Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acquired immunodeficiency syndrome (AIDS) was first detected in Costa Rica in 1983. For four years most known cases were in hemophiliac men. Thereafter, AIDS in homosexual and bisexual men predominated. By December 31 of 1993, 563 persons had been diagnosed with the syndrome, 71% of them homosexual and bisexual men, 10% heterosexual men and women, 6% hemophiliacs, 2% intravenous drug abusers (IVDA's), 2% women and men who had blood transfusions, 1.4% infants born to HIV-infected mothers and 7% unknown. The epidemics in homosexual/bisexual men and in heterosexual women and men are rising; cases in infants and in persons who received blood or coagulation factors, are stagnant. The steady increase in AIDS among women is linked to exposure to bisexual partners. The moderate nature of the national epidemic reflects, in part, the low incidence of IVDA, the universal screening of blood donors for antibodies to the human immunodeficiency virus (HIV) since 1985, and the prompt banning of unsafe coagulation factors. The projection of AIDS for the year 2000 is 2,304 cases (606 accumulated incidence per million inhabitants). A national educational campaign, radio and television programs and other preventive actions, apparently did not influence the rate of receptive anal intercourse without condom (about 80%) during 9 years of the epidemic. Persons with HIV/AIDS often are deprived of social and medical benefits or are subjected to harassment and exploitation by the health sector. More efficient prevention must target children, adolescents and adults in reproductive age, to promote safer lifestyles, through education and counseling effected through primary health care.
Cell Mol Biol (Noisy-le-grand) 1995
PMID:HIV/AIDS in Costa Rica: epidemiological and sociological features, 1993. 857 48

Since the discovery of human immunodeficiency retrovirus, the drug arsenal against retrovirus has rapidly increased. Concomitantly, new challenges in the therapy of acquired immune deficiency syndrome have arisen, including drug toxicities, drug resistance, and the development of various cancers as effective therapies prolong survival. Tamoxifen, a nonsteroidal antiestrogen with a low incidence of side effects, is widely used in cancer therapy; it is known to exert pleiotropic activities by binding essentially to the estrogen receptor and other unidentified proteins. In the present work, quantification of the p24 core protein of human immunodeficiency virus 1 produced by infected lymphocytes shows an inhibitory effect of tamoxifen on virion production. Moreover, we assume that this effect is not mediated by the estrogen receptor because antiestrogen ligands interacting with the antiestrogen-binding site exhibit efficacy related to their affinity for this site, although specific antiestrogens of the estrogen receptor are ineffective.
Mol Pharmacol 1996 Jul
PMID:Ligands of the antiestrogen-binding site are able to inhibit virion production of human immunodeficiency virus 1-infected lymphocytes. 870 Jan 22

Expression screening in Xenopus oocytes has been used to isolate a cDNA from rat jejunal epithelium encoding an intestinal/kidney Na(+)-dependent nucleoside transporter protein named rCNT1 [J. Biol. Chem. 269:17757-17760 (1994)]. rCNT1 is predicted to have 648 amino acid residues (relative molecular mass, 71,000) with 14 potential transmembrane domains and belongs to a new family of transporter proteins. Recombinant rCNT1 transports physiological pyrimidine nucleosides and adenosine. In the current investigation, functional expression in Xenopus oocytes was used to determine whether recombinant rCNT1 also transports antiviral pyrimidine nucleoside analogs. The recombinant protein mediated Na(+)-dependent transport of both 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). Apparent K(m) values of '0.5 mM were obtained for both [3H]AZT and [3H]ddC influx compared with 37 microM for [3H]uridine influx, with Vmax/Km ratios of 0.048, 0.039, and 0.57 for AZT, ddC, and uridine, respectively. Extracellular AZT and ddC stimulated rCNT1-mediated efflux of [3H]uridine from preloaded oocytes. These experiments provide direct evidence for Na(+)-dependent transport of AZT and ddC and suggest that members of the cNT family may be involved in the intestinal absorption and renal handling of pyrimidine nucleoside analogs used to treat acquired immune deficiency syndrome.
Mol Pharmacol 1996 Aug
PMID:Transport of the antiviral nucleoside analogs 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine by a recombinant nucleoside transporter (rCNT) expressed in Xenopus laevis oocytes. 870 Jan 47

Vpr is a virion-associated protein of human immunodeficiency virus type 1 (HIV-1) whose function in acquired immune deficiency syndrome (AIDS) has been uncertain. We previously employed yeast as a model to examine the effects of Vpr on basic cellular functions; intracellular Vpr was shown to cause cell-growth arrest and structural defects, and these effects were caused by a region of Vpr containing the sequence HFRIGCRHSRIG. Here we show that peptides containing the H(S/F)RIG amino acid sequence motif cause death when added externally to a variety of yeast including Saccharomyces cerevisiae, Kluyveromyces lactis, Candida glabrata, Candida albicans and Schizosaccharomyces pombe. Such peptides rapidly entered the cell from the time of addition, resulting in cell death. Elevated levels of ions, particularly magnesium and calcium ions, abrogated the cytotoxic effect by preventing the Vpr peptides from entering the cells. Extracellular Vpr found in the serum, or breakdown products of extracellular Vpr, may have similar effects to the Vpr peptides described here and could explain the death of uninfected bystander cells during AIDS.
Mol Microbiol 1996 Mar
PMID:Extracellular addition of a domain of HIV-1 Vpr containing the amino acid sequence motif H(S/F)RIG causes cell membrane permeabilization and death. 873 Aug 61

