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J Nishimura

Publications and source records attributed to J Nishimura.

At least 181 records · Page 10Linked to original sources
PubMed1991

Calpain and kininogen mediated inflammation.

On the basis of previous findings that N-acetyl nonapeptide from the human calpain I large subunit has chemotactic activity for neutrophils, more than 30N-acetyl and unmodified peptides which have N-terminal amino acid sequences of the large and small subunits of calpains I and II were synthesized and their chemotactic activity was estimated. In addition to the above N-acetyl nonapeptide from the calpain I large subunit, an unmodified nonapeptide from the calpain II large subunit and several N-acetyl peptides of different lengths from the small subunit showed chemotactic activity. Furthermore, when calpain was incubated with either high molecular weight or low molecular weight kininogen, kinin liberation occurred with simultaneous inhibition of calpain by kininogen. These data suggest that chemical mediators generated from the calpain-kininogen system may participate in migration and accumulation of neutrophils to the inflammatory locus.

Amino Acid Sequence↗
PubMed1991

Energetic aspects of the regulation of Ca++ sensitivity of permeabilized rabbit mesenteric artery: possible involvement of a second Ca++ regulatory system in smooth muscle contraction.

The effects of phosphagen concentrations and adenosine-5'-O-(2-thiodiphosphate)(ADP beta S), a nonhydrolyzable ADP analog, on the pCa++ tension relationships were investigated, using alpha-toxin permeabilized rabbit mesenteric artery. The removal of creatine phosphate (CP) greatly affected the Ca++ sensitivity and induced a leftward shift of the pCa++ tension curve. Addition of ADP beta S (10-300 microM) also caused a leftward shift of the pCa++ tension curve. Ca++ solutions (0.3-10 microM) containing 0.1 mM ATP did not induce contraction. However, the addition of CP in the presence of 0.1 mM ATP dose-dependently increased force development which reached a maximum around 3 mM CP. A 10 microM Ca++ solution containing 0.1 mM ATP and 1 mM CP was much more effective in inducing contraction than a 10 microM Ca++ solution containing 1.1 mM ATP alone, although the total concentration of phosphagen (ATP + CP) was the same. Application of 0.1 mM ATP solution containing various concentrations of Ca++ after the maximal Ca+(+)-induced contraction relaxed the tissue, with the higher Ca++ concentrations inducing the faster relaxation. The same pattern of the relaxation was seen when the tissue was pretreated with adenosine-5'-O-(3-thiotriphosphate) beforehand. The contractile state observed in the Ca+(+)-free solution containing 0.1 mM ATP and 0.1 mM CP was completely relaxed by 1 mM vanadate, consistent with the idea that the sustained contraction was due to accumulation of the actomyosin-ADP complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1991

Alpha-interferon reduces in vivo phosphorylation of P210bcr/abl protein during hemin-induced erythroid differentiation of K-562 cells.

alpha-Interferon (IFN-alpha) is important in the management of chronic myelogenous leukemia (CML). The P210bcr/abl fusion protein, with enhanced tyrosine kinase activity, is implicated in the pathogenesis and progression of the disease. To elucidate the inhibitory mechanism of IFN-alpha on CML cell proliferation, we studied the effect of IFN-alpha on P210bcr/abl in K-562 cells. The phosphorylated level of P210bcr/abl was not altered by treatment with IFN-alpha alone despite its inhibiting cell proliferation. However, when K-562 cells were treated with either a low (5 x 10(2) U/ml) or high (10(4) U/ml) concentration of IFN-alpha in the presence of hemin, P210bcr/abl protein activity decreased through reduction of in vivo phosphorylation, but not through inhibition of de novo protein synthesis. Furthermore, hemoglobin content was increased by IFN-alpha at both low and high concentrations in tandem with hemin-induced erythroid differentiation and the change in P210bcr/abl. These results demonstrate that IFN-alpha synergises hemin-mediated erythroid differentiation as it reduces the in vivo tyrosine phosphorylation of P210bcr/abl in K-562 cells.

Blast Crisis↗
PubMed1991

[Intestinal T-cell lymphoma (so-called malignant histiocytosis of the intestine) complicated by multiple perforations].

We describe a case of intestinal T-cell lymphoma which was histologically diagnosed of malignant histiocytosis of the intestine. A 47-year-old man was admitted to our hospital because of fever and generalized lymphadenopathy. Mild anemia, leukocytosis, positive CRP and a high level of LDH were noted. Pathological finding of the lymph node was compatible with dermatopathic lymphadenopathy with a slight increase in atypical lymphoid cells. At the 14th day after admission, he suffered from abdominal pain and was diagnosed as having perforative peritonitis. In laparotomy, the infiltration of histiocyte-like atypical cells were found around a site of small perforation of the terminal ileum. The findings were compatible with that of malignant histiocytosis of the intestine (MHI). He had recurrent perforations of the small intestine and died of peritonitis and sepsis at the 42nd day. Southern blot analysis of the biopsied lymph node showed TCR-beta gene rearrangement. Some patients diagnosed clinically and pathologically as having MHI may have a T-cell lymphoma like our case.

