Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high-performance liquid chromatographic (HPLC) assay was developed for pyrimethamine in plasma, red blood cells (RBCs), and buffer for the purpose of studying its plasma protein binding and RBC partitioning. Pyrimethamine (1000 ng/ml) was 94% bound to plasma proteins on average, depending on the pH of plasma. A comparison of the lower and upper range of plasma concentrations that would be achieved after a malaria prophylaxis dosing regimen (25 mg/week) showed that the fraction unbound was significantly lower at 120 ng/ml than at the upper plasma concentration of 360 ng/ml, 3.5 vs 4.9%, respectively. Nonlinear regression of the effect of albumin concentration (g/L) on plasma binding yielded the equation: fraction unbound = 1/[(0.421 * albumin concentration) + 1] (R2 = 0.99). There was no binding to normal levels of alpha 1-acid glycoprotein (AAG). The mean ratio of the concentration of pyrimethamine in RBCs to that in plasma (RBC:plasma ratio) was 0.42, while the mean RBC:buffer ratio was 5.2. Binding to hemolysate did not account for all of the RBC uptake, suggesting that binding to or partitioning into RBC membranes may be important. Because pyrimethamine binding depends on both albumin concentration and pyrimethamine concentration in the plasma, these studies predict greater free fractions of pyrimethamine associated with the higher doses given for toxoplasmosis (75 mg/day) and with the hypoalbuminemia associated with AIDS and malaria.
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PMID:Binding of pyrimethamine to human plasma proteins and erythrocytes. 228 Oct 36

Human immunodeficiency virus (HIV) infection is associated with a profound impairment of T cell function. Hence, enhancement of T cell reactivity to viral and bacterial antigens is important in the treatment of patients with AIDS. To develop tools for amplifying T cell reactivity, we have immunized mice with human helper T cell clones and selected monoclonal antibodies (MAbs) that enhance in vitro blastogenic responses. MAb NDA5, which recognizes the leukocyte common antigen CD45, amplifies human T cell responses to mitogens and soluble antigens including HIV-1 glycoprotein (gp)-120 and peptides derived from the HIV-1 gp-120 sequence. In the presence of MAb NDA5, peripheral blood mononuclear cells (PBMC) from healthy, HIV-1-seronegative individual displayed augmented blastogenic responses to HIV-1 gp-120 and to HIV-1 gp-120 synthetic peptides. In vitro memory responses to various vaccines and to alloantigens were also enhanced in cultures with MAb. Similarly, the response of PBMC from AIDS patients to pokeweed mitogen, HIV-1 gp-120, and tetanus toxoid was enhanced with MAb NDA5. The finding that the in vitro immune response of patients with AIDS can be amplified with MAb NDA5, suggests that the in vivo immune response of immunodeficient individuals can also be enhanced.
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PMID:Amplification of T cell blastogenic responses in healthy individuals and patients with acquired immunodeficiency syndrome. 231 25

Acquired immunodeficiency syndrome (AIDS) is initiated by the attachment of the human immunodeficiency virus (HIV) to a surface glycoprotein CD4 present on T4 helper/inducer lymphocytes, monocytes/macrophages and other cells. A simple octapeptide (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH, peptide T) seems to inhibit HIV infectivity and to activate human monocyte chemotaxis. In order to study in vitro metabolic stability and structure-activity relationships, peptide T and a number of analogues were prepared and tested on human monocytes by chemotactic assay. Peptide T and the shorter fragments T(3-8)-OH and T(4-8)-OH displayed potent bioactivity (maximal chemotactic activity in the range 10(-11)-10(-10) M). The C-terminal heptapeptide showed a reduction of potency, while further truncations at N-terminus of T(4-8)-OH abolished the biological action. In the octapeptide series, whereas the alpha-amino butyric acid (Abu) substitution for Thr4 was well tolerated, the same "slight" structural change at Thr5 or Thr8 was very detrimental. Finally, [D-Asn6]T(1-8)-OH analogue has low chemotactic activity. All these results indicate that i) the C-terminal pentapeptide is the minimum sequence required for bioactivity, ii) residues 5 to 8 appear to play a crucial biological role, iii) peptide T chemotaxis is mediated, at least in part, through the polar properties of Thr side chains at the critical positions 5 and 8, while the Thr4 does not interfere with biological characteristics of peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis, metabolic stability and chemotactic activity of peptide T and its analogues. 232 89

