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

The pharmacokinetics of oral administration of R 82913, or tetrahydroimidazol [4,5,1-jk]-benzodiazepin-2(1H)-one or -thione (TIBO), was compared with those of intravenous administration in five AIDS patients. TIBO was administered as a single daily 1-h infusion of 100 mg for 29 days and orally as a single daily dose for 14 days with three consecutive regimens of 100, 200, and 100 mg with probenecid (1 g) daily. Each cycle was followed by a wash-out period. Oral bioavailability of TIBO appears to be low and is not improved by the adjunction of probenecid. Trough levels obtained with oral administration systematically remained far below the 90% inhibitory concentration of TIBO against human immunodeficiency virus type 1 (HIV-1). Tolerance of TIBO was excellent. No clinical efficacy could be demonstrated. p24 antigenemia decreased significantly in one patient under intravenous therapy. TIBO derivatives are promising anti-HIV-1 agents in vitro, but improvement of oral bioavailability is needed before implementation of long-term efficacy and tolerability studies. Moreover, rapid emergence of resistance, which has been recently documented, constitutes a major problem with most nonnucleoside reverse transcriptase inhibitors.
...
PMID:Pharmacokinetics of R 82913 in AIDS patients: a phase I dose-finding study of oral administration compared with intravenous infusion. 148 34

HTLV-I is associated with a neurological syndrome designated Tropical Spastic Paraparesis/HTLV-I associated myelopathy (TSP/HAM). To determine whether HTLV-I can replicate in human primary macrophages and thus contribute to HTLV-I dissemination in the nervous system, elutriated human macrophages were infected cell-free with the HTLV-ICR and HTLV-IBOU isolates from patients with adult T-cell leukemia and TSP/HAM, respectively. Viral production was monitored by measuring the viral p24 gag antigen in the cell culture supernatant, by electron microscopy (EM) and by polymerase chain reaction (PCR) on viral DNA and RNA. The HTLV-I p24 gag antigen was detected 21 days after infection with either isolate, and the presence of mature viral particles was demonstrated by electron microscopy one month after infection. Viral sequences were amplified by PCR analysis of the infected macrophages' DNA. Spliced mRNAs for the p40tax and p27rex proteins, as well as the p12I, and p30II proteins encoded by the pX region were readily identified by reverse transcriptase PCR. Altogether, these data indicate that HTLV-I replication occurs in vitro in primary human macrophages. Whether macrophage infection occurs also in vivo and is a crucial step in the induction of the neurological manifestations observed in TSP/HAM remains an open question.
...
PMID:In vitro infection of human macrophages by human T-cell leukemia/lymphotropic virus type I (HTLV-I). 148 73

Researchers conducted hematologic tests on 66 HIV-1 positive adults from Ethiopia and compared the results with those of 137 HIV-1 patients in Stockholm, Sweden, to determine the incidence of cell-free viremia, free or complexed p24 antigen, and p24 antibody levels. They isolated HIV-1 from peripheral blood mononuclear cells in 95% and from plasma in 81% of the Ethiopian subjects. The corresponding percentages for the Swedish subjects were 95% and 92%. They found p24 antigen in only 5% of AIDS patients from Ethiopia (none for asymptomatic HIV-1 subjects) compared with 76% of Swedish patients (p .01). The Ethiopian subjects had significantly higher p24 antibody levels than did the Swedish subjects (85% vs. 52%; p = .008). The ratio between reverse transcriptase activity and p24 antigen concentration stood much higher in the Ethiopians than in the Swedes (7.5 vs. 3.6; p = .0019). These results suggested that the HIV-1 strains in the Ethiopian subjects resembled rapid high HIV-1 strains. In addition, the high degrees of cell-free viremia, relative lack of free or immune complexed p24 antigen, and a persistence of p24 antibody during the entire course of infection in Ethiopian HIV-1 infected subjects intimated that the interaction between HIV-1 and the Ethiopians may be different in Africa than it is in Europe and North America. The results of another study conducted by the researchers supported this conclusion. They included high levels of tumor necrosis factor-alpha and neopterin and low levels of interferon-alpha in HIV-1 positive Ethiopians.
...
PMID:Relationship between cell-free viraemia, antigenaemia and antibody levels in HIV-1-infected Ethiopian patients. 150 84

