Biomedical subjects

Y Komada

Publications and source records attributed to Y Komada.

At least 91 records · Page 5Linked to original sources

PubMed1995

[The first case in Japan of unstable hemoglobin, Hb Buenos Aires [beta 85 (F1) Phe-->Ser], with parvovirus B19 infection (first case in Japan)].

A 9-year-old girl was admitted to Mie University Hospital June 25, 1992, complaining of fever, skin rash and pallor. Physical examination revealed anemia and hepatosplenomegaly. Laboratory findings showed normocytic normochromic anemia, increased reticulocyte counts and remarkably decreased haptoglobin level. Red blood cells had no morphological abnormality. Bone marrow examination showed erythroid hyperplasia without abnormal cells. Hemoglobin electrophoresis showed an abnormal band. The amino acid structure and sequence of the abnormal hemoglobin was determined to be an unstable hemoglobin, Hb Buenos Aires [beta 85 (F1) Phe-->Ser]. Sequence of genomic DNA and cDNA was compatible to Hb Buenos Aires. Parvovirus B19 infection was thought to have caused severe anemia due to hemolytic crisis in this patient because its IgM antibody was positive on admission. She recovered soon without any treatment and has been followed in the outpatient clinic. Her parents and brother showed no hemoglobin abnormality.

Base Sequence↗

PubMed1994

Apoptotic cell death induced by anti-IgM antibody and phorbol esters is inhibited by interleukin-4 in human B lymphoma cell line MBC-1.

The development of B cell tolerance is believed to involve negative signaling to B cells derived from the binding of antigen to the B cell surface immunoglobulin. B cell lines that receive negative signals may provide useful models for studying the mechanisms of B cell tolerance. We have established a human B lymphoma cell line, MBC-1, positive for both surface IgM and IgD. The growth of MBC-1 cells is inhibited by anti-IgM antibody but not by anti-IgD antibody. The rapid time course of MBC-1 cell death, the morphologic feature of dying cells, and DNA fragmentation indicate that surface IgM cross-linking induces apoptotic cell death. Interestingly, interleukin-4 (IL-4) could rescue MBC-1 cells from this apoptotic signal. BCL-2 protein is neither expressed nor induced in MBC-1 cells. The treatment of MBC-1 cells with IL-4 does not interfere with mobilization of Ca2+ or induce any phenotypical change. In addition, phorbol 12-myristate 13-acetate and phorbol 12, 13-dibutyrate also induced growth inhibition followed by apoptotic cell death in MBC-1 cells. IL-4 is able to protect MBC-1 cells from cell death, but not from growth inhibition induced by protein kinase C activators. The results collectively suggest that IL-4 could inhibit the transduction of apoptotic signal following the activation of protein kinase C in MBC-1 cells.

Apoptosis↗

PubMed1994

T cell subsets in peripheral blood and cerebrospinal fluid from children with aseptic meningitis.

T cell subsets in peripheral blood (PB) and cerebrospinal fluid (CSF) obtained from patients with aseptic meningitis were studied using quantitative two-color fluorescence analysis with a flow cytometer. The percentage of HLA-DR+/CD3+ lymphocytes (activated T cells) in CSF was significantly increased in the recovery phase when compared to the acute phase, while no significant change in the activated T cells in PB was observed. More interestingly, CD4+ T lymphocytes in CSF were increased in the acute phase and subsequently decreased in the recovery phase. Instead, CD8+ T lymphocytes gradually accumulated into the CSF in the recovery phase, resulting in a successive decrease in the CD4/CD8 ratio. On the other hand, the CD4/CD8 ratio in PB remained normal during the course of aseptic meningitis. The present results suggest that T lymphocytes (CD4+ subset in the acute phase and CD8+ in the recovery phase) could be infiltrated and further activated at the site of inflammation, possibly in the subarachnoid space in the patients with aseptic meningitis.

Antibodies, Monoclonal↗

PubMed1994

Cytokines and cytokine receptors in acute lymphoblastic leukemia expressing myeloid markers--role in growth regulation.

