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)

A unique variant Philadelphia translocation accompanied by the loss of the short arm of chromosome 9 in a 32-year-old female with common acute lymphoblastic leukemia (cALL) is described. Furthermore, supernumerary chromosome 8 material was found as an insertion into the long arm of chromosome 2 and/or as ring chromosomes in addition to two normal chromosomes 8. The chromosomal abnormalities were identified by combined conventional chromosome banding analysis and fluorescence in situ hybridization (FISH). The BCR-ABL rearrangement was confirmed by FISH and reverse transcriptase-polymerase chain reaction (RT-PCR) studies. Possible mechanisms leading to this variant intra Philadelphia translocation are discussed. The aberrations found have prognostic implications, because 9p anomalies confer an adverse effect to the already poor prognosis of Philadelphia-positive ALL.
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PMID:Variant intra philadelphia translocation with rearrangement of BCR-ABL and ABL-BCR within the same chromosome in a patient with cALL. 1110 16

A multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay for both major forms of BCR-ABL was compared with fluorescence in situ hybridization (FISH), karyotyping, and Southern blotting for disease monitoring in 37 follow-up bone marrow samples from 32 patients with Ph1-positive leukemia. Of these 37 samples, 33 were from patients with chronic myeloid leukemia (CML) (26 post allogeneic bone marrow transplantation [AlloBMT] and seven during interferon-alpha therapy) and 4 from Ph1-positive acute lymphoblastic leukemia (ALL) patients (1 post AlloBMT and 3 post high dose chemotherapy). For the 27 samples studied after AlloBMT (26 CML and 1 Ph1-positive ALL) the time after transplantation ranged from 1 to 107 months (median 47.5 months). In 8 (22%) of the 37 samples there were discrepant results among methods. The discrepancy rates relative to other techniques were: karyotyping 17% (5 of 29), Southern blotting 18% (6 of 33), multiplex RT-PCR 8% (3 of 37), and FISH 8% (3 of 37). Therefore, the relative accuracy of each method for disease monitoring in Ph1-positive leukemia was: 83% (24 of 29) for karyotyping, 82% (27 of 33) for Southern blotting, 92% (34 of 37) for FISH, and 92% (34 of 37) for multiplex RT-PCR. This multiplex RT-PCR assay appears equivalent to FISH in terms of accuracy, simplicity, and turnaround time and both are superior to Southern blot and conventional cytogenetics in the laboratory monitoring of Ph1-positive leukemias.
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PMID:Comparison of a multiplex reverse transcriptase-polymerase chain reaction for BCR-ABL to fluorescence in situ hybridization, Southern blotting, and conventional cytogenetics in the monitoring of patients with Ph1-positive leukemias. 1112 44

Despite the success of potent combination therapy against HIV, a large proportion of patients experiences treatment failure. Due to the high degree of plasticity of the HIV genome, ongoing virus replication in the presence of drug pressure will result in the selection of virus mutants with reduced drug susceptibility. As a result, antiretroviral drug-resistance is a common denominator in treatment failure. Two methods, genotyping and phenotyping, are commercially available for measuring resistance in clinical samples. Whereas genotyping detects resistance-conferring mutations in the HIV reverse transcriptase and protease genes, the recombinant virus assay is a newly developed phenotyping technique which determines drug-susceptibility in a virus culture assay. With both methods, result interpretation remains challenging. Retrospective studies and randomized controlled clinical trials support the clinical utility of resistance testing in the setting of treatment failure. The optimal applications of resistance testing in a variety of other clinical settings remain to be defined.
Int J STD AIDS 2001 Mar
PMID:Antiretroviral resistance in clinical practice. 1123 66

The reverse transcriptase-polymerase chain reaction (RT-PCR) has become widely used for monitoring minimal residual disease after allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML). However, most of these studies were performed using qualitative RT-PCR, and the interpretation of the results obtained has been conflicting. The correlation of a quantitative RT-PCR test performed early after SCT (at 3 to 5 months) and long-term outcome of CML patients surviving for more than 6 months was studied. Between January 1991 and June 1999, data from 138 CML patients who received allografts were evaluated. Early RT-PCR results were classified as (1) negative if there were no BCR-ABL transcripts detected (n = 61), (2) positive at low level if the total number of BCR-ABL transcripts was less than 100 per microg RNA and/or the BCR-ABL/ABL ratio was less than 0.02% (n = 14), or (3) positive at high level if transcript levels exceeded the thresholds defined above (n = 63). Three years after SCT the cumulative incidence of relapse was 16.7%, 42.9%, and 86.4%, respectively (P =.0001). The relationship between BCR-ABL transcript level and probability of relapse was apparent whether patients had received sibling or unrelated donor SCT and also whether or not the transplantation was T cell depleted. The results suggest that quantitative RT-PCR performed early after SCT is useful for predicting outcome and may help to define the need for further treatment.
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PMID:Early detection of BCR-ABL transcripts by quantitative reverse transcriptase-polymerase chain reaction predicts outcome after allogeneic stem cell transplantation for chronic myeloid leukemia. 1123 91

