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

---

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

A model of vertical HIV transmission was developed using oral HIV-2(287) exposure of newborn Macaca nemestrina. The minimal Animal Infectious Dose for this oral route was found to be 10-fold higher than that for atraumatic viral transmission across other mucosal membranes (vaginal/rectal) of juvenile macaques. However, once infection was established, viral replication was rapid and plasma viremia could be detected by reverse-transcriptase polymerase chain reaction and viral co-culture within 1 week following exposure. No animal was resistant to infection and all macaques initially exposed to a subinfectious viral inoculum were subsequently infected by re-exposure of mucosal membranes. Higher viral load during primary infection correlated with a more rapid CD4 depletion; however, all HIV-2(287)-infected animals developed CD4 depletion during the observation period. This animal model can now be used to study early viral replication in the presence and absence of anti-retroviral agents to help identify conditions to reduce vertical HIV transmission in human newborns.
...
PMID:Viral dynamics of early HIV infection in neonatal macaques after oral exposure to HIV-2287: an animal model with implications for maternal-neonatal HIV transmission. 1207 46

The safety and efficacy of hydroxyurea with didanosine in combination with stavudine in nucleoside reverse-transcriptase inhibitor (NRTI)-experienced patients was investigated. Entry criteria included HIV-1 infected, NRTI-experienced adults, with CD4(+) counts 50-550 cells/mm(3) and viral loads >or=12,500 copies/mL. Subjects were treated with didanosine 200 mg twice a day (BID), stavudine 40 mg BID, and hydroxyurea 1000 mg daily for 16 weeks. Thirty-one HIV-1 subjects with mean bDNA viral load 1x10(5) log(10) copies/mL and mean CD4(+) T-cell counts of 231 cells/mm(3) were enrolled. A 1.3 log(10) decrease in mean viral load was seen at 12 weeks of therapy. Prior didanosine use resulted in a more rapid response to therapy compared with prior zidovudine use. Side effects consisting of neutropenia, pancreatitis, and peripheral neuropathy occurred in four subjects and resolved upon withdrawal of therapy. This non-randomized study in subjects with a mean CD4(+) T-cell count of 230 cells/mm(3) demonstrates the antiviral activity of hydroxyurea+didanosine and stavudine. Toxicities related to therapy need to be followed closely. The results support the need for a randomized, prospective study to determine the safety and efficacy of hydroxyurea plus didanosine in antiretroviral-experienced patients with CD4(+) cell counts below 300 cells/mm(3).
...
PMID:Hydroxyurea in combination with didanosine and stavudine in antiretroviral-experienced HIV-infected subjects with a review of the literature. 1280 44

This study was designed to examine the relationship between untimed antiretroviral concentrations measured in plasma samples collected for virus-load testing and response to highly active antiretroviral therapy. Plasma nonnucleoside reverse-transcriptase-inhibitor and protease-inhibitor concentrations were retrospectively measured in all virus-load plasma samples collected during the first year of therapy, for 122 patients in British Columbia, Canada, who initiated therapy between August 1996 and September 1999 and who had CD4 counts <50 cells/micro L. Drug levels were designated a priori as "low" if the concentrations were below the published Ctrough-SD. A single low drug level measured shortly after initiation of therapy (median, 6 weeks) is common (30%) and is predictive of both more-rapid immunological failure (P=.06) and failure to achieve virologic success during the first year of therapy (P=.01). These results may reflect incomplete adherence, since a strong association (P<.001) was found between low drug levels and an imperfect prescription-refill record (<95%).
...
PMID:Antiretroviral concentrations in untimed plasma samples predict therapy outcome in a population with advanced disease. 1289 41

We evaluated the efficacy of a 5-drug salvage regimen, preceded by a 12-week, structured treatment interruption (STI), in 46 multidrug-treated, human immunodeficiency virus type 1-infected patients with detectable viremia. Patients were randomly assigned to receive a 5-drug salvage regimen immediately (noninterruption [NI] group; n=24 patients) or after 12 weeks of STI (interruption [I] group; n=22 patients). At week 48, 45% of patients in the I group and 46% of patients in the NI group had virus loads <50 HIV-1 RNA copies/mL (P=.619). No differences in CD4 cell counts were seen between groups at week 48 (P=.734). A complete reversion to wild-type genotype was detected in 35% of patients in the I group, but this phenomenon did not affect the virological response. The only overall baseline factor associated with ensuing virus suppression was a lower number of nucleoside reverse-transcriptase inhibitor-resistant mutations (relative risk, 0.66; 95% confidence interval, 0.47-0.93; P=.021). A prior STI seems to confer no additional benefit to subsequent virological or immunological outcomes of a salvage regimen.
...
PMID:Role of structured treatment interruption before a 5-drug salvage antiretroviral regimen: the Retrogene Study. 1451 17

