120 results on '"Murohashi, I."'
Search Results
2. Expression of functional granulocyte colony-stimulating factor receptors on human B-lymphocytic leukemia cells
- Author
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Handa, A., Kashimura, T., Takeuchi, S., Yamamoto, A., Murohashi, I., Bessho, M., and Hirashima, K.
- Published
- 2000
- Full Text
- View/download PDF
3. New system for assessing the prognosis of refractory anemia patients
- Author
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Matsuda, A, Jinnai, I, Yagasaki, F, Kusumoto, S, Murohashi, I, Bessho, M, Hirashima, K, Honda, S, Minamihisamatsu, M, Fuchigami, K, Matsuo, T, Kuriyama, K, and Tomonaga, M
- Published
- 1999
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4. Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia
- Author
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Matsuda, A, Jinnai, I, Yagasaki, F, Kusumoto, S, Minamihisamatsu, M, Honda, S, Murohashi, I, Bessho, M, and Hirashima, K
- Published
- 1998
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5. Trisomy 8 may not be related to the pathogenesis of myelodysplastic syndromes: disappearance of trisomy 8 in a patient with refractory anaemia without haematological improvement
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Matsuda, A., Yagasaki, F., Jinnai, I., Kusumoto, S., Murohashi, I., Bessho, M., and Hirashima, K.
- Published
- 1998
6. Establishment of an interleukin-3-dependent leukemic cell line from a patient with chronic lymphocytic leukemia in the acute phase
- Author
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Tohda, S, primary, Nara, N, additional, Murohashi, I, additional, and Aoki, N, additional
- Published
- 1991
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7. Interferon-gamma enhances growth factor-dependent proliferation of clonogenic cells in acute myeloblastic leukemia
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Murohashi, I, primary and Hoang, T, additional
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- 1991
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8. Antiproliferative and differentiative effects of recombinant interleukin-4 on a granulocyte colony-stimulating factor-dependent myeloblastic leukemic cell line
- Author
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Imai, Y, primary, Nara, N, additional, Tohda, S, additional, Nagata, K, additional, Suzuki, T, additional, Nagasawa, M, additional, Murohashi, I, additional, and Aoki, N, additional
- Published
- 1991
- Full Text
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9. Tumor Necrosis Factor-? Enhances Cytokine Production by AML Blasts
- Author
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MUROHASHI, I., primary, RODRIGUEZ-CIMADEVILLA, J. C., additional, and HOANG, T., additional
- Published
- 1991
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10. Relationship between the in vitro sensitivity to cytosine arabinoside of blast progenitors and the outcome of treatment in acute myeloblastic leukaemia patients.
- Author
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Nara, N., Suzuki, T., Nagata, K., Yamashita, Y., Murohashi, I., and Adachi, Y.
- Published
- 1988
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11. Efficacy of carboplatin with an MEP (mitoxantrone, etoposide and prednisone) regimen for relapsed and CHOP-resistant diffuse large B-cell lymphomas
- Author
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Murohashi, I., Kashimura, T., Tominaga, K., Wakao, D., Takahashi, T., Akiba, M., Kishimoto, K., Yoshida, K., Yagasaki, F., and Itoh, Y.
- Published
- 2002
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12. Granulocyte-colony stimulating factor induced intranuclear endonuclease in murine leukemia cell line
- Author
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Handa, A., Kashimura, T., Yamamoto, A., Murohashi, I., Bessho, M., and Hirashima, K.
- Published
- 2000
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13. Autocrine growth mechanisms of the progenitors of blast cells in acute myeloblastic leukemia
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Murohashi, I, Tohda, S, Suzuki, T, Nagata, K, Yamashita, Y, and Nara, N
- Abstract
Autocrine growth mechanisms of leukemic blast progenitors in acute myeloblastic leukemia (AML) were investigated. Colony formation of leukemic blast progenitors was observed in 14 of 14 patients tested when purified blast cell fraction depleted of both T cells and monocytes was plated in methylcellulose without any colony-stimulating factor (CSF). However, there existed a minimal cell density required to initiate blast progenitor growth with marked patient-to-patient variation. To clarify the role of cell density on the spontaneous growth of blast progenitors, we tested whether leukemic cells produced and secreted some stimulatory humoral factor(s). Production of colony- stimulating activity (CSA) by blast cells was observed in 17 of 18 patients tested. Following further depletion of monocytes, the CSA levels decreased markedly in 14 patients, indicating that blast cells with monocytoid differentiation were responsible for CSA production. We also confirmed granulocyte colony-stimulating factor (G-CSF) and/or granulocyte macrophage-colony-stimulating factor (GM-CSF) production by leukemic blasts using specific immunologic assays. When leukemic cells were divided into nonadherent nonphagocytic cell fraction and adherent cell fraction, only nonadherent nonphagocytic cells showed clonogenecity and adherent blast cells lacked the colony-forming capacity. The results indicate that there are at least two blast cell subpopulations in AML: one is proliferating subpopulation with self- renewal capacity and the other is supporting subpopulation with functions such as CSF production. The quite intimate relationship between these two blast cell subpopulations in AML may play an important role on the growth of leukemic blast progenitors in vitro.
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- 1989
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14. Effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on blast progenitors from acute myeloblastic leukaemia patients.
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Nara, N, Murohashi, I, Suzuki, T, Yamashita, Y, Maruyama, Y, Aoki, N, Tanikawa, S, and Onozawa, Y
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- 1987
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15. Comparative effects of vinca alkaloids (VCR, VDS) and epipodophyllotoxin (VP16) on murine myeloblastic leukaemia.
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Yamashita, Y, Nara, N, Murohashi, I, Imai, Y, and Aoki, N
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- 1987
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16. Tumor Necrosis Factor-α Enhances Cytokine Production by AML Blasts.
- Author
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MUROHASHI, I., RODRIGUEZ-CIMADEVILLA, J. C., and HOANG, T.
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- 1991
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17. Autoantibody against platelet glycoprotein II b/ III a in a patient with non-Hodgkin's lymphoma
- Author
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Kubota, T., primary, Tanoue, K., additional, Murohashi, I., additional, Nara, N., additional, Yamamoto, N., additional, Yamazaki, H., additional, and Aoki, N., additional
- Published
- 1989
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18. PLATELET DYSFUNCTIONS DUE TO AN ANTI-GP Ilia AUTOANTIBODY IN A HEMORRHAGIC PATIENT WITH MALIGNANT LYMPHOMA
- Author
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Kubota, T, additional, Tanoue, K, additional, Kitagawa, H, additional, Murohashi, I, additional, Aoki, N, additional, and Yamazaki, H, additional
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- 1987
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19. Insertion (11:7) in Myelodysplastic Syndrome
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Matsuda, A., Yagasaki, F., Jinnai, I., Kashimura, T., Kusumoto, S., Murohashi, I., Bessho, M., Hirashima, K., and Mimamihisamatsu, M.
- Published
- 1998
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20. PLATELET DYSFUNCTIONS DUE TO AN ANTI-GP Ilia AUTOANTIBODY IN A HEMORRHAGIC PATIENT WITH MALIGNANT LYMPHOMA
- Author
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Kubota, T, Tanoue, K, Kitagawa, H, Murohashi, I, Aoki, N, and Yamazaki, H
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- 1987
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21. The correlation of salivary telomere length and single nucleotide polymorphisms of the ADIPOQ, SIRT1 and FOXO3A genes with lifestyle-related diseases in a Japanese population.
