Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pretreatment of mice with ammonia extract of seed shell of Pinus Koraicenis, via the intraperitoneal or intravenous route, effectively protected them from lethal infection of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The pine seed shell extract also moderately inhibited syncytium formation and cytopathogenic effect induced by human immunodeficiency virus (HIV) infection in cultured human lymphotropic virus type I (HTLV-1) positive MT-4 cells. These data suggest a medicinal potential of pine seed shell extract against opportunistic infection in HIV patients.
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PMID:Effect of pine seed shell extract on microbial and viral infection. 162 38

The glycosylation of 3,4-dicyano-2-[(ethoxymethylene)amino]pyrrole (7) with 2-deoxy-2-fluoro-alpha-D-erythro-pentofuranosyl bromide (2) furnished an anomeric mixture of nucleosides (8a,b). This mixture was separated, and the individual anomers were treated with methanolic ammonia to effect a concomitant deblocking and ring closure. This furnished both anomers of 2'-deoxy-2'-fluoro-ara-toyocamycin (9a,b). The cyano moiety of 9b was converted to the carboxamide moiety to furnish 2'-deoxy-2'-fluoro-ara-sangivamycin (10) and to the thiocarboxamide moiety to furnish 2'-deoxy-2'-fluoro-ara-thiosangivamycin (11). The target compounds 10 and 11 showed similar antiproliferative activity against L1210 cells in vitro, with IC50's of 3 and 5 microM. Antiviral evaluation revealed a somewhat different pattern of activity. All analogs, both alpha and beta anomers, were active against human cytomegalovirus (HCMV), albeit the beta anomers were most active. The beta anomers also were active against herpes simplex virus type 1 (HSV-1) and human immunodeficiency virus (HIV). Compound 10 was most active in the series, ca. 10-fold more potent than 11; IC50's for 10 ranged from 4 to 25 nM for HCMV, HIV, and varicella zoster virus (VZV) and from 30 to 500 nM for HSV-1. Even though compound 10 was cytotoxic, which will probably preclude its use as an antiviral drug (IC50's = 0.2-5.5 microM), the difference between cytotoxicity and activity against HCMV, HIV, and VZV was sufficient to indicate specific activity against a viral target.
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PMID:Synthesis and antiproliferative and antiviral activity of 2'-deoxy-2'-fluoroarabinofuranosyl analogs of the nucleoside antibiotics toyocamycin and sangivamycin. 756 46

Groups of 5'-phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-acetylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene, or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonyl-phosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by the action of ammonia in methanol. All compounds were tested for inhibition of several viruses, including human herpes simplex virus type 2 and cytomegalovirus, but showed no activity. A few compounds insignificantly inhibited human immunodeficiency virus type 1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized the anti HIV action of 3'-azido-3'-deoxythymidine, thus indirectly showing that it could be partly hydrolyzed in cell culture to corresponding thymidine.
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PMID:[Ribonucleoside and 2'-deoxyribonucleoside 5'-phosphonates: synthesis and antiviral activity]. 814 53

The majority of AIDS patients will experience some degree of dementia induced by human immunodeficiency virus (HIV-1). In this study, we report that treatment of human brain tissue with envelope gp120 of HIV-1 did not cause neuronal death but did cause astrocyte alterations and/or death. Human astrocyte cultures showed decreased expression of glial fibrillary acidic protein (GFAP), as well as the diminution of a major protein of 66 kDa. These findings are similar to the in vitro changes observed when astrocytes are exposed to ammonia and in vivo changes observed in experimental hepatic encephalopathy. We hypothesize that AIDS dementia may partially involve a perturbation of astrocyte function by gp120 that could indirectly impair neuronal function.
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PMID:HIV-1 envelope gp120 alters astrocytes in human brain cultures. 831 70

6-Chloropurine arabinoside (3a) was obtained by treatment of the 2'-O-acetylated congener (2) with ammonia in methanol. The 3',5'-di-O-tritylated riboside (6) was allowed to react with diethylaminosulfur trifluoride (DAST) in the presence of pyridine to give the 2'-deoxy-2'-fluoroarabinoside (7), from which 6-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)purine (3b) was obtained. The antiviral effects of 3a and 3b were assayed against several DNA and RNA viruses. Only 3a displayed potent activity against varicella-zoster virus (VZV). This antiviral activity was dependent on phosphorylation by the VZV-induced thymidine kinase (TK). Compound 3a showed moderate activity against other DNA viruses, herpes simplex type 1 (HSV-1) and type 2 (HSV-2), and vaccinia virus. They were equally active against TK- and TK+ strains of HSV-1, which suggests that the HSV-1-encoded TK does not play a role in the anti-HSV-1 activity. No activity was noted with any of the compounds against various RNA viruses, including human immunodeficiency virus, at subtoxic concentrations.
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PMID:Synthesis and antiviral activity of 6-chloropurine arabinoside and its 2'-deoxy-2'-fluoro derivative. 899 65