The CD4 glycoprotein serves as a receptor for the human immunodeficiency virus HIV, the etiologic agent of acquired immunodeficiency syndrome (AIDS). We have examined the expression of CD4 molecules in a clone (HT29-D4) derived from a human colon adenocarcinoma cell line. HT29-D4 cells synthesized a 60 kDa polypeptide immunoprecipitated with two anti-CD4 monoclonal antibodies after metabolic or cell surface labeling. This 60 kDa polypeptide was also immunodetected using the same antibodies in human acute lymphoblastic leukemia cells CEM which are known to express CD4. HT29-D4 cells can be induced to differentiate into enterocyte-like cells by removing glucose from the culture medium. Under these conditions, HT29-D4 cells form a polarized epithelial monolayer in which tight junctions separate the plasma membrane in an apical and a basolateral domain. The localization of CD4 molecules in differentiated HT29-D4 cells was exclusively restricted to the basolateral membrane domain as demonstrated by radioimmunoassay and indirect immunofluorescence studies. Therefore the HT29-D4 clonal cell line represents a unique model for polarized HIV infection of colonic epithelial cells and may be useful to understand some of the gastrointestinal disorders occurring in AIDS patients.
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PMID:CD4 molecules are restricted to the basolateral membrane domain of in vitro differentiated human colon cancer cells (HT29-D4). 236 56

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 23-kDa glycoprotein with remarkably diverse effects on immune and nonimmune cells. GM-CSF induces differentiation of granulocyte, macrophage, and eosinophil precursor cells. Proliferation of monocyte-macrophages, T lymphocytes, keratinocytes, and endothelial cells is also stimulated by GM-CSF. In addition, GM-CSF alters the functional properties of mature granulocytes, macrophages, eosinophils, and basophils. GM-CSF is produced by T lymphocytes, macrophages, and several cell types in extramedullary sites, where it may act in a paracrine manner to regulate the local response to antigenic challenge. Clinical trials of GM-CSF have been conducted in patients with AIDS, aplastic anemia, myelodysplastic syndromes, and sarcoma and following bone marrow transplantation and accidental radiation exposure. GM-CSF significantly increased circulating numbers of several myeloid cells and produced dose-dependent toxicity consisting primarily of myalgias, fever, fluid retention, and serosal effusions. Additional studies are needed to define the role of GM-CSF in treatment of patients with qualitative and quantitative dysfunction of immune cells.
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PMID:Granulocyte-macrophage colony-stimulating factor: pleiotropic cytokine with potential clinical usefulness. 240 68

The bovine leukemia virus is the etiological agent of a chronic lymphatic leukemia in cows, sheep, and goats. The same virus seems to induce a kind of wasting disease in experimentally infected rabbits. Antibodies to highly purified bovine leukemia viral Mr 51,000 glycoprotein and Mr 24,000 protein cross-react with human T-lymphotropic virus III/lymphadenopathy-associated virus antigens present in cultured lymphocytes of African patients suffering from acquired immune deficiency syndrome. Bovine leukemia virus has many structural and functional characteristics in common with the human T-lymphotropic viruses. The most striking feature of these retroviruses is the existence of a long open reading frame located at the 3' side of the provirus between the right end of the 3' side of env gene and the left end of the long terminal repeat. It is believed that the long open reading frame protein product acts in trans upon a number of genes to account for the biological effects of the virus.
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PMID:Bovine leukemia virus, a versatile agent with various pathogenic effects in various animal species. 241 Jan 7

