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)

(2R,4S,5S,1'S)-2-Phenylmethyl-4-hydroxy-5-(tert-butoxycarbonyl) amino-6-phenylhexanoyl-N-(1'-imidazo-2-yl)-2'-methylpropanamide (compound 2) is a tripeptide analogue inhibitor of HIV-1 protease in which a C-terminal imidazole substituent constitutes an isoelectronic, structural mimic of a carboxamide group. Compound 2 is a potent inhibitor of the protease (K(i) = 18 nM) and inhibits HIV-1 acute infectivity of CD4+ T-lymphocytes (IC50 = 570 nM). Crystallographic analysis of an HIV-1 protease-compound 2 complex demonstrates that the nitrogen atoms of the imidazole ring assume the same hydrogen-bonding interactions with the protease as amide linkages in other peptide analogue inhibitors. The sole substitution of the C-terminal carboxamide of a hydroxyethylene-containing tripeptide analogue with an imidazole group imparts greatly improved pharmacokinetic and oral bioavailability properties on the compound compared to its carboxamide-containing homologue (compound 1). While the oral bioavailability of compound 1 in rats was negligible, compound 2 displayed oral bioavailabilities of 30% and 14%, respectively, in rats and monkeys.
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PMID:An orally bioavailable HIV-1 protease inhibitor containing an imidazole-derived peptide bond replacement: crystallographic and pharmacokinetic analysis. 791 83

The discovery that humans produce nitric oxide and that this molecule plays an important role in cell communication, host resistance to infection, and perhaps in host defence to neoplastic disease, has created much interest in further research on its function in the body. A cytokine-inducible high output L-arginine/nitric oxide pathway was recently detected in patients with advanced malignancy treated with IL-2. The production of nitric oxide was thus examined in patients with advanced HIV infection and in intensive care unit control patients. Extrinsic nitrate and nitrite consumption were carefully controlled in the diet or through the use of total parenteral nutrition. Seven of eight HIV+ patients were placed into positive nitrogen balance. Nitric oxide synthesis was found to be within the normal human range. In contrast, nitric oxide synthesis in extremely ill intensive care unit patients was low normal to depressed.
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PMID:Nitric oxide synthesis in patients with advanced HIV infection. 803 24

Rapid freezing, freeze substitution and low temperature embedding were used to obtain resin-embedded specimens of HIV and SIV for morphological and immunolabelling studies, with particular emphasis on the 'lateral bodies' and p6 protein. HIV- or SIV-infected cells were fixed in 3% paraformaldehyde and cryoprotected with 0.5 M sucrose. Cells were applied to pieces of Whatman No 1 filter paper and impact-frozen onto a liquid nitrogen cooled copper block. Specimens were freeze-substituted at -90 degrees C using one of three different media: (a) absolute methanol, (b) methanol containing 0.5% uranyl acetate, and (c) methanol containing glutaraldehyde, osmium tetroxide and uranyl acetate. Specimens substituted in methanol and uranyl acetate showed both good structural preservation and retention of antigenicity. We found that the use of filter paper for supporting the specimen was an important factor in obtaining good freezing rates and was more practical than freezing mixtures of cells and gelatin. When compared with specimens prepared by conventional fixation and embedding, freeze-substituted virus particles showed a greater uniformity of shape and size and were more dense in appearance. Distinct 'lateral bodies' were not observed in freeze-substituted viruses. The viral protein p6 was widely distributed in the centre of mature virus particles.
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PMID:A morphological and immunolabelling study of freeze-substituted human and simian immunodeficiency viruses. 805 44

