Biomedical subjects

J Nishimura

Publications and source records attributed to J Nishimura.

At least 91 records · Page 5Linked to original sources

PubMed1989

Lymphoid blast crisis in a patient with Philadelphia-chromosome-negative chronic myelocytic leukemia.

A 24-year-old man with Philadelphia-chromosome (Ph)-negative chronic myelocytic leukemia (CML) developed lymphoid blast crisis. In the chronic phase, karyotype was normal and the clinical and hematological features were indistinguishable from those of Ph-positive CML. Rearrangement of the breakpoint cluster region (bcr) was observed. In the blast phase, blast cells showed early B-cell phenotype (CALLA+, Ia+, TdT+) with a rearranged immunoglobulin heavy-chain gene joining region (JH). By using an immunoblotting method and antiphosphotyrosine sera, P210bcr-abl protein was detected. The patient responded well to vincristine and prednisolone (VP) therapy. These findings support the concept that Ph-negative bcr+ CML can behave in a very similar fashion to Ph-positive CML, not only in the clinical features of the chronic phase but also in the manner of the blast crisis.

Adult↗

PubMed1989

Agonist-induced vascular tone.

The cellular mechanisms underlying the agonist-induced sustained contraction of the vascular smooth muscle are reviewed in the light of the use of Ca2+ and the change of Ca2+ sensitivity of the contractile apparatus. It is generally accepted that the main trigger for contraction of vascular smooth muscle is the elevation of intracellular Ca2+ concentration. However, the measurement of intracellular Ca2+ concentration during the sustained phase of agonist-induced contraction is reported to be lower than that of high K+ stimulation or the value obtained by the experiments with chemically skinned smooth muscle preparations. These observations indicate that a second regulatory system may exist. One possible mechanism is the effectiveness of Ca2+ use. Agonist-induced Ca2+ influx may be more effective in raising the intracellular Ca2+ in the bulk of the cytoplasm than is Ca2+ entry induced by depolarization by the inhibition of a putative sarcoplasmic reticulum buffer barrier. Another possibility is the change of Ca2+ sensitivity of the contractile apparatus. Although the survey of the recent literature concerning the phorbol ester-induced vasoconstriction tends to support a role for protein kinase C in the change of Ca2+ sensitivity of the contractile proteins, it fails to establish a clear link between receptors, protein kinase C, and myofilaments. By using new methods for permeabilizing smooth muscle fibers, which retain the function of receptors and signal transduction systems, we now provide direct evidence that the activation of G protein by norepinephrine or guanosine 5'-0-(3-triphosphate) (GTP-gamma-S), nonhydrolyzable GTP analogue, enhances myofilament sensitivity to Ca2+.

Actin Cytoskeleton↗

PubMed1989

Phosphotyrosine phosphatase activity prevents the detection of P210bcr/abl protein in mature cells in chronic myelogenous leukemia even by an immunoblotting technique.

P210bcr/abl protein with tyrosine protein kinase has been implicated in the proliferation and differentiation of chronic myelogenous leukemia cells. Using an immunoblotting technique with antiphosphotyrosine (anti-P-Tyr) antibodies, we examined whether P210bcr/abl protein was expressed in chronic phase cells in patients with chronic myelogenous leukemia (CML). We could detect P210bcr/abl protein in blast cells regardless of myeloid or lymphoid lineage but not in chronic phase cells from patients. However, in a patient with both blast cells and chronic phase cells, we could identify the protein only after the enrichment of the blast crisis cells by Percoll gradient centrifugation. When K562 cells were mixed with mature granuloid cells, the P210bcr/abl in K562 cells detected by immunoblotting was decreased. Using phosphotyrosyl proteins in K562 cells as substrates, high phosphotyrosyl (P-Tyr) phosphatase activity was observed, not only in the lysate of chronic phase cells from CML patients but also in the lysate of neutrophils from normal subjects. These findings suggest the possibility that high P-Tyr phosphatase activity prevents the detection of P210bcr/abl in CML cells in the chronic phase. The activity may be characteristic of mature cells and may regulate cellular events through dephosphorylation of P210bcr/abl.

Blast Crisis↗

PubMed1989

[A case of advanced gastric cancer with Virchow's node metastasis, responding to concomitant plasma exchange and immunochemotherapy].

We report a case of advanced gastric cancer with Virchow's node metastasis which responded to concomitant plasma exchange and immunochemotherapy. Plasma exchange was conducted three times in total (once a week) using a membrane type plasma separator, with fresh frozen plasma as exchange fluid. Immunochemotherapy was performed simultaneously using MMC, FT and OK-432. By the end of the third plasma exchange, Virchow's node was confirmed by palpation and ultrasonic examination to have vanished. Diminution of the gastric cancer, and improvement of stenosis of the stomach were confirmed under endoscopy. We surmised that plasma exchange eliminated the immunosuppressive substances in serum, and intensified the anticancer effects of MMC and FT, resulting in the disappearance of the Virchow's node and diminution of the gastric cancer itself.