An HIV-1/ATH8-cell cytopathic system was used to characterize the previously reported anti-HIV-1 activity of human saliva. Inhibitory activity was demonstrated by monitoring viable cell counts, HIV-1 p24 core antigen, and reverse transcriptase levels. Nonfiltered whole saliva, sterilized by irradiation, protected the ATH8 cells from HIV-1 infection. When HIV-1/saliva mixtures were filtered following incubation, the quantity of virus was significantly less (approximately 50%) than in HIV-1/media-filtered controls, suggesting that salivary aggregation and/or agglutination may be involved in the inhibitory activity. However, a sufficient number of apparently morphologically intact viral particles were still present in the HIV-1/saliva filtrates to lead to infection. When saliva was filtered prior to incubation with HIV-1, these filtrates showed substantial inhibitory activity, although reduced compared with that of non-prefiltered saliva. We conclude that saliva likely has several means by which to inhibit HIV-1 infectivity.
...
PMID:Further studies of salivary inhibition of HIV-1 infectivity. 151 90

To better assess the antiviral effect of zidovudine (ZDV) in vivo and understand its limitations, we have studied human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cell (PBMC) cultures from 25 ZDV-treated patients and 20 untreated controls. Three months after initiation of therapy, 9 of the 25 treated cases became negative for HIV isolation (36%). Untreated cases never converted to a negative culture. In patients treated by ZDV and who remained culture positive, the kinetics of HIV replication in PBMC culture was found to vary with time. A statistically significant delay in the production of HIV in PBMC cultures from treated cases could be demonstrated after 3 months of ZDV therapy, when compared with untreated patients. By contrast, in such untreated patients the time required to reach the peak of reverse transcriptase activity in culture decreased during the follow-up period. These changes of in vitro HIV replication kinetics as well as the change to negative culture during ZDV therapy probably reflected the reduction of the number of infected cells in vivo. These results as well as the decrease of p24 antigenemia do indicate that ZDV indeed inhibits HIV replication in vivo. However, the effect of ZDV on HIV replication kinetics in PBMC fails to reach significance at 6 months, suggesting that the antiviral effect of ZDV may decrease over time. Our results suggest that ZDV is most effective when the intensity of HIV replication in vivo is still low.
...
PMID:HIV detection in culture of peripheral blood mononuclear cells: a relevant in vitro correlate of the antiviral effect of ZDV in vivo. 151 68

Two T-cell lines were established from peripheral blood mononuclear cells of two Moroccan patients with tropical spastic paraparesis and then named PR52 and PR144. The two cell lines showed a T lineage of activated CD4+ with high density of Tac+ (IL2 receptor). No expression of CD8 was observed. The virus particles were detected by reverse transcriptase activity and the viral antigens were also detected by immunofluorescence (IF) and Western blot. After six months of culture greater than 90% of the cells exhibited HTLVI antigen by IF. Lysate virus particles on Western blot analysis revealed p19,p24, and p53 gag protein similar to those detected in C91/PL virus particles from an adult T-cell leukemia (ATL) patient. gp46 and gp61 were also weakly detected. These two T-cell lines established will serve as substrate for further comparative studies on TSP and ATL isolates.
...
PMID:Establishment of T-lymphoid cell lines from Morroccan patients with tropical spastic paraparesis. 152 May 34

Glutathione (GSH), its derivatives and N-acetylcysteine (NAC) inhibit the induction of HIV-1 expression in a chronically HIV-1-infected promonocytic cell line (U1/HIV) and peripheral blood mononuclear cells (PBMC). We have examined the effects of GSH and NAC on HIV-1 replication in human primary monocyte/macrophages cultured in vitro. Ficoll-gradient purified human monocytes were cultivated in vitro for 7-10 days and then infected with HIV-1 (Bal and Ada-M). Infection was blocked or substantially reduced by GSH or NAC (5-20 mM). Significant reduction (greater than or equal to 90%) in the amount of virus released, as determined by measuring supernatant reverse transcriptase activity and secreted p24 protein, was obtained when the cells were treated for 4 h with greater than or equal to 10 mM of GSH or NAC. The inhibitory effects of GSH and NAC were concentration dependent. This anti-HIV-1 effect persisted in these cultures for at least 35 days without evidence of significant increase in HIV-1 expression. Thus, a single pulse exposure of HIV-1-infected monocyte/macrophages with GSH or NAC led to a sustained, concentration-dependent decrease in HIV-1 p24 antigen levels, as well as, reverse transcriptase activity without producing detectable cellular toxicity in monocyte/macrophages.
...
PMID:Glutathione and N-acetylcysteine suppression of human immunodeficiency virus replication in human monocyte/macrophages in vitro. 152 May 37

