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T Hato

Publications and source records attributed to T Hato.

At least 19 recordsLinked to original sources
PubMed1995

A novel mechanism for exposure of fibrinogen binding sites on GPIIb-IIIa by a monoclonal antibody.

Conformational changes in platelet membrane glycoprotein (GP) IIb-IIIa, whose nature is not defined, lead to exposure of fibrinogen binding sites. We have reported previously that F(ab')2 fragments of a monoclonal antibody, PMA4, directed against the GPIIb-IIIa complex-specific domain, induced binding of fibrinogen to platelets without causing intracellular activation, whereas Fab did not. In this study, we examined the mechanism responsible for the difference in the ability of PMA4 F(ab')2 and Fab to expose fibrinogen binding sites. PMA4 Fab had affinity for GPIIb-IIIa similar to that of PMA4 F(ab')2. Addition of F(ab')2 goat anti-mouse Fab antibody to cross-link PMA4 Fab-bound GPIIb-IIIa molecules induced fibrinogen binding. There was a direct correlation between the number of molecules of PMA4 F(ab')2 and the amount of fibrinogen bound. PMA4 did not recognize ligand-induced binding sites (LIBS). These results suggest that the cross-linking of special sites on the GPIIb-IIIa complex-specific domain by bivalent antibody alters the conformation of GPIIb-IIIa to a state competent to bind soluble fibrinogen and that conformational changes in non-LIBS are involved in the mechanism for exposing fibrinogen binding sites on GPIIb-IIIa.

Animals↗
PubMed1995

[CD5-negative B-cell chronic lymphocytic leukemia (B-CLL) associated with massive splenomegaly and without lymphadenopathy].

A 39-year-old male was referred to our hospital in June, 1993, because of leukocytosis. Physical examinations showed massive splenomegaly without any lymphadenopathy. The white blood cell count was 13,800/microliters with 87% morphologically mature lymphocytes. Bone marrow aspirate revealed hypercellularity with 67% lymphocytes morphologically similar to peripheral lymphocytes. The lymphocytes displayed monoclonal rearrangements of immunoglobulin genes and the phenotype of CD5-CD19+CD20+ CD21+ and Smlg+. Splenectomy was effective against neutropenia and thromboytopenia. The clinical and laboratory findings of this case were unusual compared to those of typical B-CLL in massive splenomegaly, no lymphadenopathy and CD5-phenotype, suggesting the heterogeneity of B-CLL.

Adult↗
PubMed1994

Monoclonal proliferation of double-negative (CD4-CD8-) T-cells bearing T-cell receptor-alpha beta followed by subsequent development of Hodgkin's disease.

Expression of CD4 or CD8 on the cell surface is an important guide for discriminating the immunologic functions of T-cells. However, a minor T-cell subset lacking both CD4 and CD8 molecules but bearing the usual form of T-cell receptor (TCR)-alpha beta (CD4-CD8-TCR-alpha beta+ T-cells) has recently been found not only in mice but also in humans, and the clinical relevance of this newly defined subpopulation to human diseases is now of considerable interest. The authors present a patient in whom CD4-CD8-TCR-alpha beta+ T-cells showed monoclonal proliferation in the peripheral blood for more than 3 years, then disappeared spontaneously, followed by subsequent development of Hodgkin's disease. The pathologic roles of double-negative T-cell proliferation in this case are discussed from the viewpoint of premalignancy in lymphoproliferative diseases.

Angiolymphoid Hyperplasia with Eosinophilia↗
PubMed1994

Successful treatment of transfusion-associated graft-versus-host disease.

We present an immunocompetent patient with transfusion-associated graft-versus-host disease (GVHD), in which chimaerism of peripheral blood lymphocytes was demonstrated by analysis of a highly polymorphic genome. The patient was treated successfully with anti-CD3 monoclonal antibody, OKT3 and cyclosporin A. Although it is undoubtedly important to prevent transfusion-associated GVHD by irradiation of cellular blood components, intensive therapy with OKT3 and cyclosporin A in the early phase of onset may be effective for treatment of this potentially fatal condition. The mechanism of the effectiveness of this treatment for transfusion-associated GVHD is discussed.