There is no evidence that cancer cells including leukemic cells are immortal. It has been clearly indicated that certain cytokines can significantly stimulate leukemic cell proliferation in vitro, and sustain the circuit of autocrine or paracrine stimulation. The biological roles of cytokines and cytokine receptors have been intensively investigated in acute leukemia. Recently coexpression of both lymphoid and myeloid features on a single leukemic cell has been well recognized using a flowcytometric technique. Studies of ALL cells expressing myeloid markers (My+ ALL) have indicated that the profiles of cytokines and cytokine receptors expressed by My+ ALL show both similarities and differences to those in My- ALL or acute myelogenous leukemia (AML), suggesting that My+ ALL cells may originate from uncommitted hematopoietic precursor cells coexpressing features of both lymphoid and myeloid lineages. The exact assessment of cytokine response of leukemic cells would provide an important tool for phenotyping acute leukemia based on the growth properties of the cells (cytokine phenotyping), in addition to the morphologic classification and immunological surface phenotyping. Additionally alteration of sensitivity to cytotoxic anticancer drugs by cytokine stimulation may be the new strategy for biologic therapy of acute leukemia.

Antigens, Surface↗

PubMed1994

Shedding of CD9 antigen in acute lymphoblastic leukemia.

A leukemia-associated CD9 glycoprotein antigen released into the extracellular milieu from acute lymphoblastic leukemia cells has been detected using a unique lectin-monoclonal antibody immunoassay. It has been demonstrated that the release of CD9 antigen is an active process and is associated with active cell growth. In addition, the difference of carbohydrate moiety, and hence glycosylation, in the CD9 antigen derived from lymphoblasts and neuroblasts was verified using lectin affinity chromatography. The lectin affinity of the carbohydrate moiety of lymphoblast CD9 antigen would indicate the presence of N-linked oligosaccharide chains having groups of N-acetyl glucosamine residues, a mannose core and a terminal D-galactose. The soluble CD9 antigen is specifically detected in plasma from ALL patients at the time of diagnosis, in cerebrospinal fluid from patients with central nervous system involvement, and spent medium from CD9-positive leukemic blasts obtained at the time of diagnosis. Interestingly when bone marrow cells taken from patients in complete remission were studied, a distinct amount of CD9 antigen was released into spent medium in some of the cases. All of these patients have subsequently developed hematological relapse. The present data suggest that shedding of CD9 antigen by leukemic cells may enable the clinical monitoring of residual leukemic cell burden.

Antigens, CD↗

PubMed1993

Low R-wave amplitude in the right precordial leads in children with symptomatic doxorubicin cardiomyopathy.

Electrocardiographic (ECG) findings were studied in four patients with doxorubicin cardiomyopathy. In all patients with congestive heart failure (CHF), the ECGs had a low R-wave and low R/S ratio in lead V1. Our study suggests that increased injury to myocardial cells in the regions of the anterior septum and anterior left ventricular wall may be important in the pathogenesis of doxorubicin cardiomyopathy. Eight years later, cardiac recovery from CHF occurred with a normal ECG and left ventricular ejection fraction in one patient, indicating that CHF may be reversible in certain cases.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Human promyelocytic cell line HL60 has the specific binding sites for prolactin and its ornithine decarboxylase, DNA synthesis and cellular proliferation are induced by prolactin.

Human prolactin (hPRL) induced ornithine decarboxylase (ODC) activity, subsequently DNA synthesis and cellular proliferation on human promyelocytic cells, HL60, cultured in a serum-free medium. HL60 cells had 2100 specific binding sites for hPRL per cell, showing a dissociation constant of 1.1 x 10(-10) M. Binding of 125I-PRL to the cells was not blocked by simultaneous addition of human growth hormone. ODC activity and DNA synthesis were activated maximally at 5 and 20 h, respectively, after the addition of 0.05 nM hPRL. These effects of PRL on cellular proliferation, ODC activity and DNA synthesis were abolished by the simultaneous addition of anti-hPRL antibody. Simultaneous addition of an irreversible inhibitor of ODC, difluoromethyl ornithine (DFMO), also abolished the inductions of ODC and DNA synthesis by hPRL. The inhibitory effect of DFMO on hPRL-induced DNA synthesis was reversed by the addition of putrescine to the culture medium. These results suggest that hPRL binds to the prolactin receptor on HL60 cells and induces ODC activity to increase cellular polyamine levels, which eventually stimulates DNA synthesis and cellular proliferation.

