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

---

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

A number of cytokines have been shown to have stimulatory activity on multipotent haematopoietic precursors. These include kit ligand (KL), interleukins (IL) 1, 3 and 6 and granulocyte macrophage-colony stimulating factor (GM-CSF). Using reverse transcriptase/polymerase chain reaction method (RT/PCR) we have examined the expression of these cytokines, the c-kit and IL-6 receptors, in long-term bone marrow culture (LTC) adherent layer cells in human bone marrow hypoplasia syndromes. Disorders studied include Fanconi's anaemia (FA, n = 16), idiopathic aplastic anaemia (AA, n = 11), Seckel's syndrome (n = 2), dyskeratosis congenita (n = 2), Shwachman-Diamond syndrome (n = 1), thrombocytopenia with absent radii syndrome (n = 1), acquired amegakaryocytosis (n = 1), paroxysmal nocturnal haemoglobinuria (n = 1) and acquired agranulocytosis (n = 1). IL-6 and GM-CSF expression appeared reduced in most patients with FA, suggesting that impaired production of these cytokines may contribute to the bone marrow failure seen in most patients with FA. In contrast, abundant IL-6 and GM-CSF expression were seen in most patients with AA when compared with the FA group and controls; these may be mediators of a stromal response in this disorder. No obvious differences were seen between the different patients' groups and controls in expression of the other cytokines or cytokine receptors studied.
...
PMID:The expression of cytokine and cytokine receptor genes in long-term bone marrow culture in congenital and acquired bone marrow hypoplasias. 751 72

Hantavirus pulmonary syndrome is an acute pneumonitis with a high mortality rate that is caused by a newly recognized hantavirus. Four Corners virus (also known as Muerto Canyon virus and Sin Nombre virus) is enzootic among deer mice (Peromyscus maniculatus). Incidental transmission to humans can result in a disease characterized by rapidly progressive respiratory insufficiency, diffuse noncardiogenic pulmonary edema, vascular volume contraction with hemoconcentration, lactic acidosis, depressed cardiac output, and cardiac dysrhythmias preterminally. The onset of pulmonary edema is preceded by a prodrome of fever and severe myalgias. Characteristic laboratory abnormalities include thrombocytopenia, leukocytosis with prevalent immature myeloid cells, and the presence of immunoblastic lymphocytes in the peripheral blood. Agent-specific diagnosis is based on the detection of Four Corners virus-specific antibodies in serum by Western blot assays and the detection of Four Corners virus RNA in peripheral blood mononuclear cells by the reverse transcriptase-polymerase chain reaction. Effective treatment depends on the rapid institution of intensive care support.
...
PMID:Hantavirus pulmonary syndrome: clinical, diagnostic, and virologic aspects. 866 54

We have previously described the private or family platelet antigen, Gro(a), which was identified in a case of neonatal alloimmune thrombocytopenia. The Gro(a) antigen was found to be located on the GP IIIa (beta3) subunit of the GP IIb/IIIa complex, the most prominent fibrinogen receptor of platelets. Initial experiments to characterize the Gro(a) antigen at the molecular genetic level were unsuccessful. We therefore decided to use a different strategy to unravel the molecular basis of this antigen. Platelet GP IIIa mRNA of a Gro(a+) and a Gro(a-) donor was amplified with suitable primers in a reverse transcriptase-polymerase chain reaction (RT-PCR) and subjected to single-strand conformational polymorphism (SSCP) analysis. Three regions of the amplified GP IIIa cDNA derived from the Gro(a+) donor showed a different SSCP pattern when compared to that of the Gro(a-) donor. Direct nucleotide sequence analysis of these three segments revealed that two of them contained silent substitutions, A1163C, A1553G and G1565A. The first and the latter changes were described previously. In the third segment a G1996A mutation was found, predicting an arginine --> histidine substitution at position 633 of the mature glycoprotein. PCR-ASRA (allele-specific restriction enzyme analysis) performed on cDNA as well as on genomic DNA with the restriction enzyme MaeIII showed that the His633 form of GPIIIa is restricted to the Gro(a+) phenotype. The observed mutation is three amino acids upstream of the mutation underlying the HPA-8/Sr system (Arg636Cys), suggesting this region of GP IIIa to be susceptible for mutations. Moreover, the presence of a silent mutation and two low-frequency forms of the silent polymorphisms strongly suggests that the G1996A mutation did not occur in a direct ancestral allele.
...
PMID:The Arg633His substitution responsible for the private platelet antigen Gro(a) unravelled by SSCP analysis and direct sequencing. 916 97