Adult↗
PubMed1994

Acute transformation of chronic large granular lymphocyte leukemia into an aggressive form associated with preferential organ involvement.

In most patients with large granular lymphocyte (LGL) leukemia, the disease appears to progress slowly if at all, and no therapy is generally required. We present a patient with CD3+ CD8+ CD16+ LGL leukemia, who showed a benign clinical course for more than 7 months without therapy, but subsequently developed aggressive disease. A feature of considerable interest was the transformation into an acute or aggressive form in this patient affected preferentially the liver and spleen, and was not associated with the hematologic features of the circulating leukemic cells, as assessed by morphologic, phenotypic and molecular analyses. The patient was treated with combination chemotherapy; this resulted in clinical remission with persistence of the abnormal clone in the peripheral blood. The mechanism responsible for the preferential organ involvement and the process of progression from the chronic to the acute form in this case are discussed from the viewpoint of a lymphoproliferative disorder.

Aged↗
PubMed1993

Malignant lymphoma originating from the earliest T-lineage precursor cell.

The earliest T-lineage precursor cells with a CD3-CD4+CD8- phenotype and germline-state T-cell receptor (TCR) genes have recently been identified in the murine thymus. We report a case of malignant lymphoma that was considered to originate from the human counterpart of this newly defined murine T-cell population. The surface phenotype of the lymphoma cells was CD2+CD3-CD4+CD8-CD25-CD34-CD44+HLA-DR+. TCR-beta, -gamma, -delta chain genes and immunoglobulin heavy and light chain genes were all in a germline state. These characteristics were markedly similar to those of the murine earliest T-lineage precursor cells. The present case thus strongly suggests the presence of the human counterpart of this novel murine T-cell population.

Adolescent↗
PubMed1993

Immunological analysis of T cells bearing T cell receptor alpha/beta or gamma/delta in patients with granular lymphocyte proliferative disorder.

Immunological analysis of 2 cases of granular lymphocyte proliferative disorder with clonal expansion of CD3+4-8+ T cells bearing either T cell receptor alpha/beta (patient 1) or T cell receptor gamma/delta (patient 2) is reported. Significant cytotoxic activity against K562 was observed in peripheral blood mononuclear cells (PBMC) isolated from patient 2, but not in PBMC from patient 1, although the cytotoxic activity of patient 1 could be augmented following incubation with anti-CD3 monoclonal antibody (MoAb). Northern blot analysis revealed that perforin mRNA was expressed in both patients. Proliferative response to phytohemagglutinin, anti-CD3 MoAb and 12-O-tetradecanoylphorbol-13-acetate was low in PBMC from both patients compared to that from healthy controls. Cytoplasmic free calcium of PBMC from the 2 patients increased similarly to that of healthy controls after treatment with anti-CD3 MoAb.

Adult↗
PubMed1992

Adult T cell leukemia associated with eosinophilia: analysis of eosinophil-stimulating factors produced by leukemic cells.

The mechanism of eosinophilia in a patient with adult T cell leukemia (ATL) was investigated. A 61-year-old woman with ATL presented marked eosinophilia. No parasite infections or allergic diseases were found in this patient. The number of eosinophils fluctuated in parallel with that of ATL cells during her clinical course. The patient's serum and the culture supernatant of ATL cells showed eosinophil colony-stimulating activity. Northern blot analysis of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5), which are known eosinophil CSFs, showed that only GM-CSF but not IL-3 or IL-5 was expressed in freshly separated and cultured ATL cells. Since neutrophil and monocyte numbers did not increase, it is suggested that GM-CSF and unknown cytokines other than IL-3 and IL-5 produced by ATL cells synergistically stimulated eosinophil precursors in the present case.