Histiocytic Sarcoma↗
PubMed1990

Enhanced synthesis of heat shock proteins and augmented thermotolerance after induction of differentiation in HL-60 human leukemia cells.

The effects of the induction of differentiation were investigated on the expression of heat shock proteins (hsps) and thermotolerance. The synthesis of the major hsps in response to heat stress was markedly enhanced in HL-60 human leukemia cells after differentiation. An increased amount of mRNA transcripts for hsp 70 was also noted. In addition, induction of differentiation resulted in acquisition of greater resistance to heat, which may be advantageous since cells in the peripheral blood must survive many stresses.

Blotting, Northern↗
PubMed1990

Neutrophil chemotactic activity of N-terminal peptides from the calpain small subunit.

On the basis of previous findings that N-acetyl nonapeptide from the human calpain I large subunit has chemotactic activity for neutrophils, a series of peptides with the N-terminal sequence of the calpain small subunit were synthesized and their chemotactic activity was examined. Potent activity was found in N-acetyl tetra, hepta, octa, nona and a larger peptide of 13 residues, although N-acetyl tripeptide showed only weak activity and N-acetyl penta and hexa peptides showed almost no activity. Since the small subunit is identical in calpains I and II, the results indicate that both calpains could be precursor proteins of chemotactic factors for neutrophils.

Amino Acid Sequence↗
PubMed1990

The transferrin receptor system is not involved in the pathogenesis of hematological disorders with 3q inversion.

To clarify the idea that an alteration of the transferrin receptor (TF-R) gene, localized to 3q26, may be of pathogenetic significance in hematological disorders with 3q anomaly, we studied the TF-R systems of erythroblasts from both functional and genetic aspects. The patient described here had refractory anemia with an excess of blasts (RAEB), with paracentric inversion, inv(3)(q21q26). The patient had the characteristic findings of micromegakaryocytosis and thrombocytosis, with giant platelets. There was no functional abnormality of TF-R as far as number of binding sites, affinity, molecular weight, or recycling kinetics were concerned. Furthermore, we could not recognize any rearrangement of the TF-R gene with Southern blot analysis. These data suggest that TF-R is not involved in the pathogenesis of leukemogenesis and thrombocytosis of the disease.

Chromosome Inversion↗
PubMed1990

Treatment of platelet-alloimmunization with cyclosporin A in a patient with aplastic anemia.

The development of alloantibodies to platelets is a major problem in the supportive management of thrombocytopenia in patients with severe aplastic anemia. We report here a case of aplastic anemia refractory to platelet transfusion. An immunosuppressant, cyclosporin A, which was used for the therapy of aplastic anemia, modulated alloimmunization to platelets in this patient, followed by repeated platelet transfusion. The treatment reduced platelet alloantibodies detected by anti-human immunoglobulin lymphocytotoxicity test, with change of the CD4/CD8 ratio in T lymphocytes in peripheral blood. These results suggest the usefulness of cyclosporin A for the prevention of platelet alloimmunization.

Adult↗
PubMed1990

Major prognostic factors of Japanese patients with lymphoma-type adult T-cell leukemia.

Fifty-three Japanese patients with the lymphoma-type adult T-cell leukemia (ATL) were analyzed to study the prognostic value of various clinical findings recorded at the time of diagnosis. All patients were positive for human T-cell leukemia virus type I (HTLV-I) antibody and demonstrated monoclonal integration of HTLV-I proviral DNA in their malignant cells. The important individual variables detected in a previous univariate analysis were placed in a multiple regression model to identify the major prognostic factors for survival. This analysis showed that serum lactate dehydrogenase (LDH), calcium, and total protein levels had a strong predictive relationship with the length of survival (in descending order of importance). Among the 53 patients, 46 were dead at the time of analysis. The cause of death in relation to the duration of survival is also reviewed in this article.

Adult↗
PubMed1990

Mechanisms involved in the development of adriamycin resistance in human leukemic cells.

We have developed three adriamycin (ADR)-resistant K562 sublines with different degrees of resistance. These sublines show a decreased accumulation and an increased efflux of ADR in proportion to the degree of resistance. Two membrane proteins (mol. wt 170,000 and 230,000) reactive with monoclonal antibody against P-glycoprotein were highly expressed in both the K562/ADR200 and the K562/ADR500 subline. Less resistant K562/ADR80 cells contained only small amounts of mol. wt 230,000 protein. Thus, the level of P-glycoprotein expression was not proportionate to the degree of ADR efflux. Verapamil treatment could not completely reverse ADR resistance. No significant change of glutathione-s-transferase activity nor in the level of DNA topoisomerase II was detected in resistant sublines. In our sublines it seems that P-glycoprotein is one of the mechanisms for resistance, but additional mechanisms may be involved.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Lineage non-specific down regulation of P210bcr/abl in the CML cell line, KU-812-F, during differentiation.

