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)

In July 1990 in Zaire, a 36-year-old man was admitted to the University Clinic in Kinshasa for intense headaches, fever, vertigo, vision troubles, hallucinations, and irregular speech. He exhibited moderate wasting, left facial paralysis, and prurigo spots on the legs. Laboratory examinations revealed HIV seropositivity, antibodies to cryptococci, protein in the cerebrospinal fluid, and glucose in the cerebrospinal fluid. He was placed on 400 mg/d fluconazole. He died on August 4, two days after slipping into a coma. Cryptococcus neoformans var. gattii was isolated. The man had lived in a free union with two women. One died in 1989 of an illness characterized by persistent fever, considerable wasting, and pulmonary tuberculosis. The other woman is still alive although often having febrile episodes. She is HIV seropositive. Before AIDS arrived, cryptococcosis was rare in Zaire and Cryptococcus neoformans var. gattii was the most common etiologic agent. With AIDS, cryptococcosis has become an opportunistic infection. Since 1983, all cryptococcosis cases at the university clinics were a complication of AIDS. Cryptococcus neoformans var. neoformans was the etiologic agent in all these cases. It is possible that exposure to neoformans variety is more common than exposure to gattii variety. It is therefore an epidemiologic problem intimately associated with the geographic topography specific to ecological niches of these two varieties. Neoformans variety is found in pigeon droppings, while gattii variety has never been found in bird droppings. Gattii's natural host is the eucalyptus tree, found in Zaire. The case lived 400 m from a eucalyptus plantation. He was the only gattii variety cryptococcosis case in 1990-1991 among the 49 cryptococcosis cases at the Kinshasa University Clinics. In conclusion, gattii variety rarely causes cryptococcosis among AIDS patients because its natural reservoir is rare in urban areas where the AIDS epidemic is centered.
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PMID:[Cryptococcosis caused by Cryptococcus neoformans var. Gattii. A case associated with acquired immunodeficiency syndrome (AIDS) in Kinshasa, Zaire]. 149 13

The antiviral activity of 6-0-butanoylcastanospermine (MDL 28,574) [50% inhibitory concentration (IC50: 1.1 microM)] in JM cells infected with a recent isolate of HIV-1 (GB8), was compared with other inhibitors of glycoprotein-processing enzymes. N-butyldeoxynojirimycin (BuDNJ), deoxynojirimycin (DNJ), castanospermine (CAST) or the reverse transcriptase inhibitor 2'3'-dideoxycytidine (ddC) had activities of 56, 560, 29 and 0.1 microM, respectively. MDL 28,574 was at least 50 times more active than BuDNJ and less active but better tolerated in cell culture than ddC, two compounds currently undergoing clinical trials. The CAST derivative showed good protection in H9 cells infected with HIV-1 (RF; IIIB; U455), and HIV-2 (ROD), although the potency was less than that seen in the JM/GB8 system. HIV-1 glycoproteins, gp160 and gp120, synthesized in H9 cells chronically infected with HIV-1 (RF) and treated with MDL 28,574, were characterized by an increase in relative molecular weight of approximately 7-8000 kD. The ratio of gp120 to gp160 was markedly reduced in treated cells and provided further evidence that cleavage of the gp160 precursor molecule is a major consequence of the inhibition of glycoprotein processing. The intracellular target for MDL 28,574 was verified as alpha-glucosidase-I of the processing enzymes by the analysis of high-glucose glycopeptides recovered from treated mouse cells. This activity correlated with the antiviral effect observed against the growth of a mouse retrovirus, Moloney murine leukemia virus (MOLV), in mouse cells.
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PMID:6-0-butanoylcastanospermine (MDL 28,574) inhibits glycoprotein processing and the growth of HIVs. 165 79

Mycoplasmas have been isolated from patients with acquired immunodeficiency syndrome (AIDS) and they may contribute to the pathogenesis of this disease. We have isolated repeatedly a previously unknown mycoplasma from the urine of an HIV-positive male homosexual and, subsequently, from the urine of 5 HIV-positive patients with AIDS. The mycoplasma was not found in the urine of 98 healthy control subjects. The organism has an unusual tip-like structure with densely packed fine granules and metabolizes both glucose and arginine for growth. Antigenic and DNA analyses show the organism to be distinct from other known mycoplasmas. The mycoplasma displays in-vitro activities associated with virulence in vivo. In addition, electronmicroscopy shows that the mycoplasma can invade and attach to various human and animal cells. We are investigating whether the new mycoplasma has a role in human disease.
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PMID:Newly discovered mycoplasma isolated from patients infected with HIV. 168 19