The gag-pol coding region of the HIV-2BEN genome was expressed in CV-1 cells infected with four recombinant vaccinia viruses (VV). These recombinant VV encoded either the whole gag-pol region or the gag gene including the protease-coding region of the pol gene or the gag gene truncated at its 3'-end or only the pol gene. The HIV-2BEN gag precursor p55, its mature cleavage products p24 and p17 as well as the pol reverse transcriptase (RT) p66 were detected in VV-infected CV-1 cells. The p55 and two intermediate cleavage products p40 and p35 were myristilated. Comparison to lysates of permanently HIV-2BEN-infected Molt 4 clone 8 cells revealed that several additional gag and pol proteins were present in the VV-infected CV-1 cells. Deletion of the gag and pol overlapping region coding for the viral protease prevented cleavage of the recombinant gag precursor. Electron microscopy of VV-infected CV-1 cells revealed budding structures and immature as well as mature retroviral particles formed by the recombinant gag proteins. Striking differences in the ability to form complete particles were observed between the different recombinant VV. Expression of the truncated gag gene led to the formation of budding structures, but completely budded circular particles were not detectable. Such particles were produced by expression of the whole gag gene and the protease. Mature virions with an internal core structure were only detected in VVgagpol-infected cells. From these findings we conclude that the 3'-end of the gag gene coding for the p16 protein is essential for the formation of complete HIV-2 particles and that the pol proteins support the assembly of the viral core.
...
PMID:Morphogenesis of recombinant HIV-2 gag core particles. 152 43

Fresh urine pellets from human immunodeficiency virus type 1 (HIV-1)-seropositive individuals were examined for the presence of the HIV-1 genomic sequence and gene products. By using the polymerase chain reaction technique, HIV-1 DNA proviral sequences were detected in 53 of 80 (66.25%) fresh urine pellets from HIV-1-seropositive individuals, while urine pellets from all 24 healthy heterosexual controls were negative. HIV-1 RNA in urine pellets was detected by reverse transcriptase polymerase chain reaction in 2 of 43 (4.7%) HIV-1-seropositive individuals. In addition, HIV-1 p24 core antigen was demonstrated in 3 of 80 urine pellets from HIV-1-seropositive individuals by enzyme-linked immunosorbent assay. Moreover, HIV-1 p24 core antigen and HIV-1 RNA were shown in the cellular component of urine pellets from HIV-1-seropositive individuals by immunohistochemical staining and in situ hybridization. These results indicate that HIV-1 can be present in urine pellets from HIV-1-infected individuals.
...
PMID:Detection of human immunodeficiency virus type 1 (HIV-1) in urine cell pellets from HIV-1-seropositive individuals. 158

Recent findings have indicated that megakaryocytes may be susceptible to human immunodeficiency virus (HIV) infection, suggesting a potential role for megakaryocytes as viral reservoirs in HIV-infected patients. We report that the megakaryocytic cell line Dami could be productively infected with the HTLV III-B strain of HIV-1, in 26 different experiments (results of 16 experiments are reported); productive infection lasted up to 30 weeks. Despite a lack of detectable surface expression of the CD4 molecule and very low levels of CD4 mRNA, between 40% and 60% of megakaryocytic cells produced viral proteins after contact with HIV-1. Neither cytopathogenic effects nor syncytial formation was observed. Production of high levels of functional viral particles was indicated by analysis of p24 protein levels, reverse transcriptase activity, ultrastructural studies, and the capacity of supernatants from infected Dami cells to infect the Molt-4 T-lymphocytic cell line. HIV-1 RNA and protein levels in infected Dami cells were enhanced by treatment with tumor necrosis factor-alpha (TNF-alpha), and decreased by treatment with interferon-alpha (IFN-alpha) and IFN-gamma. Transient transfection of the megakaryocytic cells with various constructs of the HIV-1 promoter (LTR) linked to the luciferase reporter gene suggested that the effect of TNF-alpha was related, as in monocytic and T-cell lines, to transactivation of the enhancer region of the HIV-1 LTR. These findings indicate that signals provided by the immune system may modulate HIV-1 expression in cells of the megakaryocytic lineage.
...
PMID:Productive human immunodeficiency virus-1 infection of megakaryocytic cells is enhanced by tumor necrosis factor-alpha. 158 16


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

---