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)

Cryopreservation and glycerol preservation are 2 successful methods for long-term preservation of human cadaver skin. Preservation is subjected to strict criteria to minimize the risk of disease transmission. This investigation compares the effects of glycerol preservation and cryopreservation on the inactivation of HIV-1. The effects of glycerol preservation and cryopreservation on inactivation of both extracellular and intracellular HIV-1Ba-L were investigated. After exposing HIV-1Ba-L-infected material to various concentrations of glycerol or to 10% dimethyl sulfoxide followed by cryopreservation, uninfected peripheral blood mononuclear cells were added to the treated material. At different time points during the culture, supernatants were taken to quantify HIV-1Ba-L and reverse transcriptase levels to determine HIV-1Ba-L infectivity. Cell-free HIV-1Ba-L was inactivated within 30 minutes in 70% and 85% glycerol. Also, intracellular HIV-1Ba-L in infected peripheral blood mononuclear cells or infected cadaver skin was completely inactivated by glycerol treatment in vitro. Cryopreservation did not show any extracellular or intracellular HIV-1Ba-L inactivation. Glycerol preservation--but not cryopreservation--of human cadaveric donor skin can inactivate both extracellular and intracellular HIV-1.
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PMID:The 1998 Lindberg Award. Comparison of glycerol preservation with cryopreservation methods on HIV-1 inactivation. 984 39

The behavior of the cytolytic peptide fragment 828-848 (P828) from the carboxy-terminus of the envelope glycoprotein gp41 of HIV-1 in membranes was investigated by solid-state 2H NMR on P828 with the selectively deuterated isoleucines I3, I13, I16, and I20. The quadrupole splittings of the I3 side chain show significant sensitivity to the main phase-transition temperature of the lipid, consistent with partial penetration of the N-terminal peptide region into the hydrophobic core of the membrane. In contrast, the quadrupole splittings of I13, I16, and I20 are in agreement with a location of the C-terminal portion of the peptide near the lipid/water interface. The perturbation of the bilayer by the peptide was studied by 2H NMR on sn-1 chain deuterated 1-stearoyl-2-oleoyl-sn-glycero-3-phosphoserine membranes. Peptide incorporation results in a significant reduction of lipid chain order toward the bilayer center, but only a modest reduction near the lipid glycerol. These observations suggest a penetration of the partially structured peptide backbone into the membrane/water interface region that reduces lateral packing density and decreases order in the hydrophobic core. In addition, the structure of the peptide was investigated free in water and bound to SDS micelles by high-resolution NMR. P828 is unstructured in water but exists in a flexible partially helical conformation when bound to negatively charged liposomes or micelles. The flexible helix covers the first 14 residues of the peptide, whereas the C-terminus of the peptide, where three of the six positively charged arginine residues are located, appears to be unstructured. The peptide-induced changes in lipid chain order profiles indicate that membrane curvature stress is the driving force for the cytolytic behavior of P828.
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PMID:Site-specific deuterium order parameters and membrane-bound behavior of a peptide fragment from the intracellular domain of HIV-1 gp41. 1032 Mar 63

Allogeneic split skin grafts are used widely in the treatment of burns. The relative simplicity of glycerol preservation of skin suggests it will be used increasingly in areas of high HIV-1 seroprevalence. The ability of glycerol preservation to inactivate HIV-1 present in skin graft infected in vitro was determined using a macrophage tropic strain HIV-1 as a cell-free virus suspension, within infected PBMCs, or within in vitro HIV-1 infected fresh cadaveric split skin. Different temperatures and concentrations of glycerol were used and infectivity determined by coculture with mitogen activated peripheral blood mononuclear cells (PBMCs) and measurement of reverse transcriptase activity after 7-10 days. Cell-free HIV-1 was inactivated within 30 min at 4 degrees C in glycerol concentrations of 70% or higher. During similar exposure cell- or skin-associated HIV-1 titer was reduced but not eliminated with 70% and 85% glycerol at 4 degrees C. HIV-1 was recovered consistently from skin stored in 85% glycerol at 4 degrees C for up to 72 hr but virus isolation was infrequent after storage for more than 5 days. At 20 degrees C or 37 degrees C, 70% or 85% glycerol could inactivate cell- or skin-associated HIV-1 within 8 hr. The initial glycerolization procedures and the storage at 4 degrees C eliminated effectively HIV-1 from skin.
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PMID:Efficacy and kinetics of glycerol inactivation of HIV-1 in split skin grafts. 1059 19

