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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 325 records · Page 18Linked to original sources

Erythroid progenitors in tumor-bearing mice: erythroid inhibitory factors produced by adenocarcinoma-755.

Adenocarcinoma-755-bearing C57BL/6 mice developed anemia with the growth of the tumors. The numbers of granuloid and monocytoid progenitors (colony-forming unit in culture, CFU-C) of the bone marrow and spleen and the peripheral blood WBC counts increased in tumor-bearing mice. The erythroid progenitors (erythroid colony-forming units, CFU-E; erythroid burst-forming units, BFU-E) of the bone marrow showed a marked decrease, overcoming their increase in the spleen in tumor-bearing mice. Fractionation of conditioned medium of tumor cells led to the isolation of a protein of 80-kd molecular weight that stimulated murine CFU-C growth and inhibited the CFU-E and BFU-E growth in a dose-dependent manner. These results indicate that erythroid inhibitory factors produced by tumors exist in tumor-bearing mice. Erythroid inhibitory factors might also exist in non-hematological malignancies of humans, and they might be one of the mechanisms of anemia.

Adenocarcinoma↗

[The successful use of natural alpha-interferon single therapy in multiple myeloma of IgD (lambda)-type].

We have successfully treated multiple myeloma of IgD (lambda) type [IgD (lambda) -MM] by natural alpha-interferon (alpha-IFN) single therapy. A 45 year-old man was admitted to Tokyo Medical College Hospital because of general fatigue in August, 1989. Immunoelectrophoresis, bone marrow biopsy and systemic bone survey revealed IgD (lambda) -MM with Bence Jones (BJ) proteinuria and slightly osteolytic lesions. We started treating him with natural alpha-IFN single therapy. Three months later, serum IgD markedly decreased and BJ proteinuria disappeared. Bone marrow, which had been packed with myeloma cells at the admission, was almost replaced by normal hematopoietic cells. In April 1990, he is still free of disease with only alpha-IFN single therapy. This result might suggest that alpha-IFN single therapy is effective for IgD-MM.

Humans↗

[IgD-lambda multiple myeloma associated with bone marrow fibrosis].

A few cases of multiple myeloma associated with myelofibrosis has been reported. In Japan, such cases have been less reported. We report a case of IgD-myeloma with remarkable marrow fibrosis. A 44-year-old female was admitted to our hospital because of back pain. On admission her peripheral blood revealed anemia and leukopenia. Serum immunoelectrophoresis revealed M-protein of IgD and serum IgD level remarkably increased to 5420 mg/dl. Bone marrow aspiration resulted in dry tap every three times and its biopsy at iliac bone showed remarkable infiltration of myeloma cell and remarkable increase of reticulin fiber with marked decrease of normal hematopoietic cells. Her liver and spleen were not palpable and tear drop cells of erythrocytes were not shown in peripheral blood. We could not find view of myelofibrosis with chronic myeloproliferative disorders. Multiple myeloma associated with myelofibrosis is a interesting syndrome as clinical signs and course. So further investigation must be needed.

Adult↗

High-dose cytosine arabinoside as consolidation chemotherapy for acute nonlymphocytic leukemia in remission.

A controlled study was conducted to evaluate the efficacy of high-dose cytosine arabinoside (Ara-C) in consolidation therapy of acute nonlymphocytic leukemia in remission. Twenty-seven patients with acute nonlymphocytic leukemia during their first complete remission were divided into two groups. The high-dose Ara-C group (15 patients) received two courses of high-dose Ara-C and daunorubicin, i.e., 3 g/m2 of Ara-C IV over 1 h every 12 h eight times followed by 25 mg/m2 per day daunorubicin IV bolus for 2 days, and no maintenance chemotherapy. The control group (12 patients) received the conventional consolidation therapy (usually 7 days administration of 200 mg/m2 of behenoyl-arabino-furanosylcytosine and 2 to 3 days administration of 25 mg/m2 of daunorubicin) repeated every 3 to 4 months for more than 2 years. There were no significant differences in the duration of remission and survival between the two groups. It is suggested that high-dose Ara-C consolidation is worth employing in the treatment of acute nonlymphocytic leukemia because of its convenience for patients.

Adolescent↗

Rossette formation between stromal and hemopoietic cells: a simple assay for the supportive activity of stromal cells.

