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)

Chromosome imbalance (aneusomy) is the leading known cause of both spontaneous abortion and mental retardation in human beings. The primary abnormality is thought to result from quantitative changes of transcription products from the unbalanced genetic material. To document this point, I compared chromosome 21-specific transcription in skin fibroblasts from subjects with monosomy 21, disomy 21 (normal), and trisomy 21 (Down syndrome). Polyadenylylated RNA [poly(A)-RNA], which is enriched in messenger and messenger-precursor RNA sequences, was isolated from the above fibroblast lines. Radioactive DNA (cDNA) complementary to these RNAs was synthesized with reverse transcriptase (RNA-dependent DNA polymerase). These cDNAs were hybridized with (i) DNA from a cell line with a mouse genome plus human chromosome 21 and (ii) mouse DNA. Subtraction of the amount of hybridization in experiment ii from that in experiment i yielded a measure of human chromosome 21-specific RNA sequences. The results were consistent with gene dosage at the transcriptional level; for monosomy 21-derived cDNA, 0.6% (of the total cDNA) hybridized specifically to human chromosome 21; for disomy 21-derived cDNA, 2% hybridized; and for trisomy 21-derived cDNA, 3% hybridized. Thus, for DNA sequences on chromosome 21 in human skin fibroblasts, transcription depends on DNA dosage. Characterization of the chromosome 21-specific RNA sequences quantitated in these experiments could help to elucidate the mechanisms by which abnormal karyotypes result in abnormal phenotypes.
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PMID:Down syndrome: gene dosage at the transcriptional level in skin fibroblasts. 15 66

We have isolated a lymphoid cell line, MDS, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines, MDS-T, by transfecting MDS cells with pHXBc2, and MDS-I, by infecting MDS cells with HIV-1IIIB. In 24 hr, 1 x 10(5) MDS-T or MDS-I cells produce 46 ng of p24 per ml and reverse transcriptase that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in MDS-T and MDS-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the MDS cells with the anti-CD4 antibody Leu 3a. For over a year MDS-T and MDS-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the MDS cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12-myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of reverse transcriptase production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication.
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PMID:Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line. 143 50

The short segments of cDNA encoding glycoprotein (GP)Ib alpha, GPIIb, GPIIIa and platelet factor (PF) 4 were amplified using reverse transcriptase-polymerase chain reaction (RT-PCR) in order to characterize various types of megakaryoblasts. Cell lines with megakaryocytic features (K562, CMK and HEL) were tested. GPIb alpha, GPIIb and GPIIIa mRNAs were found to be present in K562, CMK and HEL cells, while only HEL cells expressed PF4 or mRNA. These results suggested that megakaryoblastic cell lines could be categorized into two groups, one with the PF4 transcript and the other without it. PF4 mRNA was present in the cells obtained from one Down's syndrome patient with transient myeloproliferative disorder and in one patient with primary myelofibrosis and megakaryoblastosis. On the other hand, one patient with acute megakaryoblastic leukemia transformed from refractory anemia had a poor prognosis with megakaryoblastic leukemia cells which expressed no PF4 mRNA. These observations suggested that the expression of PF4 mRNA in peripheral blood megakaryoblasts may indicate the absence of a true leukemic process.
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PMID:Detection of platelet-specific protein mRNAs in different megakaryoblasts using the reverse transcriptase polymerase chain reaction. 149 50

The amyloid precursor protein (APP), which is localized on both human chromosome 21 and its murine counterpart, chromosome 16 and which is involved in the formation of deposits in Alzheimer's disease, could be shown to bind effectively to a glytolytic enzyme: rat glyceraldehyde 3-phosphate dehydrogenase (Gapdh). We report here the isolation of a cDNA of murine Gapdh from mouse chromosome 16 (MMU16) originating from microclones of the distal part of MMU16 and the use of homologous genomic DNA sequences to further screen a cDNA phage library. The cDNA was sequenced, confirmed by polymerase chain reaction following reverse transcriptase (RT-PCR) and the open reading frame was expressed in vitro. The possible localization of Gapdh on MMU16--which may provide a mouse model for Down's syndrome and Alzheimer's disease--may lead to new insights into glycolysis and its role in the two syndromes.
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PMID:Isolation of glyceraldehyde 3-phosphate dehydrogenase (Gapdh) cDNA from the distal half of mouse chromosome 16: further indication of a link between Alzheimer's disease and glycolysis. 789 98

