[Erythropoietin gene regulation].
Explore the source record for details and available documents.
Anemia↗
Biomedical subjects
S Imagawa
Publications and source records attributed to S Imagawa.
[Erythropoietin and hypoxia responsive system].
Explore the source record for details and available documents.
Anemia↗
Further investigation of phenanthroindolizidine alkaloids from Tylophora tanakae.
In addition to ten alkaloids previously described, we have isolated two alkaloid N-oxides from Tylophora tanakae MAXIM. (Asclepiadaceae). Further, the polar fraction of the leaves and caules of this plant cultivated in a farm afforded two new polar alkaloids. The structures of the four products were determined. The relation between the structure and cytotoxic activity of this group of alkaloids is discussed.
Alkaloids↗
[Retrospective analysis of elderly patients > or = 60 years of age with acute leukemia].
A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.
Aclarubicin↗
Negative regulation of the erythropoietin gene expression by the GATA transcription factors.
We examined regulation of the human erythropoietin (Epo) gene through the GATA sequence in the Epo promoter and showed that Hep3B and HepG2 cells express human GATA-2 (hGATA-2) mRNA and protein. Nuclear extracts of QT6 cells transfected with hGATA-1, 2, or 3 transcription factors showed specific binding to the GATA element in the human Epo gene promoter by gel mobility shift assay. Transient transfection of Hep3B cells with hGATA-1, 2, or 3 showed that each of these transcription factors significantly decreased the level of expression of Epo mRNA as assessed by a competitive polymerase chain reaction. Transient transfection of Hep3B cells with hGATA-1, 2, and 3 and an Epo-reporter gene (growth hormone [GH]) construct showed significant inhibition of the Epo promoter. Antisense oligonucleotide for hGATA-2 transcription factor significantly increased the Epo protein in Hep3B cells under 1% O2 for 24 hours incubation. Furthermore, transient transfection of Hep3B cells with hGATA-1, 2, and 3 and an Epo-reporter gene (luciferase) construct also showed significant inhibition of the Epo promoter. However, transfection of the mutated GATA sequence of the Epo-luciferase gene with hGATA-1, 2, and 3 interfere with the inhibition of the Epo promoter. We conclude that the hGATA-1, 2, and 3 transcription factors specifically bind to the GATA element in the human Epo gene promoter and negatively regulate Epo gene expression.
Base Sequence↗
Therapy-related leukemia with a novel 21q22 rearrangement.
We present a case of a 59-year-old Japanese man with therapy-related acute myeloblastic leukemia (AML) after the chemotherapy for non-Hodgkin's lymphoma (NHL). Accumulated doses of cyclophosphamide, procarbazine, doxorubicin, mitoxantrone, and etoposide were 18,300 mg, 3000 mg, 580 mg, 100 mg, and 4150 mg, respectively, which had been administered for the treatment of NHL. Myeloblasts in the peripheral blood increased 43 months after the onset of NHL. He was diagnosed as having AML (M2; FAB classification). The karyotype of the bone marrow cells in the present case contained the following abnormalities: t(2;21)(q21;q22), t(8;21)(q22;q22), and add(13)(q34). In the present case, 645 base pairs of chimeric mRNA were detected by reverse transcription-polymerase chain reaction, indicating the presence of AML1/MTG8 rearrangement. Translocation (2;21)(q21;q22) has not been described previously to our knowledge. It is interesting that the breakpoint of 21q22 existed both in t(2;21) and t(8;21). The disrupted AML1 gene resulting from two 21q22 rearrangements may be involved in the pathogenesis of AML in the present case. The clinical importance of therapy-related AML having the 21q22 rearrangement remains to be examined.
Aclarubicin↗
Philadelphia chromosome-negative cells with trisomy 8 after busulfan and interferon treatment of Ph1-positive chronic myelogenous leukemia.
A 48-year-old Japanese man with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) was treated with busulfan followed by interferon-alpha (IFN-alpha). Ten months after IFN-alpha treatment, Ph1(-) cells with trisomy 8 were detected by the conventional banding technique and fluorescence in situ hybridization (FISH) analysis. Add(Y)(q12) was also found in Ph1(-) cells with trisomy 8. Although Ph1(+) cells disappeared after the treatment with IFN-alpha, Ph1(-) cells with trisomy 8 did not. We summarize four previous case reports of Ph1(+) CML developing Ph1(-) cells with trisomy 8. All four patients had received busulfan and IFN-alpha. These drugs may be related to the ontogenesis of Ph1(-) cells with trisomy 8, but the significance of Ph1(-) cells with trisomy 8 is not known, and further observation is needed.