- Author
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Han X, Kubota R, Tanaka KI, Hayashi H, Seki M, Sakai N, Kawaguchi-Ihara N, Arakawa K, and Murohashi I
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- Adult, Aged, Aged, 80 and over, Female, Humans, Hypertension epidemiology, Japan epidemiology, Male, Middle Aged, Saliva, Adiponectin genetics, Forkhead Box Protein O3 genetics, Hypertension genetics, Neoplasms epidemiology, Neoplasms genetics, Polymorphism, Single Nucleotide, Sirtuin 1 genetics, Telomere metabolism
- Abstract
Background: It has been reported that genetic factors are associated with risk factors and onset of lifestyle-related diseases, but this finding is still the subject of much debate., Objective: The aim of the present study was to investigate the correlation of genetic factors, including salivary telomere length and three single nucleotide polymorphisms (SNPs) that may influence lifestyle-related diseases, with lifestyle-related diseases themselves., Methods: In one year at a single facility, relative telomere length and SNPs were determined by using monochrome multiplex quantitative polymerase chain reaction and TaqMan SNP Genotyping Assays, respectively, and were compared with lifestyle-related diseases in 120 Japanese individuals near our university., Results: In men and all participants, age was inversely correlated with relative telomere length with respective p values of 0.049 and 0.034. In men, the frequency of hypertension was significantly higher in the short relative telomere length group than in the long group with unadjusted p value of 0.039, and the difference in the frequency of hypertension between the two groups was of borderline statistical significance after adjustment for age (p = 0.057). Furthermore, in men and all participants, the sum of the number of affected lifestyle-related diseases, including hypertension, was significantly higher in the short relative telomere length group than in the long group, with p values of 0.004 and 0.029, respectively. For ADIPOQ rs1501299, men's ankle brachial index was higher in the T/T genotype than in the G/G and G/T genotypes, with p values of 0.001 and 0.000, respectively. For SIRT1 rs7895833, men's body mass index and waist circumference and all participants' brachial-ankle pulse wave velocity were higher in the A/G genotype than in the G/G genotype, with respective p values of 0.048, 0.032 and 0.035. For FOXO3A rs2802292, women's body temperature and all participants' saturation of peripheral oxygen were lower in the G/T genotype than in the T/T genotype, with respective p values of 0.039 and 0.032. However, relative telomere length was not associated with physiological or anthropometric measurements except for height in men (p = 0.016). ADIPOQ rs1501299 in men, but not the other two SNPs, was significantly associated with the sum of the number of affected lifestyle-related diseases (p = 0.013), by genotype. For each SNPs, there was no significant difference in the frequency of hypertension or relative telomere length by genotype., Conclusion: Relative telomere length and the three types of SNPs determined using saliva have been shown to be differentially associated with onset of and measured risk factors for lifestyle-related diseases consisting mainly of cardiovascular diseases and cancer., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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22. Chloroquine Inhibits Self-Renewal of Blast Progenitors Synergistically With Phytochemicals or Nonsteroidal Anti-inflammatory Drugs in Hematological Malignant Cell Lines.
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Kawaguchi-Ihara N, Zhao Y, Nakamura S, Suzuki K, Zhang YI, Tohda S, and Murohashi I
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- Ascorbic Acid pharmacology, Blast Crisis drug therapy, Blast Crisis pathology, Cell Line, Tumor, Cell Self Renewal drug effects, Chloroquine pharmacology, Hematologic Neoplasms pathology, Humans, Indomethacin pharmacology, Neoplastic Stem Cells, Nitrobenzenes pharmacology, Resveratrol pharmacology, Stem Cells drug effects, Sulfonamides pharmacology, Tumor Stem Cell Assay, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Hematologic Neoplasms drug therapy, Phytochemicals pharmacology
- Abstract
Background: This study examined whether and how chloroquine inhibits blast progenitor self-renewal (SR) synergistically with phytochemicals or nonsteroidal anti-inflammatory drugs in seven hematological malignant cell lines., Materials and Methods: Vitamin C, resveratrol, cyclo-oxygenase inhibitor NS-398 and indomethacin heptyl ester (Ind) were added to cell culture with or without 3 μM chloroquine., Results: Chloroquine synergistically inhibited blast colony formation in methylcellulose with vitamin C, resveratrol, NS-398 and Ind in one, two, none and one cell lines, respectively, in a total of four out of 28 conditions. Chloroquine synergistically inhibited blast progenitor SR in suspension with vitamin C, resveratrol, NS-398 and Ind in four, six, one and five cell lines, respectively, in a total of 16 out of 28 conditions. In contrast, chloroquine abolished SR inhibition by another agent in four out of 28 conditions., Conclusion: Chloroquine exerted a marked synergistic inhibition of blast progenitor SR, but not blast colony formation., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2019
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23. Effects of Nonsteroidal Anti-inflammatory Drugs on the Self-renewal Capacity of Blast Progenitors in Hematological Malignancies.
- Author
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Yi Z, Yan Z, Miyahara K, Shimada M, Tanaka KI, Hayashi H, Ihara N, and Murohashi I
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- Apoptosis drug effects, Cell Line, Tumor, Hematologic Neoplasms, Humans, Telomerase metabolism, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cell Self Renewal drug effects, Indomethacin pharmacology, Nitrobenzenes pharmacology, Sulfonamides pharmacology
- Abstract
Background: With our newly established long-term suspension culture, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the self-renewal capacity of blast progenitors in seven hematological malignant cell lines., Materials and Methods: Cyclo-oxygenase inhibitors NS-398 (NS) or indomethacin heptyl ester (indomethacin) at 30 μM was added to the cell culture. In U-937 cells, indomethacin was added at 0.3 or 3 μM., Results: In all cell lines, the agents significantly and markedly inhibited blast colony formation (BCF) and telomerase activity, respectively. Significant exponential clonogenic cell growth was noted under all 23 conditions with or without the agent. The relative slope (SLP) of the line (SLP
agent /SLPcontrol ) reflects the level of self-renewal induced by the agent and self-renewal was inhibited (relative SLP at 0.9 or below) in four out of 16 conditions, including in U-937 cells treated with 0.3 or 3 μM indomethacin, in Daudi cells treated with indomethacin and in U-266 cells treated with NS. Indomethacin enhanced senescence, necrosis and apoptosis in U-937 and Daudi cells, whereas NS reduced apoptosis in U-937 cells and had no effect on senescence, necrosis and apoptosis in Daudi cells. In U-266 cells, NS enhanced senescence and necrosis, whereas indomethacin reduced apoptosis. There was no significant correlation between the control of BCF and relative SLP., Conclusion: NSAIDs enhance or reduce stress responses, inhibit telomerase activity and differentially regulate BCF and self-renewal., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)- Published
- 2017
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24. Establishment of a quenching probe method for detection of NPM1 mutations in acute myeloid leukemia cells.
- Author
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Kawaguchi-Ihara N, Itoh M, Murohashi I, and Tohda S
- Abstract
Nucleophosmin (NPM1) mutations, generally consisting of a four base-pair insertion, are present in ~60% of all cytogenetically normal acute myeloid leukemia (AML) cases. The mutation is clinically significant as an important prognostic factor. Direct sequencing is the current standard method of mutation detection, however, it is quite costly and time consuming. The present study aimed to establish a highly sensitive quenching probe (QP) method to detect NPM1 mutations efficiently. Melting curve analysis was performed using a QP, following polymerase chain reaction for amplification of the involved region of the gene. The curve derived from the fluorescent intensity with respect to the temperature of OCI/AML3, a heterozygous NPM1 mutant AML cell line, was W-shaped with melting peaks at 61°C and 68°C. That of M-07e, the homozygous wild type cell line, was V-shaped with a melting peak at 68°C. Thus, the curve derived from the mutant allele was easily discriminated from that of the wild-type allele. The mutant allele was detected in concentrations as low as 3% as determined by a subsequent sensitivity study. With a short testing time and a high sensitivity, this assay was applicable for NPM1-mutated AML patient samples and is appropriate for screening NPM1 mutations. It does require further examination as to whether it would be useful as a detection method for other mutant alleles since NPM1 mutations may consist of 61 known types of mutant sequences. To the best of our knowledge, this is the first report describing the QP method for the detection of NPM1 mutations.