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder described as a clinical triad of thrombocytopenia, eczema, and immunodeficiency. The gene responsible for WAS encodes a 502-amino acid proline-rich protein (WASp) that is likely to play a role in the cytoskeleton reorganization and/or in signal transduction of hematopoietic cells. However, the function and the regulation of the WAS gene (WASP) have not yet been clearly defined. We have studied WASP expression at the transcriptional level in freshly isolated mature peripheral blood cells and during hematopoietic development. For this purpose, we have isolated CD34+ hematopoietic precursor cells from cord blood. These cells were cultured in vitro with various growth factors to generate committed or mature cells belonging to different hematopoietic differentiation pathways, such as granulocytic (CD15+) cells, monocytic (CD14+) cells, dendritic (CD1a+) cells, erythroid lineage (glycophorin A+) cells, and megakaryocytic cells (CD41+). We have shown by reverse transcriptase polymerase chain reaction analysis that the WASP transcript is ubiquitously detectable throughout differentiation from early hematopoietic progenitors, including CD34+CD45RA- and CD34+CD45RA+ cells, to cells belonging to different hematopoietic lineages, including erythroid-committed and dendritic cells. In addition, Northern blot analysis showed that peripheral blood circulating lymphocytes (CD3+ and CD19+ cells) and monocytes express WASP mRNA. Several hematopoietic cell lines were tested and higher levels of expression were consistently detected in myelomonocytic cell types. By contrast, primary nonhematopoietic cells, including fibroblasts, endothelial cells, and keratinocytes, were consistently negative for WASP mRNA.
...
PMID:Expression of Wiskott-Aldrich syndrome protein (WASP) gene during hematopoietic differentiation. 920 40

Hepatitis C virus (HCV) has been recognized as the cause of thrombocytopenia occurring in patients with chronic hepatitis C, possibly through autoimmune mechanisms. A patient is described with B cell chronic lymphocytic leukaemia, presenting with a marked leuko-thrombocytopenia and an associated mild haemolysis secondary to HCV infection, in the absence of clinical and biochemical signs of hepatitis. Anti-HCV antibodies were detected in the serum both by ELISA and RIBA but not 2 months before the onset of cytopenia. The presence of HCV RNA was documented both in the peripheral blood mononuclear cells and in the bone marrow by reverse transcriptase polymerase chain reaction of the 5' untranslated region of the viral genome. Of interest, HCV RNA was also found in the serum, showing that viraemia was associated with the presence of circulating anti-HCV antibodies. HCV genotyping, performed by PCR amplification of the core region, revealed the presence of an unclassifiable genotype. The hypothetical mechanisms leading to HCV-induced cytopenia in this patient are briefly discussed. Treatment with corticosteroids was effective in controlling blood cell counts, without increasing viraemia and deterioration of liver disease. HCV infection should be considered in the differential diagnosis of possible causes of cytopenia, mainly in immunosuppressed patients, even in absence of clinical and biochemical signs of hepatitis.
...
PMID:Hepatitis C virus-induced leuko-thrombocytopenia and haemolysis. 933 31

