Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684275 (haemophilia)
 10,958 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytotoxic T lymphocyte (CTL) responses to human immunodeficiency virus type 1 (HIV-1) gag proteins were studied prospectively in 17 children (12 infected) born of mothers with HIV-1 seropositivity and in five pediatric patients with hemophilia infected by transfusion of HIV-1-contaminated factor VIII concentrate. B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-1 gag gene products were combined with autologous peripheral blood mononuclear cells to detect circulating CTLs. Effector cells were defined by monoclonal antibody-mediated, complement-dependent cytolysis. Circulating HIV-1 gag-specific cytotoxic responses were detectable in 4 of 5 HIV-1-infected pediatric hemophilic patients, and were similar in magnitude to those previously described in adults. In contrast, circulating HIV-1 gag-specific cytolysis was detectible in only 3 of 12 vertically infected children. Depletion data revealed that the majority of detectible gag-specific cytolysis was CD8 T cell-mediated. No apparent relationships between CD4 T cell counts, CD8 T cells counts, or serum p24 antigen levels and CTL responses were seen. Deficient CTL development may, in part, explain the more rapid onset of symptomatic disease following vertical HIV infection.
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PMID:Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children. 190 19

Heat-treated factor VIII has been implicated in the transmission of HIV to hemophiliacs. Previously, evidence has been limited to documenting cases of seroconversion following administration of heat-treated factor VIII. Here, we present evidence of active HIV infection, i.e., infected and not merely sensitized following factor VIII injections. Six Canadians with hemophilia had seroconverted during a longitudinal study of their HIV immune status. Two of the three patients tested by this method demonstrated HIV gag-specific sequences upon amplification by polymerase chain reaction. In addition, HIV-1 virus was isolated from peripheral blood lymphocytes of one of these two persons as shown by reverse transcriptase activity of culture supernatants as well as neutralizable p24 antigen. This, we believe, is the first evidence of active HIV infection following administration of 60 degrees C, 30 h heat-treated factor VIII.
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PMID:Laboratory evidence of active HIV-1 infection in Canadians with hemophilia associated with administration of heat-treated factor VIII. 210 24

A DNA clone of HIV-1, JH3, was isolated from a Japanese patient with hemophilia and the gag and env genes were sequenced. The nucleotide and deduced amino acid sequences were similar to those reported and showed high divergence in the env gene, particularly in the extracellular domain of the env. The genetic variation of JH3 isolated from a Mongolian was within the range of those of isolates from whites and blacks. The gag and env polypeptides were efficiently expressed in E. coli as fusion proteins with beta-galactosidase, and the products were shown to be useful as diagnostic reagents.
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PMID:Nucleotide sequences of gag and env genes of a Japanese isolate of HIV-1 and their expression in bacteria. 266 97

Antibody to human T-cell lymphotropic virus type I (HTLV-I) was measured in 49 Japanese patients (48 with hemophilia) infected with human immunodeficiency virus type 1 (HIV-1) and in 18 hemophiliacs who were not infected with HIV-1, by use of an enzyme-linked immunosorbent assay (ELISA). The antigen used was a gag-env hybrid protein constructed in vitro and expressed in Escherichia coli. This assay detected a specific antibody against HTLV-I. Four of the 18 HIV-1-negative hemophiliacs (22%) were positive for anti-HTLV-I antibody; their geometric mean titer was 951 U/ml. Seven of the 12 patients (58%) with acquired immune deficiency syndrome (AIDS) were positive for anti-HTLV-I antibody, and 8 of 35 HIV-1 + AIDS-free carriers (23%) were positive. The difference between the prevalence of HTLV-I infection in the two groups was statistically significant (p less than 0.0297). The geometric mean titer of antibody in the patients with AIDS was 318 U/ml and that for the HIV-1 + AIDS-free carriers was 1,496 U/ml. These findings suggest that HTLV-I infection could be one of the factors in the development of AIDS in individuals infected with HIV-I.
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PMID:Frequent infection with human T-cell lymphotropic virus type I in patients with AIDS but not in carriers of human immunodeficiency virus type 1. 272 72

The affinity of anti-gag antibody was studied for up to 9 years (1984-1993) in sera from 15 HIV-1+ patients with haemophilia. On the basis of their 1993 clinical status patients were divided into two groups: (i) patients who remained asymptomatic (n = 9); and (ii) those who progressed to AIDS between late 1987 and 1993. The affinity constants of antibody for p24 and p17 were determined by a double isotope fluid-phase radioimmunoassay; and the relationships between antibody affinity and titre, patient clinical course, CD4 cell counts and p24 antigenaemia were analysed. The affinity of p24- and p17-specific antibody was up to 100 times greater in asymptomatic patients than in patients who progressed to AIDS. Patients who developed AIDS either lost or failed to develop high-affinity antibodies early in the infection. Asymptomatic patients maintained high-affinity antibodies for several years; however, in some of these patients the affinity of anti-p24 and p17 antibodies subsequently fell later in the study period. The presence of low-affinity antibody and progressive reduction in the titre of specific antibody were earlier predictors of disease onset than CD4 cell counts. The failure to either develop or maintain high affinity gag-specific antibody suggests an early impairment of T helper function in individuals who progressed to AIDS. The presence of antibody of high affinity could be essential in controlling virus replication and the onset of AIDS.
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PMID:The affinity of IgG antibodies to gag p24 and p17 in HIV-1-infected patients correlates with disease progression. 785 Oct 8

Since 1984, unheated porcine clotting factor VIII (Hyate:C) has been used to treat severe bleeding episodes in persons with hemophilia who have antibodies to human clotting factor. We document the presence of porcine endogenous retrovirus (PERV) in plasma samples of pigs and in clinical lots of Hyate:C. Both gag and pol PERV RNA sequences were detected by reverse-transcriptase (RT) polymerase chain reaction in 13 of 13 lots of Hyate:C tested. Among 10 of these lots, RT activity also was detected, which confirms the presence of retroviral particles. To assess the transmission of PERV to Hyate:C recipients, we tested serum specimens from 88 recipients of Hyate:C and 23 noninfused control subjects for anti-PERV antibodies by using a Western blot assay. None of the samples was positive. Our data document that PERV particles are a common contaminant of Hyate:C products and suggest that the risk of PERV transmission from these percutaneous exposures is very low.
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PMID:Evidence of porcine endogenous retroviruses in porcine factor VIII and evaluation of transmission to recipients with hemophilia. 1117 Sep 92

The practical application of gene transfer as a treatment for genetic diseases such as cystic fibrosis or hemophilia has been hindered, in part, by low efficiencies of vector delivery and transgene expression. We demonstrated that a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the envelope glycoprotein from the baculovirus Autographa californica (GP64) efficiently transduces and persistently expresses a reporter gene in respiratory epithelium in the absence of agents that disrupt cellular tight junction integrity. GP64-pseudotyped FIV also efficiently transduced murine hepatocytes after tail vein delivery. To improve the FIV-based vector, we tested the contribution of a series of modifications to luciferase expression in vitro and in vivo. These modifications included the addition of spleen necrosis virus U5 (SNV U5) and mutation of the major splice donor and gag start codon located in the packaging region of the FIV transgene plasmid. After vector modification, we observed significantly enhanced expression of luciferase in respiratory epithelia after nasal application and in the liver after tail vein delivery. In addition, we observed significantly enhanced human factor VIII production after tail vein delivery. These sequential modifications provide an improved FIV lentivirus platform for gene therapy applications and may be applied to other retroviral vectors.
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PMID:Enhanced gene expression conferred by stepwise modification of a nonprimate lentiviral vector. 1805 20