- Published
- 2016
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25. Promotion of the self-renewal capacity of human leukemia cells by sonic hedgehog protein.
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Kawaguchi-Ihara N, Okuhashi Y, Itoh M, Murohashi I, Nara N, and Tohda S
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- Animals, Cell Line, Tumor, Cell Proliferation drug effects, Cell Shape drug effects, Clone Cells, Gene Expression Regulation, Leukemic drug effects, Humans, Leukemia genetics, Lymphoma pathology, Mice, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Tumor Stem Cell Assay, Hedgehog Proteins pharmacology, Leukemia pathology
- Abstract
Background: Hedgehog (Hh) signaling is involved in cancer cell growth. However, the effects of Hh stimulation on leukemia cells are unknown., Materials and Methods: The effects of recombinant sonic Hedgehog (Shh) protein on the in vitro growth of one B-lymphoma and four myeloid leukemia cell lines were examined., Results: Shh stimulation had no significant effect on the short-term growth of whole cell populations in any of the five cell lines. However, Shh promoted clonogenic cell recovery after suspension culture, suggesting promotion of leukemia stem or progenitor cell amplification in three cell lines. The lack of Hh receptors in one cell line and endogenous Shh expression in another were possible reasons for the lack of effects of Shh in these cases., Conclusion: These results suggest that Shh stimulation promotes the self-renewal capacity of leukemia stem cells in some cell lines. Inhibition of Hh signaling could represent a novel therapeutic approach in leukemia.
- Published
- 2011
26. Promotion of the self-renewal capacity of human acute leukemia cells by Wnt3A.
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Kawaguchi-Ihara N, Murohashi I, Nara N, and Tohda S
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- ADP-ribosyl Cyclase 1 biosynthesis, Acute Disease, Antigens, CD34 biosynthesis, Calcium-Binding Proteins biosynthesis, Calcium-Binding Proteins genetics, Cell Growth Processes drug effects, Cell Line, Tumor, Gene Expression drug effects, Humans, Intercellular Signaling Peptides and Proteins biosynthesis, Intercellular Signaling Peptides and Proteins genetics, Leukemia, Myeloid genetics, Leukemia, Myeloid metabolism, Leukemia, Myeloid pathology, Membrane Proteins biosynthesis, Membrane Proteins genetics, Neoplastic Stem Cells drug effects, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma pathology, RNA, Messenger biosynthesis, RNA, Messenger genetics, Receptor, Notch1 biosynthesis, Receptor, Notch1 genetics, Recombinant Proteins pharmacology, Serrate-Jagged Proteins, Wnt3 Protein, Wnt3A Protein, Leukemia, Myeloid drug therapy, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Wnt Proteins pharmacology
- Abstract
Background: Wnt/beta-catenin signaling is involved in the growth of various types of cancer cells. Wnt3A has been reported to promote the self-renewal of hematopoietic stem cells., Materials and Methods: The effects of recombinant Wnt3A protein on the in vitro growth of four acute myeloid leukemia (AML) and four acute T-lymphoblastic leukemia (T-ALL) cell lines was examined., Results: Wnt3A stimulation either had no effect on, or slightly suppressed, the short-term growth of these cell lines. In three cell lines, Wnt3A promoted clonogenic cell recovery after suspension culture, suggesting the promotion of the self-renewal capacity of leukemic stem or progenitor cells. Immunoblot analysis showed that Wnt3A stimulation reduced phosphorylated beta-catenin and increased beta-catenin in these cells, indicating that Wnt3A stimulation activated Wnt/beta-catenin signaling., Conclusion: Wnt3A stimulation did not promote the growth of whole cell populations, but did promote the self-renewal of leukemic stem/progenitor cells in some AML and T-ALL cell lines.
- Published
- 2008
27. Lactate dehydrogenase-linked immunoglobulin Akappa in a patient with nonimmune chronic idiopathic neutropenia.
- Author
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Ihara N, Murohashi I, Itho M, Amino I, Yoshida K, Matsuda A, and Bessho M
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- Adult, Autoimmune Diseases enzymology, Blood Cell Count, Female, Flow Cytometry, Humans, Immunoglobulin A immunology, Isoenzymes blood, Killer Cells, Natural physiology, L-Lactate Dehydrogenase chemistry, Uterine Cervical Neoplasms surgery, Autoimmune Diseases blood, Immunoglobulin A blood, L-Lactate Dehydrogenase blood, Neutropenia immunology
- Abstract
A 39-year-old patient with cervical cancer, stage Ia, was successfully treated by total hysterectomy. Then, after sustained neutropenia for more than 4 years and coincident with its exacerbation, the serum lactate dehydrogenase (LD) level started to elevate and reached a plateau. A test for antineutrophil antibody was negative and LD-3-linked IgAkappa, which may be responsible for high LD activity, was confirmed. The absolute number of blood NK cells was reduced, and a diagnosis of nonimmune chronic idiopathic neutropenia of adult was made. The successive occurrence of these 3 disorders may be based on interrelated immunological abnormalities.
- Published
- 2006
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28. Serum levels of Thl/Th2 cytokines, angiogenic growth factors, and other prognostic factors in young adult patients with hemophagocytic syndrome.
- Author
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Murohashi I, Yoshida K, Ihara N, Wakao D, Yagasaki F, Nakamura Y, Kawai N, Matsuda A, Jinnai I, and Bessho M
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- Adult, Female, Growth Substances blood, Humans, Immunity, Cellular, Interleukin-10 immunology, Interleukin-18 immunology, Lymphohistiocytosis, Hemophagocytic immunology, Male, Prognosis, Th1 Cells, Th2 Cells, Angiogenic Proteins blood, Cytokines blood, Lymphohistiocytosis, Hemophagocytic blood
- Abstract
Serum levels of T helper 1 (Th1)/T helper 2 (Th2) cytokines, angiogenic growth factors, and other prognostic factors were measured in 5 young adult patients with virus-associated hemophagocytic syndrome (HPS). Levels of 2 Th1 cytokines (interleukin [IL]-18 and tumor necrosis factor-alpha), 2 Th2 cytokines (IL-10 and IL-6), and 2 angiogenic growth factors (soluble intercellular adhesion molecule-1 and hepatocyte growth factor) were high in all of the patients examined, whereas those of Th1 cytokines such as IL-12 and macrophage inflammatory protein-1a were normal or low. Levels of IL-18 and IL-10 were highest in case 2, with a fatal outcome, and were lowest in case 4, with rapid recovery within 1 month. Although IFN-gamma levels were not elevated in 2 patients (cases 3 and 5), IL-18 levels were markedly high in both of these cases and the IL-6 level was highest in case 3. In contrast with the marked increase in the level of IL-10, the levels of IL-6, sIL-2R, and ferritin decreased rapidly and returned to normal within 2 months after therapy in case 3. The IL-18 level decreased somewhat, but remained elevated for 6 months, and the patient achieved a complete response within 11 months. Taken together, our findings suggest that both IL-18 and IL-10, but not IL-12, may play important roles in young adult patients with HPS via enhancing and suppressing Th1 immune responses, respectively.
