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)

Every year, between six and eight million people worldwide develop tuberculosis and 2-3 million die of the disease. The situation is worsening due to the epidemic of human immunodeficiency virus (HIV) infection and reactivation of tuberculosis in patients with 'dual infection'. The World Health Organisation estimated that three million persons had 'dual infection' in 1990; 78% occurring in Africa. Tuberculosis, which affects adults during their most productive years and is a curable and preventable disease, has thus become a priority in the 1990s after a period of neglect. It also has some of the most cost effective health interventions available. The thrust of tuberculosis research in developing countries should be to support national tuberculosis control programmes, both in the development of their infrastructure and in research, to assist and develop tuberculosis control strategies.
CDR (Lond Engl Rev) 1991 Nov 08
PMID:Tuberculosis in developing countries. 166 56

Voluntary testing for antibody to human immunodeficiency virus (HIV) was offered to 4929 antenatal patients attending two hospitals in South Manchester during a 12 month period in 1989/90 in order to assess the feasibility of obtaining seroprevalence data by this method. Of these patients, 1728 (35%) agreed to a named test, 1396 (28%) to an unlinked anonymous test and the remaining 37% declined to be tested. The proportion of women tested increased from 22% to 88% over the period, and was similar in those with and without an identified risk factor for infection. One HIV antibody positive patient was found; she was tested anonymously and had no identified risk. The substantial cost in time and money required to establish the universal voluntary testing programme and the incomplete patient compliance confirm the importance of the unlinked anonymous surveys currently being established in the UK to monitor seroprevalence in sentinel populations.
CDR (Lond Engl Rev) 1991 Dec 06
PMID:Voluntary antenatal HIV testing--results of a pilot study. 166 60

The high affinity binding site for human immunodeficiency virus (HIV) envelope glycoprotein gp120 resides within the amino-terminal domain (D1) of CD4. Mutational and antibody epitope analyses have implicated the region encompassing residues 40-60 in D1 as the primary binding site for gp120. Outside of this region, a single residue substitution at position 87 abrogates syncytium formation without affecting gp120 binding. We describe two groups of CD4 monoclonal antibodies (mAbs) which recognize distinct epitopes associated with these regions in D1. These mAbs distinguish between the gp120 binding event and virus infection and virus-induced cell fusion. One cluster of mAbs, which bind at or near the high affinity gp120 binding site, blocked gp120 binding to CD4 and, as expected, also blocked HIV infection of CD4+ cells and virus-induced syncytium formation. A second cluster of mAbs, which recognize the CDR-3 like loop, did not block gp120 binding as demonstrated by their ability to form ternary complexes with CD4 and gp120. Yet, these mAbs strongly inhibited HIV infection of CD4+ cells and HIV-envelope/CD4-mediated syncytium formation. The structure of D1 has recently been solved at atomic resolution and in its general features resembles IgVk regions as predicted from sequence homology and mAb epitopes. In the D1 structure, the regions recognized by these two groups of antibodies correspond to the C'C" (Ig CDR2) and FG (Ig CDR3) hairpin loops, respectively, which are solvent-exposed beta turns protruding in two different directions on a face of D1 distal to the D2 domain. This face is straddled by the longer BC (Ig CDR1) loop which bisects the plain formed by C'C'' and FG. This structure is consistent with C'C'' and FG forming two distinct epitope clusters within D1. We conclude that the initial interaction between gp120 and CD4 is not sufficient for HIV infection and syncytium formation and that CD4 plays a critical role in the subsequent virus-cell and cell-cell membrane fusion events. We propose that the initial binding of CD4 to gp120 induces conformational changes in gp120 leading to subsequent interactions of the FG loop with other regions in gp120 or with the fusogenic gp41 potion of the envelope gp160 glycoprotein.
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PMID:A region in domain 1 of CD4 distinct from the primary gp120 binding site is involved in HIV infection and virus-mediated fusion. 170 42

