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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous experiment a group of 15 specified pathogen free (SPF) cats were experimentally infected with a Swiss isolate of feline immunodeficiency virus (FIV). A group of 15 SPF cats served as FIV negative controls. Nine cats of each group were vaccinated with a recombinant feline leukemia virus (FeLV) vaccine, six cats in each group with a placebo vaccine. All vaccinated cats developed high antibody titers to FeLV and were protected against subsequent FeLV challenge infection. In both control groups five of six cats became persistently infected with FeLV. Unexpectedly, the primary immune response to the vaccine antigen was significantly higher in the FIV positive group than in the FIV negative. The secondary response was stronger in the FIV negative cats. The goal of the present investigation was to further study the immune response in these 30 cats. They were immunized twice with the synthetic peptide L-tyrosine-L-glutamic acid-poly(DL-alanine)-poly(L-lysine) (TGAL) 21 days apart. Blood samples were collected on four occasions during the immunization process. They were tested for antibodies to TGAL, complete blood cell counts and CD4+, CD8+ and pan-T-lymphocyte counts. The following observations were made: (1) in contrast to the FeLV vaccine experiment, the primary immune response to TGAL was not significantly stronger in the FIV positive cats when tested by enzyme-linked immunosorbent assay (2). The absolute size of the CD4+ lymphocyte population was distinctly smaller in the FIV positive than in the FIV negative cats. The lowest CD4+ values were found in the dually FIV/FeLV infected cats. (3) A population of CD8+ lymphocytes was identified that was characterized by a distinctly weaker fluorescence. The size of this population increased in FIV positive and decreased in FIV negative cats during the TGAL immunization experiment. (4) The CD4+:CD8+ ratio increased in FIV negative cats during TGAL immunization from 1.9 to 2.3. In contrast, in FIV positive animals the CD4+:CD8+ ratio decreased significantly from 1.9 to 1.3 during the same period. From these and earlier data it was concluded that in short-term FIV infection the immune response to T-cell dependent antigens may be increased over that of the controls. Immune suppression develops gradually with duration of the infection. The significant drop of the CD4+:CD8+ ratio over a 5 week immunization period suggests that antigenic stimulation may accelerate the development of immune suppression in FIV positive cats. If this is a general feature, FIV infection may provide a particularly interesting model for studying the pathogenesis of AIDS.
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PMID:Immunization-induced decrease of the CD4+:CD8+ ratio in cats experimentally infected with feline immunodeficiency virus. 136 9

Benzylated peptides with a primary amino acid sequence corresponding to either human CD4(81-92) (#18), or chimpanzee CD4(81-92) (#18C), were equipotent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection of CD4+ cells and high-affinity binding of 125I-gp120 to CD4+ cells. The chimpanzee-based CD4(81-92) peptide, however, which differs from the human peptide by a single amino acid substitution (E for G) at position 87, was considerably less potent than the human CD4(81-92)-based peptide congener to inhibit HIV-1-induced cell-cell fusion. These data suggest that a portion of the CD4 molecule contained within the sequence CD4(81-92) is involved in binding gp120 during both HIV-1 infection and HIV-1-induced syncytium formation in human cells, but that the presence of a glutamic acid at position 87 in this sequence is more critical for the CD4/gp120 interaction leading to syncytium formation than for the CD4/gp120 interaction leading to primary infection of CD4-positive cells. The region CD4(81-92) may critically contribute to CD4-mediated HIV-1 pathogenesis in humans, and its alteration might explain the lack of pathogenic sequelae of HIV-1 infection in chimpanzees.
AIDS Res Hum Retroviruses 1991 Jun
PMID:Synthetic peptides allow discrimination of structural features of CD4(81-92) important for HIV-1 infection versus HIV-1-induced syncytium formation. 193 Dec 30

Human immunodeficiency virus (HIV-1) associated wasting is an increasingly common clinical manifestation of AIDS. The pathogenesis of wasting is multifactorial and includes reduced caloric intake as a major contributing mechanism. The perceptions of taste and smell play an important role in stimulating caloric intake and in optimizing nutrient absorption through cephalic phase reflexes. The purpose of this study was to evaluate the degree of losses in taste and smell function that occur in subjects infected with HIV. Taste and smell function was evaluated in 40 HIV infected individuals and 40 healthy control subjects matched for age, sex, race, smoking behavior, and number of years of education. Chemosensory tests administered to subjects included taste and smell detection thresholds, taste and smell memory tests, taste and smell discrimination tests, and taste and smell identification tasks. Significant differences were observed between experimental and control subjects in glutamic acid taste detection threshold (p < 0.001), quinine hydrochloride taste detection threshold (p < 0.001), menthol smell detection threshold (p < 0.001) and in the taste identification task (p = 0.006). Overall the results suggest abnormalities in the peripheral and central nervous systems, and subjective distortion of taste and smell. A significant correlation was not established between CDC classification of HIV infection and taste and smell function, although trends were observed suggesting worsening function with progression of HIV disease. These results document significant taste and smell losses in HIV infected subjects which may be of clinical significance in the development or progression of HIV associated wasting.
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PMID:Taste and smell losses in HIV infected patients. 756 32