We compared immune restoration in patients who suppressed human immunodeficiency virus type 1 replication after treatment with a protease inhibitor (PI) plus nevirapine or with 3 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine. Changes in total and memory CD4 and CD8 cells were similar in the groups, as were decreases in immune activation (e.g., CD38 and HLA-DR) and increases in CD28 expression. Increases in naive CD4 and CD8 cells tended to be greater in the NRTI-treated group, with differences in naive CD4 cells significant at weeks 8 and 12 (P<.05) but not at week 48. Lymphocyte apoptosis decreased in both groups, but the week-1 decrease was greater in the PI-treated group (P<.02). Lymphocyte proliferation and skin-test responses were comparable. We find little evidence for differences in the major direct immunologic effect of PI versus NRTI regimens and propose that effects observed elsewhere were indirect, mediated through antiviral activity or adaptation of the virus to selection pressure.
...
PMID:Immune reconstitution is comparable in antiretroviral-naive subjects after 1 year of successful therapy with a nucleoside reverse-transcriptase inhibitor- or protease inhibitor-containing antiretroviral regimen. 1462 69

The prevalence of transmitted resistance to antiretroviral drugs varies geographically, with little known about this effect in Asia. In Korea, zidovudine has been widely administered, without charge, through the National AIDS program since the early 1990s; with other potent antiretroviral agents also being introduced in the late 1990s. An analysis of the drug susceptibility to antiretroviral drugs was performed by genotyping of the drug-resistant mutations in HIV on plasma samples from 50 HIV-infected patients who had received no treatment, between February 1998 and November 2002, which was interpreted according to the consensus guidelines of the International AIDS Society-USA panel. The median CD4 cell count was 100 cells/mm3; the mean plasma RNA level was (5.19 +/- 0.56) log copies per milliliter. Of the 50 subjects tested 4 (8.0%) had one or more major drug-resistance mutation. The prevalence of resistance to multiple classes of drugs was 2.0%. No mutations, associated with resistance to non nucleoside reverse transcriptase inhibitors, were identified. Resistant mutations of the reverse-transcriptase gene were found at codons 67, 70, 118, 215, and 219, and a resistant mutation of the protease gene was found only at codon 46 (2.6%, 1 of 39). There was an 8.0% prevalence of primary drug resistance to antiretroviral drugs in Korean patients infected with HIV-1.
...
PMID:Genotypic resistance of antiretroviral drugs among drug-naive HIV type 1 patients with the background of long-term access-easy zidovudine therapy. 1468 24

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop systemic lupus erythematosus (SLE)-like disease. The natural history of the pulmonary involvement and the underlying mechanism of leukocyte infiltration into the lungs of MRL/lpr mice and SLE patients remains elusive. We aimed to investigate the expression profiles of chemokines and chemokine receptors in the lung of the SLE-prone mouse. We examined the correlation between lung inflammation and expression of IP-10 (interferon-gamma-inducible protein 10), a CXC chemokine, and TARC (thymus- and activation-regulated chemokine), a CC chemokine, in MRL/lpr mice, MRL/Mp-+/+ (MRL/+) mice, and C57BL/6 (B6) control mice. The extent of cell infiltration in the lung was assessed histopathologically. Reverse transcriptase PCR showed up-regulation of IP-10 mRNA expression in the lungs (P < 0.05) of MRL/lpr mice, in comparison with MRL/+ or B6 mice. The increase paralleled increased expression of a specific IP-10 receptor, CXCR3, and correlated with the degree of infiltration of mononuclear lymphocytes. In contrast, lung expression of TARC and its specific receptor, CCR4, were suppressed in MRL/lpr mice. Immunohistology showed that macrophage-like cells were the likely source of IP-10. Flow cytometric analyses revealed that the CXCR3-expressing cells were mainly infiltrating CD4 T cells and macrophages, which correlated with the degree of mononuclear lymphocyte infiltration. Recent data suggest that Th1 cells and Th1-derived cytokines play an important role in the development of SLE-like disease in MRL/lpr mice. Our results suggest that IP-10 expression in the lung is involved, through CXCR3, in the pathogenesis of pulmonary inflammation associated with migration of Th1 cells.
...
PMID:Enhanced expression of interferon-inducible protein 10 associated with Th1 profiles of chemokine receptor in autoimmune pulmonary inflammation of MRL/lpr mice. 1497 41