- Published
- 2006
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29. Soluble transferrin receptor and its ratio to erythroblasts in bone marrow may be a new diagnostic tool to distinguish between aplastic and refractory anemia.
- Author
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Matsuda A, Misumi M, Shimada T, Yoshida K, Yagasaki F, Ito Y, Kawai N, Murohashi I, Hirashima K, and Bessho M
- Subjects
- Adult, Aged, Aged, 80 and over, Bone Marrow Cells, Diagnosis, Differential, Erythrocyte Count, Female, Humans, Male, Middle Aged, Solubility, Anemia, Aplastic diagnosis, Anemia, Refractory diagnosis, Erythroblasts cytology, Receptors, Transferrin blood
- Abstract
Myelodysplastic syndromes (MDS), especially refractory anemia (RA) are very heterogeneous diseases regarding their morphological, biological and clinical features. One important clinical problem is the difficulty of diagnosis. Soluble transferrin receptors (sTfRs) reflect the erythropoietic activity in the bone marrow (BM). To establish whether determination of serum sTfR could be useful for the differential diagnosis between RA and aplastic anemia (AA), we measured the serum sTfR concentrations, BM cellularity and BM erythroblast percentages in 14 untreated AA and 7 untreated RA patients. The serum sTfR levels of the RA patients (820.1 +/- 402.8 ng/ml) were significantly higher than those of the AA patients (491.1 +/- 195.2 ng/ml; p = 0.0207). However, the serum sTfR values of RA and AA patients also overlapped. A new index, the 'sTfR-E index' [the ratio of serum sTfR level (ng/ml) to BM cellularity (%) x BM erythroblasts (%)] is proposed, which is expected to reflect the number of transferrin receptors (TfR) on the cell membrane per BM erythroblast. The sTfR-E index values of the 7 RA patients (0.395 +/- 0.234) were significantly lower than those of the 14 AA patients (2.669 +/- 1.633; p = 0.0003). The sTfR-E index values of AA and RA patients overlapped only marginally. In conclusion, the sTfR-E index may be a useful new diagnostic tool to distinguish between AA and RA patients., (Copyright 2004 S. Karger AG, Basel)
- Published
- 2004
- Full Text
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30. Differential response to stem cell factor and Flt3 ligand by the FAB subtype in acute myeloid leukemia clonogenic cells.
- Author
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Murohashi I, Yoshida K, Kishimoto K, Takahashi T, Wakao D, Jinnai I, Yagasaki F, Kawai N, Suzuki T, Matsuda A, Hirashima K, and Bessho M
- Subjects
- Acute Disease, Blast Crisis drug therapy, Blast Crisis pathology, Cell Division drug effects, Clone Cells, Granulocyte Colony-Stimulating Factor pharmacology, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Humans, Interleukin-3 pharmacology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Leukemia, Myeloid pathology, Leukemia, Myelomonocytic, Acute pathology, Recombinant Proteins pharmacology, Retrospective Studies, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha pharmacology, Leukemia, Myeloid drug therapy, Leukemia, Myelomonocytic, Acute drug therapy, Membrane Proteins pharmacology, Stem Cell Factor pharmacology
- Abstract
Proliferative response of blast clonogenic cells to various hematopoietic growth factors (HGF), including stem cell factor (SCF) and flt3 ligand (FL) was investigated in 100 patients with acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) in myeloid crisis (MC). The frequency of spontaneous colony formation was significantly high in CML in MC (55%) and AML French-American-British (FAB) subtype M4 (48%) compared with M2 (16%). No spontaneous colony was formed in any of the patients with M1 and M3. The frequency of proliferative response to various HGF alone and in combination according to FAB subtype and CML in MC was as follows: that to granulocyte colony-stimulating factor (G-CSF) was lowest in M1 and CML in MC (50%) compared with other FAB subtypes (>or=86%), that to granulocyte-macrophage CSF (GM-CSF) was lowest in CML in MC (44%) compared with FAB subtypes (>or=74%), and that to interleukin-3 (IL-3) was lowest in CML in MC (30%) compared with FAB subtypes (>or=78%). SCF and FL stimulated blast colony formation in 11% and 17% of patients with M3, respectively, but there was no response to both, and in 60% and 57% of patients with CML in MC, respectively, with 14% showing a response to both. The frequency of proliferative response to both SCF and FL increased in the order of M1 (33%), M2 (63%), M4-5 (95%), and M6 (100%). The results are summarized as follows: absence of spontaneous colony formation and response to HGF other than SCF and FL, designated as HGF-dependent growth (M3); spontaneous colony formation and lowest response to HGF, designated as autonomous growth (CML in MC); and spontaneous colony formation and highest response to HGF including SCF and FL, designated as autocrine growth (M4-6). M1 and M2 were intermediate between CML in MC and M4-6. The relation between in vitro growth pattern of blast clonogenic cells and prognosis in AML FAB subtype and CML in MC is discussed.
- Published
- 2002
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31. Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation.
- Author
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Yagasaki F, Wakao D, Yokoyama Y, Uchida Y, Murohashi I, Kayano H, Taniwaki M, Matsuda A, and Bessho M
- Subjects
- Amino Acid Sequence, Base Sequence, Female, Humans, In Situ Hybridization, Fluorescence, Middle Aged, Molecular Sequence Data, Proto-Oncogene Proteins c-ets, Receptor, Fibroblast Growth Factor, Type 3, Reverse Transcriptase Polymerase Chain Reaction, ETS Translocation Variant 6 Protein, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 4, DNA-Binding Proteins genetics, Lymphoma, T-Cell genetics, Oncogene Proteins, Fusion genetics, Protein-Tyrosine Kinases, Receptors, Fibroblast Growth Factor genetics, Recombinant Fusion Proteins genetics, Repressor Proteins genetics, Translocation, Genetic
- Abstract
Fusions of the ETV6/TEL gene to receptor or protein tyrosine kinases (TKs), such as PDGFRbeta, JAK2, ABL, ABL2, TRKC, and Syk, have been reported in various hematological malignancies. Expression of the resultant chimeric proteins is believed to lead to constitutive TK activity through activation by the helix-loop-helix (HLH) domain of ETV6. We identified a novel ETV6 partner gene, fibroblast growth factor receptor 3 (FGFR3), in a patient with peripheral T-cell lymphoma (PTCL) with a t(4;12)(p16;p13) translocation. The ETV6-FGFR3 transcript showed a fusion of exon 5 of ETV6 to exon 10 of FGFR3, resulting in an open reading frame for a chimeric protein consisting of the HLH domain of ETV6 and the TK domains of FGFR3. This is the first report of ETV6 and FGFR3 involvement in PTCL.
- Published
- 2001
32. [Classification of malignant lymphomas].
- Author
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Murohashi I
- Subjects
- Hodgkin Disease pathology, Humans, Lymphoma, Non-Hodgkin pathology, Hodgkin Disease classification, Lymphoma, Non-Hodgkin classification
- Abstract
Hodgkin's disease is characterized by malignant tumor in lymphoid tissue, excluding non-Hodgkin's lymphomas and lymphoid leukemias. It can be diagnosed by the characteristic histologic picture, which contains Reed-Sternberg cells. The Rye classification for Hodgkin's disease has been useful to date, however, since non-Hodgkin's lymphomas were first recognized as a distinct group a variety of classifications have been proposed although none are entirely satisfactory. At present, it is concluded that the most practical approach to lymphoma categorization is simply to define the diseases with the currently available morphologic, immunologic, and genetic techniques, and use the REAL and WHO classifications for lymphoid malignancies. It is important to develop more concise and practical classifications in the future.