We have used HIV1-NDK-infected HT29 cells grown on permeable substratum to study the polarity of virus maturation in human intestinal cells. When cultured in glucose-containing medium, these cells are mostly undifferentiated. The removal of glucose from the medium allowed the emergence of a selected differentiated subpopulation which continued to produce viral particles in the culture supernatant. The polarity of viral production was evaluated by harvesting virus from the two sides of the monolayer. Seventy-five percent of released HIV was found on the basolateral side of the monolayer. Mature viral particles were observed by electron microscopy near the apical (luminal) and the basolateral (serosal) membrane. These data suggest that epithelial cells of the colon productively infected by a selected strain of HIV are able to produce the virus through both sides of the epithelium but mainly through the serosal side.
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PMID:Selected human immunodeficiency virus replicates preferentially through the basolateral surface of differentiated human colon epithelial cells. 172 May 92

To test whether clinically stable human immunodeficiency virus (HIV) infection, like other infections, is associated with insulin resistance and increased insulin clearance, we measured the sensitivity to insulin and insulin clearance using the euglycemic insulin clamp technique in 10 clinically stable outpatients with symptomatic HIV infection (Centers for Disease Control [CDC] group IV) and 10 healthy controls. During administration of 0.8 and 4 mU insulin.kg-1.min-1, HIV-infected men had 40% (P less than .02) and 83% (P less than .01) higher rates of insulin clearance when compared with healthy controls. Despite significantly lower steady-state insulin concentrations (42 +/- 2 v 52 +/- 4 microU/mL, P less than .05, and 255 +/- 17 v 392 +/- 14 microU/mL, P less than .001, patients v controls), patients and controls had similar total glucose uptake (7.99 +/- 0.81 v 7.92 +/- 0.44 mg.kg-1.min-1 and 14.00 +/- 0.81 v 13.65 +/- 0.65 mg.kg-1.min-1, patients v controls). In the postabsorptive state, no differences were found between patients and controls in insulin levels (7 +/- 1 microU/mL in both) and endogenous glucose production (2.52 +/- 0.07 and 2.24 +/- 0.17 mg.kg-1.min-1, respectively), but plasma glucose levels in the patients (5.02 +/- 0.15 mmol/L) were significantly lower when compared with controls (5.46 +/- 0.14 mmol/L, P less than .05). The results indicate that HIV-infected men have increased rates of insulin clearance and increased sensitivity of peripheral tissues to insulin, which makes HIV infection unique with regard to glucose and insulin metabolism.
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PMID:Insulin sensitivity and insulin clearance in human immunodeficiency virus-infected men. 164 Aug 55

Fifteen male homosexual subjects (mean age 31.6 +/- 7.2 yr) who were asymptomatic, but HIV-1 seropositive (HIV+) were compared to 15 male age-matched HIV-1 seronegative (HIV-) subjects using resting PET/FDG studies and MR scans. Mean cerebral metabolic rates for glucose (mg/100 g/min) in the HIV+ and HIV- subjects were 7.7 +/- 1.7 and 7.0 +/- 2.1, (p = 0.44), respectively. An index of regional metabolic asymmetry for the whole brain was 5.8% +/- 3.2% in the HIV+ and 2.7% +/- 2.3% in the HIV- (p = 0.002), and the difference was most prominent in the prefrontal area. Significant asymmetries were found in 10/15 HIV+ subjects, primarily in prefrontal (7/15) and premotor (4/15) regions. MRI scans showed no abnormalities on clinical or quantitative evaluation in HIV+ subjects. Upon follow-up of HIV+ subjects over 18-40 mo, seven became symptomatic, of which two died. There was no relationship between the presence of PET scan abnormalities and earlier onset of symptomatic disease.
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PMID:Metabolic asymmetries in asymptomatic HIV-1 seropositive subjects: relationship to disease onset and MRI findings. 188 May 74

