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)

Kaposi's Sarcoma (KS) in young individuals is unusual and most often associated with cellular immunodeficiency caused by infective or other neoplastic diseases. It has recently been highly associated with the Acquired Immunodeficiency Syndrome (AIDS). We report the case of a heterosexual 29 year aged man with no evidence of underlying malignancy or infectious diseases. Antibodies to the Human Immunodeficiency Virus (HIV) were absent on repeat testing. His immunological profile demonstrated elevated number of CD8+ cells, normal number of CD3+ and CD4+ cells and hypogammaglobulinemia. These data are distinctly different from those described with AIDS associated KS. The development of KS in young individuals of mediterranean origin may reflect mild degree of immune abnormalities in the absence of infection with HIV.
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PMID:Kaposi's sarcoma in a young man in absence of AIDS or other known causes of immune suppression. 343 54

A 65-year-old man with insulin-dependent diabetes developed intractable pruritus preceding weight loss and increasing fatiguability. Esophagogastroduodenoscopy revealed infection with Candida, cytomegalovirus, and Cryptosporidium. His T cell helper/suppressor ratio was inverted, and the serum human immunodeficiency virus (HIV) antibody was positive. Results of an extensive evaluation for internal malignancy were negative. Despite optimal care, the patient died 12 weeks after his initial hospitalization. We believe that HIV infection should be added to the list of underlying disorders that may present with pruritus.
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PMID:Pruritus as a presenting sign of acquired immunodeficiency syndrome. 358 90

A six-month-old male infant, whose elder brother had died of progressive vaccinia due to combined immunodeficiency, contracted varicella-zoster infection, and died of disseminated varicella ten days after onset of the disease. As with his elder brother, the blood levels of immunoglobulins were normal, and specific varicella antibodies appeared in his serum, although in low concentrations. His T-lymphocytes, although their number was subnormal, could be stimulated with phytohaemagglutinin, and production of migration inhibitory factor could also be demonstrated. The necropsy confirmed thymic dysplasia. In addition to histological changes, severe combined immunodeficiency and foci of malignant lymphoma were present. On this basis the disease was classified, according to the WHO recommendations, as severe combined immunodeficiency with B lymphocytes, complicated by malignant lymphoma.
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PMID:Generalized varicella in severe combined immunodeficiency with B lymphocytes. 697 57

The differences in substrate specificity between Moloney murine leukemia virus protease (MuLV PR) and human immunodeficiency virus (HIV) PR were investigated by site-directed mutagenesis. Various amino acids, which are predicted to form the substrate binding site of MuLV PR, were replaced by the equivalent ones in HIV-1 and HIV-2 PRs. The expressed mutants were assayed with the substrate Val-Ser-Gln-Asn-Tyr decreases Pro-Ile-Val-Gln-NH2 (decreases indicates the cleavage site) and a series of analogs containing single amino acid substitutions in positions P4(Ser) to P3'(Val). Mutations at the predicted S2/S2' subsites of MuLV PR have a strong influence on the substrate specificity of this enzyme, as observed with mutants H37D, V39I, V54I, A57I, and L92I. On the other hand, substitutions at the flap region of MuLV PR often rendered enzymes with low activity (e.g. W53I/Q55G). Three amino acids (His-37, Val-39, and Ala-57) were identified as the major determinants of the differences in substrate specificity between MuLV and HIV PRs.
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PMID:Mutational analysis of the substrate binding pocket of murine leukemia virus protease and comparison with human immunodeficiency virus proteases. 749 42

A 27-year-old male who visited our hospital because of pneumonia was diagnosed as hyper-IgM immunodeficiency syndrome. His serum IgM level was markedly elevated, while the serum level of IgD was normal with a markedly decreased level of serum IgG and IgA. The proportion of T and B cells of peripheral blood lymphocytes was normal. However, B cells bearing surface IgG or IgA were not detectable by immunofluorescence technique. There was a consanguineous marriage in his family, suggesting that his disorder was caused by a genetic abnormality such as X-linked recessive and also autosomal recessive inheritance, although further study is necessary. CD40 ligand cDNA did not appear to contain any abnormal changes within the coding region.
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PMID:An adult diagnosed as hyper-IgM immunodeficiency syndrome. 749 74

In order to facilitate the purification of recombinant proteins for immunization purposes, for example through the construction of solid matrix-antibody-antigen (SMAA) complexes, two small but different tag sequences were attached to the N- and C-termini of recombinant proteins. The 12-amino-acid N-terminal tag (His) contained an array of six histidines which permitted first-step purification by nickel-affinity column chromatography. The C-terminal tag (Pk) was a 14-amino-acid oligopeptide recognized by the monoclonal antibody (mAb) SV5-P-k. The mAb SV5-P-k was linked to a solid matrix and the solid matrix-antibody complexes were saturated with PK-linked recombinant antigens to generate SMAA complexes. The procedure used for construction of the SMAA complexes also acted as a second purification step. Neither of the tag sequences was cleaved from the recombinant proteins before immunization. This two-step purification procedure was used to construct SMAA complexes containing either p17 or reverse transcriptase (rt) of simian immunodeficiency virus (SIV). Mice immunized with these complexes had high antibody titres recognizing both the respective recombinant and native SIV proteins. A weak antibody response was also measured against both the terminal tags. The advantages of using simple dual purification procedures for isolating tag-linked recombinant proteins for use in vaccines are discussed.
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PMID:Two-tag purification of recombinant proteins for the construction of solid matrix-antibody-antigen (SMAA) complexes as vaccines. 750 59