Binding Sites↗

PubMed1993

Role in growth regulation of cytokines and cytokine receptors in acute lymphoblastic leukaemia expressing myeloid markers.

The biological roles of cytokines and cytokine receptors were examined in acute lymphoblastic leukaemia cells expressing myeloid antigens (My+ ALL). Interleukin-3 (IL-3), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), and low molecular-weight B-cell growth factor (LW-BCGF) could induce DNA synthesis in certain cases of My+ ALL. Whereas in My- ALL the stimulatory effects were shown only with LW-BCGF. Acute myelogenous leukaemia (AML) cells were activated with multiple cytokines including interleukin-1 (IL-1), IL-3, G-CSF and GM-CSF. Specific receptors for IL-1 and IL-3 were strongly expressed on both My+ and My- ALL cells. These receptors, however, were weakly detectable on AML cells. Additionally we studied the production of tumour necrosis factor-alpha and IL-1 by leukaemic blasts and found that distinct amounts of both cytokines were released from My+ ALL cells and AML cells, but not from My- ALL cells. The profiles of cytokines and cytokine receptors expressed by My+ ALL showed both similarities and differences to those in My- ALL or AML. The proliferation of My+ ALL cells was dependent on multiple cytokines that would regulate growth and maturation in a lineage-restricted fashion. These data suggested that My+ ALL cells might originate from uncommitted haematopoietic precursor cells coexpressing features of both lymphoid and myeloid lineages.

Antigens, CD↗

PubMed1992

Acute megakaryoblastic leukemia with translocation t(1;22)(p13;q13) in a 10-week-old infant.

A 10-week-old girl without Down syndrome developed an acute megakaryoblastic leukemia (AMKL). Bone marrow aspirates and biopsy showed megakaryoblastic infiltration with myelofibrosis. The diagnosis was made based on the findings that the positive reactions of leukemic cells to platelet peroxidase and to monoclonal antibodies which recognize platelet-specific surface glycoprotein (GP) IIb/IIIa and GP78. The blasts also showed myeloid and monocytoid differentiation antigens. The leukemic cells had a karyotype of 46,XX,t(1;22)(p13;q13). Our case and two other infantile cases reported by other investigators establish the novel association of the t(1;22) with AMKL.

Antibodies, Monoclonal↗

PubMed1992

Cellular immunosuppression in children with acute lymphoblastic leukemia: effect of consolidation chemotherapy.

The present study was designed to evaluate the chemotherapy-induced cellular immunosuppression in 20 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy. Peripheral blood was serially obtained from leukemic children during vincristine/cyclophosphamide/6-mercaptopurine/prednisone combined consolidation chemotherapy. The mean absolute number of peripheral blood lymphocytes as well as the mean absolute numbers of lymphocyte subsets (T cells, T cell subsets, B cells, and natural killer cells) from leukemic children before consolidation chemotherapy were all significantly lower than in control subjects; however, the percentages of lymphocyte subsets were similar in both groups. After consolidation chemotherapy, the percentages of CD4+ T lymphocytes and natural killer (NK) cells were significantly decreased and the percentages of monocytes and CD8+ T lymphocytes were significantly increased. Phytohemagglutinin- and 12-O-tetradecanoylphorbol-13-acetate-induced production of interleukin-2 (IL-2) and NK-cell-mediated cytotoxic activity by peripheral blood mononuclear cells (PBMC) were also substantially decreased in the post-therapy groups. NK activity correlated with the percentage of NK cells in PBMC. In contrast, OK432-induced production of tumor necrosis factor alpha (TNF alpha) and killer activity against NK-resistant target cells were significantly increased after therapy as compared with the pre-therapy and control groups. TNF alpha production correlated with the percentage of monocytes in PBMC. These results demonstrate that substantial quantitative and qualitative chemotherapy-induced abnormalities of the cellular immune system are present in the majority of patients treated with ALL. It is also suggested that the increased TNF alpha production by monocytes and the appearance of potent killing activity against NK-resistant targets might compensate for the defects of IL-2 production and NK activity during intensive consolidation chemotherapy.

