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)

Germ-line heterozygous mutations in the hematopoietic transcription factor AML1 (RUNX1) have been identified in patients with familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML), which is characterized by thrombocytopenia, abnormal platelet function, and propensity to myeloid malignancies. We identified a novel mutation in the AML1 gene in an FPD/AML pedigree characterized by a single nucleotide deletion that generates a frameshift and premature chain termination (Pro218fs-Ter225). Both wild-type and mutant transcripts were expressed in affected individuals by allele-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Thrombopoietin (TPO) binds to the Mpl receptor and is the major regulator of megakaryopoiesis. To explore the mechanisms underlying thrombocytopenia, we studied the TPO/Mpl pathway in this newly identified pedigree. TPO levels were mildly to moderately elevated. On flow cytometry and immunoblotting, Mpl receptor expression was decreased and TPO-induced signaling was impaired. While no mutations were identified in the MPL gene by sequence analysis, low MPL mRNA levels were found, suggesting decreased gene expression. Of particular interest, several AML1-binding motifs are present in the MPL promoter, suggesting MPL is an AML1 target. In conclusion, we identified a C-terminal AML1 mutation that leads to a decrease in Mpl receptor expression, providing a potential explanation for thrombocytopenia in this FPD/AML pedigree.
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PMID:Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutation. 1574 Dec 16

We describe a patient with acute promyelocytic leukemia (APL) and the karyotype 46,XX,i(17)(q10) with PML-RARA fusion gene detected by fluorescence in situ hybridization (FISH) and nested reverse transcriptase-polymerase chain reaction (RT-PCR). FISH using dual-color translocation probes for PML (promyelocytic leukemia) and RARA (retinoic acid receptor-alpha) showed fusion signal for PML-RARA on both arms of i(17q). The patient attained complete remission (CR) with all-trans retinoic acid treatment and became PML-RARA negative. One year later, while PML-RARA negative on FISH and RT-PCR, the patient presented with thrombocytopenia. Bone marrow examination suggested an acute monoblastic leukemia (AML-M5a) including the karyotype 46,XX,t(8;16) (p11.2;p13.3),inv(11)(p15q22 approximately q23)[11]/47,idem,+i(8)(q10)[9]. She is currently in CR. The occurrence of therapy related acute leukemia after successful therapy for APL is an emerging problem.
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PMID:Acute promyelocytic leukemia with PML-RARA fusion on i(17q) and therapy-related acute myeloid leukemia. 1589 84

Crimean-Congo hemorrhagic fever (CCHF) is endemic in certain rural areas of Pakistan. Since the discovery of CCHF virus (CCHFV) in the country in the 1960s, there have been 13 outbreaks in addition to sporadic cases. An outbreak during 2000 coincided with the movement of sacrificial animals from rural to urban areas for the festival of Eid-ul-Azha. Diagnosis was suspected in patients with fever and thrombocytopenia, and confirmed retrospectively using immunoassays and reverse transcriptase-PCR. Patients were given platelet, plasma and red cell infusions. Management varied due to unfamiliarity with the condition and its treatment, lack of availability of diagnostic laboratory tests and limited supply of ribavirin. Inadequate antiviral treatment and late presentation probably contributed to the death of six of the eight patients. Renal failure, disseminated intravascular coagulation and persistent high-grade fever were associated with mortality. The nucleotide sequence of the small genomic RNA segment of the CCHFV isolated in this outbreak was found to be very closely related to the CCHFV strains previously isolated in Pakistan.
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PMID:Crimean-Congo hemorrhagic fever: experience at a tertiary care hospital in Karachi, Pakistan. 1593 14

Nucleoside analogue reverse transcriptase inhibitors (NRTIs) have substantially lowered the risk of the mother-to-child transmission of HIV. Evidence of mitochondrial toxicity in vitro, in animal models and in adult HIV-infected patients, has raised concern about the perinatal safety of these antiretrovirals. In zidovudine-exposed, but HIV-uninfected infants, transient anaemia and additional long-term blood abnormalities (neutropenia, thrombopenia and lymphopenia) and hyperlactatemia have been documented. The overall risk of mortality and congenital abnormalities does not appear to be increased, but rare mitochondrial events cannot be excluded for lack of statistical power. French data suggest an above background incidence of mitochondrial symptomatology. Preclinical data demonstrate zidovudine also to be a carcinogen. Long-term systematic follow-up of exposed babies in large cohorts is needed, as are randomised trials with NRTIs carrying a lower risk of mitochondrial toxicity.
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PMID:Mitochondrial disease in the offspring as a result of antiretroviral therapy. 1661 Sep 67

