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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On February 23, 1995, Serono Symposia/USA sponsored a meeting of leading endocrine researchers in the field of wasting disorders to compare notes and to advance knowledge about AIDS-related wasting. Presenter Richard Rabkin, MD, of Columbia University, reported on a study of 72 men who completed a 12-week trial of biweekly testosterone replacement therapy. Mean weight increased significantly and body composition changes were noted. Of particular interest was speaker Morris Schambelan, MD, of San Francisco General Hospital, who presented "The Use of Anabolic Agents in HIV Infection". Schambelan reported on a study of HIV-positive patients who received recombinant human growth hormone (Serostim) for wasting. The study results showed both total body weight and lean body mass gain, along with simultaneous decreases in fat levels. Patients in the study had documented nitrogen level changes and protein oxidation changes. Schambelan's use of a nitrogen-retention assay and a new body-scanning system may pave the way for future Food and Drug Administration (FDA) approval of anabolic agents for the treatment of wasting. Carl Grunfeld, MD, ruled out some of the previously theorized causes of wasting. Finally, Gilla Kaplan, MD, reported on preliminary results from the thalidomide study at Rockefeller University, which show that thalidomide helps patients with HIV and tuberculosis by reducing weight loss.
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PMID:Turning the corner on wasting? A symposium on wasting disorders. 1136 43

The nutritional abnormalities resulting from HIV/AIDS are discussed, including the consequences of wasting and its profound effects on patient quality of life. Deficits of vitamins A, E, B6 and B12, and riboflavin, zinc, and copper have been found in asymptomatic HIV-positive persons. The nutrient abnormalities may be linked to HIV disease progression. The cyclic process of contracting infections, requiring increased nutrients, is discussed. How the body suffering from HIV/AIDS-related wasting reacts to daily protein loss is examined, focusing on nitrogen depletion and increased lipogenesis.
HIV Hotline 1998 May
PMID:Nutritional abnormalities in HIV/AIDS. 1136 62

Some new fused heterobicyclic nitrogen systems such as 1,2,4-triazino[3,4-b] [1,3,4] thiadiazolones/thiadiazinones 4-15 and the related compounds 16-21 have been synthesized from treatment of 4-amino-3-mercapto-6-substituted-1,2,4-triazin-5-ones 1 with bifunctional oxygen and halogen compounds via heterocyclization reactions. Structures of the products have been deduced from their elemental analysis and spectral data. Significant anti-HIV and anticancer activities were observed in vitro for some members of the series, compounds 1e, 4e, 4f, 5, 6 and 16 showing a significant activity in Leukemia, Lung, Breast and CNS anticancer evaluation.
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PMID:Synthesis of heterobicyclic nitrogen systems bearing the 1,2,4-triazine moiety as anti-HIV and anticancer drugs, part III. 1140 May 52

Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems, yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAPE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAPE. The preparation of these CAPE isothiocyanates, required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta-mercaptoethanol (beta-ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAPE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta-ME for catalytic activity. Although in these latter enzymes, CAPE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies, is that upon binding of CAPE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands.
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PMID:Arylisothiocyanate-containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase. 1142 64

HIV-1 infection is associated with a dramatic reduction in antioxidative molecules both at the cellular level and in the circulation. This is particularly so for lactoferrin, an iron-binding protein involved in natural defenses (antimicrobial and antiviral activities, etc.) and found in whole secretions, including milk and mucus. In addition to its ability to chelate iron ions, lactoferrin inhibits hydroxy radical formation and interacts with nitric oxide (NO). Levels of plasma lactoferrin decreased in HIV-1-infected patients in correlation with progression of the disease, and highly specific anti-lactoferrin autoantibodies increased. This profile was specific to HIV-1 infection; it was not found in HIV-2-infected patients. In parallel with the drop in lactoferrin, a marked increase in circulating nitrogen derivatives was observed in HIV-1-infected patients, whereas low levels were found in normal donors and in HIV-2-infected patients. These data suggested hyperstimulation of the NO pathway throughout HIV-1 but not HIV-2 infection. This overproduction of NO could play an important role in the development of AIDS symptoms and signs.
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PMID:Differential pattern in circulating nitrogen derivatives, lactoferrin, and anti-lactoferrin antibodies in HIV type 1 and HIV type 2 infections. 1148 21

Multiple-quantum 2D and 3D bi-directional HCNCH experiments are presented for the correlation of base and ribose protons/carbons in 13C/15N labeled HIV-1 TAR RNA. In both 2D and 3D experiments, the magnetization of H1' is transferred to H6/H8 and H1' through H1'-C1'-N1/9-C6/8-H6/8 and H1'-C1'-N1/9-C1'-H1' pathways, and the magnetization of H6/8 is transferred to H1' and H6/8 through H6/8-C6/8-N1/9-C1'-H1' and H6/8-C6/8-N1/9-C6/8-H6/8 pathways. Chemical shifts of four different nuclei (H1', C1', C6/8 and H6/8) are sampled in the 2D experiment. The correlation of base and ribose protons/carbons is established by the rectangular arrangement of crossover and out-and-back peaks in the proton/carbon correlated spectrum. The rectangular connections can be further resolved using the nitrogen dimension in a 1H/13C/15N 3D experiment. Furthermore, by taking advantage of the well separated chemical shifts of N1 (pyrimidine) and N9 (purine), the 2D spectrum can be simplified into two sub-spectra based on their base type. Both experiments were tested on a 13C/15N labeled 27-mer HIV-1 TAR RNA containing a UUCG hairpin loop.
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PMID:Novel 2D and 3D multiple-quantum bi-directional HCNCH experiments for the correlation of ribose and base protons/carbons in 13C/15N labeled RNA. 1149 47