Antineoplastic Agents↗
Erythropoietin gene expression by hydrogen peroxide.
We examined the effect of H2O2 on the regulation of the human erythropoietin (Epo) gene through the GATA sequence in the Epo promoter in Hep3B cells. The addition of exogenous H2O2 in Hep3B cells inhibited hypoxia-induced Epo production of mRNA as assessed by competitive polymerase chain reaction (PCR) and protein by EIA. Likewise, menadione, which increased production of endogenous H2O2, inhibited hypoxia-induced Epo production in Hep3B cells. Furthermore, the expression of the human GATA (hGATA) transcription factor was increased dose-dependently by the addition of H2O2 or menadione in Hep3B cells as assessed by gel mobility shift assay. We concluded that H2O2 inhibits Epo gene expression, because it enhanced the expression of the hGATA transcription factor. Our findings support the hypothesis that GATA is a transcription factor for the Epo gene acting through the oxygen sensor.
Cells, Cultured↗
GATA transcription factors negatively regulate erythropoietin gene expression.
We examined regulation of the human erythropoietin (Epo) gene through the GATA sequence in the Epo promoter, and demonstrated that Hep3B and HepG2 cells express human GATA-2 (hGATA-2) mRNA and protein. Nuclear extracts of QT6 cells transfected with hGATA-1, -2 or -3 transcription factors revealed specific binding to the GATA element in the human Epo gene promoter by gel mobility shift assay. Transient transfection of Hep3B cells with hGATA-1, -2 or -3 demonstrated that each of these transcription factors significantly decreased the level of expression of Epo mRNA as assessed by a competitive polymerase chain reaction. Furthermore, transient transfection of Hep3B cells with hGATA-1, -2 and -3 and and Epo reporter gene construct showed significant inhibition of the Epo promoter. We conclude that the hGATA-1, -2 and -3 transcription factors specifically bind to the GATA element in the human Epo gene promoter and negatively regulate Epo gene expression.
Anaerobiosis↗
[Retrospective analysis on 21 patients with follicular lymphoma].
We retrospectively analyzed the clinical data of the 21 patients with follicular lymphoma admitted to our institution from 1977 to 1994. The frequency of follicular lymphoma was 9.1% in the 231 patients with non-Hodgkin's lymphoma. Overall survival rates at 1 year, 3 years, and 5 years were 90.2%, 78.2%, and 52.1%, respectively. The median follow-up of surviving patients and time to treatment failure (TTF) was 43 months and 30 months, respectively. The median time from disease progression to death was 171 days. In univariate analysis, factors associated with poor survival were stage IV (Ann Arbor staging system), anemia (hemoglobin level less than 10g/dl), bone marrow involvement, two or more extranodal sites, and failure in induction of complete remission (CR) in the entire course. Factors associated with short TTF were anemia, bone marrow involvement, and failure in induction of CR. In multivariate analysis, induction of CR affected survival and TTF independently.
Adult↗
Methicillin-resistant Staphylococcus aureus: colonization and development of infection in patients with haematological disorders.
A retrospective study of 53 patients with haematological disorders whose bacterial cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA), was performed to analyse the risk factors for MRSA infection, and the prognostic factors. Sixteen patients showed colonization by MRSA but never developed infection(C), 16 showed colonization and subsequent infection(C-I), while 21 had MRSA infection at the time of first culture (I). Poor performance status, thrombocytopenia, increased serum urea nitrogen and decreased serum cholinesterase were more prominent in (I) than (C) + (C-I). The risk factors associated with the development of infection from colonization were age and serum cholinesterase. In addition, lower respiratory tract infection as a type of infection, non-remission status of the haematological malignancy and an inappropriate antibiotic therapy were associated with a poor prognosis for MRSA infection.
Blood Urea Nitrogen↗
B-cell lymphoma terminating in acute monoblastic leukemia.
A case of CD11b-, CD14- and CD36-positive B-cell lymphoma terminating in acute monoblastic leukemia is presented. The patient was initially suspected as having angiotrophic lymphoma due to proliferation of lymphoma cells within the sinusoid of the liver and clinical signs. Following chemotherapy, the lymphoma cells were converted into CD11b- and CD36-positive monoblasts. Lineage switching of B-cell lymphoma to acute monoblastic leukemia may have occurred in this case.
Humans↗
Retinoic acid up-regulates erythropoietin production in hepatoma cells and in vitamin A-depleted rats.
