Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Site-directed mutagenesis has been used to assess the importance of lysine 263 in substrate binding of human immunodeficiency virus-1 (HIV-1) reverse transcriptase. Previous studies have indicated that lysine 263 functions in the binding of 2'-deoxynucleoside 5'-triphosphate (dNTP) substrates (Basu, A., Tirumalai, R. S., and Modak, M. J. (1989) J. Biol. Chem. 264, 8746-8752). We studied this interaction directly by using site-specific mutagenesis to change lysine 263 to a serine. Highly purified mutant enzyme K263S bound natural dNTP substrates and primed polynucleic acid substrates with equal affinity when compared to the wild type reverse transcriptase. No difference was observed in the binding of 3'-azido-2',3'-dideoxythymidine 5'-triphosphate to the mutant reverse transcriptase on the basis of Km and Ki determinations. The serine substitution had no effect on RNase H activity. These results indicate that lysine 263 is not essential in the binding of substrates to HIV-1 reverse transcriptase.
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PMID:Biochemical analysis of human immunodeficiency virus-1 reverse transcriptase containing a mutation at position lysine 263. 767 98

A minimal kinetic mechanism for HIV reverse transcriptase (RT)-catalyzed RNA-dependent and DNA-dependent DNA polymerization was determined by pre-steady-state kinetic methods to be: [formula: see text] where E, TP, dNTP, and PPi are RT, template-primer, 2'-deoxynucleoside 5'-triphosphate, and inorganic pyrophosphate, respectively. Defined sequence template-primers that encode for incorporation of dTTP were prepared by annealing either a 44-mer RNA template or a 44-mer DNA template (of the same sequence) to a 21-mer DNA primer (r44:d21-mer and d44:d21-mer, respectively). The values of the above kinetic constants were determined for dTMP and 3'-azido-3'-deoxythymidine 5'-monophosphate (AZTMP) incorporation into both template primers. The kcat and Km values calculated from these kinetic constants were similar to the values directly determined from steady-state experiments. Further, the net rate constants for processive incorporation of three successive nucleotides into the r44:d21-mer were similar indicating that a rate-determining step did not follow catalysis. A 20-fold difference in the rate constants (kp) for incorporation of dTMP into the r44:d21-mer versus the d44:d21-mer was largely responsible for the difference in the calculated processivity numbers of 340 and 5, respectively. Finally, the rate constant for pyrophosphorolysis of the 3'-AZTMP-terminated r44:d21-mer (kpyro) was similar to the rate constant for dissociation of the chain-terminated template primer from the enzyme (koff) indicating that millimolar concentrations of intracellular inorganic pyrophosphate would be required for pyrophosphorolysis of AZTMP-terminated retroviral genomes.
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PMID:Human immunodeficiency virus reverse transcriptase. A kinetic analysis of RNA-dependent and DNA-dependent DNA polymerization. 768 54

During the early stages of human immunodeficiency virus (HIV) infection, although symptoms are absent and viral replication in peripheral blood mononuclear cells is low, substantial levels of HIV replication can be documented in lymphoid tissue [G. Pantaleo, C. Graziosi, J.F. Demarest, L. Butini, M. Montroni, C.H. Fox, J.M. Orenstein, D.P. Kotler, and A.S. Fauci, Nature (London) 362:355-358, 1993, and J. Embretsen, M. Zupancic, J.L. Ribas, A. Burke, P. Racz, K. Tenner-Tacz, and A.T. Haase, Nature (London) 362:359-362, 1993]. This observation suggests that earlier treatment of HIV infection may be indicated and that strategies for enhancing drug targeting to the lymphoid tissue reservoris of HIV infection may be beneficial. To address this issue, we synthesized dioleoylphosphatidyl-ddC (DOP-ddC) and dipalmitoylphosphatidyl-3'-azido-3'-deoxythymidine (DPP-AZT), phospholipid prodrugs which form lipid bilayers and which are readily incorporated into liposomes. The anti-HIV activity of DOP-ddC was similar to that of ddC in HIV type 1-infected HT4-6C cells, but DPP-AZT was considerably less active than AZT in HT4-6C cells. Liposomes containing DOP-[3H]ddC or DPP-[3H]AZT administered intraperitoneally to mice produced greater levels of total radioactivity over time in plasma, spleen, and lymphoid tissue relative to the results with [3H]ddC and [3H]AZT, respectively. DPP-AZT administered intraperitoneally in liposomes as a single daily dose to mice infected with Rauscher leukemia virus prevented increased spleen weight and reverse transcriptase levels in serum with a dose-response roughly comparable to that of AZT given continuously in the drinking water. DOP-ddC, DPP-AZT, and lipid conjugates of other antiretroviral nucleosides may provide higher levels of drug over time in plasma and in lymph nodes and spleen, important reservoirs of HIV infection, and may represent an interesting alternative approach to antiviral nucleoside treatment of AIDS.
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PMID:Phosphatidylazidothymidine and phosphatidyl-ddC: assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in Rauscher leukemia virus-infected mice. 769 64