CML cell line, KU-812-F, originally established from a patient with Philadelphia-chromosome-positive chronic myelocytic leukemia has maintained the ability to differentiate into both granuloid (basophilic) and erythroid lineages. The expression of P210bcr/abl in KU-812-F cells during differentiation was studied by immunoblotting and immunoprecipitation. Immunoblotting with anti-phosphotyrosine sera revealed the down-regulation of P210bcr/abl in both granuloid and erythroid lineages. Immunoprecipitation with anti-abl antibodies of 35S-methionine-labelled cells revealed a reduced rate of synthesis of P210bcr/abl protein. Cytotoxic agents that caused growth inhibition of the cells did not alter the expression of P210bcr/abl. These results indicate that the down regulation of P210bcr/abl protein is a lineage non-specific event accompanied by differentiation.

Cell Differentiation↗
PubMed1990

Molecular heterogeneity of beta-thalassaemia in the Japanese: identification of two novel mutations.

Five unrelated Japanese beta-thalassaemia genes, from one homozygote and four heterozygotes, have been systematically characterized using DNA polymorphism analysis, polymerase chain reaction, dot-blot hybridization and direct sequencing of amplified genomic DNA. Four different molecular defects were observed on three different beta-globin gene frameworks. One of these, the A----G mutation in the TATA box, a previously described mutation, was detected by dot-blot hybridization in one homozygote and one heterozygote with the beta-globin gene of framework 2. The second mutation is a C----T substitution at position 654 of IVS-2, the mutation commonly found in Chinese, which was associated with the framework 1 gene. Another two mutations, both associated with framework 3 genes, are novel ones; an amber mutation in codon 90 (GAG to TAG) and a frameshift (+G) insertion in codon 54, both of which cause a beta 0-thalassaemia phenotype by premature termination of the beta-globin chain synthesis.

Adult↗
PubMed1990

A genetic defect of erythrocyte band 4.2 protein associated with hereditary spherocytosis.

We report two patients with hereditary spherocytosis associated with band 4.2 protein deficiency from a Japanese family. The defect of band 4.2 protein was confirmed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) not only in freshly prepared white ghosts but also in washed whole erythrocytes. The finding was quite reproducible and was also recognized postsplenectomy. The interaction of ankyrin with band 3 in the patients' ghosts was stable both at low ionic strength and at acidic pH. Our results suggested that band 4.2 protein might not be essential for the structural stability of band 3-ankyrin interaction. On the other hand, membrane protein phosphorylation studies revealed an increased phosphorylation of spectrin/ankyrin, band 3 and band 4.1 in the patients' erythrocytes as compared with normal cells. The finding might be related to a dysregulation of protein phosphorylation which could result in membrane instability in affected cells. Band 4.2 deficiency is an inherited disorder in association with hereditary haemolytic anaemias and seems to be relatively prevalent in the Japanese population.

Adult↗
PubMed1990

Evidence for increased myofilament Ca2+ sensitivity in norepinephrine-activated vascular smooth muscle.

The agonist-induced change in Ca2+ sensitivity of smooth muscle myofilaments was investigated in intact and permeabilized vascular preparations isolated from the rat and the rabbit. In intact rat mesenteric artery, membrane depolarization by 80 mM K+ solution or alpha-adrenergic stimulation by norepinephrine (NE) increased tension monotonically with increasing extracellular Ca2+ concentration ([Ca2+]e). The [Ca2+]e-tension curve generated during activation by NE was located to the left of that during activation by high K+. The protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA) shifted the high K+ [Ca2+]e-tension curve to the left but did not affect the NE curve. In rat mesenteric artery permeabilized by alpha-toxin, tension was measured while the intracellular free Ca2+ concentration ([Ca2+]i) was controlled using 2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N'N'-tetraacetic acid and Ca2+ buffer solutions. The alpha-toxin-permeabilized fibers developed tension as a function of Ca2+ concentration. TPA and guanosine 5'-[gamma-thio]triphosphate (GTP gamma S, a nonhydrolyzable GTP analogue) significantly shifted the pCa-tension curve to the left. In intact rabbit inferior vena cava, tension was recorded simultaneously with [Ca2+]i as measured by fura-2. TPA caused a gradual increase in tension without change in [Ca2+]i. In rabbit mesenteric artery permeabilized by alpha-toxin, the tissue still responded to NE, indicating that alpha-adrenergic receptors remained intact. The response to NE was augmented by GTP and inhibited by guanosine 5'-[beta-thio]diphosphate (GDP beta S, a nonhydrolyzable GDP analogue) suggesting that a G protein is coupled with the alpha-adrenergic receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1990

Abnormality of platelet membrane glycoprotein GPIIb in a myelodysplastic syndrome with 3q inversion presenting with marked dysmegakaryopoiesis.

Platelet membrane glycoproteins were analyzed in a case of myelodysplastic syndrome with inv(3) (q21q26) presenting with prominent dysmegakaryopoiesis by three different labelling techniques for surface proteins. Markedly decreased level of platelet membrane glycoprotein GPIIb was observed in the patient's platelets by terminal sialic acid labelling method, whereas no significant changes in the levels of glycoproteins including GPIIb could be detected either by penultimate galactose labelling or by tyrosine/histidine labelling. These results indicate a decreased sialylation of GPIIb in the patient's platelets, implying aberrant process in thrombopoiesis in the disease.

Bone Marrow Examination↗