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)

The determination of hydrogen in exhaled air by gas chromatography was used for investigation of patients with relapsing diarrhea of various genesis. An increased H level on an empty stomach, regarded as a sign of bacterial growth in the intestine, was detected in 45% of examines, mainly in celiac disease immunodeficiency, intestinal tuberculosis, diverticulosis, diabetic enteropathy, and erosive duodenitis. An increase in the H level in exhaled air after a lactose tolerance test (50 g of lactose) made it possible to diagnose lactose deficiency in 38% of patients with chronic relapsing diarrhea. In the irritable colon syndrome lactose deficiency was detected in 40% of patients.
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PMID:[Hydrogen test: its diagnostic possibilities in intestinal diseases]. 229 Mar 43

Seventeen paediatric patients with immunodeficiency syndromes (10 with selective IgA deficiency, four with panhypogammaglobulinaemia, and three with selective T cell deficiency) were investigated for bacterial overgrowth of the small intestine and gut permeability to macromolecules. Five of 12 patients showed viable bacterial counts of more than 2 x 10(5)/ml in jejunal fluid. Bacterial overgrowth was also confirmed indirectly by breath hydrogen determination, which was higher than 10 ppm in four of the five patients with positive jejunal culture. Gut permeability to lactulose and L-rhamnose was abnormal in 16 of the 17 immunodeficient patients, who also had higher mean urinary excretion ratios than control subjects-mean (SD) values were 0.216 (0.160) and 0.029 (0.002), respectively. These studies indicate that bacterial overgrowth of the small intestine is a common feature in immunodeficient patients, regardless of the immunological abnormality. Moreover, these patients have an increased gut permeability to macromolecules.
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PMID:Jejunal bacterial overgrowth and intestinal permeability in children with immunodeficiency syndromes. 238 10

Goldmann tonometer tips were inoculated with 5 X 10(5) IU of cell-free or cell-associated human immunodeficiency virus type 1 (lymphadenopathy virus type 1 isolate) or 10(4) plaque-forming units of herpes simplex virus type 1 (McKrae strain) or type 2 (Hicks strain). In an effort to mimic a "worst case" clinical scenario, each respective virus was allowed to air dry on the tonometer tip for 10 minutes. Inoculated tonometers were then (1) not treated, (2) wiped with a disposable (Kim-wipe) tissue or sterile gauze; (3) wiped with sterile gauze soaked with 3% hydrogen peroxide; or (4) wiped with a 70% isopropyl alcohol swab. The hydrogen peroxide treatment and the alcohol wipes both completely disinfected the tonometer tips for human immunodeficiency virus type 1 and herpes simplex virus types 1 and 2, whereas wiping with a sterile gauze or tissue was not effective. Wiping the Goldmann tonometer tip with an isopropyl alcohol swab and then allowing the alcohol to evaporate provides a ready and efficient means of inactivating these three enveloped viruses.
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PMID:Disinfection of Goldmann tonometers against human immunodeficiency virus type 1. 247 33

Natural antiviral activity can be mediated by the interferon-induced synthesis of 2',5'-oligoadenylates (2-5As) and subsequent RNase L activation by these molecules. Analogues of 2-5A that are biologically active and metabolically stable were synthesized and analyzed for antiviral activity against the human immunodeficiency virus type 1 (HIV-1). Replacement of the 3' hydroxyl group of the adenosine moieties of 2-5A with hydrogen atoms (i.e., cordycepin analogues of 2-5A) converted authentic 2-5A trimer into anti-HIV-1 agents in vitro. These cordycepin analogues of 2-5A also inhibited partially purified HIV-1 reverse transcriptase. Introduction of chirality into the 2',5'-phosphodiester internucleotide linkages or 5'-phosphate moieties of the 2-5A molecule (i.e., phosphorothioate analogues of 2-5A) converted authentic 2-5A into more potent inhibitors of HIV-1 reverse transcriptase. However, these phosphorothioate 2-5As demonstrated little or no anti-HIV-1 activity in vitro. Thus, some analogues of 2-5A may form a class of anti-HIV-1 drugs with possible pleiotropic activities that include activation of latent RNase L and inhibition of reverse transcription.
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PMID:Phosphorothioate and cordycepin analogues of 2',5'-oligoadenylate: inhibition of human immunodeficiency virus type 1 reverse transcriptase and infection in vitro. 247 14