With the increasing prevalence of HIV infection/AIDS and the extending range of care and treatment, the economic implications of the various prevention and control strategies, and of treatment, have become the subject of interest to policy-makers, public health specialists and health economists. This paper presents an overview of the methods used for the economic analysis of AIDS/HIV infection. It proposes an activity-oriented, cost center-based model for the costing of the economic impact of AIDS, using cost figures in Singapore since 1985, when the National AIDS Control Program was started. Priorities for future research are also identified.
Asia Pac J Public Health 1994
PMID:An economic analysis of AIDS--towards a proposed model of costing: a Singapore experience. 779 52

Seventeen asymptomatic HIV infected patients were studied for their phagocyte function in vitro, in comparison with that of eight normal healthy persons. Chemiluminescence was measured using whole blood by means of a microtitreplate luminometer. Light indices, cumulative light indices and rapidity of responses were recorded. The patients had a lower phagocyte count (13.17 +/- 0.85 x 10(9)/l) but a more rapid and intense chemiluminescence response. The latter was demonstrated by a higher peak light index and cumulative response. The observed enhanced phagocyte activity may reflect an early failure of T cell regulatory functions, or a compensatory mechanism in response to the underlying immunodeficiency.
Asian Pac J Allergy Immunol 1993 Dec
PMID:Enhanced phagocyte chemiluminescence in asymptomatic HIV infection. 791 5

During November 1993-October 1994 tuberculin skin test reactivity (PPD-Thai Red Cross: 0.1 ml of 10 IU) was determined among 399 asymptomatic HIV-1 positive subjects and 405 healthy volunteers, 10% (40/399) had PPD-TRC induration 0-2 mm compared with 4.2% (17/405) (p = 0.001) and 43.4% (173/399) had induration > or = 10 mm compared with 53.8% (218/405) (p = 0.003) of healthy volunteers. However, the percentage of the PPD-TRC induration 5-9 mm was similar among HIV-1 seropositive subjects and healthy volunteers as 37.6% (150/399) vs 34.8% (141/405) (p = 0.4). The mean PPD-TRC reaction of HIV-seropositive subjects were 6.4 +/- 0.9 mm vs. 11.0 +/- 0.5 mm among those with CD4 lymphocyte counts 200-299 cells/mm3 compared with those > or = 300 cells/mm3 (p < 0.001). We provide support for use of induration of > or = 5 mm of PPD-TRC skin reaction for evidence of latent infection with Mycobacterium tuberculosis as the CDC recommendation in asymptomatic HIV-seropositive subjects. Consideration of tuberculosis chemoprophylaxis should have benefit, particularly in areas where M.tuberculosis is highly prevalent such as Thailand. However, among HIV-1 seropositive carriers with negative tuberculin (PPD-TRC) skin tests, there needs to be a careful evaluation and follow-up for evidence of tuberculous infection.
Asian Pac J Allergy Immunol 1995 Dec
PMID:A comparative study of tuberculin skin test reactivity between asymptomatic HIV-1 seropositive subjects and healthy volunteers. 870 42