Hemopoietic stromal cells play an important role in the proliferation and differentiation of hemopoietic cells in vitro. Recently, it has been emphasized that the attachment of hemopoietic cells to stromal cells is the first step in this process and that this is necessary in hemopoiesis in vitro. A rosette formation technique was developed to quantitatively measure this attachment. The murine leukemic cell line ELM-D, which grows only in close contact with stromal cells, was used to represent hemopoietic cells. Rosettes were formed with about 75% of the normal murine bone marrow derived hemopoietic supportive stromal cells (MS-1). However, ELM-D formed rosettes with only 15% of the hemopoietic non-supportive stromal cells (MS-K). The maximum rosette formation was obtained at an ELM-D to MS-1 ratio of 20:1. When MS-1 and MS-K were mixed and seeded as stromal cells, MS-K did not alter the attachments of ELM-D to MS-1; the percentage of rosette formation increased in parallel with the increase in the number of MS-1 cells in the stromal layer. These findings suggest that MS-K does not have an inhibitory effect. Rosette formation is a simple, quantitative technique for assaying the hemopoietic supportive activity of stromal cells in vitro.

Animals↗

[Immunogenotypic and clonal culture studies in Philadelphia chromosome-positive acute leukemia].

Molecular analysis and blast colony assay were performed on patients with Philadelphia chromosome-positive acute leukemia (Ph+ AL). All patients were diagnosed as ALL- L2 and 3 were My+ ALL. Nine of the 12 cases had rearranged immunoglobulin heavy chain, and 4 had rearranged TCR beta. TCR gamma rearrangement was noted in 3 patients, and TCR delta involvement was also noted in 6 patients. Clonal culture analysis revealed that leukemia cells of M-BCR rearranged Ph+ AL cases had a potential to proliferate by myelopoietic CSFs and ILs, however, M-BCR nonrearranged Ph+ AL did not. These results indicate biological and immunogenotypic heterogeneity of Ph+ AL.

Acute Disease↗

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: a pilot study which raises important questions.

Acute lymphoblastic leukemia (ALL) patients with a Philadelphia chromosome (Ph+ ALL) were treated with a combination of antineoplastic drugs recommended for both myeloid and lymphoid leukemia (BHAC-DMPV: behenoylcytosine arabinoside, daunorubicin, 6-mercaptopurine, prednisolone, and vincristine). Ph+ ALL patients with chromosome breaks which occur within the major breakpoint cluster region (M-BCR rearranged Ph+ ALL) were treated with natural interferon-alpha (IFN-alpha) after entering complete remission. In this study, four of seven patients with Ph+ ALL had M-BCR rearrangement, and all achieved complete remission with karyotypic normalization. Subsequent cytogenetic analysis during complete remission in two ALL patients with M-BCR rearrangement revealed that the percentage of bone marrow cells with the Ph chromosome increased, while the bone marrow maintained remission status. This cytogenetic-hematological discrepancy led us to consider that M-BCR rearranged Ph+ ALL might be a variant of chronic myelogenous leukemia, therefore, three Ph+ ALL patients with M-BCR rearrangement were treated with IFN-alpha after achieving complete remission. In contrast, only one of three patients with M-BCR non-rearranged Ph+ ALL obtained complete remission.

Adult↗

A Ki-1 (CD30)-positive T (E+, CD4+, Ia+)-cell line, DL-40, established from aggressive large cell lymphoma.

A new human lymphoma cell line, designated DL-40, was established from the peripheral blood of a 64-year-old woman with leukemic conversion of aggressive large cell lymphoma. The cell line grew in suspension with or without forming clumps of cells and exhibited large, round, or multiple nuclei in the relatively abundant cytoplasm that was positive for acid phosphatase. The cells expressed a Ki-1 antigen (CD30), E+, CD2+, CD4+, CD45+, Ia+ phenotype and had rearranged T-cell receptor beta chain but were negative for CD15, HTLV-I, and Epstein-Barr virus nuclear antigen. Chromosome analysis of this cell line showed a human female karyotype with complex hyperdiploid abnormalities. DL-40 cells produced tumors histologically similar to the original lymphoma when transplanted into nude mice and immunosuppressed hamsters. The DL-40 cell line could provide a useful tool for the understanding of biology of the Ki-1-positive non-Hodgkin's lymphoma.

Antigens, Differentiation↗

Change in a complex translocation involving band 7q34 and 9p- in a case of T-cell lymphoblastic lymphoma.

The authors report a case of T-cell type non-Hodgkin's lymphoma (NHL) in which neoplastic cells possessed a three-way translocation involving chromosomal bands 3q21, 7q34, and 22q11, as well as partial monosomy of the short arm of chromosome 9. In the literature, most reported cases of 7q32-q36 abnormalities had T-cell type leukemia/lymphoma and were younger than 20 years. Two NHL cases, including the current case, were diagnosed as having lymphoblastic lymphoma with a leukemic transformation. The neoplastic cells of the reported cases commonly showed CD2 (E-rosette receptors) and CD38. All 17 patients but three manifested a mediastinal mass at diagnosis and seven had central nervous system lesions or pleural infiltration. Furthermore, five of the 19 reported cases also showed 9p- change.