Oligonucleotide recognition offers a powerful chemical approach for the sequence-specific binding of double-helical DNA. In the pyrimidine-Hoogsteen model, a binding size of greater than 15 homopurine base pairs affords greater than 30 discrete sequence-specific hydrogen bonds to duplex DNA. Because pyrimidine oligonucleotides limit triple helix formation to homopurine tracts, it is desirable to determine whether oligonucleotides can be used to bind all four base pairs of DNA. A general solution would allow targeting of oligonucleotides (or their analogs) to any given sequence in the human genome. A study of 20 base triplets reveals that the triple helix can be extended from homopurine to mixed sequences. Guanine contained within a pyrimidine oligonucleotide specifically recognizes thymine.adenine base pairs in duplex DNA. Such specificity allows binding at mixed sites in DNA from simian virus 40 and human immunodeficiency virus.
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PMID:Recognition of thymine adenine.base pairs by guanine in a pyrimidine triple helix motif. 254 39

The intestinal microflora of 18 patients with severe B-cell immunodeficiency was studied by determination of short-chain fatty acids (SCFAs) and other intestinal microflora-associated characteristics in the faeces. Glucose-hydrogen (H2) breath test was also performed. The results were within normal values in most of the patients, indicating no major pathologic changes in the intestinal bacterial microflora. These findings do not indicate any important role of the mucosa-associated B-cell system in the regulation of the composition and metabolic activity of the intestinal microflora.
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PMID:Short-chain fatty acids and other intestinal microflora-associated characteristics in faeces of patients with severe B-cell immunodeficiency. 278 88

Nuclease-resistant phosphorothioate analogues of oligodeoxynucleotides (oligos) were synthesized by sulfurization of either internucleoside phosphite linkages, in a repetitive manner during chain extension, or internucleoside hydrogen phosphonate linkages, in a single step following chain assembly. These analogues were tested as antiviral agents against human immunodeficiency virus (HIV). In a cytopathic effect inhibition assay using HIV-uninfected susceptible T cells (tetanus toxoid-specific normal T cells) co-cultured with irradiated chronically HIV-infected cells, phosphorothioate oligomers inhibited the cytopathic effect and replication of several isolates of HIV-1 and HIV-2. Thus phosphorothioate analogues of oligos could inhibit cell-to-cell transmission of the virus as well as the infection by cell-free virus particles and also could inhibit a variety of isolates of human retroviruses.
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PMID:Synthesis of phosphorothioate analogues of oligodeoxyribonucleotides and their antiviral activity against human immunodeficiency virus (HIV). 324 33

The natural product of the Red Sea sponge Verongia sp., identified as 3,5,8-trihydroxy-4-quinolone, was found to be a potent inhibitor of the RNA-directed DNA synthesis of the reverse transcriptases (RTs) of human immunodeficiency viruses type 1 and type 2 (HIV-1 and HIV-2, respectively). This inhibition was unaffected by the nature of the primer template used for DNA synthesis. The DNA-dependent DNA polymerase activity was inhibited to a lesser extent, whereas the ribonuclease H (RNase H) function associated with both HIV RTs was only slightly inhibited. The inhibition by the trihydroxyquinolone is reversible and noncompetitive with respect to both substrates--dTTP and the template primer poly(rA)n.oligo(dT)12-18. The inhibitor binds HIV-1 RT with a high affinity (Ki = 0.46 microM). This compound was shown also to inhibit the catalytic activities of the RT of murine leukemia virus, establishing the general inhibitory effect on retroviral RTs. Introductions of acetyl or methoxy moieties at positions with potential activity have generated three synthetic analogs of the natural compound. Only one analog, 5,8-dimethoxy-4-quinolone, exhibited an inhibition potency similar to that of the unmodified compound. Analysis of the three analogs has led us to the conclusion that the hydroxyl group at the ortho position to the carbonyl group in the pyridinone ring is a key structural element for the inhibitory activity. Thus, it could well be that the inhibitor interacts with the enzyme through a hydrogen bond of this hydroxyl group. We hope that the identification of the inhibitory site of the compound might be an important step toward the rational design of new potent anti-HIV RT drugs.
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PMID:3,5,8-Trihydroxy-4-quinolone, a novel natural inhibitor of the reverse transcriptases of human immunodeficiency viruses type 1 and type 2. 751 Sep 44