Animals↗

PubMed1992

Recombinant human granulocyte colony-stimulating factor enhanced cytotoxicity of Ara-C in Ara-C-resistant leukemic cells from a patient with biphenotypic leukemia in cell kinetic quiescence.

In vitro preincubation with recombinant granulocyte colony-stimulating factor(rhG-CSF, 100 ng/ml) enhanced the cytotoxicity of 1-beta-D-arabinofuranosylcytosine(Ara-C) in leukemic cells resistant to Ara-C from a patient with biphenotypic leukemia. Treatment of the cells with rhG-CSF resulted in a 17-fold increase in DNA synthesis, 4.6-fold increase in percentage of S-phase, and a two-fold increase in Ara-CTP formation. Maximal effect was observed at 72 h of incubation. Combination chemotherapy with rhG-CSF and Ara-C to the patient showed remarkable cytoreduction. These results indicate that recruitment of resistant leukemic cells in cell kinetic quiescence is inducible by rhG-CSF and that it is possible enhancement of the cytotoxicity to cell cycle-specific drugs such as Ara-C.

Cell Cycle↗

PubMed1992

Activation of lymphocytes by varicella-zoster virus (VZV): expression of interleukin-2 receptors on lymphocytes cultured with VZV antigen.

The expression of human leukocyte antigen (HLA-DR) and interleukin-2 receptor (IL-2R; alpha and beta subunits) was significantly increased in peripheral blood mononuclear cells (PBMC) from varicella-zoster virus (VZV)-seropositive donors when PBMC were cultured with VZV antigen for 6 days. The increased expression of HLA-DR and IL-2R was observed in both CD4+ and CD8+ lymphocytes, which suggests that both types of lymphocytes from VZV-seropositive donors were activated when PBMC were cultured with VZV antigen. Adding anti-IL-2R alpha did not inhibit lymphocyte proliferation in response to VZV antigen, although marked inhibition was obtained by adding anti-IL-2R beta. No IL-2 was detected in the supernatant of PBMC cultured with VZV antigen; however, antibody to IL-2 inhibited lymphocyte proliferation on exposure to VZV antigen. These results indicate that IL-2 and expression of IL-2R beta are essential to lymphocyte activation by VZV antigen.

Adult↗

PubMed1992

Shedding of CD9 antigen by bone marrow cells from patients with acute lymphoblastic leukaemia.

The levels of soluble CD9 antigen released into spent medium from bone marrow (BM) cells were assayed using a unique enzyme-linked immunosorbent assay. We demonstrated that a considerable amount of soluble CD9 antigen was consistently detected in the spent medium from CD9+ leukaemic blasts, but little from normal or regenerating BM cells. The sensitivity and specificity of CD9 antigen assay were tested. First, BM cells taken from patients in complete morphologic remission (CR) were studied, and the distinct level of CD9 antigen was detected in 16.3% of the cases. Second, the outcome of leukaemic patients with significant shedding of CD9 antigen from BM cells while in CR was investigated: all patients have developed systemic relapse within 5-24 (median 15.4) weeks. In contrast, 24/34 patients without the increase of CD9 antigen levels are still in CR (follow-up 19-149 weeks, median 56.2 weeks). Only 10 patients in this group have relapsed so far. No false-positive results were detected with this sensitive assay for soluble CD9 antigen, and the introduction of appropriately planned prospective studies is justified on the basis of these observations.

Antigens, CD↗

PubMed1992

Expression of IL-2 receptor/p75 on lymphocytes from patients with rubella.

We analyzed the Interleukin-2 receptor (IL-2R) expression on fresh lymphocytes from three patients with rubella. Flow cytometric analysis demonstrated that lymphocytes from the patients expressed a considerable amount of IL-2R/p75 recognized by Mik-beta 1 monoclonal antibody (MoAb), although they did not react with anti-IL-2R/p55 (CD25) MoAb. The expression of IL-2R/p75 reached a peak at the end of the acute phase of illness. Fresh lymphocytes from rubella patients showed a marked proliferative response to IL-2, which was completely inhibited by Mik-beta 1, indicating that their IL-2R is a functional receptor. The present data suggest that IL-2R/p75 expression is involved in the host immune response triggered by the rubella virus.