- Published
- 2001
33. The pathogenetic mechanism of myeloid malignancies associated with deletions of the long arm of chromosome 20 can not be explained by a "one hit" model. An acute myeloid leukemia patient who developed with 20q- clone during complete remission for 9 years.
- Author
-
Matsuda A, Jinnai I, Yagasaki F, Ito Y, Ito K, Kusumoto S, Murohashi I, Bessho M, and Hirashima K
- Subjects
- Humans, Leukemia, Myeloid, Acute drug therapy, Male, Middle Aged, Remission Induction, Chromosomes, Human, Pair 20, Gene Deletion, Leukemia, Myeloid, Acute genetics
- Published
- 2000
- Full Text
- View/download PDF
34. [Salvage therapy in relapsed or refractory malignant lymphoma].
- Author
-
Kashimura T and Murohashi I
- Subjects
- Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma therapy, Combined Modality Therapy, Hematopoietic Stem Cell Transplantation, Humans, Lymphoma, Mantle-Cell therapy, Neoplasm Recurrence, Local therapy, Prognosis, Rituximab, Transplantation, Autologous, Lymphoma, Non-Hodgkin therapy, Salvage Therapy
- Abstract
High dose therapy(HDT) followed by autologous stem cell transplantation(ASCT) is a therapeutic options in chemotherapy-sensitive aggressive non-Hodgkin's lymphoma(NHL) and Hodgkin's disease at relapse. Of the patients with NHL, primary refractory disease should also be treated with such therapy. In patients with indolent lymphoma at relapse, disease free survival after treatment with purged ASCT has been shown to reach a plateau, although the therapy is a matter for debate at present. Anti-CD-20 monoclonal antibody in combination with standard- or high-dose chemotherapy is also quite effective for indolent NHL at relapse. In aggressive NHL with high- or high-intermediate international prognostic index, Burkitt's lymphoma, and mantle cell lymphoma. ASCT as front-line therapy might improve the clinical outcome.
- Published
- 2000
35. Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).
- Author
-
Yagasaki F, Jinnai I, Yoshida S, Yokoyama Y, Matsuda A, Kusumoto S, Kobayashi H, Terasaki H, Ohyashiki K, Asou N, Murohashi I, Bessho M, and Hirashima K
- Subjects
- Adult, Amino Acid Sequence, Artificial Gene Fusion, Base Sequence, Blotting, Northern, Chromosome Mapping, DNA, Neoplasm analysis, Exons, Female, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Molecular Sequence Data, Nuclear Proteins genetics, Phosphoproteins genetics, Proto-Oncogene Proteins c-ets, RNA, Neoplasm analysis, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, ETS Translocation Variant 6 Protein, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 5, Coenzyme A Ligases genetics, DNA-Binding Proteins genetics, Leukemia, Myeloid, Acute genetics, Repressor Proteins, Transcription Factors genetics, Translocation, Genetic
- Abstract
We identified a novel human long fatty acyl CoA synthetase 2 gene, ACS2, as a new ETV6 fusion partner gene in a recurrent t(5;12)(q31;p13) translocation in a patient with refractory anemia with excess blasts (RAEB) with basophilia, a patient with acute myelogenous leukemia (AML) with eosinophilia, and a patient with acute eosinophilic leukemia (AEL). ACS2 is expressed in the brain and bone marrow and is highly conserved in man and rats. The resulting ETV6/ACS2 fusion transcripts showed an out-frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the AEL case, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the AML case, and a short in-frame fusion of ETV6 exon 1 to the 3' untranslated region of ACS2 in the RAEB case. Reciprocal ACS2/ETV6 transcripts were identified in two of the cases. Fluorescence in situ hybridization (FISH) analysis with ETV6 cosmids on 12p13, and BACs and P1s on 5q31, demonstrated that the 5q31 breakpoints of the AML and AEL cases involved the 5' portion of the ACS2 gene, and that the 5q31, breakpoint of the RAEB case involved the 3' portion of the ACS2 gene. None of the resulting chimeric transcripts except for the ACS2/ETV6 transcript in the RAEB case led to a fusion protein. Disruption of the second ETV6 allele by t(12;19) was detected in the AML case by FISH analysis. These observations suggest that the disruption of ETV6 and/or ACS2 may lead to the pathogenesis of hematologic malignancies with t(5;12)(q31;p13)., (Copyright 1999 Wiley-Liss, Inc.)
- Published
- 1999
- Full Text
- View/download PDF
36. [The importance of WT1 gene expression in the detection of minimal residual disease. A comparison of WT1 AML1/MTG8 transcripts].
- Author
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Kusumoto S, Murohashi I, Bessho M, Matsumoto H, and Shimazu M
- Subjects
- Acute Disease, Adult, Aged, Core Binding Factor Alpha 2 Subunit, Female, Fusion Proteins, bcr-abl blood, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, RUNX1 Translocation Partner 1 Protein, Recombinant Fusion Proteins analysis, Recombinant Fusion Proteins blood, WT1 Proteins, Biomarkers, Tumor blood, DNA-Binding Proteins analysis, Genes, Wilms Tumor, Leukemia diagnosis, Neoplasm, Residual diagnosis, Oncogene Proteins, Fusion, Transcription Factors analysis, Transcription Factors blood, Wilms Tumor genetics
- Abstract
The Wilms tumor gene (WT1) has been reported to be a prognostic factor and a marker for the detection of minimal residual disease (MRD) in acute leukemia. Using competitive polymerase chain reaction procedures, we examined the expression of the WT1 gene in acute leukemia patients with several tumor-specific DNA markers, including bcr/abl, PML/RAR alpha, and AML1/MTG8. A strong correlation was observed between the levels of WT1 and PML/RAR alpha expression. However, AML1/MTG8 transcripts were detected at all stages of the disease even when the expression level of WT1 gene was low. From these findings, we concluded that monitoring the WT1 expression level is a useful means of determining the effectiveness of chemotherapy, and that WT1 is an effective marker for the detection of MRD, especially in acute myeloid leukemia patients with AML1/MTG8.
- Published
- 1999
37. [Non-Hodgkin's lymphoma complicated by recurrent intractable generalized herpes zoster responsive to long-term acyclovir therapy].
- Author
-
Endo K, Kobayashi Y, Kawai N, Itoh K, Tominaga K, Kusumoto S, Fukuda M, Murohashi I, Bessho M, Hirashima K, Yamazaki T, and Uno H
- Subjects
- Adult, Herpes Zoster complications, Humans, Lymphoma, Non-Hodgkin drug therapy, Male, Recurrence, Acyclovir administration & dosage, Herpes Zoster drug therapy, Lymphoma, Non-Hodgkin complications
- Abstract
A 34-year-old male with a history of chickenpox developed primary abdominal non-Hodgkin's lymphoma (diagnosed in August 1995). Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone achieved a partial remission. In July 1996, the disease recurred, and the patient received chemotherapy with carboplatine, etoposide, mitoxantrone, and prednisolone, but no response was noted. Involvement of the central nervous system and meninges was diagnosed on September 12, 1997. Blast cells were detected in the peripheral blood on September 26. Based on these findings, he was diagnosed as having leukemia. On September 27, painless vesicles developed on the left gluteal region. On October 13, the patient was hospitalized because the vesicles had spread over his entire body. Pathologic examination of the roofs of the blisters showed masses of inclusion bodies. Based on this, a diagnosis of varicella-zoster infection was made. Treatment with acyclovir (750 mg/day) for seven days failed to form crusts. New vesicles developed after the drug was discontinued, but crusts formed after acyclovir therapy was resumed. He died of interstitial pneumonia on December 21. Autopsy could not be performed. Histopathologic examination of pulmonary tissue obtained by necropsy did not reveal the presence of inclusion bodies characteristic of herpes simplex or varicella-zoster infection. Varicella-zoster virus (VZV) antigen was negative by an immunochemical staining method using monoclonal antibodies against VZV. Continuous long-term administration of acyclovir has been reported to be effective for non-Hodgkin's lymphoma complicated by recurrent intractable herpes zoster.