Human CD4 is the receptor for the gp120 envelope glycoprotein of human immunodeficiency virus and is essential for virus entry into the host cell. Sequence analysis of CD4 has suggested an evolutionary origin from a structure with four immunoglobulin-related domains. Only the two NH2-terminal domains are required to mediate gp120 binding. The extracellular segment of murine CD4 has an overall 50% identity with its human counterpart at the amino-acid level, but fails to bind gp120. To define those residues of human CD4 critical for gp120 binding, we have taken advantage of this species difference and substituted all non-conserved murine for human CD4 residues between amino-acid positions 27-167. We used oligonucleotide-directed mutagenesis to create each of 16 individual mutant human CD4 molecules containing from 1-4 amino-acid substitutions. Introduction of as few as three amino acids into corresponding positions of human CD4 abrogates gp120 binding. Furthermore, these critical residues are located in domain I with a contribution from domain II. Modelling studies using the three-dimensional coordinates of the V kappa Bence-Jones REI homodimer localize the site in domain I to the C" beta strand within CDR2 but projecting away from the homologues of principle antigen-binding regions CDR 1 and 3.
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PMID:Substitution of murine for human CD4 residues identifies amino acids critical for HIV-gp120 binding. 284 73

We report on the first four years (1990-93) of a survey within the national HIV prevalence monitoring programme. The survey's objective is to monitor the prevalence of infection with the human immunodeficiency virus (HIV) in pregnant women in London and elsewhere in England. The survey--based in forty centres that offer antenatal care in London, Greater Manchester, West Yorkshire, and adjacent non-metropolitan areas--uses repeated cross sectional serosurveillance for anti-HIV-1 and 2 and the unlinked anonymous test method on blood left over from specimens collected for antenatal screening for immunity to rubella. The seroprevalence of HIV-1 ranged from 0.007% (1 in 14,530) in non-metropolitan areas, to 0.011% (1 in 8790) in metropolitan areas outside London, and 0.23% (1 in 440) in London. Evidence of HIV-2 infection was found in only four specimens, in London (1 in 50,300). The seroprevalence of HIV-1 in London varied more than tenfold between centres, from 0.03% (1 in 3190) to 0.51% (1 in 200). The highest prevalence of infection was in London in women aged between 20 and 30 (0.30%; 1 in 335). The seroprevalence in London centres rose from 0.18% in 1990 (1 in 560) to 0.26% in 1993 (1 in 390) and the rise was significant in all age groups. If voluntary confidential HIV testing (with counselling) among pregnant women in England were to be promoted, its cost effectiveness would be greater if focused on particular centres that provide antenatal care in London.
Commun Dis Rep CDR Rev 1994 Sep 16
PMID:Survey of human immunodeficiency virus infection among pregnant women in England and Wales: 1990-93. 752 76

We describe a new active surveillance system for human immunodeficiency virus (HIV) infection in the West Midlands region, a National Health Service administrative area in central England serving a population of five million. A detailed, confidential dataset is collected on each case of HIV infection identified through laboratory reporting of positive HIV antibody tests. The consultant in communicable disease control in each district health authority responsible for the surveillance of infectious disease collects and updates the data, which are then shared with staff at the regional health authority (RHA) who maintain a regional database. Regular reports from this database allow local monitoring of the epidemic and the equitable allocation of resources.
Commun Dis Rep CDR Rev 1993 Aug 13
PMID:Active surveillance of HIV infection in the West Midlands. 769 72

Autoimmune reactivity is a consequence of infection with human immunodeficiency virus (HIV). We studied serological cross-reactions of purified pooled IgG from sera of HIV-infected individuals by using nested sets of synthetic overlapping peptides duplicating the covalent structures of T-cell receptors (TCRs) and immunoglobulin light chains and report that two processes of autoantibody production occur. (i) IgG autoantibodies to putative regulatory variable domain CDR1 and FR3 epitopes (where CDR is complementarity-determining region and FR is framework region) are present in pooled IgG from HIV-infected individuals at levels 10-fold greater than that in pooled IgG from healthy humans. (ii) Anti-TCR autoimmunization involves antigenic mimicry between a conserved peptide stretch of the major neutralizing V3 loop determinant of HIV-1 gp120 and the conserved FR4 segment of the TCR V beta. Affinity-purified antibodies to the synthetic V3 loop peptide bound to a recombinant single-chain TCR and to a synthetic TCR joining segment peptide containing the FR4 sequence. Conversely, affinity-purified autoantibodies from pooled IgG from HIV-infected individuals to the TCR peptide bound the V3 loop peptide and a single-chain TCR. Inhibition studies indicated that the cross-reactive immunizing antigen was the V3 loop. These results bear upon the impact of HIV infection on immune regulation and on the selection of peptides for vaccine development.
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PMID:Autoantibodies to the alpha/beta T-cell receptors in human immunodeficiency virus infection: dysregulation and mimicry. 797 73