Acyclovir is an effective drug for the treatment of HSV and VZV infections, which after phosphorylation to the triphosphate, inhibits viral DNA polymerase. Acyclovir has low oral bioavailability, therefore prodrugs have been developed, and the L-valyl ester, valaciclovir, recently has been licensed for the treatment of shingles. Ganciclovir is used against CMV, and famciclovir, a lipophilic prodrug of penciclovir, is marketed for shingles. The acyclic nucleoside phosphonates are active against thymidine kinase-resistant viral strains. Promising analogs are PMEA (in clinical trial for the treatment of AIDS) and (S)-HPMPC (good in vivo activity against HSV, VZV, CMV, and EBV). Oligonucleotides incorporating acyclic nucleosides at the 3'-and 5'-ends, or constituted of amino acyclic nucleosides, are resistant to cleavage by nucleases and may be useful in antisense and/or antigene therapy. HEPT is active against HIV-1: It binds in a hydrophic pocket on reverse transcriptase, rather than in the polymerase active site. Some acyclic nucleosides are potent inhibitors of purine and pyrimidine nucleoside phosphorylase. These compounds may have a therapeutic niche in combination therapy with antiviral and anticancer nucleosides, and in the treatment of diseases involving the T-cell.
Mol Biotechnol 1996 Apr
PMID:Acyclic nucleosides as antiviral compounds. 873 25

AZT is widely used in combination with other potentially myelotoxic drugs. Bone marrow suppression may limit the vigor of therapy directed at HIV itself, opportunistic infections, and/or AIDS-associated malignancies. Evidence from an HL60 model suggests that toxicity is of most concern with simultaneous use of multiple agents, and that staggered use of different agents may in some cases be a more effective strategy.
Res Commun Mol Pathol Pharmacol 1995 Dec
PMID:AZT modulation of trimetrexate myelotoxicity: evidence from an HL60 model. 874 86

Cryptococcus neoformans is an encapsulated fungus that causes a life-threatening meningoencephalitis in patients with AIDS. Monoclonal antibodies to the capsular glucuronoxylomannan can modulate the infection in mice, but the epitopes on this complex polysaccharide recognized by protective and non-protective antibodies have not been defined. We have used 2H1, one of our most protective antibodies, to screen phage display peptide libraries for peptide mimotopes that would allow us to explore the fine specificity of anti-cryptococcal polysaccharide antibodies. Hexa- and decapeptides have been identified with sequence homologies that define four motifs: 1, (E)TPXWM/LM/L; 2, W/YXWM/ LYE; 3, DWXDW; and 4, (Ar)WDGQ(Ar). Peptides representing these motifs compete with each other for a shared binding site that overlaps the polysaccharide binding site. Motifs 1 and 2 confer high affinity binding, and PA1, which displays a motif 1 peptide with the sequence LQYTPSWMLV, binds to 2H1 with a Kd of 295 nM. Analysis of the interaction between the 2H1 binding peptides and 24 structurally related anti-polysaccharide antibodies reveals a complex pattern of reactivity that strongly suggests binding to or close to the complementary determining regions. Furthermore, those antibodies that have been shown to have different specificity, and in some cases different protective potential, do not bind any of the peptides selected by the protective 2H1 antibody. This study shows that peptide mimotopes for a complex microbial polysaccharide can be identified by screening phage peptide libraries and demonstrates the usefulness of such peptides in analyzing closely related interactive sites of proteins in general and of antibodies in particular.
J Mol Biol 1996 Aug 09
PMID:Peptide libraries define the fine specificity of anti-polysaccharide antibodies to Cryptococcus neoformans. 876 Apr 99

Neurological disease directly attributable to HIV-1 infection (HIV dementia) is one of the most frequent disorders in persons with AIDS. HIV-1 dementia is associated with neuronal loss, but occurs in the absence of direct viral infection of neurons, suggesting that neurological damage occurs by an indirect mechanism. Recent studies have identified a number of candidate HIV-1 neurotoxins that may cause neuronal damage through common pathways involving the induction of oxidative stress and excitotoxicity. These findings suggest new therapeutic approaches to the prevention and treatment of HIV-1-induced neurological disease.
Mol Med Today 1996 Jan
PMID:Neuropathogenesis of AIDS. 879 47

The past five years have witnessed tremendous growth in the field of gene therapy, with pre-clinical and clinical gene therapy trials for diseases as diverse as cancer, AIDS and atherosclerosis. These studies have utilized many different vectors and target organs in order to achieve therapeutic effects. In this review, we examine the rationale for using skeletal muscle as a target tissue for gene therapy, discuss the wide array of vectors that have been used for muscle-based gene therapy, summarize the disease-targets that have been approached using these techniques, and discuss some of the obstacles that remain to be overcome en route to successful muscle-based human gene therapy.
Mol Med Today 1996 Apr
PMID:Muscle-based gene therapy: realistic possibilities for the future. 879 79

DNA amplification using dihydrofolate reductase (DHFR) primers in bronchoalveolar lavage fluids (BALFs) from patients with Pneumocystis carinii (PC) pneumonia yielded low sensitivity and specificity. Amplified products of BALFs from an AIDS patient without PC pneumonia and five patients with PC pneumonia were cloned and sequenced. All samples showed the same sequence without any homology with DHFR cDNA of rat PC, or with any DHFR sequences in databases at the DNA or amino acid level. The data demonstrate that these DHFR primers amplify a non-specific region of DNA with a sequence unrelated to the human PC DHFR gene both in PC positive and in PC negative samples. This finding precludes the use of these DHFR primers for the diagnosis of PC pneumonia in respiratory specimens.
Mol Cell Probes 1996 Jun
PMID:Non specific PCR products using rat-derived Pneumocystis carinii dihydrofolate reductase gene-specific primers in DNA amplification of human respiratory samples. 879 72


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