Monoalkyl ether lipid analogues of foscarnet (phosphonoformate, PFA) exhibit substantially greater in vitro antiviral activity than unmodified PFA against human immunodeficiency virus type 1 (HIV-1). Our previous studies indicate that the length of the alkyl chain must be 14-22 carbons for optimal antiviral activity. To further evaluate the structure-activity relationship, we prepared 1-O-octadecyl-sn-glycerol analogues of PFA with various substitutions at the sn-2 position of glycerol and determined the effect of structure on in vitro antiviral activity and selectivity against HIV-1 in MT-2 and CD4-expressing HeLa cells (HT4-6C). We also studied combinations of zidovudine with PFA, 1-O-octadecyl-2-O-methyl-sn-glycero-3-PFA, or 1-O-octadecyl-sn-glycero-3-PFA and calculated their combination index values against HIV-1 in HT4-6C cells. Alkyl substitutions of one to four carbons at the sn-2 position of glycerol showed optimal antiviral activity. Both alkyl ether lipid analogues were strongly synergistic with zidovudine over a wide range of drug ratios and concentrations. 1-O-octadecyl-sn-glycerol analogues of PFA have selective antiviral properties and warrant further evaluation as potential antiretroviral drugs.
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PMID:In vitro anti-HIV-1 activity of sn-2-substituted 1-O-octadecyl-sn-glycero-3-phosphonoformate analogues and synergy with zidovudine. 1090 Dec 92

We sought to determine the efficacy of amniotic membrane transplantation (AMT) in the reconstruction of ocular surface. AMT was performed on 40 eyes with following indications: I, persistent corneal ulceration (n = 12); II, impending perforation (n = 6); III, persistent epithelial defect on the corneal graft (n = 6); IV, recurrent pterygia (n = 10), and V, risk of conjunctival scarring (n = 6). Amniotic membrane was prepared from a fresh placenta under sterile conditions, washed with BSS containing penicillin, streptomycin, neomycin and amphotericin B and stored at -80 degrees C in 1:1 InoSol:Glycerol solution. Donor serological test for HIV, HBV and HCV were all negative. Associated surgical procedures according to indication were performed. Healing of the corneal ulcer in Group I was obtained in 67% of eyes at 1-3 weeks after surgery, Group II: AMT was followed by 'a chaud' keratoplasty in 33% and by planned keratoplasty in 67% patients, Group III: healing of the defect in 33% of eyes in 2-5 postoperative weeks, Group IV: no recurrence of pterygium ingrowth in 70% in the follow up period of 6-14 months, and V: 84% of patients had good eye motility without any synechia formation. We concluded that AMT have shown to be effective in enhancing healing of the corneal defects, in prevention of symblepharon formation and recurrent pterygium ingrowth. In case of impending perforation, AMT alone was not a method of treatment but is useful as a first step procedure in preparing the eye for the corneal transplantation.
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PMID:Human amniotic membrane in the reconstruction of the ocular surface. 1094 47

HIV protease inhibitors (HPIs) are potent antiretroviral agents clinically used in the management of HIV infection. Recently, HPI therapy has been linked to the development of a metabolic syndrome in which adipocyte insulin resistance appears to play a major role. In this study, we assessed the effect of nelfinavir on glucose uptake and lipolysis in differentiated 3T3-L1 adipocytes. An 18-h exposure to nelfinavir resulted in an impaired insulin-stimulated glucose uptake and activation of basal lipolysis. Impaired insulin stimulation of glucose up take occurred at nelfinavir concentrations >10 micromol/l (EC(50) = 20 micromol/l) and could be attributed to impaired GLUT4 translocation. Basal glycerol and free fatty acid (FFA) release were significantly enhanced with as low as 5 micromol/l nelfinavir, displaying fivefold stimulation of FFA release at 10 micromol/l. Yet, the antilipolytic action of insulin was preserved at this concentration. Potential underlying mechanisms for these metabolic effects included both impaired insulin stimulation of protein kinase B Ser 473 phosphorylation with preserved insulin receptor substrate tyrosine phosphorylation and decreased expression of the lipolysis regulator perilipin. Troglitazone pre- and cotreatment with nelfinavir partly protected the cells from the increase in basal lipolysis, but it had no effect on the impairment in insulin-stimulated glucose uptake induced by this HPI. This study demonstrates that nelfinavir induces insulin resistance and activates basal lipolysis in differentiated 3T3-L1 adipocytes, providing potential cellular mechanisms that may contribute to altered adipocyte metabolism in treated HIV patients.
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PMID:The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes. 1137 44

