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Biomedical subjects

H Okawa

Publications and source records attributed to H Okawa.

At least 19 recordsLinked to original sources
PubMed1992

Signal transduction by interleukin 2 in human T cells: activation of tyrosine and ribosomal S6 kinases and cell-cycle regulatory genes.

The early events of signal transduction associated with interleukin-2 (IL-2) binding to its receptor were examined using a human IL-2 dependent T-cell line, Kit225. Cell cycle analysis showed that 90% of Kit225 cells were in the G0/G1 phase after a 72-hr incubation in the absence of exogenous IL-2. At this point, stimulation of the cells with IL-2 resulted in the rapid initiation of RNA and DNA synthesis by 9 and 20 hr, respectively. Within 5 min after addition of IL-2, rapid activation of tyrosine and ribosomal S6 kinases was detected. Addition of IL-2 also increased mRNA levels for c-fos, c-myc, IL-2 receptor alpha, and IL-2 receptor beta chain. These events increased in the absence of detectable changes in free cytosolic [Ca2+]i, inositol phosphate metabolism, or the activity of several kinases including cAMP-dependent protein kinase, Ca2+/calmodulin-dependent protein kinase, or protein kinase C. These findings demonstrate that the signals triggered by IL-2 binding to its receptors are quickly transduced into the nucleus with increased mRNA transcription of activation-associated genes. Furthermore, the data indicate that tyrosine and ribosomal S6 kinases may be important for IL-2-induced cell growth.

Calcium↗
PubMed1992

Primary hepatocellular carcinoma with severe hypoglycemia: involvement of insulin-like growth factors.

We report a case of severe hypoglycemia and hepatic masses suspected to be an insulin-like growth factor-II (IGF-II)-producing hepatocellular carcinoma. A 62-year-old man presented with mental disorder in the night and early morning associated with extremely low blood sugar levels (less than 21 mg/dl). Computerized axial tomography and ultrasonography revealed a massive tumor in the right lobe of the liver with multiple secondary nodules, and a tumor thrombus in the portal vein. At autopsy 107 days after admission, the liver weighed 3070 g, histologically showing an Edmondson type II tumor with liver cirrhosis. IGF-II in plasma (899 ng/ml) and tumor tissue (2.4 micrograms/g) was higher than that in normal plasma (374-804 ng/ml) and non-tumor liver tissue (0.2 micrograms/ml), while IGF-I (14 ng/ml) was significantly reduced. IGF-II, probably produced by the liver tumor, appeared to be involved in the mechanism of hypoglycemia.

Carcinoma, Hepatocellular↗
PubMed1992

Peroxidase-negative and myelomonocytic antigen-positive acute leukemia.

Between 1983-1988 bone marrow samples obtained from 195 peroxidase-negative leukemia patients were analyzed for their surface antigens. Thirteen of these patients (6.7%) had myelomonocytic-positive and lymphoid-negative antigens. These leukemic cells reacted with CD13 in eight patients, CD33 in seven, CD11 in six and CDw41 in two. In none of these patients did the leukemic cells react with CD1, CD2, CD3, CD4, CD5, CD8, CD10, CD19 or CD20. Leukemic cells from two patients were reactive with CD7. These leukemic cells demonstrated L2 morphology in 11 patients and L1 morphology in one patient. The leukemic cells from the final patient were diagnosed as those of leukemic transformation of myelodysplastic syndrome. Chromosomal abnormality was observed in approximately half of the patients examined (6/10). Cytochemical analysis revealed that the leukemic cells were negative for periodic acid Schiff stain but positive for acid phosphatase. The prognosis of these patients was markedly poor as compared to acute lymphocytic leukemia or typical peroxidase-positive nonlymphocytic leukemia. Complete remission was induced in only 30% of patients and duration of survival was short (4.7 months). This suggests that myelomonocytic antigen-positive peroxidase-negative acute leukemia is a distinct type of leukemia and may require more aggressive therapy to improve survival.

Acid Phosphatase↗
PubMed1992

[Quantitative analysis of cytoplasmic myeloperoxidase positive leukemic cells by FCM].

Development of a fixation allowed flow cytometric analysis of nuclear and intracellular antigen in leukemic cells. In this paper the analyzing procedure of cytoplasmic myeloperoxidase by FCM was described. This procedure is more sensitive than cytochemical staining of fixed cell smears and more specific than cell surface immunophenotyping by CD13, CD14, CD33. So, this technique is useful for classification of myelogenous leukemic cells especially MO type leukemia by FAB classification. This technique also allowed two color analysis of cell surface antigens and cytoplasmic antigens. Mixed lineage leukemia can be easily and accurately classified by using of this procedure.