- Published
- 1999
- Full Text
- View/download PDF
38. [Atypical chronic myeloid leukemia presenting with trilineage dysplasia and IgG (lambda) type monoclonal gammopathy].
- Author
-
Itoh K, Kashimura T, Kobayashi Y, Yagasaki F, Sakata T, Kawai N, Matsuda A, Kusumoto S, Fukuda M, Ino H, Murohashi I, Jinnai I, Yoshida S, Bessho M, Saitoh M, and Hirashima K
- Subjects
- Aged, Bone Marrow Cells pathology, Fusion Proteins, bcr-abl genetics, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive classification, Male, Immunoglobulin gamma-Chains blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative pathology, Paraproteinemias complications
- Abstract
A 78-year-old man was diagnosed as leukocytosis in February 1994. Physical examination revealed marked hepatosplenomegaly. A peripheral blood examination disclosed 95,090/microliter leukocytes without hiatus leukemicus, 6.5 g/dl Hb, and 15.0 x 10(4)/microliter platelets. The neutrophil alkaline phosphatase score was 27, and serum VB12 was above 1,600pg/ml. IgG was identified as monoclonal immunoglobulin of type lambda. Bone marrow specimens demonstrated marked granulocytic hyperplasia. Neither the Philadelphia chromosome (Ph1) nor BCR gene rearrangement was detected; hence, the diagnosis of Ph1 (-) chronic myeloid leukemia (CML) was made. The patient was treated with hydroxyurea and low-dose VP-16 with no improvement, and died of pneumonia and sepsis in June 1995. This case was considered to be consistent with atypical CML (aCML) according to the FAB classification because monocytosis was not observed. It seems likely and interesting that the coexistent monoclonal gammopathy and aCML might have arisen from common abnormal hematopoietic stem cells.
- Published
- 1999
39. [Waldenström's macroglobulinemia effectively treated with chronic daily oral administration of low-dose etoposide].
- Author
-
Itoh K, Shimada T, Horibe T, Kawai N, Sakata T, Fukuda M, Murohashi I, Bessho M, Takeuchi H, and Hirashima K
- Subjects
- Administration, Oral, Aged, Drug Administration Schedule, Female, Humans, Lymph Nodes pathology, Waldenstrom Macroglobulinemia pathology, Etoposide administration & dosage, Nucleic Acid Synthesis Inhibitors administration & dosage, Waldenstrom Macroglobulinemia drug therapy
- Abstract
A 77-year-old woman with complaints of fever and systemic lymphadenopathy was admitted to our hospital on February 16, 1995. Serum IgM was elevated to 2,097 mg/dl. Lymph node biopsy showed diffuse infiltration with lymphoplasmacytoid cells. Thus, she was diagnosed as having Waldenström's macroglobulinemia. Considering her age and congestive heart failure, she was treated with oral administration of low-dose etoposide (25 mg/day). Splenomegaly and superficial lymphadenopathy disappeared after one course of therapy. Until her death due to pneumonia, complete remission continued for one year without any symptoms and adverse effects except for mild diarrhea. Low-dose etoposide therapy was considered to be well tolerated and useful for elderly patients with Waldenström's macroglobulinemia.
- Published
- 1998
40. Therapy-related AML after successful chemotherapy with low dose etoposide for virus-associated hemophagocytic syndrome.
- Author
-
Takahashi T, Yagasaki F, Endo K, Takahashi M, Itoh Y, Kawai N, Kusumoto S, Murohashi I, Bessho M, and Hirashima K
- Subjects
- Adult, Dose-Response Relationship, Drug, Histiocytosis, Non-Langerhans-Cell virology, Humans, Leukemia, Myelomonocytic, Acute genetics, Male, Treatment Outcome, Antineoplastic Agents therapeutic use, Etoposide therapeutic use, Histiocytosis, Non-Langerhans-Cell drug therapy, Leukemia, Myelomonocytic, Acute chemically induced
- Abstract
A 19-year-old male patient with virus associated hemophagocytic syndrome (VAHS) began receiving chemotherapy including etoposide (cumulative dose of 900 mg/m2 intravenously) and Ara-C (cumulative dose of 360 mg/m2 intravenously) in July 1994. He achieved complete remission, but developed acute myelomonocytic leukemia (AML, FAB M4) with t(9;11)(p22;q23) in March 1997 and a rearrangement of the MLL gene was also recognized. The MLL gene rearrangement is closely associated with secondary leukemia with an 11q23 translocation. It is highly likely that this case of AML was caused by the cytostatic treatment the patient received, including etoposide for VAHS.
- Published
- 1998
- Full Text
- View/download PDF
41. [Acute promyelocytic leukemia relapse as leukemia cutis shortly after complete remission with all-trans retinoic acid].
- Author
-
Itoh K, Gotoh W, Yagasaki F, Itoh Y, Kawai N, Matsuda A, Tominaga K, Kusumoto S, Ino H, Murohashi I, Jinnai I, Takeuchi H, Bessho M, and Hirashima K
- Subjects
- Humans, Male, Middle Aged, Recurrence, Remission Induction, Leukemia, Promyelocytic, Acute drug therapy, Leukemia, Promyelocytic, Acute pathology, Leukemic Infiltration pathology, Skin pathology, Tretinoin therapeutic use
- Abstract
A 56-year-old man was admitted to our hospital in September, 1996. Chromosomal translocation (15; 17) and a PT-PCR study for PML-RAR alpha mRNA were positive in bone marrow aspirates, and acute promyelocytic leukemia was diagnosed. After CR was obtained with all-trans retinoic acid (ATRA) followed up with chemotherapy, the RT-PCR became negative. When he was readmitted in April, 1997, skin eruption on his chest and extremities were observed. Specimens taken for biopsy revealed leukemia cutis, and RT-PCR became positive in the same specimen. Bone marrow PT-PCR was also positive without abnormal promyelocytes. Although he was treated with oral ATRA 80 mg/day again, no significant improvement in leukemia cutis was noted. After combined therapy with Ara-C and acularubicin, skin eruption disappeared and bone marrow RT-PCR became negative. A second CR was then obtained. Although it is unknown whether the administration of ATRA is related to extramedullary relapse or not, we recommend combined chemotherapy for such cases.