Adult↗

Growth factors involved in lymphocyte differentiation.

We report here that an interleukin-3-dependent precursor B-cell line, LyD9, differentiated in vitro into mature B cells, producing immunoglobulin (Ig)M and IgG by co-culture with bone marrow stroma cells. Induced LyD9 cells underwent heterogenous immunoglobulin gene rearrangement and synthesized mRNAs encoding immunoglobulin mu (mu), gamma (gamma) and kappa (kappa) chains. LyD9 was also shown to differentiate into myeloid cells. We have established an interleukin-4-dependent derivative clone K-4 that is an intermediate between myeloid-lymphoid cells and the LyD9 clone. This differentiation required direct contact between LyD9 and stromal cells.

Animals↗

[Fundamental evaluation of bone densitometry using dual energy X-ray absorptiometry (DEXA)].

A newly developed instrument based on dual energy X-ray absorptiometry (DEXA), Hologic QDR-1000, was evaluated fundamentally and clinically. Image quality was quite satisfactory though radiation exposure was minimal, 780.2 nC/kg (3.024 mR) for lumbar measurement. Reproducibility of the repeated measurement of a phantom was fairly good; 0.343 CV% in a same day and 0.520 CV% in a long period. Accuracy determined by measurement of potassium phosphate solution was also satisfactory. Bone mineral densities measured by this instrument were fairly correlated with those measured by single energy quantitative CT; coefficient was 0.740 for 17 patients. Mix-DP plates of more than 10 cm thick overestimated the bone mineral densities of a phantom. Bone mineral densities of Japanese normal volunteers were in the normal range (mean +/- 2SD) of the Americans though mostly lower than the mean. In patients with spondylosis deformans or prominent aortic calcification, bone mineral densities might be overestimated. Lateral view was obtainable though its reproducibility was not good. Positioning especially for measuring femoral neck was quite critical for reproducible measurement. In conclusion, this new instrument is quite accurate and satisfactory for clinical application to measuring bone mineral densities.

Absorptiometry, Photon↗

Cytogenetic findings in adult acute leukemia and myeloproliferative disorders with an involvement of megakaryocyte lineage.

Cytogenetic analyses were performed on 12 adult patients with abnormal megakaryoblastic proliferation which was detected by ultrastructural cytochemical study (platelet peroxidase) and platelet-megakaryocytes-specific monoclonal antibodies (TP-80, Plt1, AN51, and KOR-77). The patients consisted of two patients with myelodysplastic syndromes (MDS), three with acute megakaryoblastic leukemia (AMKL), six with megakaryoblastic transformation in Philadelphia-positive chronic myelogenous leukemia (CML-meg-BC), and one case of chronic myeloproliferative disorder (CMPD). Among them, an inversion of the long arm of chromosome 3 [inv(3)(q21q26)] was found in one AMKL patient with a normal platelet count. Chromosome change at band 3q26 was also found in one MDS patient without thrombocythemia. Furthermore, the long arm of chromosome 13, where rearrangements in myelofibrosis are clustered (13q12----q22) was seen in one MDS patient. Trisomoy of chromosome 19 was found in one AMKL patient and three CML-meg-BC patients. These findings indicate that cytogenetic abnormalities involving 3q26, 13q, and trisomy 19 are associated with hematologic neoplasia with megakaryocytic lineage in adult patients, although these abnormalities were not related to the survival of the patients. During the period of this study, two acute myelogenous leukemia patients (AML-M2 and AML-M5b) with chromosome rearrangements at band 3q21 and thrombocythemia were found, indicating that chromosome abnormality at band 3q21 is related to quantitative platelet dysfunction, whereas that at 3q26 is related to hematologic malignancies with a proliferation of megakaryocytic lineage.

Adolescent↗

Platelet peroxidase-like activity detected in mature erythroblasts from a patient with pernicious anemia.

We report a case of pernicious anemia in which the possession of platelet peroxidase (PPO)-like activity was proved in its erythroblasts. PPO-positive cells were found in a distinct minor population of hemoglobinized (as a mean of differentiated) erythroid cells in the bone marrow before treatment, but these cells disappeared following therapy with vitamin B12. The present report is considered to be the first case to identify PPO-like activity in mature erythroblasts from the nonmalignant clone. The existence of PPO in erythroid lineage in cases with pernicious anemia is discussed.

Adult↗