The CDR-3 region of CD4 has been proposed to be involved in the fusion reaction between human immunodeficiency virus type 1 (HIV-1) and CD4+ cells, either at a stage involving virus binding or subsequent to virus binding. Part of the evidence for this has been the observation that monoclonal antibodies (MAbs) to CDR-3 block HIV infection potently without strongly inhibiting the binding of monomeric gp120 to CD4. Here I show that, in a system using oligomeric, virion-bound gp120, a MAb to CDR-3 resembles those to CDR-2 in that it inhibits soluble CD4 binding to virions. Consequently, ternary complexes of MAb-soluble CD4-gp120 cannot be detected with CDR-2 MAbs and are detectable only at a very low level with a CDR-3 MAb, but they clearly form when a control MAb to CD4 domain 4 is used. Although not in direct conflict with previously published data on the role of CDR-3 MAbs in the inhibition of HIV-1 infection, these experiments do not support the hypothesis that the CDR-3 region is specifically involved in virus entry at a postbinding stage.
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PMID:A monoclonal antibody to the CDR-3 region of CD4 inhibits soluble CD4 binding to virions of human immunodeficiency virus type 1. 849 74

The role of the CDR-3-like loop of the first domain of the CD4 molecule in infection by the human immunodeficiency virus type 1 (HIV-1) is controversial. In an attempt to determine whether the strong negative charge in the CDR-3-like loop influences HIV-1 infection we have substituted by mutagenesis negative for positively charged residues at position 87/88 and 91/92. These mutations were shown to have no obvious effect on CD4 conformation outside of the CDR-3-like loop. Infection of cells expressing the E87K/D88K substitution mutant resulted in a selective reduction in infectivity for certain HIV-1 viruses compared to cells expressing wile-type CD4. Viruses Hx10, HxB2, and MN were 4- to 13-fold less efficient at infecting the E87K/D88K mutant, whereas SF2, RF, and NDK yielded an efficiency of infection similar to, or slightly greater than, that of the wild type. To investigate the step at which infectivity was selectively reduced, we compared early events in the life cycles of Hx10 and SF2 viruses using PCR entry and gp120-binding assays. Both gp120 binding and virus entry were reduced for Hx10 on the mutant CD4-expressing cells as compared to wild-type CD4-expressing cells, whereas no difference was seen in either assay with SF2. Although relatively small in magnitude, the contribution of the CDR-3-like loop to the overall CD4-gp120 interaction may serve to modify the binding and entry of certain virus isolates.
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PMID:Selective effects of electrostatic changes in the CD4 CDR-3-like loop on infection by different human immunodeficiency virus type 1 isolates. 882 16

Individuals seropositive for human immunodeficiency virus type 1 (HIV) express elevated levels of autoantibodies (AAbs) directed against recombinant T-cell receptors (TCRs) and synthetic peptide epitopes duplicating beta chain markers. We performed longitudinal studies of anti-TCR AAbs in HIV-1-infected individuals, making comparisons with uninfected sera and sera from other individuals infected with a nonviral agent. We determined levels of autoantibodies by titration using enzyme-linked immunosorbent assay (ELISA) and developed a means for characterizing "autoantibody CDR recognition spectrotypes" for individual sera. Antibody levels against certain defined synthetic epitopes were substantially elevated in HIV-infected subjects relative to reactivities by control groups. Individual sera showed relatively high AAb levels to a subset of CDR1 peptide epitopes. Two patients who subsequently developed AIDS showed particular reactivity to Vbeta2.1, 8.1, 10.1, and 22.1 epitopes. Our results show that production AAbs to TCR Vbeta epitopes is a general consequence of HIV infection. The response is individual but shows some restriction and shifts in AAb subpopulations often occur with time.
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PMID:Analysis of autoantibodies to T-cell receptors among HIV-infected individuals: epitope analysis and time course. 900 Apr 86


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