirenz (Sustiva). The groups are concerned that these drugs will be priced significantly higher than other nucleoside analogs and non-nucleoside reverse transcriptase inhibitors. The statement notes that higher survival rates should insure drug manufacturers of a steady supply of patients, allowing them to lower prices and still make a profit. Both drugs are appropriate for treatment-naive and treatment-experienced patients, making the potential market for them large. The letter is sponsored by the Fair Price Working Group, which includes members from Project Inform, ACT UP/New York, the San Francisco AIDS Foundation, GMHC Treatment Issues, Foundation for AIDS and Immune Research, and AIDS Treatment News. Contact information is included.
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PMID:New drug pricing consensus letter, sign-ons requested. 1136 62

An advisory committee of the Food and Drug Administration (FDA) has recommended accelerated approval for abacavir (ABC, Ziagen). The approval decision was not unanimous due to concerns of drug toxicity. Three percent of those taking the drug have developed severe allergic reactions, and at least eight people have died of complications related to the allergic reaction. Abacavir works by attacking the viral enzyme reverse transcriptase (RT), and it is related to other drugs such as AZT, 3TC, d4T, ddI, and ddC. Abacavir should be taken twice daily, in combination with other anti-HIV medications.
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PMID:Abacavir gets green light from FDA advisory board. Food and Drug Administration. 1136 24

Ribavirin (Rebetol) is Schering Corporation's newly approved drug. It is used in combination with interferon for treatment of chronic hepatitis C in patients whose compensated liver disease has not been treated or who have relapsed after interferon monotherapy. Results of clinical trials are summarized, and dosing options and side effects are detailed. Similar information is provided for abacavir (Ziagen), Glaxo-Wellcome's new nucleoside analog reverse transcriptase inhibitor (NRTI) that is used in combination therapy to treat HIV.
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PMID:Product information. 1136 50

Abacavir sulfate (Ziagen) received accelerated approval for treatment of HIV infection from the Food and Drug Administration (FDA). It is the fifteenth approved anti-HIV drug. Abacavir, manufactured by Glaxo Wellcome, is currently the most powerful of the nucleoside analogue reverse transcriptase inhibitors (NRTIs). Side effects include nausea, vomiting, fatigue, headache, and diarrhea. A serious hypersensitivity reaction occurs in approximately 5 percent of patients taking the drug. Patients who experience this reaction can never take the drug again, because subsequent reactions can be fatal. Drug interactions may be minimal, as abacavir is not metabolized by the same enzymes that metabolize several other anti-retrovirals. Resistance is also discussed and clinical data from studies are presented.
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PMID:Abacavir sulfate (Ziagen). 1136 89

Federal HIV treatment guidelines will soon include recommendations about selecting salvage therapy and will provide advice on understanding the increasingly complex science of cross-resistance and HIV mutations. The increasing number of HIV drugs makes selecting a salvage therapy more difficult. The guidelines will upgrade the nucleoside analog reverse transcriptase inhibitor abacavir (Ziagen) to an alternative treatment. In addition, hypersensitivity to abacavir and the differences in progression of HIV disease between women and men are described.
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PMID:Next HIV guidelines likely to include salvage therapy. 1136 17

Updated government guidelines for the treatment of HIV disease were published recently. Developed by 30 leading researchers, clinicians, and community advocates, "Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents" can help healthcare practitioners and patients in planning the course of HIV treatment. The new guidelines include a recommendation that abacavir (Ziagen), the newly approved nucleoside analog reverse transcriptase inhibitor, be listed as an alternative treatment, not a preferred one. The Guidelines also discuss the use of hydroxyurea. The internet address, where the full report can be found, is provided. Information is also provided for ordering a print copy of the guidelines or listening to a recording of discussion groups concerning the Guidelines.
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PMID:Updated HIV treatment guidelines available. 1136 62


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