Blotting, Northern↗
PubMed1992

[Inversion of chromosome 16 observed in acute myeloblastic leukemia (M2) with biphenotypic surface markers lacking monocytosis and eosinophilia].

Inversion of chromosome 16 was found in a 73-year-old female with acute myeloblastic leukemia (FAB:M2). Complete remission was achieved by combined chemotherapy (DNR, Ara-C, 6-MP, Prednisolone), but she relapsed 6 months later without CNS involvement and died of respiratory failure presumably due to cerebrovascular accident during remission reinduction chemotherapy. Biphenotypic surface markers (CD2+ and CD13+) were observed on relapse. Eosinophilia was not observed throughout. Our patient and the other reported case suggest that biphenotypism and the lack of eosinophilia and monocytosis in inv (16) leukemia may be correlated with a poor prognosis.

Aged↗
PubMed1992

Exposure of platelet fibrinogen receptors by a monoclonal antibody to the GPIIb-IIIa complex, PMA4.

We found that a monoclonal antibody to the glycoprotein (GP) IIb-IIIa complex, PMA4, induces fibrinogen binding to platelets, and we examined the mechanism involved. Affinity chromatography and crossed immunoelectrophoresis showed that PMA4 recognized an epitope on the GPIIb-IIIa complex-specific domain. The binding of 125I-fibrinogen to platelets was induced by PMA4 in a concentration-dependent manner and was blocked by EDTA, RGDS peptides and an anti-GPIIb-IIIa monoclonal antibody, PMA1. Binding of the divalent antibody to the GPIIb-IIIa complex was necessary to induce fibrinogen binding and subsequent platelet aggregation, since Fab fragments, unlike PMA4 IgG and F(ab')2 fragments, did not induce fibrinogen binding or aggregation. The PMA4 IgG induced fibrinogen binding, serotonin secretion, and Ca2+ mobilization, whereas F(ab')2 induced fibrinogen binding only. In addition, F(ab')2-induced fibrinogen binding was not abolished in the presence of aspirin, H-7, a protein kinase C inhibitor, PGE1 or dibutyryl cyclic AMP. These results demonstrate that the binding of PMA4 divalent molecules to the GPIIb-IIIa complex can expose platelet fibrinogen receptors in the absence of the stimulatory effects of intracellular mediators on platelets. Thus, we conclude that the fibrinogen receptors on the GPIIb-IIIa complex can be exposed by direct action of the antibody on the complex molecules.

Antibodies, Monoclonal↗
PubMed1991

Proliferation of double-negative (CD4-CD8-) T cells bearing T-cell receptor-alpha beta in a haemophiliac with human immunodeficiency virus type 1 infection and factor VIII inhibitor: functional properties of double-negative T-cell receptor-alpha beta+ T cells.

We present a patient with haemophilia A showing human immunodeficiency virus type 1 (HIV-1) infection and factor VIII inhibitor in whom a novel T-cell subpopulation, double-negative (CD4-CD8-) T cells bearing T-cell receptor (TCR)-alpha beta, proliferated polyclonally in the peripheral blood. An interleukin-2-dependent T-cell line with a CD4-CD8-TCR-alpha beta+ phenotype was established from the peripheral blood lymphocytes of the patient, and its biological functions were studied. It was found that the CD4-CD8-TCR-alpha beta+ T cells possessed both HLA-unrestricted cytotoxicity and helper function for immunoglobulin production by B cells. In addition, these T cells were found to produce interferon-gamma and interleukin-2 following activation via CD3-TCR complexes. These data demonstrating the multifunction of these newly defined CD4-CD8-TCR-alpha beta+ T cells thus suggest that these cells play an important role in protection against HIV infection. The mechanism of production of factor VIII inhibitor in the present case is also discussed focusing on the CD4-CD8-TCR-alpha beta+ T cells.

Adult↗
PubMed1990

Induction of platelet Ca2+ influx and mobilization by a monoclonal antibody to CD9 antigen.