- Published
- 1998
42. Magnetic resonance imaging patterns in patients with multiple myeloma.
- Author
-
Kusumoto S, Jinnai I, Itoh K, Kawai N, Sakata T, Matsuda A, Tominaga K, Murohashi I, Bessho M, Harashima K, and Heshiki A
- Subjects
- Adult, Aged, Aged, 80 and over, Bence Jones Protein analysis, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Survival Rate, Multiple Myeloma diagnosis
- Abstract
Sixty-one consecutive patients with multiple myeloma were studied with magnetic resonance (MR) imaging of the spine. Sagittal T1-weighted and short inversion time (TI) inversion recovery (STIR) images were obtained. The MR patterns of the bone marrow were classified as diffuse (D) (n=26), nodular (N) (n=11), D+N (n=13) or normal (n) (n=11). Abnormal patterns were seen in 50 (82%) of the 61 patients. Correlations were found between the MR imaging patterns and some laboratory findings (WBC, haematocrit, platelet count, serum albumin, and percentage of marrow plasmacytosis). The survival of the patients with abnormal MRI patterns was significantly poorer than that of the patients with normal patterns. However, the survival of patients with a nodular pattern did not differ from those with a normal pattern. The MR imaging pattern of the bone marrow in patients with multiple myeloma is a useful factor in the assessment of prognosis.
- Published
- 1997
- Full Text
- View/download PDF
43. Differential regulation by hematopoietic growth factors of apoptosis and mitosis in acute myeloblastic leukemia cells.
- Author
-
Murohashi I, Yoshida K, Handa A, Murayoshi M, Yoshida S, Jinnai I, Bessho M, and Hirashima K
- Subjects
- Cell Cycle drug effects, Cyclin-Dependent Kinase Inhibitor p21, Cyclins genetics, Cyclins metabolism, DNA Fragmentation, Gene Expression Regulation, Neoplastic, Granulocyte Colony-Stimulating Factor pharmacology, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Humans, Interleukin-3 pharmacology, Proto-Oncogenes, Stem Cell Factor pharmacology, Tumor Necrosis Factor-alpha pharmacology, Tumor Suppressor Protein p53 metabolism, Apoptosis drug effects, Hematopoietic Cell Growth Factors pharmacology, Leukemia, Myeloid, Acute pathology, Mitosis drug effects
- Abstract
We evaluated the effects of various hematopoietic growth factors (HGFs) on the prevention of apoptosis in blasts from 19 patients with acute myeloblastic leukemia (AML) by assessing DNA ladder formation. After incubation without HGF, apoptosis was noted in all but two patients. HGFs prevented, did not affect, or enhanced apoptosis in 39 (60%), 14 (22%), or 12 (18%) of 65 suspension cultures, respectively. HGFs that prevented apoptosis also stimulated and/or synergized blast colony formation in 35 of 39 corresponding methylcellulose cultures. HGFs that alone stimulated colony formation also prevented apoptosis in all but two of 28 corresponding suspension cultures. In contrast, HGFs that did not prevent apoptosis also failed to stimulate growth in 17 of 26 corresponding methylcellulose cultures. HGFs that enhanced apoptosis alone never stimulated colony formation. After incubation, we noted enhanced c-fos and cjun genes as well as induction of p21 protein. An appropriate dose of HGF elevated c-fos, reduced c-jun and p21, induced G1/S transition, and inhibited apoptosis. In two patients, apoptosis was not induced after incubation. Cells not treated with HGF expressed no c-fos, c-jun, or c-myc, and remained in G0/G1. Taken together, our results support the conclusion that not only c-fos, cjun, and c-myc, but also p53 and p21 are required for blast apoptosis. HGF differentially prevents apoptosis and induces mitosis, and both events seem to be integral to the self-renewal of AML clonogenic cells.
- Published
- 1997
44. Bone marrow patterns in patients with aplastic anaemia and myelodysplastic syndrome: observations with magnetic resonance imaging.
- Author
-
Kusumoto S, Jinnai I, Matsuda A, Murohashi I, Bessho M, Saito M, Hirashima K, Heshiki A, and Minamihisamatsu M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Anemia, Aplastic drug therapy, Bone Marrow drug effects, Female, Humans, Lumbar Vertebrae pathology, Male, Middle Aged, Myelodysplastic Syndromes drug therapy, Thoracic Vertebrae pathology, Anemia, Aplastic pathology, Bone Marrow pathology, Magnetic Resonance Imaging, Myelodysplastic Syndromes pathology
- Abstract
Bone marrow magnetic resonance imaging (MRI) was obtained in 48 patients with myelodysplastic syndrome (MDS) (35 cases) or aplastic anaemia (AA) (13 cases). The lower thoracic and lumbar spine were evaluated on sagittal plane using a 1.5 Tesla superconducting MR unit with a surface coil. Pulse sequence of STIRs (TR 2000 msec, TI 160 msec, TE 20 msec) were applied. Four distinct patterns of signal intensity (SI) on the STIR images were classified as follows: pattern 1, homogeneously low SI; 2, marginally high SI; 3, heterogeneously high SI; 4, homogeneously high SI. In all 13 patients with AA, STIR images initially revealed pattern 1. In 25 of 35 cases with MDS patients, the STIR images were initially classified as pattern 3. The STIR images of 6 AA and 5 MDS patients with a clinical response to treatment showed pattern 2 similar to that of normal marrow distribution. The STIR images of MDS patients showed an abnormal distribution of SI. Significant signal changes in the STIR images can be observed in successive examinations of the patients, thus facilitating follow-up of the disease and treatment. MRI of the bone marrow provides a noninvasive means of grossly examining a large fraction and is a useful technique in patients with aplastic anaemia or myelodysplastic syndrome.
- Published
- 1997
- Full Text
- View/download PDF
45. [Plasma cell leukemia associated with monocytosis].
- Author
-
Yoshida K, Aida K, Horibe T, Kashimura T, Handa A, Matsuda A, Murohashi I, Jinnai I, Ino H, Bessho M, Takeuchi H, Saito M, Hirashima K, and Kimura F
- Subjects
- Humans, Male, Middle Aged, Leukemia, Plasma Cell complications, Leukocytosis etiology, Monocytes
- Abstract
A 51-year-old man was admitted to our hospital in December 1993, because of fatigue. Peripheral blood tests showed a WBC of 49,400/microliter with 36% plasma cells and 35% monocytes, Hb 14.5 g/dl, and Plt 137,000/microliter. Bone marrow aspirate revealed hypercellularity with 48.7% plasma cells and 22.4% monocytes. Plasma cells in blood were positive for CD38 and PCA-1. Serum calcium, IgA and M-CSF levels were elevated to 14.1 mg/dl, 2,337 mg/dl and 2.7 ng/ml, respectively. Immunoelectrophoresis of serum and urine revealed IgA lambda type M protein and lambda type Bence Jones protein, respectively. Rearrangements of immunoglobulin heavy chain and light chain were demonstrated by Southern blotting analysis. Plasma cell leukemia (IgA lambda type) was diagnosed. He was treated with combination chemotherapy and IFN-alpha and achieved complete remission. However, he suffered a meningeal relapse in February 1995, and died in April 1996. It seems likely that the enhanced production of M-CSF by myeloma cells and/ or activated B cells stimulated monocyte production.