The effects of point mutations of the conserved Asp443, Glu478, Asn494, and Asp498 residues in the RNase H domain of human immunodeficiency virus type I (HIV-1) reverse transcriptase (RT) have been analyzed. The mutants fell into two classes: (i) functional RT, but not detectable ribonuclease H activity, and (ii) uncharacterizable phenotype due to protein instability in the context of the RT/protease Escherichia coli co-expression system (Mizrahi, V., Lazarus, G. M., Miles, L. M., Meyers, C. A., and Debouck, C. (1989) Arch. Biochem. Biophys. 273, 347-358). The only mutation in the former class was D443A, whereas those in the latter included D443E, E478D, E478Q, D498E, D443A/D498N, D443E/D498N, D443Q/D498N, N494A, N494D, and N494Q. The results were interpreted in terms of the x-ray crystal structure of the HIV-1 RNase H domain (Davies, J. F., II, Hostomaska, Z., Hostomsky, Z., Jordan, S. R., and Matthews, D. A. (1991) Science 252, 88-95) and a general acid-general base hydrolysis mechanism (Katayanagi, K., Okumura, M., and Morikawa, K. (1993) Proteins Struct. Funct. Genet. 17, 337-346). The data suggested that structural perturbations within the RNase H domain interfered with maturation of the pol precursor by HIV-1 protease. Analysis of selected D443/D498 double mutants suggested that the destabilization caused by the D498N mutation could be suppressed by the formation of a new hydrogen bond between Asn498 and Asn443.
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PMID:Mutagenesis of the conserved aspartic acid 443, glutamic acid 478, asparagine 494, and aspartic acid 498 residues in the ribonuclease H domain of p66/p51 human immunodeficiency virus type I reverse transcriptase. Expression and biochemical analysis. 751 54

Structural and biochemical evidence strongly supports a heterodimeric (p66p51) active form for human immunodeficiency virus-1 reverse transcriptase (RT). Heterodimer stability was examined by sedimentation analysis as a function of temperature and ionic strength. Using NONLIN regression software, monomer-dimer-trimer and monomer-dimer-tetramer association models gave the best fit to the analytical ultracentrifuge sedimentation equilibrium data. The heterodimer is the predominant form of RT at 5 degrees C, with a dimerization Ka value of 5.2 x 10(5) M-1 for both models. Ka values of 2.1 x 10(5) and 3.8 x 10(5) M-1 were obtained for the respective association models at 20 degrees C. RT in 50 and 100 mM Tris, pH 7.0, completely dissociates at 37 degrees C and behaves as an ideal monomeric species. The dissociation of RT as a function of increasing temperature was also observed by measuring the decrease in sedimentation velocity (sw,20). If the stabilization of the heterodimer was due primarily to hydrophobic interactions we would anticipate an increase in the association from 21 degrees C to 37 degrees C. The opposite temperature dependence for the association of RT suggests that electrostatic and hydrogen bond interactions play an important role in stabilizing heterodimers. To examine the effect of ionic strength on p66p51 association we determined the changes in sw,20 as a function of NaCl concentration. There is a sharp decrease in sw,20 between 0.10 and 0.5 M NaCl, leading to apparent complete dissociation. The above results support a major role for electrostatic interactions in the stabilization of the RT heterodimer.
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PMID:Human immunodeficiency virus-1 reverse transcriptase heterodimer stability. 753 May 41


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