We report the case of a 17-year-old male who was admitted to the emergency department in cardiogenic shock and multiorgan failure due to fulminant myocarditis. The following days the patient developed anemia, thrombocytopenia, and hepatosplenomegaly. Bone marrow examination showed many mature histiocytes with active hemophagocytosis. Nested reverse transcriptase-PCR molecular analysis of blood samples and sequencing of the amplified alleles confirmed enteroviral infection. Our patient was treated with inotropic agents and immunoglobulin, and recovered completely. This is the first report that documents concomitant presentation of fulminant myocarditis and hemophagocytic syndrome due to enteroviral infection.
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PMID:Enterovirus-induced fulminant myocarditis and hemophagocytic syndrome. 1673 67

HIV antiretroviral therapy (ART)-related hepatotoxicity is a significant clinical problem, resulting in severe elevations of liver enzymes and, potentially, liver failure and death. We retrospectively determined baseline clinical predictors of severe hepatotoxicity (SH; serum aminotransferases or total bilirubin >5 times and >2.5 times the upper limit of normal [ULN], respectively) among 8,851 subjects enrolled in 16 Adult AIDS Clinical Trial Group studies from October 1989 to June 1999. Subjects were divided into the following treatment categories: single nucleoside reverse transcriptase inhibitors (NRTIs), multiple NRTIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs) combined with NRTIs, and the protease inhibitor (PI) indinavir (IDV) combined with NRTIs. SH occurred in 824 (9.3%) subjects, in 613 (6.92%) in the first 6 months and in another 211(2.38%) in the subsequent 6 months of study ART. Consistent with other reports, baseline elevation in serum aminotransferases was a significant risk factor for SH for all regimens. Risk factors not previously identified included concomitant hepatotoxic medications, thrombocytopenia, and renal insufficiency. Hepatitis C virus coinfection was associated with an increased risk of SH (odds ratio [OR] = 2.7; P < 0.003). In conclusion, this study identified known and previously unreported risk factors for severe hepatotoxicity that should be considered before the initiation of ART.
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PMID:Predictors of antiretroviral-related hepatotoxicity in the adult AIDS Clinical Trial Group (1989-1999). 1696 41

Oxidative stress is known to play an important role in the pathogenesis of certain severe illnesses in preterm infants. The enzyme heme oxygenase-1 (HO-1) participates in cytoprotection against oxygen radical injury. We have previously described the role of HO-1 in physiologic adaptation by demonstrating the induction of HO-1 in healthy mature neonates and asymptomatic preterm infants. Our current aim was to investigate the HO-1 expression in preterm infants with respiratory distress syndrome (RDS). We collected venous blood samples from 28 preterm infants with RDS on the 1st, 3rd and 5th days after birth. The HO-1 mRNA expression was determined by means of a competitive reverse transcriptase PCR technique, and a quantitative blood count was performed on the residual blood sample. A significant increase in HO-1 expression was found in the preterm infants with RDS as compared with both the healthy mature and the asymptomatic premature groups. The elevation was approximately eight-fold. The platelet count displayed a significant negative association with the HO-1 expression, and in the RDS prematures with thrombocytopenia the HO-1 induction was significantly greater than in those with a normal platelet count. In conclusion, the RDS of prematures is accompanied by an elevated HO-1 expression during the first 5 days of life, consistent with the inflammatory and oxidative characteristics of the disease.
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PMID:Increased heme oxygenase-1 expression in premature infants with respiratory distress syndrome. 1830 21