A 68 year-old-man was first found to have CLL with IgG, kappa monoclonal gammopathy 6 years ago. Bestrabucil (total dose 35,150 mg) was taken orally from August 1989 to December 1989. Etoposide (total dose 23,100 mg) was then orally administered from January 1990 to December 1995. He was then referred to our hospital in January 1996 because of progressive anemia and thrombocytopenia. Peripheral blood showed a WBC of 21,200/microliter with 4% myeloblasts and 79% lymphocytes, Hb 7.9 g/dl and Plt 5 x 10(4)/microliter. The serum level of lysozyme was increased (75.6 micrograms/ml). Bone marrow aspiration disclosed hyper-cellularity with proliferation of the blasts and a monocytoid cell population, which cytochemical studies demonstrated to be of the myelo-monocytic series, thus indicating acute myelogenous leukemia (AML-M4) superimposed on CLL. Surface marker analysis of bone marrow mononuclear cells revealed reactivity for CD 11c, CD13, CD15, CD33, HLA-DR. The karyotype was normal. Southern blot analysis and reverse transcriptase-polymerase chain reaction did not reveal rearrangement of the MLL gene. Complete remission was achieved by chemotherapy consisted of BHAC, idarubicine, 6MP, vincristine and predonisolone. Long-term treatment with oral etoposide may contribute to secondary AML.
...
PMID:[Acute myelogenous leukemia (M4) occurring during chronic lymphocytic leukemia]. 942 40

We have evaluated the susceptibility to human immunodeficiency virus (HIV)-1 infection of in vitro grown megakaryopoietic progenitors/precursors and maturing megakaryocytes (MKs), based on the following approach: (1) human hematopoietic progenitor cells (HPCs), stringently purified from peripheral blood and grown in serum-free liquid suspension culture supplemented with thrombopoietin (Tpo), generated a relatively large number of >/= 98% to 99% pure megakaryocytic precursors and then mature-terminal MKs; (2) at different days of culture (ie, 0, 5, 8, 10) the cells were inoculated with 0.1 to 1.0 multiplicity of infection (m.o.i.) of the lymphotropic NL4-3 or 0.1 m.o.i. of the monocytotropic BaL-1 HIV-1 strain; (3) finally, the presence of viral mRNA and proteins was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR)/in situ hybridization and antigen capture assays, respectively, on day 2 to 12 of culture. MKs derived from day 0 and day 5 BaL-1-challenged cells do not support viral replication as assessed by p24 enzyme-linked immunosorbent assay (ELISA) and RT-PCR. On the contrary, HIV transcripts and proteins were clearly detected in all NL4-3 infection experiments by RT-PCR and p24 assay, respectively, with the highest viral expression in day 5 to 8 challenged MKs. In situ hibridization studies indicate that the percentage of HIV+ MKs varies from at least 1% and 5% for day 0 and day 5 infected cells, respectively. Production of an infectious viral progeny, evaluated by the capability of culture supernatants from day 5 NL4-3-challenged MKs to infect C8166 T-lymphoblastoid cell line, was consistently observed (viral titer, approximately 5 x 10(3) tissue culture infectious dose50/mL/10(6) cells). Exposure of MKs to saturating concentration of anti-CD4 OKT4A monoclonal antibody (MoAb), which recognizes the CD4 region binding with the gp120 envelope glycoprotein, markedly inhibited HIV infection, as indicated by a reduction of p24 content in the supernatants: because the inhibitory effect was incomplete, it is apparent that the infection is only partially CD4-dependent, suggesting that an alternative mechanism of viral entry may exist. Morphologic analysis of day 12 MKs derived from HPCs infected at day 0 showed an impaired megakaryocytic differentiation/maturation: the percentage of mature MKs was markedly reduced, in that approximately 80% of cells showed only one nuclear lobe and a pale cytoplasm with few granules. Conversely, megakaryocytic precursors challenged at day 5 to 8 generated fully mature day 10 to 12 MKs showing multiple nuclear segmentation. Thus, the inhibitory effect of HIV on the megakaryopoietic gene program relates to the differentiation stage of cells subjected to the viral challenge. Finally, HPCs treated with 20 or 200 ng/mL of recombinant Tat protein, analyzed at different days of culture, showed an impaired megakaryocytopoiesis comparable to that observed in HIV-infected cells, thus suggesting that Tat is a major mediator in the above described phenomena. These results shed light on the pathogenesis of HIV-related thrombocytopenia; furthermore, they provide a model to investigate the effects of HIV on megakaryocytic differentiation and function.
...
PMID:Productive human immunodeficiency virus-1 infection of purified megakaryocytic progenitors/precursors and maturing megakaryocytes. 945 52

