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K Niiya

Publications and source records attributed to K Niiya.

At least 91 records · Page 5Linked to original sources
PubMed1991

[Factor VIII epitopes recognized by inhibitors in hemophiliacs].

A 44-year-old male hemophiliac with high titer anti-factor VIII antibody (66 bethesda units/ml) was admitted on November 11, 1989 because of epigastralgia and melena. A gastric ulcer with a spurting artery was revealed by an upper gastrointestinal endoscopy. Infusion of activated prothrombin complex concentrates and endoscopical ethanol injection to the bleeding vessel were ineffective. After clipping of the vessel, the bleeding was completely ceased. The inhibitor antibody was purified by Sephacryl S 200 and Protein A cellulofine column chromatography. Purified IgG showed factor VIII inhibitor activity. Factor VIII epitopes recognized by the inhibitors was examined by western blotting. Factor VIII concentrate purified by the antigen. This factor VIII preparation was composed of a doublet of light chains (M.W. 80 kD) and 3 heavy chains (M.W. 160-200 kD) when examined by SDS-PAGE followed by immunoblotting using monoclonal antibodies against factor VIII light and heavy chains. The inhibitor in this case reacted to the heavy chains of factor VIII, whereas antifactor VIII antibody in the other case reacted to the light chain of factor VIII.

Adult↗
PubMed1991

[Production and secretion of the plasminogen activator inhibitor type-2 in a leukemia cell line].

Differentiation-linked expression of plasminogen activator inhibitor-2 (PAI-2) was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid, dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, granulocyte-colony stimulating factor, and interleukin-6 (IL-6)] into the culture medium of a promyelocytic leukemia cell line PL-21. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amounts of the latter in the culture medium and in the cell lysate were approximately 10 times and 2,500 times, as much, respectively, as those of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-alpha and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity. PAI-2 antigen was demonstrated in the cell lysates of various leukemia cells by Western blotting technique using a monoclonal antibody against the PAI-2 purified from PL-21 culture medium. PAI-2 antigen was frequently detected in the plasmas from the patients whose peripheral leukocytes were more than 10,000/microliters.

Cell Differentiation↗
PubMed1990

Isochromosome 11q in acute monoblastic leukemia (M5a).

An isochromosome 11q in a patient with M5a type acute monoblastic leukemia is reported. The leukemic cells had a few azurophilic and alpha-naphthyl butyrate esterase-positive granules in the cytoplasm. Electron microscopy showed indented nuclei, abundant perinuclear fibrous bundles, and small lysosomes which were characteristic of monocytoid cells. A strong inhibitory activity against urokinase was detected in the cell lysates as compared with other leukemic cells. Cytogenetic analysis of the leukemic cells showed the karyotype 47, XY, +i(11q), which has not been observed hitherto in acute monocytic leukemia.

Chromosome Aberrations↗
PubMed1990

A plasminogen activator inhibitor-2 from a promyelocytic leukemia cell line, PL-21, binds to the carboxy-terminal chain of plasminogen activators.

A promyelocytic leukemia cell line, PL-21, was found to produce an inhibitor of plasminogen activators (PAI). The PAI reacted to anti-PAI-2 but not anti-PAI-1 anti-serum and had an apparent molecular weight of 43 kDa on unreduced SDS-PAGE. The PAI inhibited not only urokinase-type plasminogen activator (u-PA) but single- and two-chain tissue-type plasminogen activators (t-PAs) on plasminogen-containing fibrin plate. It formed SDS-stable complexes with both t-PA and u-PA but not with prourokinase as demonstrated by both fibrin zymography and immunoblotting using anti-PA and anti-PAI-2 antisera after SDS-PAGE. These complexes were still present even after reduction with dithiothreitol. The PAI appears to bind to the carboxy-terminal chain of both PAs, because the part of the band corresponding to the carboxy-terminal chain of PAs moved to an upper position as a result of complex formation when two-chain form of PAs were incubated with the PAI and analyzed by SDS-PAGE followed by immunoblotting.

Amino Acid Sequence↗
PubMed1990

Thrombocytopenic purpura in a patient with lupus anticoagulant: requirement of both immunosuppressive and antithrombotic therapies.