Previous investigations of the potential of metal-organic compounds as inhibitors of human immunodeficiency virus type I protease (HIV-1 PR) showed that the copper(II) complex diaqua [bis(2-pyridylcarbonyl)amido] copper(II) nitrate dihydrate and the complex bis[N2-(2,3,6-trimethoxybenzyl)-4-2-pyridinecarboxamide] copper(II) behaved as inhibitors of HIV-1 PR. In a search for similar readily accessible ligands, we synthesised and studied the structural properties of N2-(2-pyridylmethyl)-2-pyridinecarboxamide (L) copper(II) complexes. Three different crystal structures were obtained. Two were found to contain ligand L simultaneously in a tridentate and bidentate conformation [Cu(L(tri)L(bi))]. The other contained two symmetry-related ligands, coordinated through the pyridine nitrogen and the amide oxygen atoms [Cu(L(bi))(2)]. A search of the Cambridge Structural Database indicated that L(tri) resulting from nitrogen bound amide hydrogen metal substitution is favoured over chelation through the amide oxygen atom. In our case, we calculated that the conformation of L(tri) is 11 kcal/mol more favourable than that of L(bi). ESI-MS experiments showed that the Cu(L(bi))(2) structure could not be observed in solution, while Cu(L(tri)L(bi))-related complexes were indeed present. The lack of protease inhibition of the pyridine carboxamide copper(II) complexes was explained by the fact that the Cu(L(bi)L(tri)) complex could not fit into the HIV-1 active site.
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PMID:Synthesis and structural analysis of the copper(II) complexes of N2-(2-pyridylmethyl)-2-pyridinecarboxamide. 1156 26

Twenty-six simple isoquinolines and 21 benzylisoquinolines were tested for antimicrobial, antimalarial, cytotoxic, and anti-HIV activities. Some simple isoquinoline alkaloids were significantly active in each assay, and may be useful as lead compounds for developing potential chemotherapeutic agents. These compounds include 13 (antimicrobial), 25, 26, and 42 (antimalarial), 13 and 25 (cytotoxic), and 28 and 29 (anti-HIV). A quaternary nitrogen atom of isoquinolium or dihydroisoquinolinium type may contribute to enhanced potency in the first three types of activities. In contrast, anti-HIV activity was found with tetrahydroisoquinoline and 6,7-dihydroxyisoquinolium salts.
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PMID:Simple isoquinoline and benzylisoquinoline alkaloids as potential antimicrobial, antimalarial, cytotoxic, and anti-HIV agents. 1159 68

High DNA viral load in Human Papillomavirus type 16 cervical dysplastic lesions has been proposed as a marker of progression towards malignancy. To evaluate the prognostic value of DNA viral load in infection by HPV type other than HPV-16, a longitudinal study of patients with Anogenital Condylomata (AC) was designed. The study included 40 patients, 25 men and 15 women. Clinical data were collected through standard interview and routine serum analyses. Viral type in lesions was assayed by PCR with general primers (MY09-MY11) and Restriction Fragment Length Polymorphism (RFLP). Viral load was determined by PCR end point determination with type specific primers on serial sample dilutions. The duration of ano-genital lesions upon liquid nitrogen standard cryotherapy or Podofillin chemotherapy was correlated with viral and clinical data. Patients with higher lesional viral load at study entry showed a markedly longer disease clinical course than patients with lower viral loads. The HPV-6 was observed in 31 out of 40 patients (77.5%), much more frequently than HPV-11 (7/40 17.5%), the latter being associated with higher titres of viral load. Two cases (5%) remained undetermined. No HPV-16 or other high-risk type was detected, while HPV-61, not uncommon in Italy, was found once in a double infection carried by an HIV positive patient. No significant association was observed between clinical outcome and demographic and epidemiological data, or risk factors.
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PMID:Detection of HPV in genital condylomata: correlation between viral load and clinical outcome. 1171 18

In 2HJ(NN)-COSY experiments, which correlate protons with donor/acceptor nitrogens across Nd...HNa bonds, the receptor nitrogen needs to be assigned in order to unambiguously identify the hydrogen bond. For many situations this is a non-trivial task which is further complicated by poor dispersion of (Na,Nd) resonances. To address these problems, we present pulse sequences to obtain direct, internucleotide correlations between protons in uniformly 13C/15N labeled nucleic acids containing Nd...HNa hydrogen bonds. Specifically, the pulse sequence H2(N1N3)H3 correlates H2(A,omega1):H3(U,omega2) protons across Watson-CrickA-U and mismatched G.A base pairs, the sequences H5(N3N1)H1/H6(N3N1)H1 correlate H5(C,omega1)/H6(C,omega1):H1(G,omega2) protons across Watson-Crick G-C base pairs, and the H2(N2N7)H8 sequence correlates NH2(G,A,C;omega1):H8(G,A;omega2) protons across G.G, A.A, sheared G.A and other mismatch pairs. These 1H-1H connectivities circumvent the need for independent assignment of the donor/acceptor nitrogen and related degeneracy issues associated with poorly dispersed nitrogen resonances. The methodology is demonstrated on uniformly 13C/15N labeled samples of (a) an RNA regulatory element involving the HIV-1 TAR RNA fragment, (b) a multi-stranded DNA architecture involving a G.(C-A) triad-containing G-quadruplex and (c) a peptide-RNA complex involving an evolved peptide bound to the HIV-1 Rev response element (RRE) RNA fragment.
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PMID:1H-1H correlations across N-H...N hydrogen bonds in nucleic acids. 1182 50


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