Despite association with adverse clinical outcome, human immunodeficiency virus (HIV)-associated malnutrition has been relatively refractory to conventional nutrition management. Consequently, a prospective randomized trial was conducted to evaluate a new peptide-based enteral formula (NEF) in contrast to a standard enteral formula (SEF) in patients with HIV infection. Eighty early-stage largely asymptomatic patients were randomized into a dietary regimen supplemented with either a ready-to-feed NEF (18.7% protein, 65.5% carbohydrate, 15.8% fat; 1.28 kcal/ml) or SEF (14% protein, 55% carbohydrate, 31% fat; 1.06 kcal/ml). Patients received 2-3 8-oz cans of the NEF or SEF supplement per day for 6 mo. Parameters evaluated at 0 (baseline), 3, and 6 mo included adherence, weight change, anthropometric measurements, serum biochemical indices, gastrointestinal symptoms, physical performance, and intercurrent health events (including hospitalizations). For the 56 evaluable patients, those supplemented with NEF maintained their body weight significantly (p = 0.04) better, had significantly (p = 0.03) more stable triceps skin-fold measurements, and had significantly (p = 0.04) lower blood urea nitrogen than patients consuming the SEF supplement. Consumption of the NEF supplement was also associated with significantly reduced hospitalizations during the 3- to 6-mo evaluation period (p = 0.02). The NEF supplement was well tolerated and did not result in untoward clinical effects. These data suggest that supplemental use of an NEF provides superior nutritional management compared with an SEF for patients with early-stage HIV infection.
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PMID:Long-term effects of early nutritional support with new enterotropic peptide-based formula vs. standard enteral formula in HIV-infected patients: randomized prospective trial. 811 Nov 47

Nutritional support of patients with HIV or acquired immune deficiency syndrome (AIDS) has many similarities to other disease states in that the same nutritional products and techniques are used. Some patients with HIV, and many with AIDS without secondary infection, experience a metabolic milieu similar to patients with cancer cachexia. In providing dietary counselling to the HIV patient, we encounter many of the obstacles that must be overcome to improve nutrition in cancer: anorexia, gastrointestinal discomfort, lethargy, and poor nutrient utilization, which limit the ability for nutritional repletion. When a secondary infection is superimposed on HIV, patients resemble more highly catabolic trauma patients or patients in the intensive care unit (ICU), where, despite aggressive efforts to feed, there is usually a net nitrogen wasting leading to the more rapid development of cachexia. However, even in this setting, feeding will limit substantially net catabolism when compared to total starvation. Because the nutritional needs of HIV patients vary greatly, individual strategies have to be designed as the patient moves through the stages of disease. Patients are generally able to consume adequate nutrition either as regular food or dietary supplements during the latency period of viral replication. Once secondary infections become prevalent, artificial diets administered by tube or by vein may be required during the period of active secondary infections, with dietary supplements often helpful during more quiescent periods. Patients with HIV are among the most challenging for clinicians providing nutritional support. Knowledge from treatment of patients with other diseases may be useful, but more data must be gathered on the unique aspects of aetiology and treatment of the anorexia, malabsorption, and ultimate wasting associated with AIDS.
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PMID:Nutrition support and the human immunodeficiency virus (HIV). 811 86

The advent of methods for preparing 15N- and 13C-labeled RNA oligonucleotides holds promise for extending the size of RNA molecules that can be studied by NMR spectroscopy. A practical limitation is the expense of the 13C label. It may therefore sometimes be desirable to prepare a relatively inexpensive 15N-labeled sample only. Here we show that the two-bond 1H-15N HSQC experiment can be used on 15N-labeled RNA to correlate the intranucleotide H1' and H8,H6,H5 resonances indirectly through the shared glycosidic nitrogen. The nonrefocused version of a standard HSQC experiment for 2D proton-detected 1H-15N chemical-shift correlation is applied in order to minimize the sensitivity loss due to the relatively fast spin-spin relaxation of RN oligonucleotides. The experiment is applied to the 30-nucleotide RNA RBE3 which contains the high-affinity binding site of the RRE (rev response element) for the Rev protein of HIV. The results indicate that this simple experiment allows a straightforward identification of the base proton resonances CH5, CH6, UH5, UH6, purine H8, and AH2 as well as the intranucleotide H1' and H8,H6,H5 connectivities. When combined with a NOESY experiment, complete sequential assignments can be obtained.
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PMID:Correlation of nucleotide base and sugar protons in a 15N-labeled HIV-1 RNA oligonucleotide by 1H-15N HSQC experiments. 813 Jun 37