Retinoic acid (RA) stimulated the production of erythropoietin (Epo) in a human hepatoma cell line, HepG2 cells. The stimulation was due to the accumulation of Epo mRNA. The Epo production in HepG2 cells was also dependent on O2 tension for cell culture but the enhancement of Epo production by RA was independent of O2 tension, indicating that RA exerts its effect through a pathway different from O2. Oral administration of RA to the vitamin A-depleted rats elevated the concentration of Epo in serum. These results suggest that RA up-regulates EPO production in vivo as well as in vitro.
Animals↗
Positive and negative regulation of the erythropoietin gene.
In order to investigate positive and negative regulatory elements of the erythropoietin (Epo) gene, synthetic oligonucleotides were designed to control Epo transcription by means of an antigen strategy. We devised a new method for detecting regulatory elements of genes that have a weak promoter. Synthetic oligonucleotides were incubated with Hep3B cells in the presence or absence of CoCl2 or hypoxia. To exclude the effect of translational regulation, Epo mRNA concentration was determined by competitive polymerase chain reaction. The addition of antisense oligonucleotide for CACCC elements decreased the production of Epo mRNA in a dose-dependent fashion when cells were stimulated by CoCl2 or hypoxia. In contrast, the addition of antisense oligonucleotide for the GATA element caused a dose-dependent stimulation of Epo mRNA production either in the presence or absence of CoCl2 or hypoxia. Triple helix formation was revealed by electrophoresis. CACCC elements were demonstrated to be positive regulatory elements of the Epo gene, whereas the GATA element was a negative regulatory element. Furthermore, by gel mobility shift assays, we demonstrated evidence for the presence of factors in Hep3B cell nuclear extract that specifically bind to CACCC or GATA elements. Based on these observations, we presented the possibility that triple helix formation could serve as a novel means for transcriptional regulation of the gene.
Base Sequence↗
Development of acute myeloblastic leukaemia in a case of aplastic anaemia treated with granulocyte colony-stimulating factor.
We report a case of aplastic anaemia (AA) treated with granulocyte colony-stimulating factor (G-CSF) terminating as acute myeloblastic leukaemia (AML). Because of severe pneumonia, 250 micrograms of G-CSF was administered for 30 d to promote neutrophil recovery. Following G-CSF therapy, myeoblasts appeared, and the diagnosis of AML was then made. The myeloblasts proliferated in response to G-CSF in vitro and in vivo. In AA, development of AML after treatment with G-CSF is rare. Therefore a careful observation for leukaemic transformation is necessary in long-term administration of G-CSF for AA.
Aged↗
[A case of acute promyelocytic leukemia (APL) with myeloblastoma in the oral cavity developing after receiving all-trans retinoic acid (ATRA)].
A 44-year-old woman was diagnosed as having acute promyelocytic leukemia (APL) in April 1988. On her first admission, chromosomal translocation (15; 17), +8, and +12 was detected. When she was readmitted to our hospital with the second relapse in May 1990, t(3; 13) and +8 was detected, instead of t(15;17). Complete remission was re-achieved with VP-16, MIT, and BHAC, but the third relapse occurred in September 1990. After obtaining informed consent, she was given etretinate 40 mg per day orally for 17 days, without any effect on leukemia. She was then given all-trans retinoic acid (ATRA) 60 mg per day orally for 29 days. Although a mild granulocytic recovery was observed, no sufficient hematological recovery was obtained (minor response). Besides common side effects of ATRA, such as dry skin and hypertriglycedemia, she had a myeloblastoma in the oral cavity, but it is unknown whether the symptom was a complication of ATRA therapy or not.
Administration, Oral↗
Macrophage colony-stimulating factor and platelet recovery after chemotherapy.
Explore the source record for details and available documents.
Adult↗
[Treatment of 71 adult acute lymphoblastic leukemia].
From 1975 to 1989, 71 acute lymphoblastic leukemia patients aged 15 to 81 years (median 46 years) were treated at Jichi Medical School. Fifty-eight patients (81.7%) achieved complete remission (CR). Median CR duration was 219 days, and the probability of being in continuous CR at 3 years was 8.9%. Median survival was 462 days, and the probabilities of being alive at 3 and 5 years were 19.8% and 7.3%, respectively. The new regimen introduced from 1987 consisted of remission induction with L-asparaginase, daunomycin, vincristine and prednisolone, followed by intensive consolidation and maintenance. However, the treatment failed to improve outcome. The factor unfavorable for achieving early CR after first-line treatment regimen was the presence of myeloid antigen, and that for achieving final CR after second-line treatment regimen was advanced age. The factors unfavorable for remission duration were high leukocyte count and late CR. Those unfavorable for survival were advanced age and elevated blood urea nitrogen. Further improvement in the design of new protocols which include the use of several cytokines and autologous bone marrow transplantation may result in prolonged disease-free survival.
Adolescent↗