The high event-free survival rates of Down syndrome (DS) children with acute myeloid leukemia (AML) are due, in part, to increased in vitro sensitivity of DS myeloblasts to cytosine arabinoside (ara-C) and daunorubicin and the greater generation of ara-C triphosphate (ara-CTP) from ara-C compared with myeloblasts from non-DS patients (Taub et al, Blood 87:3395, 1996). This study further explores the molecular basis of chemotherapy sensitivity of DS AML patients by examining the expression of chromosome 21-localized genes in myeloblasts from newly diagnosed AML patients. Transcript levels of two chromosome 21-localized genes, cystathionine-beta-synthase (CBS) and superoxide dismutase (SOD), measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), were 12.0- and 3. 8-fold higher in DS compared with non-DS myeloblasts (P <.0001 and P <.0001, respectively). Conversely, there were no significant increases in transcripts for 2 other chromosome 21-localized genes, carbonyl reductase and the reduced folate carrier. CBS transcript levels correlated with both in vitro ara-C sensitivity measured by the 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium-bro mid e (MTT) assay (P =.003) and the generation of (3)H-ara-C triphosphate (ara-CTP) after in vitro incubations with 5 micromol/L (3)H-ara-C (P =.0003). Transcripts of deoxycytidine kinase were 2.6-fold higher in DS compared with non-DS cells and may be a factor in the enhanced metabolism of ara-C in DS cells. There was no significant correlation of SOD transcripts with in vitro ara-C and daunorubicin sensitivities. Increased CBS transcripts could result in elevated CBS activity, which modulates ara-C metabolism by altering reduced folate pools, deoxycytidine triphosphate pools, S-adenosylmethionine levels, and/or methylation of the deoxycytidine kinase gene. The further identification of the molecular mechanisms of chemotherapy sensitivity of DS AML patients may lead to significant improvements in the treatment and cure of AML.
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PMID:Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down syndrome and non-Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. 1043 27

We report a boy with Down's syndrome (DS) who developed myelodysplastic syndrome (MDS) after spontaneous remission of transient myeloproliferative disorder (TMD) at birth. Chromosomal analysis of the blasts in the MDS phase demonstrated t(7;11)(p13;p14) which had not been detected in the TMD phase. NUP98-HOXA9 chimera mRNA, which is known to be involved in t(7;11)(p15;p15) translocation in acute myeloid leukemia (AML), was not detected by reverse transcriptase-polymerase chain reaction, and NUP98 rearrangement was not detected by Southern blot analysis of the blasts in the MDS phase. Reciprocal translocation is very rare in AML/MDS in DS, and the t(7;11)(p13;p14) found in our patient was different from the recurrent translocation t(7;11)(p15;p15) previously reported.
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PMID:Down's syndrome with myelodysplastic syndrome showing t(7;11)(p13;p14). 1093 66

Recently, some Alzheimer-associated genes have been found: amyloid precursor protein (APP), apolipoprotein E (apoE), presenilin 1 (PS-1) and presenilin 2 (PS-2). First, we examined mutations of APP, PS-1, and PS-2 genes in familiar Alzheimer's disease (FAD) (7 cases) found in San-in district by single-strand conformation polymorphism and sequence analysis. These seven cases with FAD did not show any mutations of APP, PS-1, and PS-2 genes. Other susceptibility genes of FAD still remain to be not identified. Many reports have established that apoE genotype distribution for the epsilon 4 allele is a susceptibility factor for the earlier onset and more rapid progression of Alzheier's disease (AD). However, the cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors may be associated with development of SAD. Second, we investigated the association between polymorphisms of the estrogen receptor (ER) alpha gene and SAD. The frequencies of P and X alleles in SAD were significantly higher than those in the control group (p < 0.05). Polymorphisms of the ER alpha gene may be a genetic risk factor for SAD. The apoE genotype is a genetic factor closely related SAD, but it is not full by appreciated how apoE has an effect on developing AD. There are few reports on the quantitative change of apoE, namely the expression of apoE mRNA. Third, ApoE mRNA level in the brains of patients with Alzheimer's disease (27 cases) and Down's syndrome (11 cases) was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ApoE mRNA level in the DS as well as AD was significantly higher than that in control group (p < 0.05, p < 0.05, respectively). High levels of apoE mRNA in AD and DS may play an important role in the development of Alzheimer pathology.
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PMID:[Causative genes in Alzheimer's disease]. 1130 15