We conducted a feasibility study of continuous etoposide infusion, which was expected to suppress DNA repair after radiation, combined with radiation in patients with advanced non-small cell lung cancer (NSCLC). Between July 1995 and January 1997, 10 patients with NSCLC were registered. Thirty-six mg/m2/day etoposide was infused continuously for a mean of 19 days (range 14-26). Patients tolerated a mean total dose of accelerated hyperfractionated thoracic radiotherapy (1.5 Gy twice per day) of 52.6 Gy (range 33-60). The primary tumors of 7 patients showed partial responses and distant metastasis progression occurred before primary tumor progression in all 7 responders. The hematological adverse effects of chemoradiotherapy were grade 3 or 4 leukopenia in all 10 patients, grade 3 anemia developed in 3, and 2 had grade 3 thrombocytopenia. Six patients contracted infections and one of them died of pneumonia. The major non-hematological adverse effect was esophagitis, which was grade 3 in 3 patients, one of whom died of renal dysfunction. The serum etoposide concentrations were 1.6-2.0 microgram/ml, except in one patient, who had liver dysfunction due to B-type hepatitis. DNA repair gene XRCC1 mRNA expression in peripheral blood mononuclear cells was analyzed, using the reverse transcriptase-polymerase chain reaction, in 8 patients and was suppressed during etoposide infusion in 2. No relationship was observed between serum etoposide concentration and XRCC1 expression and clinical outcome. In conclusion, continuous etoposide infusion combined with thoracic radiation induces severe toxicity and should be given only after careful consideration.
...
PMID:A feasibility study of continuous etoposide infusion combined with thoracic radiation for non-small cell lung cancer. 1002 87

We have succeeded in stably maintaining the entire genome of SIVmac239 as a plasmid clone. Supercoiled proviral plasmid DNA was inoculated intramuscularly into two adult rhesus macaques and into a neonate. All three animals became viremic and seroconverted. Viral kinetics were followed prospectively by quantitative competitive reverse transcriptase polymerase chain reaction (QC-RT-PCR), measurement of proviral DNA load in peripheral blood mononuclear cells (PBMCs) by PCR, and virus isolation by cocultivation. The infant developed high virus loads and succumbed to AIDS and SIV-associated nephropathy at 10 weeks postinoculation. Both adults are still living but have progressed to AIDS; one adult has also developed severe thrombocytopenia. We conclude that infection through intramuscular inoculation of cloned plasmid DNA encoding the entire proviral genome is reproducible and will provide a useful tool for studying viral pathogenesis.
...
PMID:Viremia and AIDS in rhesus macaques after intramuscular inoculation of plasmid DNA encoding full-length SIVmac239. 1019 54

The positive predictability of anti-HCV ELISA is low, especially, in blood donors and in healthy populations. False positive anti-HCV results pose some difficulties in medical practice and in blood screening. The aim of this study was to identify the factors associated with true hepatitis C virus (HCV) infection among anti-HCV ELISA-positives. A case-control analysis was conducted using 354 subjects who were positive for anti-HCV ELISA. All subjects were tested for true HCV infection using the reverse transcriptase polymerase chain reaction (RT-PCR). Tests for serum alanine aminotransferase (ALT), fasting glucose, HBsAg, anti-HBc antibody, alpha-fetoprotein, platelet count and ultrasound of liver were also performed. Epidemiological data were obtained by self-administered questionnaires. Out of 354 subjects, 202 (57.1%) were positive for HCV by RT-PCR and 152 were negative and used as the control group. In multivariate analysis, blood transfusion (odds ratio, OR 2.3, 95% confidence interval, CI 1.3-4.0), elevated ALT (OR 2.2, 95% CI 1.2-4.3) and higher anti-HCV ELISA ratios (more than 3; OR 1.7, 95% CI 1.3-2.1) were associated with true HCV infection. Thrombocytopenia was also associated with the presence of HCV in univariate analysis. These results suggest that a history of blood transfusion, elevated ALT and a high score on anti-HCV ELISA ratios are associated with true HCV infection among anti-HCV ELISA-positives.
...
PMID:Factors associated with positive predictability of the anti-HCV ELISA method with confirmatory RT-PCR. 1064 40


<< Previous 1 2 3 4 5 Next >>

---