Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-Ethoxy-8-methyl-5,6-dihydro-7H-cyclopenta[f]isoquinolin-5-one (2) was converted to 6-carbethoxymethyl-3-ethoxy-8-methyl-5,6-dihydro-7H-cyclopenta[f]isoquinolin-5-one (6) through an oxalyl derivative. Treatment of 6 with ammonia gave the corresponding amide 7 which on sodium borohydride reduction and subsequent dehydration yielded 6-carbamylmethyl-3-ethoxy-8-methyl-7(5)H-cyclopenta[f]isoquinoline (9). The analogous ester 10 was similarly obtained from 6. Numerous attempts to dealkylate the 3-ethoxy group of 9 or 10 failed. However, 6 coould easily be dealkylated on heating with 25% hydrochloric acid in a sealed tube.The ester, 6-carbethoxymethyl-8-methyl-5,6-dihydro-7H-cyclopenta[f]isoquinoline-3(2H),5-dione (11), so obtained was converted to the corresponding amide 12 which on reduction with sodium borohydride and subsequent dehydration afforded the desired compound, 6-car-bamylmethyl-8-methyl-7(5)H-cyclopental[f]isoquinolin-3-(2H)-one (1). 1 was found to be mildly cytotoxic againstL5178Y mouse leukemia cells in culture.1 was also found to bind to native calf thymus DNA. 1 inhibited RNA synthesis by a DNA-dependent RNA polymerase and a higher inhibition of RNA synthesis was observed when poly(dG-dC) was used as a template than when poly(dA-dT) was used. A significant increase of thermal transition temperature of calf thymus DNA and poly(dG)-poly(dC) was observed in the presence of 1. The accumulated evidence demonstrates that 1 interacts weakly with calf thymus DNA and interacts preferentially with poly(deoxyribonucleotides)-containing GC pairs.
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PMID:Cyclopenta[f]isoquinoline derivatives designed to bind specifically to native deoxyribonucleic acid. 2. Synthesis of 6-carbamylmethyl-8-methyl-7(5)H-cyclopenta[f]isoquinolin-3(2H)-one and its interaction with deoxyribonucleic acids and poly(deoxyribonucleotides). 109 35

Twenty six patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) treated with IFN-alpha were classified on the basis of the fusion pattern of BCR/ABL chimeric mRNA determined by a reverse-transcriptase-polymerase chain reaction (RT-PCR) method. The relationship between the fusion pattern of BCR/ABL mRNA and the clinical outcome was also analysed. Twelve patients showed M-bcr exon 3/ABL exon 2 (B3/A2) chimeric mRNA and nine had M-bcr exon 2/ABL exon 2 (B2/A2) mRNA. Eleven of the 12 patients with B3/A2 achieved complete hematological response with IFN-alpha therapy, as did three of the nine patients with B2/A2. The mean duration to blastic crisis was significantly longer in the B3/A2 patients (mean 52.4 months) than in the B2/A2 patients (mean 26.2 months) (p less than 0.01). These results suggest that the fusion pattern of BCR/ABL mRNA may affect the therapeutic response to IFN-alpha and clinical outcome in CML patients.
Leukemia 1992 Sep
PMID:Possible correlation between fusion pattern of BCR/ABL mRNA and clinical response to alpha-interferon in chronic myelogenous leukemia. 151 6

Fifty-seven Thai herbs and spices were examined for their retroviral reverse transcriptase inhibitory activity. All herbs and spices were extracted with hot-water and methanol. Reverse transcriptase inhibitory activity of the extracts was determined by using Moloney Murine Leukemia Virus reverse transcriptase (M-MuLV-RT) reacted with 3H-dTTP and radioactivity measured with a scintillation counter. Eighty-one per cent (46/57) of hot-water extracts and 54% (31/57) of methanol extracts showed inhibitory activities. At a concentration of 125 micrograms/ml, 13% (6/46) of hot-water extracts, namely Eugenia caryophyllus Bullock et Harrison, Phyllanthus urinaria Linn., Terminalia belerica Roxb., Nelumbo nucifera Gaertn., Psidium guajava Linn. and Lawsonia inermis Linn., had a relative inhibitory ratio (IR) over 50%. They showed ratios of 100%, 91%, 75%, 74%, 61% and 60%, respectively. For methanol extracts, only 10% (3/31) had IR values over 50%. They were T. belerica, E. caryophyllus and N. nucifera which exhibited IR values of 83%, 54% and 54%, respectively.
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PMID:Retroviral reverse transcriptase inhibitory activity in Thai herbs and spices: screening with Moloney murine leukemia viral enzyme. 752 65