Cystathionine-beta-synthase (CBS) catalyzes the condensation of serine and homocysteine to form cystathionine, an intermediate step in the synthesis of cysteine. We previously described essential transactivating roles for specificity protein 1 (Sp1), Sp3, nuclear factor Y (NF-Y), and USF-1 in the regulation of the CBS-1b promoter. Differential binding of Sp1/Sp3 to the CBS-1b promoter due to differences in Sp1/Sp3 phosphorylation, and Sp1/Sp3 synergism with NF-Y might, in part, explain cell-specific patterns of CBS expression. In this report, the roles of various NF-YA isoforms in influencing cell-specific differences in CBS gene expression were determined in HT1080 and HepG2 cells. Seven unique NF-YA isoforms were detected in HT1080 by reverse transcriptase-PCR (RT-PCR) and DNA sequencing, characterized by deletions in the glutamine-rich and/or serine/threonine-rich domains. Only four of the seven NF-YA isoforms were found in HepG2 cells. The six alternatively spliced NF-YA isoforms all showed significantly less synergistic transactivation of the CBS-1b promoter with Sp1 than wild-type NF-YA, as determined by cotransfections in Drosophila SL2 cells with NF-YB and NF-YC. Further, all six alternatively spliced NF-YA isoforms inhibited the synergistic transactivation of the CBS-1b promoter by wild-type NF-Y and Sp1. Thus, the cellular distributions of these alternatively spliced NF-YA isoforms could impart an important cell-specific component to CBS transcriptional regulation, by virtue of their abilities to directly synergize with Sp1/Sp3 and interfere with transactivation of the CBS-1b promoter by wild-type NF-Y. Characterization of CBS promoter structure and function should clarify the molecular bases for variations in CBS gene expression in genetic diseases and the relationship between CBS and Down's syndrome (DS).
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PMID:Synergistic regulation of human cystathionine-beta-synthase-1b promoter by transcription factors NF-YA isoforms and Sp1. 1242 42

Patients with Down syndrome appear to be protected from the development of atherosclerosis. On the contrary, hyperhomocysteinemia is associated with an increased risk for atherosclerosis. As hyperhomocysteinemia due to cystathionine beta synthase deficiency is associated with a decreased expression of paraoxonase-1, a major anti-atherosclerotic component secreted by the liver, we aimed to analyze the expression of paraoxonase-1 and cystathionine beta synthase in Down syndrome fetal liver by quantitative real-time reverse transcriptase-polymerase chain reaction. Paraoxonase-1 was up-regulated in Down syndrome fetal liver, while cystathionine beta synthase gene expression in Down syndrome fetuses was similar to the gene level in control fetuses. Moreover, there was no evidence for an association between paraoxonase-1 genotypes influencing paraoxonase-1 gene expression and Down syndrome. Since most serum paraoxonase-1 is synthesized in the liver, an increase of hepatic paraoxonase-1 expression might be one of the factors which could explain the low incidence of atherosclerotic vascular disease in Down syndrome.
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PMID:Paraoxonase-1 expression is up-regulated in Down syndrome fetal liver. 1680 76

Down's syndrome (DS), a chromosomal abnormal genetic disease caused by a local or total copy of chromosome 21, leads to patients suffering from delayed body growth, special facies, mild to moderate mental retardation and other symptoms, seriously affecting the life of patients. The aim of the present study was to examine the association between Down's syndrome critical region 4 (DSCR4) gene methylation in plasma in high-risk pregnant women with DS in early pregnancy (hereinafter referred to as pregnant women in early pregnancy) and DS, in order to screen new epigenetic markers for the clinical diagnosis of DS. DNA in peripheral blood cells and plasma in pregnant women in early pregnancy were treated with hydrosulphite. DSCR4 genes with different methylation levels were amplified by methylation-specific polymerase chain reaction (PCR), and the methylation difference of the CpG site of the DSCR4 amplification product in peripheral blood DNA was verified via restriction endonuclease analysis. The expression of DSCR4 with different methylation levels in peripheral blood of pregnant women in early pregnancy were detected via reverse transcriptase-quantitative PCR (RT-qPCR), and the DSCR4 gene functions were studied via the intervention in DSCR4 expression with small interfering RNA (siRNA). Methylation-specific PCR and restriction endonuclease analysis revealed that DSCR4 genes were differentially methylated in peripheral blood DNA in pregnant women in early pregnancy. Additionally, DSCR4 showed a low methylation status in plasma but a high methylation status in peripheral blood cells. RT-qPCR revealed that non-methylated DSCR4 was highly expressed in the peripheral blood of pregnant women in early pregnancy, and thus was an epigenetic marker of fetal DS. siRNA results showed that the downregulation of DSCR4 inhibited cell migration and invasion, but had no effect on cell proliferation. The results suggest that the DSCR4 gene was differentially methylated in peripheral blood DNA in pregnant women in early pregnancy. Furthermore, DSCR4 exists in a non-methylated state in plasma and in a hyper-methylated state in blood cells. DSCR4 can therefore promote the migration and invasion of trophocytes and serve as an epigenetic marker of non invasive clinical diagnosis of DS.
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PMID:Association between DSCR4 gene methylation in plasma in early pregnancy and Down's syndrome. 2945 78


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