Antibodies, Monoclonal↗
PubMed1991

A B cell line from a patient with pure red cell aplasia produces an immunoglobulin that suppresses erythropoiesis.

A 4-year-old boy with pure red cell aplasia was investigated. Immunophenotypic analysis of peripheral blood lymphocytes revealed a marked increase of CD20+ cells, which fell from 25.9% in the active stage to 9.7% in remission. The plasma contained a suppressive activity against CFU-e and BFU-e formation by the patient's bone marrow cells, which disappeared when the disease went into remission. Prednisone (2 mg/kg/day) therapy was tried for 5 weeks, but produced no improvement. Subsequently, high-dose gamma-globulin therapy induced complete remission of anemia. A lymphoblastoid B cell line obtained from the patient before therapy produced a factor that suppressed erythropoiesis but not granulopoiesis. The suppressive activity resided in the immunoglobulin fraction and was adsorbed by an anti-immunoglobulin column. These results indicate that expansion of B cells producing an immunoglobulin which suppressed erythropoiesis was involved in the pathogenesis of the disease in this patient.

B-Lymphocytes↗
PubMed1990

Phenotypic profile and functions of T cell receptor-gamma delta-bearing cells from patients with primary immunodeficiency syndrome.

TCR-gamma delta-bearing T cells have been reported to be increased in several immunodeficient patients. However, their functional role and phenotypic characterization have not yet been well documented. In this study we examined the surface phenotypes and functional properties of TCR-gamma delta+ cells from several patients with primary immunodeficiency syndrome. It was demonstrated that TCR-gamma delta+ cells detected by TCR-delta 1 mAb were increased in some of the patients, particularly in patients with Wiskott-Aldrich syndrome and severe combined immune deficiency. The TCR-gamma delta+ cells showed such a unique profile that more than 60% of the cells expressed delta-TCS1, which is normally present in a lesser amount, and that most of the cells lacked CD5 T lineage marker. TCR-gamma delta+ cells from the patients with primary immunodeficiency syndrome served as NK cells as observed in normal individuals, while displaying weak LAK and allogeneic cell-specific killer activities. The TCR-gamma delta+ cells were classified into several subpopulations according to their antigenic phenotype, then their NK activity of normal individuals and patients, lymphokine-activated killer and allo-specific killer activities of normal individuals were compared among the subpopulations. Delta-TCS1+ cells mediated almost the same killer activities as total TCR-gamma delta+ cells, whereas CD8+ TCR-gamma delta+ cells displayed stronger cytotoxic activities in both normal subjects and the patients with primary immunodeficiency syndrome.

Antibodies, Monoclonal↗
PubMed1990

Mass screening for neuroblastoma in Japan. Committee of the Neuroblastoma Mass Screening Study of the Japanese Society of Pediatric Oncology.

The present status of NB mass screening in Japan, which is the first national trial in the world, is presented. This program was conducted in cooperation with infants' mothers, local health centers, screening centers and hospitals. Three hundred and thirty-seven cases detected by the program, from the start in Kyoto in 1974 to the end of 1989, are analyzed. As many cases were detected at early stages, 97% of them were expected to be cured. Several clinical, technical and programmatic problems are also discussed.

Child↗
PubMed1989

Phenotypical and functional heterogeneity of the large granular lymphocytes increased after various treatments in a patient with combined immunodeficiency.

A boy with combined immunodeficiency having low natural killer (NK)-cell activity received thymopoietin pentapeptide (TP-5) treatment, transplanted with T cell-depleted HLA-haploidentical bone marrow (BMT) cells from his father and with thymus tissue from an infant at different times during the first year of life. He showed a marked increase in large granular lymphocytes (LGL) both during the treatment with TP-5 and after BMT. The LGL generated following TP-5 injection had a T3+Leu11- surface phenotype and low NK activity. In contrast, the LGL appearing after BMT showed T3-, Leu7+, and/or Leu11+ surface phenotypes, had high NK- and K-cell activities, and were lymphokine-activated killer (LAK)-cell precursors. These killer activities were assigned to the Leu7-Leu11+ subset and proved to be of recipient origin. LGL proliferation following BMT was accompanied by neutropenia, which was improved in association with a reduction in the number of LGL and the appearance of T cells of BMT donor origin following thymus transplantation. This suggested the inhibition of granulopoiesis by the LGL and an in vitro study revealed that the Leu7+Leu11- subset of LGL suppressed the growth of granulocyte/macrophage colony-forming units. These results indicated that phenotypically different LGL could be generated by different treatments and that the LGL showing NK activity were distinct from those regulating granulopoiesis. It was also suggested that the generation of LGL was controlled by T cells.

Adjuvants, Immunologic↗
PubMed1989

The increase of non-MHC-restricted cytotoxic cells (gamma/delta-TCR-bearing T cells or NK cells) and the abnormal differentiation of B cells in Wiskott-Aldrich syndrome.

