Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Thirty-nine patients from the Nebraska Regional Hemophilia Center were studied for the prevalence and titers of antibodies to HTLV-III/LAV, and for clinical symptoms of possible progression toward the acquired immunodeficiency syndrome (AIDS). Fourteen of 26 (54%) patients with hemophilia A were positive for HTLV-III/LAV antibodies as determined by immunofluorescence and Western blotting. Retrovirus was detected in cultured lymphocytes of two out of three seropositive individuals by reverse transcriptase assay and molecular hybridization with cloned HTLV-III/LAV probe. Of the twelve factor VIII-deficient patients who were seronegative, one had received only heat-treated factor VIII concentrates, six only cryoprecipitate or fresh frozen plasma, two prothrombin complex concentrates, one had not been transfused since 1983, and two had never been transfused. None of the patients treated only with factor IX concentrates, volunteer donor plasma, or cryoprecipitate had HTLV-III/LAV antibodies. In 12 of 14 seropositive hemophiliacs, titers of serum antibodies to HTLV-III/LAV ranged from 1:1,280 to 1:10,240, indicating a strong immune response against HTLV-III/LAV antigens and/or persistent infection with the virus. In spite of the possible exposure to HTLV-III/LAV during the past four years, none of the patients in this group had AIDS. Whether or not this group of patients has developed immunity to the AIDS retrovirus remains to be determined.
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PMID:HTLV-III/LAV antibodies and virus in hemophilia patients in Nebraska: survey and initiation of a prospective study. 242 67

The management of haemophilia has been greatly complicated by the clinical sequelae of viral infection acquired through contaminated blood products. Many haemophiliacs have been infected by several viruses and the interaction between these viruses may be complex. In a cohort of 42 anti-HCV positive haemophiliacs, five were also found to be positive for HBsAg. All five were HCV reverse transcriptase/PCR negative compared to the 4/37 (11%) anti-HCV positive haemophiliacs who were HBsAg negative (P = 0.0001). We have identified a striking interaction between hepatitis C (HCV) and hepatitis B (HBV) in haemophiliacs co-infected by these agents, suggestive of the phenomenon of viral interference.
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PMID:Interaction of hepatitis B and hepatitis C infection in haemophilia. 751 Sep 94

The molecular characterization of mutations in haemophilia A patients in this study was carried out by PCR-SSCP, Southern blotting, and reverse transcribed-PCR. A multiplex PCR in which four to eight exons were co-amplified was developed to reduce the time needed for screening the coding region of the factor VIII gene. PCR-SSCP was used to screen for small molecular defects, and reverse transcriptase PCR combined with Southern blotting was used to screen DNA for the inversions that occur frequently in intron 22 of the factor VIII gene. A group of 35 haemophilia A patients was analysed by these methods and 31 mutations were detected. In one patient two mutations were identified. The cases of mild and moderate haemophilia A showed changes in single nucleotides which predicted amino acid changes. The patients affected by severe haemophilia A showed two types of mutations. First, deletions or insertions that result in a frameshift in the coding DNA sequence were observed. Second, inversions were found which result in a disruption of the gene. With the screening strategies used we succeeded in elucidating an abnormality in the factor VIII gene in 30/35 haemophilia A patients.
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PMID:Screening for mutations in haemophilia A patients by multiplex PCR-SSCP, Southern blotting and RNA analysis: the detection of a genetic abnormality in the factor VIII gene in 30 out of 35 patients. 779 69

The objective of this study was to further evaluate the relative safety of extracorporeal photopheresis in the treatment of patients with AIDS-related complex. Twenty patients with AIDS-related complex, three from the initial report and 17 additional patients, were enrolled. The patient population had various risk factors. There were nine homosexuals, five heterosexual consorts of human immunodeficiency virus (HIV)-positive patients, four reformed i.v. drug abusers, and two hemophilia patients. The patients received monthly treatment with extracorporeal photopheresis. In 16 of the 19 patients, this study provides evidence of clinical stability over a longer period. The relative stability of beta 2-microglobulin and neopterin levels demonstrates that photopheresis therapy does not have an untoward effect on the degree of activation of the immune system with respect to induction of HIV replication. Antibody titers to the major viral antigens, envelope glycoproteins (gp) 120 and 41, reverse transcriptase enzyme gp 66/31 and 55, and the core protein p24 remained stable throughout the course of therapy. A subjective improvement was noted in the majority of patients. The evaluation of T-cell subsets revealed that the photopheresis treatment did not have a detrimental effect on CD3 and CD8 cells. Some decreases were noted in the CD4 cell counts but the decline may be less than is normally seen at corresponding stages of HIV infection. Skin test responsivity improved in 11 patients, remained unchanged in seven patients, and declined in two. The preliminary results suggest that in HIV disease, extracorporeal photopheresis is safe and warrants a prospective controlled trial.
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PMID:Extracorporeal photopheresis in the treatment of AIDS-related complex: extended trial. 809 83

Factor IX concentrates unlike factor VIII concentrates have not to date been associated with the transmission of hepatitis A virus (HAV). A retrospective study by reverse transcriptase polymerase chain reaction on a batch of factor IX concentrate used to treat two haemophilia B patients who developed jaundice and IgM anti-HAV antibodies within 50 days of factor IX administration in 1985 revealed the presence of HAV RNA. These findings indicate that factor IX concentrates can transmit HAV and that appropriate viral inactivation steps to inactivate nonenveloped viruses as well as enveloped viruses are necessary to ensure the safety of factor IX concentrates.
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PMID:Hepatitis A transmission by factor IX concentrates. 935 23