The heterodimeric human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is composed of p66 and p51 subunits, p66 being the catalytic subunit. Our earlier investigation on the role of p51 in the catalytic process has shown that the p51 subunit facilitates the loading of the p66 subunit onto the template primer (TP). We had postulated that the beta7-beta8 loop of the p51 subunit may be involved in opening the polymerase cleft of p66 for DNA binding [Pandey, V. N., et al. (1996) Biochemistry 35, 2168]. We report here that deletion or alanine substitution of four residues of the beta7-beta8 loop results in severe impairment of the polymerase function of the heterodimeric enzyme. The enzyme activity was restored to the wild-type levels when the mutant p66 subunit was dimerized with the wild-type p51, suggesting that the intact beta7-beta8 loop in the p51 subunit is indispensable for the catalytic function of p66. Further, the template primer binding ability of the enzyme was significantly reduced upon deletion or alanine substitution in the beta7-beta8 loop. Interestingly, the loss of the TP binding ability of the mutant p66 was restored upon dimerization with wild-type p51. Examination of the glycerol gradient ultracentrifugation analysis revealed that while the wild-type HIV-1 RT sediments as a dimeric protein, the mutant enzymes carrying deletion or alanine substitution in both the subunits sediment predominantly as monomeric proteins, suggesting their inability to form stable dimers. In contrast, mutant p66 dimerized with wild-type p51 (p66delta/p51WT and p66Ala/p51WT) sedimented at the dimeric position. Taken together, these results clearly implicate the importance of the beta7-beta8 loop of p51 in the formation of stable functional heterodimers.
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PMID:The beta7-beta8 loop of the p51 subunit in the heterodimeric (p66/p51) human immunodeficiency virus type 1 reverse transcriptase is essential for the catalytic function of the p66 subunit. 1158 49

We studied aspects of metabolism in subcutaneous adipose tissue (SAT) in 40 human immunodeficiency virus (HIV)-infected subjects with and without lipodystrophy and in healthy control subjects. HIV-infected subjects without lipodystrophy had less SAT and visceral adipose tissue (VAT). Glycerol release was higher in both HIV-infected groups, especially those without fat redistribution. Tumor necrosis factor (TNF) release from SAT and serum soluble TNF receptor 2 concentrations were significantly higher in HIV-infected individuals with lipodystrophy. The absolute production of acylation-stimulating protein (ASP) and the percentage conversion of the complement protein to ASP were significantly lower in HIV-infected subjects with lipodystrophy. Further studies are needed to dissect the factors that mediate lipoatrophy in HIV infection.
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PMID:Studies of adipose tissue metabolism in human immunodeficiency virus-associated lipodystrophy. 1294 74

HIV-1 and influenza viral fusion peptides are biologically relevant model fusion systems and, in this study, their membrane-associated structures were probed by solid-state NMR (13)C chemical shift measurements. The influenza peptide IFP-L2CF3N contained a (13)C carbonyl label at Leu-2 and a (15)N label at Phe-3 while the HIV-1 peptide HFP-UF8L9G10 was uniformly (13)C and (15)N labeled at Phe-8, Leu-9 and Gly-10. The membrane composition of the IFP-L2CF3N sample was POPC-POPG (4:1) and the membrane composition of the HFP-UF8L9G10 sample was a mixture of lipids and cholesterol which approximately reflects the lipid headgroup and cholesterol composition of host cells of the HIV-1 virus. In one-dimensional magic angle spinning spectra, labeled backbone (13)C were selectively observed using a REDOR filter of the (13)C-(15)N dipolar coupling. Backbone chemical shifts were very similar at -50 and 20 degrees C, which suggests that low temperature does not appreciably change the peptide structure. Relative to -50 degrees C, the 20 degrees C spectra had narrower signals with lower integrated intensity, which is consistent with greater motion at the higher temperature. The Leu-2 chemical shift in the IFP-L2CF3N sample correlates with a helical structure at this residue and is consistent with detection of helical structure by other biophysical techniques. Two-dimensional (13)C-(13)C correlation spectra were obtained for the HFP-UF8L9G10 sample and were used to assign the chemical shifts of all of the (13)C labels in the peptide. Secondary shift analysis was consistent with a beta-strand structure over these three residues. The high signal-to-noise ratio of the 2D spectra suggests that membrane-associated fusion peptides with longer sequences of labeled amino acids can also be assigned with 2D and 3D methods.
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PMID:Temperature dependence and resonance assignment of 13C NMR spectra of selectively and uniformly labeled fusion peptides associated with membranes. 1474 99

Patients with HIV taking protease inhibitors were selected for the presence (five subjects) or absence (five subjects) of lipoatrophy. Following an overnight fast, subjects were given oral (2)H(2)O in divided doses (5 mL/kg body water), [U-(13)C(3)] propionate (10 mg/kg), and acetaminophen (1000 mg). Glucose (from plasma) or acetaminophen glucuronide (from urine) were converted to monoacetone glucose for (2)H NMR and (13)C NMR analysis. The fraction of plasma glucose derived from gluconeogenesis was not significantly different between groups. However, flux from glycerol into gluconeogenesis relative to glucose production was increased from 0.20 +/- 0.13 among subjects without lipoatrophy to 0.42 +/- 0.12 (P < 0.05) among subjects with lipoatrophy, and the TCA cycle contribution was reduced. Lipoatrophy was associated with an abnormal profile of glucose production as assessed by (13)C and (2)H NMR of plasma and urine.
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PMID:Glucose production pathways by 2H and 13C NMR in patients with HIV-associated lipoatrophy. 1506 35


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