It is well known that cases with multiple myeloma reveal various clinical manifestations such as pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary type hyperamylasemia and elevated serum C-reactive protein (CRP) concentration, have been reported. The elevation of CRP is thought to be related to interleukin-6 (IL-6) production by myeloma cells, because of identification of IL-6 as an autocrine and/or paracrine growth factor for myeloma cells. More recently, there have been several reports of cases with myeloma associated with hyperammonemia. This hyperammonemia is not considered to be due to liver dysfunction, because in most of these cases tests revealed normal hepatic function, and some cases showed different patterns of serum amino acid distribution than that associated with hepatic failure. However, there have been no apparent observations of ammonia production by myeloma cells. In this study, we used six human myeloma cell lines including KMS-18, which was recently established from a myeloma case associated with hyperammonemia. These lines were treated with MRA (mycoplasma removal agent) to observe ammonia production in vitro. They produced and released significantly higher levels of ammonia into culture medium than non-myeloma hematological cell lines or the HepG2 human hepatic carcinoma cell line. Although attempts to analyze the relative expression levels of the enzymes related to ammonia biosynthesis using the reverse transcriptase-polymerase chain reaction assay failed to detect any differences between these myeloma lines and other cell lines, in vitro excess ammonia production by the myeloma cells was confirmed and the relevance to clinical manifestations is discussed.
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PMID:In vitro excess ammonia production in human myeloma cell lines. 966 3

Synthesis of (R)-(-)- and (S)-(+)-synadenol (1a and 2a, 95-96% ee) is described. Racemic synadenol (1a + 2a) was deaminated with adenosine deaminase to give (R)-(-)-synadenol (1a) and (S)-(+)-hypoxanthine derivative 5. Acetylation of the latter compound gave acetate 6. Reaction with N, N-dimethylchloromethyleneammonium chloride led to 6-chloropurine derivative 7. Ammonolysis furnished (S)-(+)-synadenol (2a). Absolute configuration of 1a was established by two methods: (i) synthesis from (R)-methylenecyclopropanecarboxylic acid (8) and (ii) X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. Racemic methylenecyclopropanecarboxylic acid (10) was resolved by a modification of the described procedure. The R-enantiomer 8 was converted to ethyl ester 13 which was brominated to give vicinal dibromides 14. Reduction with diisobutylaluminum hydride then furnished alcohol 15 which was acetylated to the corresponding acetate 16. Alkylation-elimination procedure of adenine with 16 yielded acetates 17 and 18. Deprotection with ammonia afforded a mixture of Z- and E-isomers 1a and 19 of the R-configuration. Comparison with products 1a and 2a by chiral HPLC established the R-configuration of (-)-synadenol (1a). These results were confirmed by X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. The latter forms a pseudosymmetric dimer with adenine-adenine base pairing in the lattice with the nucleobase in an anti-like conformation. Enantiomers 1a and 2a exhibit varied enantioselectivity toward different viruses. Both enantiomers are equipotent against human cytomegalovirus (HCMV) and varicella zoster virus (VZV). The S-enantiomer 2a is somewhat more effective than R-enantiomer 1a in herpes simplex virus 1 and 2 (HSV-1 and HSV-2) assays. By contrast, enantioselectivity of antiviral effect is reversed in Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1) assays where the R-enantiomer 1a is preferred. In these assays, the S-enantiomer 2a is less effective (EBV) or devoid of activity (HIV-1).
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PMID:(R)-(-)- and (S)-(+)-Synadenol: synthesis, absolute configuration, and enantioselectivity of antiviral effect. 985 93