Renal tissues from 15 cats naturally infected with feline immunodeficiency virus (FIV) were examined histologically, immunohistochemically and ultrastructurally. Renal function and urinary proteins were also studied. Kidney abnormalities were found in 12 cats and were characterized by mesangial widening with segmental to diffuse glomerulosclerosis and presence of IgM and C3, and scanty IgG deposits in the mesangium. Tubulointerstitial lesions were also present. In 6 cats the lesions were severe enough to cause marked increase in blood urea nitrogen and creatinine, and heavy glomerular nonselective proteinuria. These findings suggest that a renal involvement is a frequent occurrence in FIV-infected cats. As the histopathological features observed were similar to those described in HIV-infected patients, FIV-infected cats may represent a valuable model for a better understanding of HIV-associated nephropathy in humans.
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PMID:Renal involvement in feline immunodeficiency virus infection: a clinicopathological study. 832 63

Patients infected with HIV-1 experience several hyperproliferative skin disorders, including seborrheic dermatitis, ichthyosis, and psoriasis. Transgenic mice carrying a subgenomic HIV-1 proviral construct lacking the gag and pol genes were found to develop proliferative epidermal lesions, manifested as diffuse epidermal hyperplasia in homozygous transgenic mice and benign papillomas in heterozygous transgenic mice. Nonpapillomatous skin from both homozygotes and heterozygotes expressed viral RNA, and the viral envelope protein gp120 was localized to the suprabasal keratinocyte. Papillomas contained increased amounts of both viral mRNA and envelope glycoprotein. Exposure of transgenic mice to doses of ultraviolet B (UV-B) irradiation that induced cutaneous injury increased viral gene expression and resulted in the development of papillomas within 14-21 days. Cutaneous injury induced by phenol and liquid nitrogen had similar effects. These data support a role for HIV-1 gene products in the pathogenesis of proliferative epidermal disorders associated with HIV-1 infection. Further, they suggest that the process of wound repair increases HIV-1 gene expression in this transgenic mouse model.
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PMID:Cutaneous disorders and viral gene expression in HIV-1 transgenic mice. 847 18

A series of phosphonoalkenyl and (phosphonoalkenyl)oxy derivatives of purines and a pyrimidine were synthesized. These compounds are the first reported acyclonucleotides which incorporate the alpha,beta-unsaturated phosphonic acid moiety as the phosphate mimic and include compounds in which the acyclic substituent is attached to N-9 of a purine or N-1 of a pyrimidine by either a nitrogen-carbon or a nitrogen-oxygen bond. The phosphonoalkenyl-substituted compounds 7a-c, 8a-c, 9, 10, and 12 were prepared either by Mitsunobu coupling of alcohols with purine or pyrimidine derivatives or by alternative alkylations of the heterocyclic bases. The (phosphonoalkenyl) oxy derivatives 7d-g, 8d-g, and 11 were synthesized by coupling of alcohols with 9-hydroxypurines or a 1-hydroxypyrimidine under Mitsunobu conditions. The novel acyclonucleotides were tested for activity against herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), visna virus, and human immunodeficiency virus type 1 (HIV-1). Guanine derivatives were moderately to extremely cytotoxic, but the adenines were less toxic to cells. At the concentrations tested, (Z)-isomers in the unbranched series had no activity against herpes viruses or HIV-1. (E)-9-[(4-Phosphonobut-3-enyl) oxy]adenine (7d) displayed selective activity against HIV-1, (E)-2,6-diamino-9-(4-phosphonobut-3-enyl) purine (9) showed selective antiretrovirus activity, and (E)-9-[2-(hydroxymethyl)-4-phosphonobut-3-enyl]adenine (7c) showed selective antiherpesvirus (VZV and CMV) activity.
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PMID:Novel acyclonucleotides: synthesis and antiviral activity of alkenylphosphonic acid derivatives of purines and a pyrimidine. 849 3

354 sera from venous blood of patients with various rheumatic diseases and AIDS were assayed for the presence of reactive nitrogen intermediates. Compared to healthy individuals, the serum levels of nitric oxides from patients with connective tissue diseases and inflammatory rheumatic diseases were elevated (P < 0.01) by 170-600% and those from HIV-infected patients by 220%.
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PMID:[Increased level of nitrogen radicals in serum of patients with rheumatic diseases and AIDS]. 851 67


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