Nonimmunogenic character of native DNA, and its high immunogenicity when presented in complex with the DNA-binding proteins indicate that the latter might contain molecular triggers of anti-DNA response. To find if this is the case, we have evaluated the autoimmunogenic potential of the main DNA-binding domain of HIV-1 reverse transcriptase that belongs to the canonical helix-loop-helix type. BALB/c mice were immunized with a peptide representing the domain, alone or in complex with the fragmented human DNA in the presence of an adjuvant. Mice were assessed for specific antibodies, autoantibodies against a panel of self-antigens; glomerular immunoglobulin deposition; and for the signs of autoimmune disease, such as proteinuria, and changes in the blood components. Immunization with the adjuvanted peptide-DNA complex induced autoantibodies against double-stranded DNA, histones, heterochromatin, and kidney proteins; glomerular IgG and IgA deposition; proteinuria; thrombocytopenia, and anemia. Altogether, this identifies the helix-loop-helix DNA-binding domain as one of the molecular triggers of autoimmunity to DNA and DNA-associated proteins. The experiments cast new light on the role of the DNA-binding retroviral proteins in the induction of autoimmunity, and on the origins of autoimmune complications in the microbial infections in general. It also implies that choosing the DNA-binding proteins as vaccine candidates should be done with precaution.
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PMID:Autoimmunogenicity of the helix-loop-helix DNA-binding domain. 1918 86

An 11-year-old, intact female, Yorkshire Terrier dog was presented with epigastric bulging. Results of a CBC included mild neutrophilia and thrombocytopenia. Radiographic examination and abdominal ultrasonography revealed abundant ascites and a well-circumscribed mass in the caudal region of the spleen. Abdominocentesis revealed bloody fluid. Cytologic analysis of the fluid revealed numerous clustered and individual large cells with moderate anisocytosis and anisokaryosis. The spleen was surgically resected. An imprint smear of a white nodular tumor on the caudal pole of the spleen contained a bimorphic population of small and large lymphocytes. The cytologic diagnosis was lymphoma. Histologically, large lymphocytes with distinct borders and single nucleoli formed multiple neoplastic follicles. The final diagnosis was primary splenic lymphoma. Immunocytochemical staining results on buffy coat smears prepared from the ascites fluid showed the lymphocytes were negative for CD3 and positive for CD79a, indicating B-cell origin. Further investigation of the cell clusters using semiquantitative reverse transcriptase-PCR showed that ICAM-1, a cell-cell adhesion molecule, was overexpressed in the tumor cells, likely contributing to the clustering of neoplastic lymphocytes in the ascites fluid. Usually, round cells are not adherent; however, spontaneously detached round cells may form clusters, as in this case, and must be differentiated from epithelial tumors.
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PMID:What is your diagnosis? Ascites fluid from an 11-year-old dog with epigastric bulging. 1939 52

We describe the development and preliminary characterization of a recombinant canarypox virus vectored (ALVAC) vaccine for protective immunization of equids against African horse sickness virus (AHSV) infection. Horses (n=8) immunized with either of two concentrations of recombinant canarypox virus vector (ALVAC-AHSV) co-expressing synthetic genes encoding the outer capsid proteins (VP2 and VP5) of AHSV serotype 4 (AHSV-4) developed variable titres (<10-80) of virus-specific neutralizing antibodies and were completely resistant to challenge infection with a virulent strain of AHSV-4. In contrast, a horse immunized with a commercial recombinant canarypox virus vectored vaccine expressing the haemagglutinin genes of two equine influenza H3N8 viruses was seronegative to AHSV and following infection with virulent AHSV-4 developed pyrexia, thrombocytopenia and marked oedema of the supraorbital fossae typical of the "dikkop" or cardiac form of African horse sickness. AHSV was detected by virus isolation and quantitative reverse transcriptase polymerase chain reaction in the blood of the control horse from 8 days onwards after challenge infection whereas AHSV was not detected at any time in the blood of the ALVAC-AHSV vaccinated horses. The control horse seroconverted to AHSV by 2 weeks after challenge infection as determined by both virus neutralization and ELISA assays, whereas six of eight of the ALVAC-AHSV vaccinated horses did not seroconvert by either assay following challenge infection with virulent AHSV-4. These data confirm that the ALVAC-AHSV vaccine will be useful for the protective immunization of equids against African horse sickness, and avoids many of the problems inherent to live-attenuated AHSV vaccines.
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PMID:Protective immunization of horses with a recombinant canarypox virus vectored vaccine co-expressing genes encoding the outer capsid proteins of African horse sickness virus. 1949 Sep 59


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