Increasing evidence suggests that altered gene expression is associated with the induction and maintenance of malignancy in various organs including mouse lung adenocarcinomas. A competitive cDNA library screening (CCLS) was used to examine gene expression in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung adenocarcinomas from (C3H/HeJ x A/J])F1 mice. Comparisons of RNA expression in lung adenocarcinomas to those of normal surrounding lung tissue revealed altered expression in 220 clones from more than 50,000 clones screened. Fifty clones were selected for quantitative reverse transcriptase-polymerase chain reaction (PCR) analysis to verify altered expression. PCR primers were designed based on partial sequence analysis of the clones. Twenty-two clones were found to be differentially expressed in lung adenocarcinomas compared with normal lungs. GenBank database analysis showed that 14 of the 22 clones were homologous with known genes, whereas 8 clones contained novel sequences. Thirteen clones were down regulated in tumors compared to normal lung tissues, and 9 were overexpressed. The clones underexpressed or absent include adipocyte p27, carbonic anhydrase III, carbonyl reductase, cytochrome CYP2E1, skelemin, myosin, major urinary protein, and contrapsin. Overexpressed clones include Bruton's tyrosine kinase, cyclin D3, poly(A)-binding protein, alpha-fetoprotein, transferrin, and mouse B2 family repetitive sequence. Further examination of biologic implications of the differentially expressed genes in lung adenocarcinomas is necessary to understand their role(s) in mouse lung carcinogenesis.
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PMID:Detection of differentially expressed genes in mouse lung adenocarcinomas. 1129 25

The granulocyte-derived hemoregulatory peptide pyroGlu-Glu-Asp-Cys-Lys = pEEDCK is known to keep hematopoietic cells quiescent. When oxidized to its dimeric form (pEEDCK)2, it activates growth of hematopoietic progenitors in association with stroma-derived cytokines. (pEEDCK)2 has a Cys-Cys motif which is also a typical feature of the macrophage inflammatory protein (MIP-1alpha). The present study was designed to analyze differences between the response of normal and leukemic progenitor cells to (pEEDCK)2 or MIP-1alpha. When long-term bone marrow cultures (LTBMCs) were incubated with (pEEDCK)2 or MIP-1alpha and/or cytokines, the stimulatory effect on colony-forming units-granulocyte/erythroid/macrophage/megakaryocyte of LTBMC from chronic myeloid leukemia (CML) patients was less than 50% compared to LTBMC from healthy humans. No difference in oncogene expression could be observed in LTBMC from CML patients regarding reduction of Philadelphia chromosome-associated transcription of the BCR-ABL gene. With respect to the expression of growth and differentiation-associated genes (Galpha16, 5-lipoxygenase, phospholipaseA2, c-kit, and CD34), which were analyzed from LTBMC by semiquantitative reverse transcriptase-polymerase chain reaction, the same transcription rate was observed in CML patients and healthy donors. However, two isoforms of a key enzyme of oxidative metabolism, carnitine palmitoyltransferase (CPT1A and CPT1B), showed 50-fold higher expression rates in LTBMC cells of healthy donors compared to CML patients. It is known that a decrease in oxidative metabolism is associated with an increase in redox equivalents in malignancy. This might result in a reduction of disulphide bonds in (pEEDCK)2 or MIP-1alpha, thus inducing a downregulation of these factors in bone marrow from CML patients.
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PMID:Effect of the hemoregulatory peptide (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 and MIP-1alpha is reduced in bone marrow cultures from patients with chronic myeloid leukemia (CML). 1146 52

Healthcare workers (HCWs) worldwide risk occupational exposure to HIV and other blood-borne pathogens. Post-exposure prophylaxis (PEP) may decrease the risk of seroconversion after occupational or sexual exposure. Current guidelines recommend immediate PEP with at least 2 drugs following HIV exposure. In high-risk exposures, the guidelines recommend the use of a protease inhibitor (PI) as well as 2 reverse transcriptase inhibitors. Protease inhibitors have been associated with dyslipidaemias, other metabolic abnormalities and lipodystrophy syndromes in AIDS patients. We report a case of new transient lipid abnormalities in a HCW receiving PEP after HIV exposure. HIV medications may produce occult metabolic abnormalities in HIV-negative individuals receiving PEP. This risk should be considered during follow-up evaluation for PEP.
Int J STD AIDS 2001 Aug
PMID:Lipid abnormalities in a healthcare worker receiving HIV prophylaxis. 1148 94

Since the adoption of highly active antiretroviral therapy (HAART) in the mid-1990s, certain metabolic toxicities have been increasingly recognized. These include a fat redistribution syndrome (lipohypertrophy, lipoatrophy), hyperlipidaemia, altered glucose metabolism and insulin resistance, mitochondrial toxicity (presenting as anaemia, myopathy, pancreatitis, neuropathy, hepatic steatosis and lactic acidosis), and bone density abnormalities (osteoporosis and osteonecrosis). Metabolic complications are principally reported with protease inhibitors and nucleoside reverse transcriptase inhibitors, but may be seen with all classes of antiretroviral therapy. In this review, we summarize the epidemiology, pathogenesis and management of these various toxicities.
Int J STD AIDS 2001 Sep
PMID:The metabolic toxicities of antiretroviral therapy. 1151 63

This study concerns a patient with minor (m)-BCR/ABL transcript-positive and Philadelphia (Ph) chromosome-negative myelodysplastic syndrome (MDS). The patient was a 78-year-old man whose condition was diagnosed as refractory anemia with excess of blasts in transformation. Molecular genetic studies, using reverse transcriptase polymerase chain reaction analysis detected m-BCR/ABL messenger RNA. We used spectral karyotyping to analyze metaphase cells but could not detect a Ph chromosome. Fluorescence in situ hybridization, however, revealed fusion signals of BCR and ABL probes on an apparently normal chromosome 22.
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PMID:A variant form of myelodysplastic syndrome with Ph- minor-BCR/ABL transcript. 1153 Aug 6

In October 2000 a meeting was convened by DuPont Pharma in Scotland to discuss the role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in antiretroviral therapy. The Round Table meeting focused on comparisons between efavirenz and nevirapine in clinical studies and clinical practice, and the manuscripts published in this supplement report the most salient points from the presentations and discussions.
Int J STD AIDS 2001 Nov
PMID:The role of NNRTIs in antiretroviral combination therapy: an introduction. 1158 21


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