We found that a monoclonal antibody (MoAb) to CD9 antigen, PMA2, induced a rise in cytosolic free calcium concentration ([Ca2+]i) in fura-2-loaded platelets, and we examined whether this response was due to direct action of PMA2 on CD9 antigen. The rise in [Ca2+]i was dependent on the PMA2 concentration, irrespective of the presence or absence of extracellular Ca2+. The role of secreted adenosine diphosphate (ADP) and thromboxane in the [Ca2+]i response to PMA2 was studied using creatine phosphate/creatine phosphokinase (CP/CPK) and aspirin. Combined treatment with CP/CPK and aspirin abolished the rise in [Ca2+]i, although either CP/CPK or aspirin alone produced only partial inhibition. Inhibition of adenosine triphosphate (ATP) secretion and thromboxane B2 synthesis by an MoAb to the glycoprotein IIb-IIIa complex, PMA1, resulted in little [Ca2+]i response to PMA2. In contrast, thrombasthenic platelets, in which ATP secretion and thromboxane B2 synthesis were normal, showed a normal [Ca2+]i response. When PMA2 was added to CD9+ mononuclear cells, no rise in [Ca2+]i was observed. Thus, we conclude that binding of monoclonal immunoglobulin G molecules to the CD9 antigen raises [Ca2+]i through the effect of secreted ADP and thromboxane on platelets, and that CD9 antigen is not directly involved in induction of Ca2+ influx and mobilization.

Adenosine Triphosphate↗
PubMed1988

Expression of CD9 (p24) antigen on hematopoietic cells following treatment with phorbol ester.

Expression of the leukemia-associated cell surface antigen p24 (CD9) on human hematopoietic cell lines and B-cell chronic lymphocytic leukemia (B-CLL) cells was analyzed before and after treatment with the phorbol ester 12-o-tetradecanoyl-phorbol 13-acetate (TPA). Little or no expression of CD9 was detected in any of the cell lines used or in B-CLLs before treatment with TPA. After exposure to TPA, HL-60, Epstein-Barr virus-immortalized B-cell lines, Molt-3, MT-2 and B-CLLs showed markedly augmented CD9 expression. U937 and K562 showed slight increases of CD9 expression. However, no expression of CD9 was induced in CCRF-CEM or HUT-102. Although CD9 is known to be one of the most useful markers of pre-B-cell common acute lymphoblastic leukemia, the expression of CD9 does not seem to be restricted to any specific cell lineage and can be induced in various hematopoietic cell lineages by treatment with TPA.

Antigens, CD↗
PubMed1988

Exposure of platelet fibrinogen receptors by a monoclonal antibody to CD9 antigen.

We found that a monoclonal antibody to CD9 antigen, PMA2, induces fibrinogen binding to platelets and examined the mechanism for this. That PMA2 recognized the CD9 antigen was confirmed by its immunoblot-reactivity with a 24,000-dalton protein, reactivity with platelets and common acute lymphoblastic leukemia (ALL) cells, and competitive binding with the ALB6 antibody known as the CD9 antibody. At saturation, PMA2 bound to approximately 46,000 sites per platelet. The binding of 125I-fibrinogen to platelets occurred in a PMA2 concentration-dependent manner and was blocked by EDTA or an anti-glycoprotein (GP)IIb-IIIa monoclonal antibody. PMA2-stimulated platelets caused ATP secretion and thromboxane B2 synthesis under non-stirred conditions. The role of secreted ADP and thromboxane in fibrinogen-binding and subsequent platelet aggregation was studied using creatine phosphate/creatine phosphokinase (CP/CPK) and aspirin. CP/CPK or aspirin alone reduced fibrinogen binding to 20% to 30%; however, this binding was sufficient to support full platelet aggregation. Combined treatment with CP/CPK and aspirin abolished fibrinogen binding and aggregation. These results demonstrate that the binding of IgG molecules to the CD9 antigen exposes fibrinogen receptors through both secreted ADP and thromboxane and that either one of both can expose the receptors to an extent sufficient to aggregate platelets.

Animals↗