Classical antifolate analogues containing a novel furo[2,3-d]pyrimidine ring system which include N-[4-[N-[(2,4-diaminofuro[2,3-d]pyrimidin-5- yl)methyl]amino]benzoyl]-L-glutamic acid (1) and its N-9 methyl analogue 2 were synthesized as potential dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and as antitumor agents. Four nonclassical antifolates, 2,4-diamino-5-(anilinomethyl)furo[2,3-d]pyrimidines 3-6 with 3,4,5-trimethoxy, 3,4,5-trichloro, 3,4-dichloro, and 2,5-dimethoxy substituents, respectively, in the phenyl ring, were also synthesized as potential inhibitors of DHFRs including those from Pneumocystis carinii and Toxoplasma gondii, which are organisms responsible for opportunistic infections in AIDS patients. The classical and nonclassical analogues were obtained via nucleophilic displacements of the key intermediate 2,4-diamino-5-(chloromethyl)furo[2,3-d]pyrimidine with the appropriate (p-aminobenzoyl)-L-glutamate or substituted aniline. The key intermediate was in turn synthesized from 2,4-diamino-6-hydroxypyrimidine and 1,3-dichloroacetone. The final compounds were tested in vitro against rat liver, (recombinant) human, P. carinii, T. gondii, and Lactobacillus casei DHFRs. The classical analogues showed moderate to good DHFR inhibitory activity (IC50 10(-6)-10(-8) M) with the N-CH3 analogue 2 about twice as potent as 1. The nonclassical analogues were inactive with IC50S > 3 x 10(-5) M. The classical analogues were also evaluated as inhibitors of TS (L. casei, (recombinant) human and human CCRF-CEM), glycinamide ribonucleotide formyltransferase, and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase and were found to be inactive against these enzymes. The classical analogues (particularly 2) were significantly cytotoxic toward a variety of tumor cell lines in culture. The nonclassical analogues were marginally active. Both classical compounds were good substrates for human folylpolyglutamate synthetase. Further evaluation of the cytotoxicity of 1 and 2 in CCRF-CEM cells and its sublines, having defined mechanisms of methotrexate (MTX) resistance, demonstrated that the analogues utilize the reduced folate/MTX-transport system and primarily inhibit DHFR and that poly-gamma-glutamylation was crucial to their mechanism of action. Protection studies in the FaDu squamous cell carcinoma cell line indicated that inhibition was completely reversed by leucovorin or the combination of thymidine plus hypoxanthine. Furthermore, for compounds 1 and 2, in contrast to MTX, the FaDu cells were better protected by thymidine alone than hypoxanthine alone, suggesting a predominantly antithymidylate effect.
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PMID:Classical and nonclassical furo[2,3-d]pyrimidines as novel antifolates: synthesis and biological activities. 816 59

In a randomized crossover trial, gastric acidity and gastric microbial colonization in 19 men infected with human immunodeficiency virus (HIV) (of whom nine had AIDS) were assessed. Gastric acidity was assessed during a baseline period and following pentagastrin or glutamic acid administration. Only two (22.2%) of the nine patients with AIDS and none of the non-AIDS patients were hypochlorhydric, as determined by maximal acid output. However, 60% and 67% of patients in the HIV-infected and AIDS groups, respectively, had persistently elevated gastric pH values during the baseline period. Both pentagastrin and glutamic acid significantly increased gastric acidity. Gastric colonization with Candida albicans and gram-positive mouth flora was common. Overall, this study demonstrates that many HIV-infected patients have elevated gastric pH values that may lead to alteration in drug absorption. The large degree of intrasubject and intersubject variability observed in gastric pH suggests that, unfortunately, one cannot predict which patients will have elevated gastric pH values.
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PMID:Alterations in gastric acidity in patients infected with human immunodeficiency virus. 874 28

The genetic characterization of a foscarnet-resistant strain of varicella-zoster virus (VZV) that was isolated from a patient with AIDS is reported. Compared with the sequence of the Dumas reference strain, this strain, which was isolated from a patient in whom foscarnet treatment failed, had two point mutations. The emergence of one of the mutations, which includes a change from a glutamic acid to a lysine at position 512 in the DNA polymerase, suggests that this mutation is implicated in the VZV foscarnet resistance. The other mutation, which replaces serine 863 by a glycine, is also present in 2 susceptible strains--Oka and a wild-type isolate.
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PMID:Single amino acid change in DNA polymerase is associated with foscarnet resistance in a varicella-zoster virus strain recovered from a patient with AIDS. 985 75