- Published
- 1997
46. Granulocyte-colony stimulating factor induced apoptosis in radiation-induced murine leukemia cell line.
- Author
-
Handa A, Kashimura T, Kawano N, Yamamoto A, Yoshida S, Jinnai I, Murohashi I, Bessho M, and Hirashima K
- Subjects
- Animals, Cell Cycle drug effects, Cell Line, Genes, bcl-2, Genes, myc, Genes, p53, Humans, Kinetics, Mice, Mice, Inbred C3H, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Proto-Oncogene Proteins c-myc biosynthesis, Recombinant Proteins pharmacology, Transcription, Genetic drug effects, Tumor Cells, Cultured, Tumor Suppressor Protein p53 biosynthesis, Apoptosis drug effects, Granulocyte Colony-Stimulating Factor pharmacology, Leukemia, Myeloid pathology, Leukemia, Radiation-Induced pathology
- Abstract
Cytokines regulate proliferation and differentiation of hematopoietic progenitor cells. Recently it has been clarified that physiological cell death, apoptosis plays important role of hematopoiesis. So we evaluated the effects of granulocyte-colony stimulating factor (G-CSF) on leukemic cells, especially focused on apoptosis. Intravenous inoculation of radiation-induced murine leukemia cell line, C2M-A5 into the parent C3H mice resulted in the development of myeloid leukemia. However, the leukemic death of the mice was completely suppressed by the daily subcutaneous injection of recombinant human (rh)G-CSF from the next day (Bessho M. et al., Leuk Res 1989:13:1001-1007). In the in vitro study using C2M-A5 cells, we found that apoptosis appears on the cells at 48 hours after addition of G-CSF in culture. The cells in this stage lost the leukemogenicity to C3H mice (Bessho M. et al., Leukemia 8:1185-1190:1994). To clarify the mechanism of the induction of apoptosis by G-CSF we studied cell cycle and molecular changes in C2M-A5 cells cultured in medium with or without rhG-CSF by means of using the flowcytometry and Northern and Western blot analyses. After addition of rh G-CSF to culture, C2M-A5 cells removed to S phase, next arrested at G0/G1 phase on and after 24 hours, and 48 hours later, apoptosis was observed. Overexpression of mRNAs for c-myc (3-24 hours later) and for p53 (6-24 hours later), were observed in the cell cultured in rhG-CSF administered medium with a concomitant down-expression of bcl-2 mRNA (from 6 hours later). Tyrosine-phosphorylated protein (17 kd) appeared at 48 hours after administration of rhG-CSF to cell culture. This protein was suggested for specific apoptosis induction by rhG-CSF. These results are summarized as follows. (1) rhG-CSF induced apoptosis to C2M-A5 and deprived its leukemogenicity to mice. (2) Induction of apoptosis was associated with cell cycle and correlated to the changes of the expression rates of c-myc,p53, and bcl-2. (3) Tyrosine kinase may play an important role in apoptosis induction to C2M-A5 by rhG-CSF.
- Published
- 1997
47. [Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia in a patient who died of progressive peripheral polyneuritis and cerebral dysfunction].
- Author
-
Kishimoto K, Sakata T, Itoh K, Tominaga K, Ino H, Murohashi I, Jinnai I, Bessho M, Takeuchi H, Saitoh M, and Hirashima K
- Subjects
- Female, Humans, Immunoglobulin G, Lymph Nodes pathology, Middle Aged, Brain Diseases complications, Castleman Disease complications, Hypergammaglobulinemia complications, Lymphatic Diseases complications, Polyneuropathies complications
- Abstract
We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.
- Published
- 1997
48. p53-independent induction of p21 (WAF1/CIP1) during differentiation of HL-60 cells by tumor necrosis factor alpha.
- Author
-
Yoshida K, Murohashi I, and Hirashima K
- Subjects
- Cell Differentiation genetics, Cyclin-Dependent Kinase Inhibitor p21, HL-60 Cells, Humans, Cyclins biosynthesis, Genes, p53, Neoplasm Proteins biosynthesis, Tumor Necrosis Factor-alpha pharmacology
- Abstract
We demonstrated that tumor necrosis factor-alpha (TNF-alpha) rapidly and markedly enhances p21 gene and protein expression prior to monocytic differentiation and apoptosis in p53-null HL-60 cells. TNF-alpha induced early small and delayed large peaks of apoptosis at 6 and 48 h of incubation, respectively. At 24 h of incubation, apparent monocytic differentiation of the cells was noted. Down-regulation of c-myc and c-myb and G0/G1 arrest were observed at 6-12 and 36 h, respectively. Actinomycin D markedly inhibited TNF-alpha-induced p21 mRNA expression, suggesting that the p21 gene is induced at the transcriptional level. We confirmed that TNF-alpha induces p53-independent apoptosis in HL-60 cells, which accompanies monocytic differentiation.
- Published
- 1996
- Full Text
- View/download PDF
49. [Gaucher disease type 1, incidentally found on a periodic physical examination].
- Author
-
Yoshida K, Kawai N, Matsuda A, Murohashi I, Jinnai I, Ino H, Bessho M, Takeuchi H, Saitoh M, and Hirashima K
- Subjects
- Adult, Humans, Male, Periodicity, Gaucher Disease diagnosis, Physical Examination
- Abstract
A 33-year-old man was admitted to our hospital because of thrombocytopenia found on a periodic physical examination. Splenomegaly was recognized Peripheral blood showed WBC 4,510/microliters, Hb 12.5 g/dl, and Plt 40,000/microliters. Increased serum levels of acid phosphatase and angiotensin converting enzyme were observed on laboratory tests. Bone marrow aspirate revealed Gaucher cells. Decreased beta-glucosidase activity was demonstrated in blood leukocytes, cultured blood lymphocytes, and cultured bone marrow fubroblasts from the patient. His glucocerebrosidase genotype was T1448C/C1504T (L444P/R463C). Since neurological examination and skeletal X ray results were normal, Gaucher disease type 1 was diagnosed.
- Published
- 1996
50. [Acute myeloid leukemia (M1) following chemotherapy for Ki-1 lymphoma complicated with rheumatoid arthritis].
- Author
-
Yoshida K, Endoh K, Itoh Y, Kawai N, Matsuda A, Murohashi I, Jinnai I, Ino H, Bessho M, and Takeuchi H
- Subjects
- Female, Humans, Lymphoma, Large-Cell, Anaplastic complications, Middle Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Arthritis, Rheumatoid complications, Leukemia, Myeloid, Acute chemically induced, Lymphoma, Large-Cell, Anaplastic drug therapy, Neoplasms, Second Primary chemically induced
- Abstract
A 58-year-old woman complicated with rheumatoid arthritis (RA) was admitted to our hospital with right axillar lymphadenopathy and splenomegaly in November 1992. She was diagnosed as an anaplastic large-cell lymphoma (Ki-1 +) (stage IIIB) on the histological findings of the right axillar lymph nodes. She was treated with 11 courses of CHOP regimen between February 1992 and May 1993, and with mitoxantrone, etoposide (VP-16) and predonisolone in April 1992 and May 1993. The right axillar lymph nodes and spleen were irradiated at a dose of 36Gy in October 1992 and May 1993 respectively. In May 1993, peripheral blood showed WBC 89,000/microliter with 96% myeloblasts, Hb 8.3 g/dl, and Plt 124,000/microliter. Bone marrow aspirate revealed hypercellularity with 90% myeloblasts, which were positive for CD13 and HLA-DR. She was diagnosed as AML (M1). The karyotype showed normal. Southern blot analysis did not reveal the rearrangement of the MLL gene. She received the BHAC-DMP regimen and obtained complete remission. However, she relapsed during consolidation therapy, and died of cerebral bleeding. An autopsy revealed absence of a residual tumor. The mean interval from exposure to alkylating agent to the onset of secondary leukemia has been reported to be about 5 years, in contrast to a shortened interval of about 2 years for VP-16-induced leukemia. In our patient, it took only 1 year to have AML following chemotherapy for Ki-1 lymphoma. This suggests that her AML might be induced not only by treatments for RA and Ki-1 lymphoma, but also by immunological background such as RA.
- Published
- 1995
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