A 33 year old woman with severe thrombocytopenic purpura complicated by typical lupus anticoagulant developed repeated spontaneous abortion, deep venous thrombosis, and cerebral thrombosis. The platelet count fluctuated from 4,000 to 400,000/mm3 during the 13 year clinical course. The physical and laboratory findings at the time of severe thrombocytopenic purpura were compatible with the criteria of idiopathic thrombocytopenic purpura except for positive lupus anticoagulant. Both immunosuppressive therapy with prednisolone and antithrombotic therapy with warfarin and aspirin were necessary for the control of bleeding and venous and arterial thrombosis.

Adult↗
PubMed1988

Generation and characterization of peptide-specific antibodies that inhibit von Willebrand factor binding to glycoprotein IIb-IIIa without interacting with other adhesive molecules. Selectivity is conferred by Pro1743 and other amino acid residues adjacent to the sequence Arg1744-Gly1745-Asp1746.

We have generated antibodies against a synthetic peptide corresponding to the sequence of human von Willebrand factor (vWF) between residues Glu1737-Ser1750 which includes the Arg-Gly-Asp sequence common to several adhesive molecules. Two anti-peptide antibodies, one polyclonal, and one monoclonal reacted with native vWF and inhibited its binding to platelet glycoprotein (GP) IIb-IIIa, but showed negligible cross-reactivity with fibrinogen, fibronectin, and vitronectin, three other molecules that contain the sequence Arg-Gly-Asp and bind to platelets. The structural bases for the specificity of the two antibodies were evaluated by testing the ability of peptides homologous to the parent sequence, but with single amino acid substitutions, to neutralize the binding of the two antibodies to vWF. The substitution of Pro1743, the residue immediately adjacent to the Arg-Gly-Asp sequence on the amino-terminal side, with Phe resulted in a peptide that failed to interact with either antibody. Thus, Pro1743 is important for maintaining a peptide conformation recognized by two antibodies specific for the GP IIb-IIIa-binding domain of vWF. Other residues important for optimal peptide reactivity with the polyclonal antibody were Ser1742, Arg1744, and Gly1745, whereas Gly1741, Gly1745, and Asp1746, but not Arg1744, were important for reactivity with the monoclonal antibody. The epitopes of both antibodies, therefore, included at least 2 of the residues in the sequence Arg-Gly-Asp considered the common cell-binding site of adhesive molecules that interact with GP IIb-IIIa. Nevertheless, both antibodies reacted only with vWF. These studies demonstrate that peptide-specific antibodies, unlike the promiscuous GP IIb-IIIa receptor, can recognize distinctive structural characteristics of the cell-binding domain of adhesive molecules imposed by residues adjacent to the sequence Arg-Gly-Asp.

Amino Acid Sequence↗
PubMed1988

Trisomy 4 in a case of acute nonlymphocytic leukemia (M2).

Trisomy 4 in a Japanese patient with type M2 acute nonlymphocytic leukemia is reported. Karyotypic analysis was unsuccessful at diagnosis and complete remission lasted 4 years. The cytogenetic change was detected in the first and second relapses as the only chromosome abnormality. Unusual nuclear irregularities were found in many leukemic cells.

Acute Disease↗
PubMed1987

Isolation and characterization of two domains of human von Willebrand factor that interact with fibrillar collagen types I and III.

We have identified four discrete proteolytic fragments of von Willebrand factor (vWF) that define two collagen-binding domains. Two of the fragments tested, T 96 kDa and T 55 kDa, were generated by digestion with trypsin, and two, Fragments I and III, with Staphylococcus aureus V8 protease. The larger Fragment III, a disulfide-linked homodimer, extends between residues 1 and 1365 of the 2050-residue vWF subunit and comprises the sequence of all the others. T 96 kDa, also a disulfide-linked homodimer, extends between residues 449 and 728. T 55 kDa and Fragment I, both single-chain polypeptides, have a partial sequence overlap corresponding to residues 911-1114, and together extend from residue 730 to 1365. The ability of the fragments to interfere with the vWF-collagen interaction was evaluated by measuring inhibition of 125I-labeled vWF binding to fibrillar bovine collagen types I and III. All the four fragments tested inhibited binding. Native conformation was essential for expression of this function; denaturation with guanidine hydrochloride and reduction of disulfide bonds resulted in marked reduction or complete loss, respectively, of the inhibitory activity at all the concentrations tested. Two monoclonal antibodies were prepared, one directed against T 96 kDa and the other against Fragment I. Both antibodies partially inhibited vWF binding to collagen, and their inhibitory effect was enhanced when they were used together. 125I-Labeled Fragment I bound to collagen in a saturable manner, and the binding was completely blocked by both T 96 kDa and T 55 kDa. Thus, we have identified at least two distinct functional domains of vWF that concurrently mediate the vWF-collagen interaction. The two domains appear to share a common recognition site on collagen.