Previous studies showed that an isolated human immunodeficiency virus type 1 (HIV-1) RNase H domain expressed as a fusion protein is highly active in Mn2+, but activity was dependent on a hexahistidine tag located at either the carboxyl or amino terminus of the fusion protein (J. Smith and M. Roth, J. Virol. 67:4037-4049, 1993). It was postulated that a histidine tag can somehow provide a function normally associated with the DNA polymerase domain of HIV-1 reverse transcriptase. To determine the contributions of the DNA polymerase subdomains of HIV-1 reverse transcriptase to its RNase H activity, we have characterized the activity of isolated RNase H domains which include either portions of the connection, the entire connection, or both the thumb and connection as N-terminal extensions. Including increasing lengths of these domains at the N terminus of the RNase H resulted in a progressive increase in Mn(2+)-dependent RNase H activity that was independent of a histidine tag. Activity of the isolated RNase H domains was also stimulated by the addition of independently purified polymerase subdomains. Further, this stimulation was shown to be a result of direct physical interactions between the thumb, connection, and RNase H domains. The connection and thumb subdomains were shown to contribute to substrate binding. The fingers and palm subdomains were found to be essential for Mg(2+)-dependent RNase H activity.
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PMID:Contributions of DNA polymerase subdomains to the RNase H activity of human immunodeficiency virus type 1 reverse transcriptase. 752 94

An active p15 RNase H domain, consisting of amino acids 427-560 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and a genetically engineered penta-histidine N-terminal affinity tag, was expressed in Escherichia coli and purified to apparent homogeneity by immobilized metal affinity chromatography. The purified p15 RNase H domain exhibited no substrate preference for [3H]poly(rG).poly(dC) compared to [3H]poly(rA).poly(dT), in contrast with the HIV-1 RT-associated RNase H, which showed a 30-fold preference for the former substrate. Unlike the HIV-1 RT-associated RNase H, when challenged with unlabeled substrate, the recombinant p15 RNase H domain was relatively nonprocessive in RNA degradative activity of the [3H]poly(rA).poly(dT) duplex. Kinetic studies using p15 RNase H showed substrate inhibition with an apparent K(i) value of 0.12 micron for the [3H]poly(rA).poly(dT) hybrid. Substrate inhibition was not observed for the HIV-1 RT-associated RNase H. The results show that the isolated p15 HIV-1 RNase H domain is functionally distinct from the recombinant HIV-1 RT-associated RNase H.
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PMID:An active recombinant p15 RNase H domain is functionally distinct from the RNase H domain associated with human immunodeficiency virus type 1 reverse transcriptase. 752 Apr 42

The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor quinoxaline S-2720 showed a more-potent inhibitory effect on HIV-1-induced cytopathicity in CEM cells than either nevirapine, pyridinone L-697,661, bis-heteroarylpiperazine (BHAP) U-88204, TSAO ([2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5 "- (4-amino-1",2"-oxathiole-2",2"-dioxide)-N3-ethylthymine, or 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4-benzodiazepin-2(I H)-one (TIBO) R82913. The quinoxaline derivative was also markedly more inhibitory to the mutant HIV-1 strains containing in their RT Ile-100, Asn-103, Ala-106, Lys-138, Cys-181, or His-188 substitutions than were the other HIV-1-specific RT inhibitors. Moreover, quinoxaline S-2720 totally prevented HIV-1 infection and emergence of drug-resistant mutant virus strains in CEM cell cultures at concentrations (i.e., 0.35 microM) that are 10- to 25-fold lower than those required for BHAP U-88204 and nevirapine to knock out the virus. Also, the concentration-response curve for S-2720 was markedly steeper than for BHAP and nevirapine, as reflected by the ratio of the 95% to the 50% antivirally effective concentration. Lower concentrations of quinoxaline dominantly lead to the appearance of the Ala-106 RT mutation, causing low-level resistance to the compound. At higher quinoxaline concentrations, the Glu-190 RT and/or the Cys-181 RT mutation is added to the Ala-106 mutation, whereas at the highest quinoxaline concentrations, the Ala-106 mutation tends to disappear from the virus pool, leaving the Glu-190 RT and Cys-181 RT mutations as the only mutations conferring high-level resistance to the compound.
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PMID:Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase to quinoxaline S-2720. 752 84

The isolated ribonuclease (RNase) H domain of human immunodeficiency virus type 1 (HIV-1) is enzymatically inactive. The incorporation of the putative substrate binding site of Escherichia coli RNase HI (amino acid residues 76-102, the alpha c-helix and adjacent loop region) into the equivalent position of the RNase H domain of HIV-1 resulted in a highly active hybrid protein dependent on Mn2+. Similar restoration of RNase H activity has been observed when histidine residues are added to either the N- or C-terminus of the HIV-1 RNase H domain. The hybrid HIV-1/E. coli RNase H protein is approximately 10-fold more active than HIV-1 reverse transcriptase and 30-fold more active than the histidine-tagged proteins, indicating that the alpha c-helix and adjacent loop region of E. coli RNase HI is an excellent substrate binding region because of its sequence and/or location. The RNase H hybrid produced the same specific cleavage in the model tRNA(Lys3) primer removal assay as HIV-1 reverse transcriptase, showing that substrate binding and specificity are separable and that the specificity determinants are at least partially, if not totally, contained in the amino acid sequence of the hybrid protein derived from HIV-1 reverse transcriptase.
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PMID:Construction of an enzymatically active ribonuclease H domain of human immunodeficiency virus type 1 reverse transcriptase. 753 Mar 60


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