The C terminus of the human immunodeficiency virus type 1 (HIV-1) accessory protein vpr acts in viral cell cycle arrest, nuclear localization, and apoptosis. Polymorphisms in this region are described in series of long-term nonprogression cases. We determined vpr sequences of archived baseline specimens from 96 participants in a historical trial of single- versus double-nucleoside reverse-transcriptase inhibitors. These sequences were then analyzed by study-entry and -outcome characteristics such as baseline absolute CD4(+) T cell count, prior treatment, CD4(+) T cell response, and clinical endpoints. Frequency of C-terminal mutations did not correlate to any measures of disease intensity. Changes in that portion of vpr did not attenuate disease.
...
PMID:Alterations in the C-terminal region of the HIV-1 accessory gene vpr do not confer clinical advantage to subjects receiving nucleoside antiretroviral therapy. 1518 64

The aim of the present study was to evaluate the impact of highly active antiretroviral therapy (HAART) on HIV viral load of plasma and intraocular fluids in AIDS patients with ophthalmic opportunistic infections. We further compared the treatment effect of HAART on these patients. From June 1997 to July 2003, we examined and followed up the ophthalmic conditions of 49 patients receiving HAART with ophthalmic diseases during this period. The method of reverse-transcriptase polymerase chain reaction was used to detect and monitor HIV load in plasma and/or aqueous humor of AIDS patients. Before HAART, the HIV levels in the plasma and aqueous humor in 8 AIDS patients with ophthalmic opportunistic infections were significantly higher than those in 6 patients with HIV-related retinopathy (p < 0.05). Compared to the eye findings and clinical improvement, HIV loads of aqueous humor in 10 of 14 AIDS patients (6 with HIV-related retinopathy, 5 with cytomegalovirus retinitis, 2 with toxoplasmic retinitis and 1 with cryptococcal chorioretinitis) declined to undetectable levels (< 400 copies/ml) after 4-8 months of HAART. HIV virus levels in the plasma of AIDS patients were significantly decreased, and the CD4 counts of these patients were significantly increased (Wilcoxon test) after initiation of HAART.
...
PMID:The HIV RNA Levels of Plasma and Ocular Fluids in AIDS Patients with Ophthalmic Infections. 1533 14

Intrathymic (IT) delivery of donor alloantigen is a potent strategy to induce operational tolerance. In this study we determined whether this effect was dependent on direct allorecognition of the tolerogen. Ten microgrammes of plasmid, encoding either the wildtype major histocompatibility complex (MHC) class I molecule K(b) or a truncated form in which the signal sequence for translocation into the endoplasmic reticulum was deleted, preventing cell surface expression and direct allorecognition of the tolerogen, was administered intrathymically to CBA.Ca (H2(k)) recipients. In addition, recipients were treated with anti-CD4 antibody (YTA3.1) at the time of IT injection and underwent transplantation 28 days later with a fully mismatched C57BL/10 (H2(b)) cardiac allograft. Wildtype, as well as truncated K(b) genes, were able to induce long-term survival of the cardiac allografts, in contrast to empty control plasmid. Reverse-transcriptase PCR showed expression of the K(b) genes for up to 28 days in thymus and spleen of pretreated recipients. These data show that direct allorecognition of the tolerogen was not required for the induction of long-term allograft survival following the introduction of plasmid-encoded MHC alloantigen into the thymus.
...
PMID:Intrathymic delivery of plasmid-encoding endoplasmic reticulum signal-sequence-deleted MHC class I alloantigen can induce long-term allograft survival. 1537 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---