Animals↗
PubMed1987

Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation.

Platelet activation altered the binding of three monoclonal antibodies (monovalent Fab' fragment) directed against the glycoprotein (GP) IIb/IIIa complex. An increased binding of two- to threefold occurred after stimulation with thrombin or phorbol myristate acetate (PMA), with slight but significant increase in the dissociation constants (Kd) of two antibodies (LJ-CP8 and LJ-P9). In contrast, no statistically significant changes were observed with ADP-stimulated platelets. The increased binding of LJ-CP3, but not of the other two antibodies, to activated platelets decreased by 30% to 40% in the presence of EDTA at 22 to 25 degrees C. Platelets stimulated by thrombin or PMA bound more fibrinogen than did those stimulated by ADP, and significant differences in the extent but not in the affinity of fibrinogen binding were observed with various platelet agonists. When the pool of GP IIb/IIIa molecules exposed on the surface of unstimulated platelets was reacted with the monoclonal antibody LJ-CP3 to block ADP-induced fibrinogen binding and platelet aggregation, stimulation with thrombin or PMA still induced substantial binding of antibody and fibrinogen, and aggregation ensued. Therefore, platelets exposed to "strong" agonists exhibit an increased number of surface-oriented epitopes associated with GP IIb/IIIa. The GP IIb/IIIa molecules bearing these newly exposed epitopes are functional in that they can bind fibrinogen and mediate platelet aggregation.

Antibodies, Monoclonal↗
PubMed1986

Characterization of a new human lymphoma cell line (RC-K8) with t(11;14) chromosome abnormality.

A human cell line (RC-K8) that produces plasminogen activator was established from the peritoneal effusion of a patient with histiocytic lymphoma. The RC-K8 cell line grew mainly in single cell suspension and consisted of primitive cells with pleomorphic morphology. RC-K8 cells were positive for alpha-naphthyl butyrate esterase, acid phosphatase and periodic acid-Schiff stainings. Immunologic and molecular biological studies showed that RC-K8 cells reacted with monoclonal antibodies to B cell antigens (B1 and Leu12) and Ia antigen (OKIa1) and possessed immunoglobulin gene rearrangement in the absence of surface and cytoplasmic immunoglobulin. Neither Epstein-Barr virus nuclear antigen nor terminal deoxynucleotidyl transferase was detected in the cells. Chromosome analysis of RC-K8 disclosed 46 XY with complex abnormalities including t(11;14)(q23;q32). Intraperitoneal inoculation of RC-K8 cells to immunosuppressed newborn hamsters produced massive metastatic tumors in the lungs. The RC-K8 cell line will be of considerable value for the study of lymphomagenesis associated with t(11;14) and pulmonary metastasis of lymphoma cells.

Animals↗
PubMed1985

Adult T-cell leukemia in two siblings. Acute crisis of smoldering disease in one patient.

Two cases of human T-cell leukemia virus (HTLV)-positive adult T-cell leukemia (ATL) in brother and sister are presented. Six of 15 members of this family were seropositive for antibodies for ATL-associated antigens (ATLA). The sister of the ATL patient developed overt ATL after 5 years and 8 months of smoldering ATL. Immunologic examinations during the smoldering phase were normal except for negative skin tests for purified protein derivative. Factors leading to the induction of ATL among HTLV carriers remain to be studied.

Acute Disease↗
PubMed1985

Oral administration of factor VIII concentrate preparation in von Willebrand's disease.

We investigated on how to effectively administer orally factor VIII preparation to two patients with von Willebrand's disease as volunteers, and the following results were obtained: Bleeding time and aPTT were shortened, but no change of PT was observed. Factor VIII:C increased slightly, but no significant increase was observed in factor VIIIC:Ag. The recovery of factor VIII:C was 19-40%. Factor VIIIR:Ag increased slightly, but no changes of factor VIIIR:RCo were observed. In the Ristocetin induced platelet aggregation (1.5 mg/ml of ristocetin), the collected aggregation abilities were not clear. The factor VIII concentrate preparations, entrapped with liposome, were absorbed from the intestines.

Administration, Oral↗