The objective of this study was to analyze the configuration of the lymphocytes in Wiskott-Aldrich syndrome (WAS) by studying the surface antigens from nine cases using dual-color immunofluorescence analysis. All the patients showed the increase of non-MHC-restricted cytotoxic cells, namely CD3+ WT31- delta TCS1+ (gamma/delta-T cell receptor (TCR)-bearing cells) and/or CD16+ natural killer cells. The gamma/delta-TCR+ cells of WAS, however, were unique since they did not express CD5, which is present on ordinary gamma/delta-TCR+ cells. A reduced number of CD4+ cells and an increased percentage of CD11b+ Leu7+ cells within a CD8+ subset were observed in all cases. With regard to B cell subpopulations, most cases showed reduced Fc epsilon R2-bearing B cells, despite an elevated serum IgE.

Adolescent↗
PubMed1989

Lymphocytes after autologous and allogenic bone marrow transplantation.

Lymphocyte reconstitution after bone marrow transplantation (BMT) was analyzed using two-color flow-cytometry in 18 patients and the differences between allogenic and autologous BMT were studied. The CD8 (+) CD11b (+) and CD8 (+) Leu7 (+) suppressor subsets were increased while the CD4 (+) 2H4 (+) suppressor inducer subset was decreased in both groups after BMT. These variations of suppressor associated subsets persisted for more than 100 days and were considered to be related to immunologic abnormalities in post-BMT patients. In addition, Ia (+) T cells were increased in both autologous and allogenic BMT patients. This increase appears not to be caused by reaction to allo-antigens, but rather reflects the reconstitution of the lymphocyte system after BMT. In contrast, the CD16 (+) NK cell subset was increased specifically in allogenic BMT patients and only for a short time following transplantation.

Adolescent↗
PubMed1989

Interferon-induced resistance of tumor target cells against lysis by interleukin-2-activated killer cells.

IFN-gamma has been shown to decrease the susceptibility of target cells to NK cell-mediated cytotoxicity. In this report, the effect of IFN-gamma on the sensitivity of target cells to killing by various human lymphocyte cytotoxic activities such as NK/K, IL-2-augmented NK/K cell activity, and IL-2-activated killer activity were studied. Although NK-sensitive K562 cells showed marked resistance to NK cell activity as previously reported, the resistance was overwhelmed by augmentation of NK activity with IL-2. IL-2-activated killer cell activity, which can lyse NK-resistant tumor cell lines upon culture in IL-2, showed decreased cytotoxicity against most of the IFN-gamma-treated target cells tested. By contrast, no decrease of target cell sensitivity to K cells was observed, even though K cells were treated with IL-2. These findings suggest that as far as NK-resistant tumor cells are concerned, an IFN-dependent mechanism inhibits the Fc receptor-independent mediators of tumor surveillance, but not Fc receptor-dependent ones. This should be considered when planning adoptive immunotherapy of IL-2-activated killer cells for human malignancy.

Cytotoxicity, Immunologic↗
PubMed1988

Cell cycle-related expression of surface antigens on myelomonocytic leukemia cells.

We investigated the relationship between the expression of surface antigens and the cell cycle phase in leukemic cells from cell lines and one patient using two-color flow cytometry, in order to determine the reason for the uneven expression of some markers which frequently leads to equivocal results as to leukemic phenotyping. As a result, it was demonstrated that monocyte-related differentiation markers, including I2, My4, Mo1 and Mo2, on monocytoid leukemic cells are preferentially expressed at the G0/G1 phase. Consequently, it is expected that the positivities for such markers vary with the proliferation status of the leukemic cells.

Antigens, Differentiation, Myelomonocytic↗
PubMed1988

Differential effects of dibutyryl cyclic adenosine monophosphate and simple sugars on NK and LAK activities suggesting differences of their cytotoxic mechanism.

The increase of intracellular cyclic AMP levels suppresses the cytotoxic activities of lymphocytes and monosaccharides interfere with cell to cell and cell to cytokine interactions, and these effects on natural killer (NK)/antibody-dependent cell-mediated cytotoxicity (ADCC) and lymphokine activated killer (LAK) activities were examined. Dibutyryl cyclic AMP markedly suppressed NK, IL-2-augmented NK and ADCC activities in a dose-dependent manner but not previously induced LAK activity. Induction of LAK was inhibited. Dibutyryl cyclic GMP had no effect. Addition of mannose 6-phosphate and galactose 6-phosphate strongly inhibited NK and ADCC activities, but not LAK activity. These results suggest that the lytic mechanism for NK and ADCC activity is different from that of LAK activity.

Antibody-Dependent Cell Cytotoxicity↗