The delivery of the anti-HIV agent 3'-azido-3'-deoxythymidine (AZT), in its 5'-monophosphate form, (in) to human T-lymphocyte MT-4 cells in vitro through covalent coupling to neoglycoproteins was investigated. In vivo application of this drug targeting concept may lead to increased efficacy and/or diminished side effects caused by AZT during the treatment of AIDS and ARC patients. The rationale for the design of the neoglycoprotein carriers is based on the existence of sugar recognizing lectins on T-lymphocytes. Using a phenyl-linkage between sugar and Human Serum Albumin (HSA), various mannose-, fucose-, galactose-and glucose-containing neoglycoproteins were synthesized. The intrinsic anti-HIV activity of these neoglycoproteins was tested in vitro in HIV-1 infected MT-4 cells. Only the derivative having 40 moles mannose per mole protein (Man40HSA) shows pronounced anti-HIV-1 activity itself. This effect may be caused by interference of the Man40HSA with the gp120-CD4 mediated virus/MT-4 cell interaction. After conjugation with AZTMP, the mannose- as well as the fucose- and galactose-containing conjugates exhibited a pronounced activity. Conjugates of glucose-HSA and HSA displayed much less activity in spite of the fact that drug loading was considerably higher, compared with the galactose, mannose and fucose derivatives. In the series of mannose-neoglycoproteins, the Man22HSA-AZTMP conjugate was shown to be more than 30 times as active against HIV-1 compared to HSA-AZTMP. Selectivity indices of Man7 and Man22HSA-AZTMP were exceeding the AZT and AZTMP indices, indicating that these conjugates possess a more selective action. Stability experiments indicate that the potent action of the galactose-, mannose- and fucose-HSA-AZTMP conjugates is not due to a complete extracellular hydrolysis of the covalent drug-protein bond. Since Man22HSA has no intrinsic activity in the concentration range used, the antiviral effect is unlikely to be explained by synergism of the neoglycoprotein by a component of the cell membrane and subsequent internalization and release of the drug from the conjugate may play a role.
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PMID:Targeting of antiviral drugs to T4-lymphocytes. Anti-HIV activity of neoglycoprotein-AZTMP conjugates in vitro. 197 34

The highly glycosylated envelope glycoprotein (gp 160) of human immunodeficiency virus (HIV) interacts with the CD4 molecule present on the membrane of CD4+ cells and is involved in the pathobiology of HIV infection. Lectins bind glycoproteins through non-covalent interactions with specific hexose residues. The mammalian C-type lectin bovine conglutinin was examined for its ability to interact with recombinant gp160 (rgp160) produced in vaccinia virus-infected BHK21 cells. Specific binding of conglutinin to rgp160 was demonstrated by ELISA. The interaction of bovine conglutinin with rgp160 was calcium-dependent, which is characteristic of the binding of a C-type lectin to its ligand, and the binding was inhibited in a dose-dependent manner with N-acetyl-D-glucosamine. Deglycosylation of rgp160 abrogated the conglutinin binding. In addition, conglutinin exerted a dose-dependent inhibition of the binding of rgp160 to the CD4 receptor on CEM 13 cells, as demonstrated by FACS analyses. These results indicate that conglutinin may inhibit the infection with HIV-1 through its interaction with the viral envelope glycoprotein.
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PMID:Conglutinin binds the HIV-1 envelope glycoprotein gp 160 and inhibits its interaction with cell membrane CD4. 199 9

Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.
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PMID:Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120. 203 31

A strain of HIV 1 (PA 40), isolated from a patient with AIDS, showed a size variation of its external glycoprotein. This glycoprotein had an estimated molecular weight of 105 Kd and differed from that of both HIV 1 IIIb and HIV 2 Rod strains. The protein was derived from a bigger (140 Kd) precursor, detectable only in the infected cells and could incorporate labeled glucose in its prosthetic portion. The change in size of the external glycoprotein may be the result of envelope sequence variations since the unglycosylated form of the envelope precursor of PA 40 strain, detected in tunicamycin treated cells, was smaller than that of the HIV 1 IIIb strain. The different size of the external glycoprotein is a further aspect of the variability of the biological characteristic of HIV 1 strains and might be correlated with the emergence of more virulent variants which arose during the progression of the clinical disease.
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PMID:Change in size of the envelope glycoprotein of a human immunodeficiency virus 1 (HIV 1) strain. 206 12


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