Little is known about treatment of hepatitis C virus (HCV) infection in "other groups" than the general population, namely patients with hematologic or renal disorders and patients with human immune deficiency (HIV) co-infection. The aim was to better define HCV therapies in these groups. We analyzed the medical literature focusing on treatment of HCV infection in other populations to suggest conclusions about indications based on tolerance and efficacy. As in the general population, the decision to treat should be based mainly on liver pathology, and to a lesser extent on virologic profiles (genotype, quantitative viremia). Hemophilia does not modify therapeutic strategies which combine interferon-alpha and ribavirin. Similar combinations should be discussed in patients with inherited hemoglobin disorders but iron overload (secondary hemochromatosis) associated with multiple transfusions may decrease the potential efficacy of interferon-alpha and chronic anemia may limit the use of ribavirin. In hemodialyzed patients, therapy by interferon-alpha is feasible with 3 MU subcutaneously after each hemodialysis three times weekly for 6-12 months. Virologic results are at least similar to those obtained in the general population with frequent pathological improvement. Combinations are not possible because ribavirin is contraindicated for pharmacokinetic reasons. In kidney recipients, interferon-alpha is deleterious and inefficient; ribavirin monotherapy has a potential interest which remains to be evaluated. In HIV co-infected patients, treatment is mandatory given the high rate of cirrhosis and the improved survival related to multiple anti-HIV therapies (which have no clear efficacy for quantitative HCV viremia). Due to the limited efficacy of interferon-alpha monotherapy, the combination of interferon-alpha and ribavirin appears to be the logical treatment. An important point is the in vitro inhibition of phosphorylation by ribavirin of HIV reverse transcriptase inhibitors which has to be analyzed in vivo before the combination can be recommended. On the basis of the results of liver biopsy, antiviral treatments may be proposed for HCV-infected patients with hematologic or renal disorders as well as for HIV co-infected patients. The choice of therapy (monotherapy or combined therapies) should be based on the clinical situation (contraindicated with chronic anemia or renal failure, for example) and its duration on the virologic factors of response as in the general population.
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PMID:Treatment of chronic hepatitis C in special groups. 1062 89

Acute hepatitis led to abnormal coagulopathy, bleeding, and death in a nonhemophiliac infant infected with the human immunodeficiency virus, possibly due to zidovudine or ritonavir or both. Acute hepatitis during ritonavir treatment and episodes of spontaneous bleeding have been reported in patients with hemophilia. Zidovudine is associated with elevated liver enzymes, elevated bilirubin, and hepatomegaly leading to abnormal coagulopathy, bleeding, and death in adults. A temporal relationship between the start of combination antiretroviral therapy and onset of hepatosplenomegaly and rise in liver enzymes suggests that zidovudine or ritonavir, or both, are the likely cause of this adverse event. Ritonavir is believed to cause direct hepatotoxicity, probably by inducing acute mitochondrial toxicity, and may hasten reverse transcriptase inhibitor-induced liver toxicity. Liver function of patients receiving a combination of nucleoside reverse transcriptase inhibitor and protease inhibitors should be closely monitored.
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PMID:Acute hepatitis and bleeding possibly induced by zidovudine and ritonavir in an infant with HIV infection. 1099 9

To investigate the causal relationship of blood clotting factors and hepatitis A virus (HAV) infection in haemophilia patients during 1998-1999 in Korea, we performed a 1:3 matched case-control study and molecular detection of HAV from clotting factors and patients. The epidemiological investigation showed that one lot of clotting factor VIII was related epidemiologically to patients with hepatitis A with an odds ratio of 35.0, or 38.4 when adjusted for the interval between injections. We examined 17 sera collected from seven patients and 124 lots of blood clotting factors (factor VIII and factor IV) by HAV reverse transcriptase-polymerase chain reaction (RT-PCR). HAV RNA was detected in five clotting factors and six sera. The HAV sequence of one of the factor VIII samples was identical to the sequences found in three patients' sera. Findings from the laboratory and epidemiological studies suggested that the clotting factor was causally related to HAV infection in three haemophilia patients.
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PMID:Detection of hepatitis A virus from clotting factors implicated as a source of HAV infection among haemophilia patients in Korea. 1640 54

We investigated the molecular basis of a severe factor V (FV) deficiency in a Japanese female, and identified two distinct mutations in the FV gene, a novel cytosine insertion (1943insC) and a previously reported point mutation (A5279G). We expected the patient to be a compound heterozygote for those mutations, as a 1943insC, but not an A5279G, was found in the mother and a sibling. The 1943insC will cause a frame-shift after 590Gln, resulting in amino acid substitutions with two abnormal residues followed by a stop codon in the FV A2 domain (FS592X). The A5279G will cause an amino acid alteration in the FV A3 domain (Y1702C), which has been observed in several ethnic groups. We found that both mutant mRNAs were detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the patient's platelets, whereas no FV antigen and activity were detected in plasma. On the one hand, the RT-PCR signal from the FS592X-FV mutant mRNA was markedly reduced, suggesting that the RNA surveillance system would eliminate most of the abnormal FS592X-FV transcripts with a premature termination. On the other hand, expression analyses revealed that only small amounts of Y1702C-FV with a low specific activity were secreted, and that the FS592X-FV was not detected in cultured media. These data indicated that both mutant FV molecules would be impaired, at least in part, during the post-transcriptional process of protein synthesis and/or in secretion. Taken together, it seems to suggest that each gene mutation could be separately responsible for severe FV deficiency, while this phenotype is due to the in-trans combination of the two defects.
Haemophilia 2006 Mar
PMID:A case of coagulation factor V deficiency caused by compound heterozygous mutations in the factor V gene. 1647 93


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