In this study, neutrophils isolated from asymptomatic HIV positive individuals, patients with AIDS-related complex (ARC), ARC patients receiving zidovudine (AZT) and full-blown AIDS patients were assayed for their opsonophagocytic and intracellular killing activities. Progressively decreasing opsonophagocytosis of C. albicans by neutrophils correlated with increasing severity of the disease in all groups of HIV infected individuals, as compared to neutrophils isolated from healthy controls. The intracellular killing of C. albicans by neutrophils of asymptomatic and ARC patients did not differ significantly from controls. Neutrophils of ARC patients receiving AZT and AIDS patients showed a slightly decreased killing activity in comparison to that of neutrophils from healthy controls.
Asian Pac J Allergy Immunol 1996 Jun
PMID:Opsonophagocytosis and intracellular killing activity of neutrophils in patients with human immunodeficiency virus infection. 898 Aug

Kaposi's sarcoma [KS] is rare in Asian countries. Since the AIDS epidemic, KS has become the most common AIDS-related cancer reported in the international literature. Up to March 1996, 4 cases of AIDS-associated KS were histologically documented at the registry at the Maharaj Nakorn Chiang Mai University Hospital, comprising 2 adult and 2 pediatric male patients. Routes of HIV exposure included intravenous injection and heterosexual contact in adult cases, and perinatal transmission and blood transfusion in the pediatric ones. KS was present as an AIDS diagnostic condition in one of the adults and in both children. In our institution, KS was second in frequency to malignant lymphoma among AIDS patients. Predomination of non-homosexual transmission of HIV infection in this region was probably a factor associated with the rarity of AIDS-associated KS.
Asian Pac J Allergy Immunol 1996 Dec
PMID:AIDS--associated Kaposi's sarcoma: a rare entity at Maharaj Nakorn Chiang Mai Hospital. 917 25

Previous molecular epidemiological studies show that at least 2 subtypes of HIV-1 circulate in Thailand. HIV-1 subtype B or Thai genotype B was associated with an early epidemic and was prevalent in intravenous drug users. Meanwhile, HIV-1 subtype E or Thai genotype A was becoming widespread among heterosexuals. We studied the HIV subtypes of 161 HIV-1 seropositive pregnant women. Of these, 143 pregnant patients (88.8%) tested positive for subtype E alone and 8 women (5.0%) had evidence of infection with subtype B alone. There was serologic evidence of infection with a mixture of subtypes in 7 women while the infecting subtype could not be identified in the remaining 3 women. This result agrees with previous information that subtype E predominates in Thai heterosexuals.
Asian Pac J Allergy Immunol 1996 Dec
PMID:V3 peptide enzyme immunoassay for serotyping HIV-1 infected pregnant Thais. 917 26

The seropositive and latency rates of HHV6 among IVDU with positive and negative HIV and control group were demonstrated. By immunofluorescent antibody test, no differences in the seropositive rates were found among these three groups. All groups had seropositive rate at the average 89% and GMT antibody 1:26. This meant that most of them had previous infection with HHV6. In addition, HHV6-DNA was determined and classified into subgroups: HHV6A and HHV6B, by polymerase chain reaction. The prevalence of HHV6-DNA indicated HHV6 latency in vivo. High latency rate of HHV6 was found in all three groups (the average 54%). Moreover, HHV6B (49%) had a higher frequency than HHV6A (5%); HHV6a was found only in IVDU with or without HIV infection. The result suggested that the HHV6 latency in IVDU with positive HIV may possibly transactivate HIV. The pathogenesis of HHV6 in AIDS patients should be further investigated. However, this research finding is useful for treatment, health care, prevention and control of AIDS in case of dual infections and latency of herpesvirus infection in AIDS.
Asian Pac J Allergy Immunol 1997 Mar
PMID:The latency rate of human herpesvirus 6 (HHV6) in positive and negative human immunodeficiency virus (HIV) infection of intravenous drug users (IVDU). 925 45


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