Antibodies, Monoclonal↗

PubMed1991

CD34 antigen expression in children with Philadelphia chromosome-positive acute lymphoblastic leukemia.

One characteristic of Philadelphia chromosome (Ph')-positive acute leukemia is the occasional presence of both lymphoid and myeloid features in the same leukemia. This phenomenon supports the theory that this subtype of acute leukemia arises from lymphoid-myeloid stem cell, pluripotent progenitors. Very few reports, however, describe the immunophenotype, especially CD34 antigen, of Ph'-positive acute lymphoblastic leukemia (ALL). It has been shown that CD34, the human progenitor cell antigen, is found on 1% or less of normal human bone marrow cells, approximately 30% of acute leukemias, and multipotent progenitor cells; CD34 is not found on normal peripheral blood cells. A high frequency of CD34 expression was found in children with Ph'-positive ALL: CD34 was positive for all six patients tested, and one had an acute mixed-lineage leukemia. These findings suggest the involvement of a pluripotent stem cell in Ph'-positive ALL.

Antigens, CD↗

PubMed1991

Hyperimmunoglobulinemia D following cancer chemotherapy.

Five classes of serum immunoglobulin levels were investigated in 107 children with malignant or benign tumors. Hyperimmunoglobulinemia D (hyper-IgD) was observed in 31 of 82 children who were in complete remission off chemotherapy with a median follow-up of 4.5 years after cessation of chemotherapy. On the other hand, hyper-IgD was not found among 12 children with malignant or benign tumors treated with chemotherapy and a low incidence of hyper-IgD was observed during chemotherapy (1 of 13 cases). The result indicates that hyper-IgD is not uncommon in children off chemotherapy, suggesting that dysregulation of IgD synthesis persists long after cessation of antineoplastic drugs.

Adolescent↗

PubMed1990

Shedding of CD9 antigen into cerebrospinal fluid by acute lymphoblastic leukemia cells.

The accurate identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of acute lymphoblastic leukemia (ALL). We demonstrated that soluble CD9 antigen was shed into CSF obtained from children with ALL, using enzyme-linked immunosorbent assay (ELISA), which used the activity of CD9 antigen to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4, simultaneously. Using RCA1/SJ-9A4 ELISA, CD9 antigen was detectable in CSF but not in plasma from 12 cases of CD9+ ALL in central nervous system (CNS) relapse. However, CD9 antigen was not released into CSF from 11 cases of CD9- ALL with CNS involvement, 136 cases of CD9+ ALL in complete remission (CR), 29 cases of CD9- ALL in CR, or 21 cases of aseptic meningitis. Interestingly, the levels of CD9 antigen were elevated in CSF from 7 of 10 CD9+ ALL patients without cytologically proven CNS involvement at diagnosis, with subsequent return to undetectable levels after initial induction chemotherapy was begun. In addition, sequential analysis of CSF from a 5-year-old boy with CD9+ ALL in CNS relapse showed that levels of CD9 antigen correlated well with the number of leukemic cells in CSF. Serial quantitative analysis of CD9 antigen in CSF could be useful to detect the proliferation of residual leukemic cells before the clinical manifestation.

Antibody Specificity↗

PubMed1990

G-CSF enhanced granulocyte production in a child with severe neutropenia in the setting of fatal virus-associated hemophagocytic syndrome.

A 14-year-old boy with fatal varicella zoster virus-associated hemophagocytic syndrome (VAHS) was treated with recombinant human granulocyte colony-stimulating factor (G-CSF) based on the finding that the patient had severe neutropenia and possible bacterial superinfection. Support for the G-CSF therapy in VAHS is provided by the recent reports that G-CSF is relatively specific for the granulocyte lineage; it would not activate mature monocyte/macrophage/histiocyte lineage in VAHS, where the most striking morphologic feature is histiocytic hyperplasia with hemophagocytosis. He responded well to G-CSF with an elevation of neutrophil counts. There were no effects on other blood cells. The result indicates that G-CSF is useful to increase granulocyte production in severe neutropenia, even in the setting of fatal VAHS.

Adolescent↗