The chromosomal translocation t(1;19)(q23;p13) and its variant form der(19)t(1;19) found in 3-5% of acute lymphoblastic leukemia (ALL) results in the expression of the E2A-PBX1 fusion transcript. Although strongly associated with a pre-B immunophenotype, we report the occurrence of t(1;19) in bone marrow or peripheral blood in nine patients with ALL with the following immunophenotypes: pre-B ALL (four), c-ALL (two), c-ALL clg not tested (one), null-ALL (one) and mature B-ALL (one). The E2A-PBX1 fusion transcript investigated by reverse-transcriptase polymerase chain reaction (RT-PCR) was seen in all patients at diagnosis and/or on follow-up samples. Six patients are alive in first clinical remission. Of these patients, three were PCR+ve from between 2 and 38 months from diagnosis, and three were PCR-ve when examined at 5, 26 and 51 months from diagnosis. Two patients are in second remission. One was PCR+ve at 18 months, suffered a CNS relapse at 21 months but was PCR-ve 1 month later. The other was PCR+ve in remission at 2 and 11 months from diagnosis and in testicular relapse at 31 months, but was PCR-ve 5 months later. The remaining patient died 2 months from diagnosis and was not investigated in remission. The prognostic significance of these findings remains to be investigated.
Leukemia 1995 May
PMID:Expression of the E2A-PBX1 fusion transcripts in t(1;19)(q23;p13) and der(19)t(1;19) at diagnosis and in remission of acute lymphoblastic leukemia with different B lineage immunophenotypes. 776 44

A human myeloid leukemia cell line, KBM-7, was developed from a patient in the blastic phase of chronic myeloid leukemia (CML). We characterized its morphology, immunophenotype, cytogenetics, and proliferative capacity. Developed in the absence of exogenous lymphokines, KBM-7 in vitro cloning capacity actually decreased when colony-stimulating factors were added. The cells had an aberrant immature myeloid phenotype, a doubling time of 22 h in suspension cultures and a high cloning efficiency in semisolid system (24 +/- 3)%. Early passages contained one near-haploid (predominant) and one hyperdiploid stem line. Gradually the hyperdiploid stem line became predominant, reaching an average of 49 chromosomes per cell. Cells from passage 89 had two Philadelphia chromosomes [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Detailed molecular characterization of the breakpoint in the t(9;22)(q34;q11) revealed that KBM-7 had the BCR 2/ABL II splice junction. The cells had high protein kinase (p210BCR-ABL) activity and carried two identified variants of an ABL-BCR message. There was no evidence that normal BCR or c-ABL messages were expressed, assessed with the reverse-transcriptase polymerase chain reaction. When KBM-7 cells were heterotransplanted into nude mice without immunosuppressive pretreatment, one of three mice injected with 1 x 10(7) cells and all mice injected with 1 x 10(8) cells developed slowly growing granulocytic sarcomas within 6-8 weeks. These tumors were locally invasive but did not metastasize. We conclude that the KBM-7 cell line will be of value for investigating molecular events underlying neoplastic transformation in CML, in particular for studying the effects of BCR-ABL and ABL-BCR on the proliferation of CML cells in the absence of normal BCR and c-ABL messages.
Leukemia 1995 Dec
PMID:KBM-7, a human myeloid leukemia cell line with double Philadelphia chromosomes lacking normal c-ABL and BCR transcripts. 860 23

Reverse transcriptase-polymerase chain reaction is a recent technique in the diagnosis and assessment of minimal residual disease of acute promyelocytic leukemia, by amplification, of the different PML-RARalpha transcripts resulting from the t(15;17) translocation. The main issues addressed by the Second Workshop on PML-RARalpha-RT-PCR which took place in Paris, France on 17-18 December 1994, were related to (1) defining the specific pitfalls of the PML-RARalpha-RT-PCR, and means to improve the sensitivity of the technique; (2) the validity of PCR results obtained in CR to provide information on the extent of the disease; (3) the frequency and prognostic value of the different PML-RARalpha transcripts.
Leukemia 1996 Feb
PMID:RT-PCR in acute promyelocytic leukemia: second workshop of the European Retinoic Group, Paris, France, 17-18 December 1994. 863 50

Leukemia in the soft-shell clam, Mya arenaria, is characterized by tumor cells which are detected initially in the hemolymph. This disease is much more common in clams inhabiting polluted waters, suggesting an environmental component to its pathogenesis. In this study, leukemia cells were identified using a murine monoclonal antibody, 1E10, which recognizes a leukemia-specific protein expressed by tumor cells. Mutant p53 protein was detected using a murine monoclonal antibody (PAb 240) which reacts with mutant p53. Using immunofluorescence, the reactivity of clam cells to the 1E10 antibody was evaluated along with mutant p53 protein reactivity. Reverse transcriptase-polymerase chain reactions followed by sequence analyses were utilized to examine clams with hemocytes reacting with the p53 antibody for possible p53 gene mutations. Mutant p53 protein was expressed by tumor cells from five animals with advanced disease (in which greater than 90% of cells reacted with 1E10). A C-->G transversion was detected at the end of exon 6 from two of the five animals that reacted with both the mutant p53 antibody and 1E10. This substitution changes the amino acid of this codon from proline to alanine. Overall, our results suggest that environmentally induced alterations in p53 can contribute to the pathogenesis of leukemia in soft-shell clams inhabiting polluted water and/or sediment.
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PMID:Detection of mutant p53 in clam leukemia cells. 916 98