Mycobacterium avium is an intracellular pathogen that is associated with disseminated infection in acquired immunodeficiency syndrome (AIDS) patients. Human monocyte-derived macrophages were infected with M. avium strain 101 and a quinolone (Bay y 3118) was used at 8 micrograms ml-1, a concentration that kills growing bacteria but fails to eliminate static organisms. Infected monolayers were treated with Bay y 3118 for 4 days and viable bacteria obtained from the lysis of macrophages were used to infect other macrophages without passage in media. The procedure was repeated five times, after which seven different subpopulations that failed to grow within macrophages were identified. While the DNA fingerprinting confirmed that all came from the same strain, three protein profiles were observed. Static subpopulations were not killed by cytokine-stimulated macrophages, in contrast to the replicating subpopulation. Three of the static subpopulation strains were shown to be auxotrophic for glutamic acid or methionine. All seven non-duplicating subpopulation strains grew well in complete 7H10 agar. The importance of a static subpopulation of M. avium within macrophages is presently unknown. It is possible, however, that the non-growing bacteria would persist within macrophages.
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PMID:Isolation of two subpopulations of Mycobacterium avium within human macrophages. 1048 18

The World Wide Web now carries current AIDS treatment information, but due to the glut of information, the quality and credibility of information vary greatly. AIDS Treatment News is organizing a series of articles covering various areas of AIDS information that readers might seek on the World Wide Web, or elsewhere on the Internet, focusing on one or more major sites and listing others. AEGIS is considered the most comprehensive single Web site for AIDS news and general information. It maintains news reports, both current and archival, and provides current and back issues of community newsletters, fact sheets, and government documents and databases. It also has a clean user interface that is reported to be fast and flexible. Other sites include ACT UP/Golden Gate, American Medical Association, Critical Path AIDS Project, New York Academy of Medicine, and Project Inform. The Web site addresses are listed.
AIDS Treat News 1997 May 16
PMID:AIDS Internet: treatment information online. Introduction to a series. 1136 70

Cell membrane protein (CMP) profile of HIV-1 from cerebrospinal fluid (CSF) and plasma of five AIDS patients with neurologic disorders was analyzed and compared with viral quasispecies composition in these body compartments. To this aim, paired CSF and plasma samples from AIDS subjects with HIV-related neurological diseases (three HIV-1 encephalopaty (HIVE) and two primary CNS lymphoma (PCNSL)) underwent immobilized antibody capture (IAC) assay to determine the profile of CMP acquired by HIV-1. The considered CMPs were CD45RO, CD26, CD36, glut-R, N-CAM, VCAM-1, ELAM-1, CD44 and CD58, representing lymphomonocyte, neuronal and adhesion molecules. Cloning and sequencing of env and gag regions was performed to predict coreceptor usage and to analyze quasispecies compartmentalization. The results indicated that CD44 and CD58 were the most represented molecules on HIV-1 from CSF, whereas CD36 was the most abundant molecule on plasma HIV-1. V3 env aminoacidic sequences and net charge were consistent with M-R5 phenotype in all CSF and in most plasma clones. The degree of genetic heterogeneity (both complexity and diversity) in p17 gag was significantly lower in CSF-HIV than that in plasma-HIV for three patients, higher for one patient, and not significantly different for one patient, suggesting compartmentalization for all but the latter patient. When considering the pattern of CMP, the most abundant CMP observed in HIV from plasma and CSF was different in patients showing compartmentalization, while was the same in the patient without significant differences in CSF and plasma quasispecies. In conclusion, the present data on CMP pattern, V3 loop aminoacidic signature and genetic heterogeneity of HIV-1 quasispecies from CSF and plasma of HIVE patients, are consistent with a compartmentalized virus replication, at least in some patients, and with a possible different source of HIV in the two body sites, even though in a context of a largely prevalent M-R5 phenotype.
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PMID:Cell membrane proteins and quasispecies compartmentalization of CSF and plasma HIV-1 from aids patients with neurological disorders. 1573 16

The development of a prophylactic/therapeutic HIV-1 vaccine based on recombinant proteins is needed for the control of the worldwide AIDS epidemic. Subunit protein and peptide vaccines are generally very safe, with well-defined components. However, these antigens are often poorly immunogenic, and thus require the use of adjuvants to induce adequate immunity. Particulate adjuvants (e.g. micro/nanoparticles, emulsions, ISCOMS, liposomes, virosomes, and virus-like particles) have been widely investigated as HIV-1 vaccine delivery systems. Antigen uptake by antigen-presenting cells (APC) is enhanced by the association of the antigens with polymeric micro/nanoparticles. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into APC. More importantly, particulate antigens have been shown to be more efficient than soluble antigens for the induction of immune responses. Over the past two decades, we have studied the synthesis and clinical applications of core-corona polymeric nanospheres composed of hydrophobic polystyrene and hydrophilic macromonomers. Core-corona type polymeric nanospheres have applications in various technological and biomedical fields, because their chemical structures and particle size can be easily controlled. In this study, we focused on the development of a HIV-1 vaccine using polymeric nanoparticles. We evaluated the immunization strategies for HIV-1-capturing core-corona type polystyrene nanospheres that would efficiently induce HIV-1-specific IgA responses in female mice and the macaque genital tract. Moreover, based on this research, we attempted to develop novel biodegradable nanoparticles composed of poly (gamma-glutamic acid) (gamma-PGA) for protein-based vaccine delivery. These HIV-1-capturing nanospheres and protein-loaded gamma-PGA nanoparticles have shown unique potential as vaccine carriers.
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PMID:[Development of vaccine adjuvants using polymeric nanoparticles and their potential applications for anti-HIV vaccine]. 1726 51


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