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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 78 year old female was found to have pancytopenia in February 1991. Bone marrow was normocellular with 11.7% blasts and showed dysmegakaryopoietic changes. A diagnosis of MDS (RAEB) was made and she was treated with transfusions and ubenimex. Leukemic transformation was noted in July. On Admission in October 1991, her laboratory examinations revealed the following: WBC 38,900/microliters with 93% blast, Hb 8.0 g/dl, Plt 2.1 x 10(4)/microliters, a hypercellular bone marrow with 74% blasts which were negative for myeloperoxidase (MPO) by light microscopy, but were positive by electron microscopy. Surface marker for CD13 was positive. These findings corresponded to M0 of the FAB subtype. Chromosome analysis revealed Ph1 chromosome with 46XX, t (9;22) (q34;q11) in 3 of 3 cells examined, Southern analysis showed the rearrangement of the break point cluster region (bcr). Reverse transcriptase polymerase chain reaction technique demonstrated the presence of major bcr/abl mRNA. She was treated with transfusions and methyl-prednisolone. Her blast counts declined and Ph1 chromosome was only positive in 1 of 12 metaphases examined. She died of pneumonia in December 1991. Eleven cases with MDS showing Ph1 chromosome have previously been reported. The observations indicate that Ph1 chromosome positive acute leukemias were heterogenous in nature.
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PMID:[RAEB transformed into AML (M0) showing Ph1 chromosome and rearrangement of major cluster region]. 825 8

This report describes a precise molecular analysis of a rare case of Philadelphia chromosome (Ph) positive acute myeloid leukemia (AML) (FAB classification M2). Phenotypic markers were positive for cells of the myeloid lineage, but negative for B cell and T cell lineage. The leukemic cells carried a Philadelphia chromosome. Major breakpoint cluster region (M-BCR) rearrangement was detected by the Southern blot analysis. Reverse transcriptase polymerase chain reaction analysis revealed the presence of b3a2 BCR/ABL mRNA transcripts. The patient achieved complete remission by conventional remission induction therapy for acute myeloid leukemia. M-BCR rearrangement could not be detected during complete remission. After hematological remission of an 8-month duration, the patient relapsed and died of respiratory distress due to pneumonia. Our case indicate Ph-positive AML with M-BCR rearrangement actually exists. Ph-positive AML carries either M-BCR rearrangement expressing the P210 BCR-ABL or minor breakpoint cluster region (m-BCR) rearrangement producing the P190 BCR-ABL. Therefore, additional other factor (s) apart from the Ph chromosome must be responsible for the acute malignant transformation.
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PMID:Molecular analysis of a case of Philadelphia chromosome-positive acute myeloid leukemia. 906 90

A 66-year-old woman had been treated for 3 years by her local physician with Sho-saiko-to for chronic hepatitis C virus (HCV) infection and liver cirrhosis. She was admitted to our hospital because of cough, fever, and infiltrative shadows on chest x-ray films. Sho-saiko-to-induced pneumonitis was diagnosed and steroid therapy started. Though a temporary improvement was observed, interstitial pneumonitis relapsed and the patient died of respiratory failure and liver dysfunction. Autopsy findings showed diffuse alveolar damage and honeycombing. Furthermore, reverse-transcriptase polymerase chain reaction techniques detected HCV-RNA in specimens of fibrotic lung tissue. For comparison, HCV-RNA was not histologically detected in lung tissue specimens from 4 control subjects who were positive for HCV antibodies but who did not have interstitial lung disease. It was speculated that the progression of interstitial pneumonia in the present case may have been caused by HCV in combination with Sho-saiko-to-induced lung injury.
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PMID:[An autopsy case of interstitial pneumonia probably induced by Sho-saiko-to]. 1070 45