The purpose of this study was to determine the rate of whole body protein turnover (WBPT) in human immunodeficiency virus (HIV)-infected children, and to determine the relationship between WBPT and growth. The rate of WBPT was calculated from the cumulative excretion of labeled urinary ammonia after a single intravenous dose of 15N-glycine in three groups of children: 1) HIV+ with growth retardation (HIV+ Gr); 2) HIV+ with normal growth (HIV+); and 3) HIV-uninfected with normal growth (HIV-). Twenty-six children between 2 and 11 y of age were studied (10 HIV+ Gr, 12 HIV+, 4 HIV-). All children were afebrile and free of acute infection during the study. Rates of WBPT (mean +/- SD) for the study groups were: HIV+ Gr, 12.2 +/- 4.8; HIV+, 10.7 +/- 5.1; and HIV-, 8.6 +/- 2.1 g.protein.kg-1.d-1 (NS, P > 0.05). Although not statistically significant, mean WBPT was 42% greater in HIV+ Gr, and 24% greater in HIV+ compared to HIV-. Statistically significant correlations were found between WBPT and Z scores for height (r = -0.39, P = 0.05) and weight-for-age (r = -0.51, P = 0.01) and dietary intake of protein (r = 0.39, P = 0.05), and between protein balance (synthesis-catabolism) and intakes of energy (r = 0.47, P = 0.02) and protein (r = 0.40, P = 0.04). There was no statistically significant correlation between WBPT and resting energy expenditure (r = 0.27, P = 0.19), or CD4 cell number (r = 0.05, P = 0.82). These data suggest an association between increased rates of protein turnover and low weight and height-for-age Z scores, and that it may be possible to achieve positive protein balance given an adequate intake of nutrients.
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PMID:Whole body protein turnover in children with human immunodeficiency virus (HIV) infection. 1019 12

Capillary electrophoresis coupled with tandem mass spectrometry was used to indirectly separate and quantify the active metabolite of the anti-human immunodeficiency virus (anti-HIV) didanosine drug. The influence of several parameters (pH and ionic strength of volatile formic acid-ammonia buffer) upon electroosmotic flow, electrophoretic mobility and peak efficiency of several nucleosides (A, dA, ddA, C) has been studied. This paper illustrates the current importance in CE-MS technique as a complementary or substituted method to the known HPLC-radioimmunoassay or HPLC-UV method to measure levels of anti-HIV drugs. The limit of detection for 2',3'-dideoxyadenosine by this method is 2 microg 1(-1) in a formic acid-ammonia buffer (pH 2.5, 10 mM ionic strength). This methodology could be used to perform simultaneous detection of two or more anti-HIV nucleosides, such as stavudine or didanosine in combination therapy.
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PMID:Determination at ppb level of an anti-human immunodeficiency virus nucleoside drug by capillary electrophoresis-electrospray ionization tandem mass spectrometry. 1110 52

A human immunodeficiency virus type 1 (HIV-1) subtype E (CRF01_AE) variant (99JP-NH3-II) possessing an in-frame 33-nucleotide insertion mutation in the beta3-beta4 loop coding region of the reverse transcriptase (RT) gene was isolated from a patient who had not responded to nucleoside analogue RT inhibitors. This virus exhibited an extremely high level of multiple nucleoside analog resistance (MNR). Neighbor-joining tree analysis of the pol sequences indicated that the 99JP-NH3-II variant had originated from the swarm of drug-sensitive predecessors in the patient. Population-based sequence analyses of 82 independently cloned RT segments from the patient suggested that the variants with the insertion, three or four 3'-azido-3'-deoxythymidine resistance mutations, and a T69I mutation in combination had strong selective advantages during chemotherapy. Consistently, in vitro mutagenesis of a drug-sensitive predecessor virus clone demonstrated that this mutation set functions cooperatively to confer a high level of MNR without deleterious effects on viral replication capability. Homology modeling of the parental RT and its MNR mutant showed that extension of the beta3-beta4 loop by an insertion caused reductions in the distances between the loop and the other subdomains, narrowing the template-primer binding cleft and deoxynucleoside triphosphate-binding pocket in a highly flexible manner. The origin of the insert is elusive, as every effort to find a homologue has been unsuccessful. Taken together, these data suggest that (i) HIV-1 tolerates in vivo insertions as long as 33 nucleotides into the highly conserved enzyme gene to survive multiple anti-HIV-1 inhibitors and (ii) the insertion mutation augments multiple-drug resistance, possibly by reducing the biochemical inaccuracy of substrate-enzyme interactions in the active center.
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PMID:Augmentation of human immunodeficiency virus type 1 subtype E (CRF01_AE) multiple-drug resistance by insertion of a foreign 11-amino-acid fragment into the reverse transcriptase. 1135 68


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