The continuous increase in the number of acquired immunodeficiency syndrome (AIDS) cases for whom no effective therapy is currently possible mandates attempts at developing primary prevention by a vaccine. Two basic unknowns are considered important: the identification of virus-exposed, protected individuals; and the isolation of the antigen which contains epitopes which induce a protective response. Although almost all individuals exposed to human T-cell leukemia-lymphoma virus type III (HTLV-III) develop antibody, most of these do not have neutralizing antibody. The antigen which can induce the response is the major external glycoprotein, which is highly glycosylated (Mr 120,000). Based on past attempts at developing vaccines against retroviruses, the most feasible configuration will be the glycoprotein linked to its transmembrane protein and assembled into micelles or rosettes by hydrophobic bonding. Any virus preparation containing nucleic acids could be considered less safe. An advanced version of such a viral subunit presentation is matrices composed of immunostimulating complexes. This format could also be useful for the inoculation of sequence determined synthetic peptides or genetically engineered readout products of the viral envelope (env) gene. Potential problems exist in that there is extensive heterogeneity among various HTLV-III isolates, particularly in the env gene. This fact and the known relationship of HTLV-III to some lentiviruses suggest that functional antigenic variation could be encountered. The methodology of developing a vaccine against the retroviruses causing AIDS should also be helpful in designing vaccine strategies against human leukemia and lymphomas caused by other members of this virus family.
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PMID:Current status and strategies for vaccines against diseases induced by human T-cell lymphotropic retroviruses (HTLV-I, -II, -III). 241 Jan 15

The major envelope glycoprotein of the causative agent of Acquired Immune Deficiency Syndrome (AIDS) lymphadenopathy-associated virus (LAV) has been identified and characterized. The glycoprotein has an apparent molecular weight of 110,000-120,000 under denaturing conditions in polyacrylamide gel electrophoresis. Upon deglycosylation by a specific endoglycosydase, its size is reduced to 80,000. Cellular precursors of this glycoprotein have been detected with apparent molecular weight of 150,000 and 135,000. Nearly all AIDS and pre-AIDS patients have detectable antibodies against this viral glycoprotein.
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PMID:Identification and antigenicity of the major envelope glycoprotein of lymphadenopathy-associated virus. 241 18

The first human retroviruses have been discovered during the past seven years. They cause two diseases which involve disturbances of the growth of the T4-lymphocyte. This target cell type, which is central to the regulation of the immune system is induced by human T-lymphotropic virus type I (HTLV-I) to excessive proliferation (leukaemia) and by HTLV-III/LAV (lymphadenopathy associated virus) to premature death (acquired immune deficiency syndrome [AIDS]). Both also seem to be indirectly involved in several other disorders. The genetic structures of these retroviruses and the mechanisms by which they usurp host-cell functions are novel among retroviruses. The continuous increase in the number of AIDS cases for whom no effective therapy is currently possible mandates attempts at developing primary prevention by a vaccine. Based on past attempts at developing vaccines against retroviruses, the most feasible configuration will be the glycoprotein linked to its transmembrane protein. Any virus preparation containing nucleic acids could be considered less safe. Potential problems exist in that there is extensive heterogeneity among various HTLV-III isolates, particularly in the env-gene. This fact and the known relationship of HTLV-III to some Lentiviruses suggest that functional antigenic variation could be encountered. The methodology of developing a vaccine against the retroviruses causing AIDS should also be helpful in designing vaccine strategies against human leukaemia and lymphomas caused by other members of this virus family.
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PMID:[Molecular biology of human T-lymphotropic retroviruses (HTLV)]. 242 98

Human immunodeficiency virus type 1 (HIV-1, HTLV-III/LAV), the retrovirus responsible for acquired immune deficiency syndrome (AIDS), shows a high degree of genetic polymorphism, particularly in the env gene. We have examined sera from rabbits and guinea pigs immunized with gp130, a recombinant env glycoprotein, and sera from HIV-1-infected subjects, to test their capacity to neutralize a panel of genetically divergent HIV-1 isolates. The sera raised against recombinant antigen specifically neutralized the virus strain from which the env gene was cloned (HTLV-IIIB), but not an independent isolate (HTLV-IIIRF). One rabbit serum tested on seven isolates cross-neutralized two at lower titres. In contrast, human sera from Britain and Uganda, chosen for ability to neutralize HTLV-IIIRF, cross-neutralized six other HIV-1 isolates. When serum and isolate were derived from the same subject, the serum was in some cases effective at slightly lower concentrations (higher titres). Human complement did not affect neutralization titres. These findings indicate that genetically diverse HIV-1 isolates carry both variable and widely conserved antigenic epitopes for neutralizing antibodies. The identification of shared epitopes may help the development of protective vaccines.
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PMID:Variable and conserved neutralization antigens of human immunodeficiency virus. 243 24


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