A permanent cell line, HSC-M1, was established from a child with advanced CD30 (Ki-1)+ anaplastic large-cell lymphoma (ALCL). Clinical features included irritability, fever, weight loss, tender lymphadenopathy, pneumonitis, neutrophilia, and bone marrow erythrophagocytosis. While HSC-M1 cells exhibited an immunophenotype characteristic of ALCL of T-cell lineage, the cell line also demonstrated features of monocyte-macrophage lineage. Cytogenetic and polymerase chain reaction (PCR) analysis of the HSC-M1 cell line and involved bone marrow demonstrated the characteristic non-random chromosomal translocation t(2:5)(p23:q35). Reverse transcriptase PCR for mRNA expression of cytokines and cytokine receptors showed that HSC-M1 cells expressed the message for multiple cytokines and their receptors. Measurement of cytokine levels in serum samples using enzyme-linked immunosorbent assays showed increased concentrations of several cytokines. The increased levels of some cytokines correlated with disease activity and clinical symptoms. Although spontaneous production by HSC-M1 cells of some of these cytokines was demonstrated, the production of others was only detectable after stimulation with exogenous CD30 ligand. With few exceptions, there was good correlation between serum cytokine levels and cytokines produced by HSC-M1 cells. These findings indicate that cytokine production is a feature of ALCL cells and that some of the clinical manifestations in ALCL may result from cytokines produced by either the malignant or accessory cells.
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PMID:Establishment of a cytokine-producing anaplastic large-cell lymphoma cell line containing the t(2;5) translocation: potential role of cytokines in clinical manifestations. 1142 32

Human immunodeficiency virus (HIV) protease inhibitors (PIs) recently have been reported to be active against Pneumocystis carinii in cell culture. Twelve anti-HIV drugs were analyzed for their effects against rat P. carinii by an ATP cytotoxicity assay. Indinavir and saquinavir exhibited slight anti-P. carinii activity at concentrations above those that can be clinically achieved in serum; other PIs and nucleoside and nonnucleoside reverse-transcriptase inhibitors were inactive against the organism. Anti-HIV drugs, alone or in combination, did not materially reduce the organism count in the treatment of P. carinii pneumonia in immunosuppressed mice. Thus, anti-HIV drugs have little or no activity against P. carinii in these in vitro and in vivo systems. Caution should be used when interpreting reports of the susceptibility of P. carinii to anti-HIV drugs on the basis of in vitro testing only.
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PMID:Anti-human immunodeficiency virus drugs are ineffective against Pneumocystis carinii in vitro and in vivo. 1202 83

The 2 groups of human coronaviruses (HCoVs) represented by the prototype strains HCoV 229E and HCoV OC43 are mostly known as viruses responsible for common cold syndrome. HCoVs are difficult to detect, and epidemiological data are rare. From October 2000 through April 2001, we tested 1803 respiratory samples for HCoV by reverse-transcriptase polymerase chain reaction. From 8 February through 27 March 2001, HCoV OC43 was detected in samples obtained from 30 (6%) of 501 patients. The other viruses detected were respiratory syncytial virus (6.1%), parainfluenza virus 3 (1%), influenza virus A (7.8%), influenza virus B (7.2%), rhinovirus (6.4%), enterovirus (1%), and adenovirus (2%). Infection with HCoV OC43 was detected in patients of all age groups. The following clinical symptoms were noted: fever (in 59.8% of patients), general symptoms (in 30%), digestive problems (in 56.8%), rhinitis (in 36.6%), pharyngitis (in 30%), laryngitis (in 3.3%), otitis (in 13.3%), bronchitis (in 16.6%), bronchiolitis (in 10%), and pneumonia (in 6.6%). This study shows that an outbreak of HCoV OC43 respiratory infection was responsible for the lower respiratory tract symptoms observed in nearly one-third of patients identified by active surveillance for coronavirus infection.
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PMID:An outbreak of coronavirus OC43 respiratory infection in Normandy, France. 1268 10

Sendai virus may induce acute respiratory tract disease in laboratory mice and is a common contaminant of biological materials. Pneumonia virus of mice (PVM) also infects the respiratory tract and, like Sendai virus, may induce a persistent wasting disease syndrome in immunodeficient mice. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays have proven useful for detection of Sendai virus and PVM immunodeficient animals and contaminated biomaterials. Fluorogenic nuclease RT-PCR assays (fnRT-PCR) combine RT-PCR with an internal fluorogenic hybridization probe, thereby potentially enhancing specificity and eliminating post-PCR processing. Therefore, fnRT-PCR assays specific for Sendai virus and PVM were developed by targeting primer andprobe sequences to unique regions of the Sendai virus nucleocapsid (NP) gene and the PVM attachment (G) gene, respectively. The Sendai virus and PVM fnRT-PCR assays detected only Sendai virusand PVM , respectively. Neither assay detected other viruses of the family Paramyxoviridae or other RNA viruses that naturally infect rodents. The fnRT-PCR assays detected as little as 10 fg of Sendai virus RNA and one picogram of PVM RNA, respectively, andthe Sendai virus fnRT-PCR assay had comparable sensitivity when directly compared with the mouse antibody production test. The fnRT-PCR assays were also able to detect viral RNA in respiratory tract tissues and cage swipe specimens collected from experimentally inoculated C.B-17 severe combined immunodeficient mice, but did not detect viral RNA in age- and strain-matched mock-infected mice. In conclusion, these fnRT-PCR assays offer potentially high-throughput diagnostic assays to detect Sendai virus and PVM in immunodeficient mice, and to detect Sendai virus in contaminated biological materials.
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PMID:Detection of sendai virus and pneumonia virus of mice by use of fluorogenic nuclease reverse transcriptase polymerase chain reaction analysis. 1278 51