Human T cell leukemia/lymphotropic virus (HTLV) is a complex 9 kb human retrovirus with at least eight alternatively spliced mRNAs expressed from the 3' or pX region of the genome. These mRNAs allow for the expression of novel proteins from the previously recognized pX open reading frames I and II in addition to Tax, Rex and p21rex encoded from orf III and IV. These alternatively spliced messages have been detected using reverse-transcriptase polymerase chain reaction (RT/PCR) amplification in HTLV-I-transformed T cell lines as well as in peripheral blood mononuclear cells (PBMC) from infected patients with and without disease. To gain insight into the role of these alternatively spliced mRNAs in pathogenesis, we developed a semi-quantitative non-PCR-based RNase protection assay to detect and quantitate their presence in HTLV-I-infected cells. Analysis of RNA from HTLV-I-infected cells established from patients with adult T cell leukemia (ATL) as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and both IL-2-dependent and IL-2-independent HTLV-I-infected cell lines by RNase protection has confirmed the existence of all of the alternatively spliced messages in each cell line analyzed. However, the relative quantity of each message was significantly different among these lines suggesting that splice site utilization is an important viral regulatory pathway.
Leukemia 1997 Jun
PMID:Differential expression of alternatively spliced pX mRNAs in HTLV-I-infected cell lines. 917 42

The possible involvement of the human T lymphotropic viruses type I and II (HTLV-I and -II) in lymphoproliferative disorders of mature T cells other than adult T cell leukemia/lymphoma (ATLL) has been controversial. Most studies have focused primarily on the cutaneous T cell lymphomas. However, skin involvement is a frequent feature of T prolymphocytic leukemia (T-PLL) and antibodies against HTLV-I and -II have been reported in individuals with large granular lymphocytic (LGL) leukemia. We examined 36 patients with T-PLL and 28 with LGL leukemia for evidence of HTLV-I and -II. Polymerase chain reaction (PCR) was performed on DNA from fresh peripheral blood mononuclear cells (PBMCs) and PBMCs after short-term culture (STC) using primers against all parts of the HTLV-I genome (LTR, gag, env, pol, tax/rex) and against HTLV-II pol and gag. Reverse transcriptase (RT) activity was measured on supernatants from STCs using a sensitive PCR-based technique. No HTLV-I or -II sequences were found by PCR nor RT activity detected in the 64 cases. Our findings do not provide evidence of HTLV-I or -II infection in T-PLL and LGL leukemia patients from an HTLV-I nonendemic area. Previous positive reports on these disorders may represent technical artefacts, detection of endogenous HTLV-like sequences or reflect patients from endemic areas and a variable etiology of T cell diseases.
Leukemia 1997 Aug
PMID:The human T-cell lymphotropic viruses types I/II are not involved in T prolymphocytic leukemia and large granular lymphocytic leukemia. 926 85

A human acute lymphoblastic leukemia (ALL) cell line, BALM-16, was established from the peripheral blood specimen of a patient with B cell ALL L3 type (ALL-L3) in relapse. As with the original leukemia cells, the established line was negative for both cell surface and cytoplasmic immunoglobulin (Ig) chains. Absence of Ig expression was confirmed by Western blotting. Southern blot analysis demonstrated homozygous deletion of the C kappa gene, germ line configuration of the C lambda and rearrangement of IgJH genes. Cytogenetic analysis of both leukemic bone marrow and BALM-16 cells showed the t(8;22)(q24;q11) abnormality which is specifically associated with ALL-L3 and Burkitt lymphoma. The patient's serum showed hypercalcemia, prompting further investigation of the established cell lines which showed parathyroid hormone-related peptide (PTHrP) mRNA detected by reverse-transcriptase polymerase chain reaction. However, PTHrP production was not detected in the culture supernatant. The established cell line, BALM-16, could provide a useful material for analyzing the lack of Ig expression and of clarifying the pathogenesis of this type of B cell malignancy.
Leukemia 1997 Dec
PMID:A novel ALL-L3 cell line, BALM-16, lacking expression of immunoglobulin chains derived from a patient with hypercalcemia. 944 37


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