Cynomolgus macaques (Macaca fascicularis) infected with influenza virus A/HongKong/156/97 (H5N1) developed acute respiratory distress syndrome (ARDS) with fever. Reverse transcriptase/polymerase chain reaction (RT/PCR) and virus isolation showed that the respiratory tract is the major target of the virus. The main lesion observed upon necropsy, performed 4 or 7 days postinfection, was a necrotizing bronchointerstitial pneumonia, similar to that found in primary influenza pneumonia in human beings. By immunohistochemistry, influenza virus antigen proved to be limited to pulmonary tissue and tonsils. The data indicate that ARDS and multiple organ dysfunction syndrome (MODS), observed in both humans and monkeys infected with this virus, are caused by diffuse alveolar damage from virus replication in the lungs alone.
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PMID:A primate model to study the pathogenesis of influenza A (H5N1) virus infection. 1457 89

During the past years, human coronaviruses (HCoVs) have been increasingly identified as pathogens associated with more-severe respiratory tract infection (RTI). Diagnostic tests for HCoVs are not frequently used in the routine setting. It is likely that, as a result, the precise role that HCoVs play in RTIs is greatly underestimated. We describe a rapid, sensitive, and highly specific quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for the detection of HCoV that can easily be implemented in the routine diagnostic setting. HCoV was detected in 28 (11%) of the 261 clinical specimens obtained from patients presenting with symptoms of RTI ranging from common cold to severe pneumonia. Only 1 (0.4%) of the 243 control specimens obtained from patients without symptoms of RTI showed the presence of HCoV. We conclude that HCoVs can be frequently detected in patients presenting with RTI. Real-time RT-PCR provides a tool for large-scale epidemiological studies to further clarify the role that coronavirus infection plays in RTI in humans.
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PMID:Frequent detection of human coronaviruses in clinical specimens from patients with respiratory tract infection by use of a novel real-time reverse-transcriptase polymerase chain reaction. 1476 19

Severe acute respiratory syndrome coronavirus (SARS-CoV), a newly identified group 2 coronavirus, is the causative agent of severe acute respiratory syndrome, a life-threatening form of pneumonia in humans. Coronavirus replication and transcription are highly specialized processes of cytoplasmic RNA synthesis that localize to virus-induced membrane structures and were recently proposed to involve a complex enzymatic machinery that, besides RNA-dependent RNA polymerase, helicase, and protease activities, also involves a series of RNA-processing enzymes that are not found in most other RNA virus families. Here, we characterized the enzymatic activities of a recombinant form of the SARS-CoV helicase (nonstructural protein [nsp] 13), a superfamily 1 helicase with an N-terminal zinc-binding domain. We report that nsp13 has both RNA and DNA duplex-unwinding activities. SARS-CoV nsp13 unwinds its substrates in a 5'-to-3' direction and features a remarkable processivity, allowing efficient strand separation of extended regions of double-stranded RNA and DNA. Characterization of the nsp13-associated (deoxy)nucleoside triphosphatase ([dNTPase) activities revealed that all natural nucleotides and deoxynucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed slightly more efficiently than other nucleotides. Furthermore, we established an RNA 5'-triphosphatase activity for the SARS-CoV nsp13 helicase which may be involved in the formation of the 5' cap structure of viral RNAs. The data suggest that the (d)NTPase and RNA 5'-triphosphatase activities of nsp13 have a common active site. Finally, we established that, in SARS-CoV-infected Vero E6 cells, nsp13 localizes to membranes that appear to be derived from the endoplasmic reticulum and are the likely site of SARS-CoV RNA synthesis.
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PMID:Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. 1514 Sep 59


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