Adenocarcinoma↗

PubMed1989

A new analysis of natural killing activity and the role of monocytes in normal subjects.

A new analysis of natural killing activity in peripheral blood is proposed. In this new analysis, we did not use a fixed E/T ratio, which is practised in the conventional analysis. We employed the individual effector/target cell ratio (E/T ratio) according to the number of effector cells in the peripheral blood: the individual E/T ratio of the person was set precisely at the point when the effectors in 1 ml of the person's peripheral blood encountered 2 x 10(4) of target cells. Asymptomatic healthy persons were divided into high activity and low activity groups. Comparison between mononuclear and non-adherent cells in terms of natural killing activity indicated that monocytes possessed a suppressive effect on the activity. In the asymptomatic low activity group, monocytes were more strongly suppressive as the natural killing activity of non-adherent cells became higher. The degree of this suppression was controlled by the change in the ratio of monocytes over large granular lymphocytes (Mo/LGL ratio). The asymptomatic high activity group showed the same suppressive pattern as patients with common cold syndrome, who were found to be in an activated state of natural killing activity. In an activated state, the monocyte suppression was to a lesser degree although the natural killing activity was higher than that in a non-activated state. Also in an activated state, the degree of the suppression was controlled by the Mo/LGL ratio. In addition, the degree of monocyte suppressive function as determined by one Mo/LGL ratio was almost identical both in an activated state and in a non-activated state of natural killing activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Common Cold↗

PubMed1989

[Hepatic arterial infusion chemotherapy of hepatocellular carcinoma].

In 24 cases of unresectable hepatocellular carcinoma, we performed hepatic arterial catheterization and intra-arterial infusion chemotherapy. Adriamycin (ADM), Mitomycin C (MMC), 5-FU and Lipiodol (LPD) were administered an average of 13.5 times over a mean period of 106 days. Except for 5 unevaluable cases, there were 0 CR, 5 PR, 4 MR, 7 NC and 2 PD cases, for an efficiency rate of 27.8%. Complications thought to be due to the catheter included catheter blockade in 1 case (4.3%) and dermal infection of insertion site in 3 cases (13.0%). As for the results of follow-up study, one-year survival rate with this therapy was 47.8%, which compares favorably with a one-year survival rate of 30.0% in 30 cases treated only with TAE. From the above results, hepatic arterial infusion chemotherapy can be repeatedly performed on an outpatient basis, and it is considered to be a useful therapeutic method for treating unresectable hepatocellular carcinoma.

Aged↗

PubMed1989

Receptor-mediated C-kinase activation contributes to alpha-adrenergic tone in rat mesenteric resistance artery.

Small branches from the superior mesenteric arteries (100-200 microns outer diameter) freshly dissected from male Wistar-Kyoto (WKY) rats were mounted for tension recordings. Some arterial rings were left in physiological salt solution and used as intact arteries while others were made permeable with alpha-toxin and incubated in cytoplasmic substitution solution. The relationship between ambient [Ca2+] and tension development during various modes of activation was measured in both intact and permeable arterial rings. The effects of ryanodine and 12-O-tetradecanoyl phorbol-13-acetate (TPA) were tested. Ryanodine had no effect on the tone developed in response to noradrenaline, but tension was increased when the tissues were bathed in 80 mmol/l K+ and [Ca2+] was raised (10 mmol/l). If it is assumed that ryanodine acts exclusively to enhance the permeability of the sarcoplasmic reticulum in smooth muscle, these data suggest that noradrenaline-induced tone is partly due to inhibition of Ca2+ buffering in the sarcoplasmic reticulum. However, this action of noradrenaline is not as pronounced in the resistance arteries as it is in the rabbit aorta. 12-O-tetradecanoyl phorbol-13-acetate had no effect on the noradrenaline-induced contractions of the intact resistance arteries, but caused a large leftward shift in the relationship between tension and extracellular [Ca2+] when high-K+ depolarization was the stimulus. This increased sensitivity to extracellular [Ca2+] could not be explained by stimulation of the Ca2+ influx. Instead, application of TPA to the rings made permeable with alpha-toxin dramatically increased the myofilament sensitivity to Ca2+, as demonstrated by a shift to the left of the tension-intracellular-[Ca2+] curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Selective blockade of alpha 1-adrenoceptors of porcine vascular smooth muscle cells by bunazosin.

The characteristics of bunazosin binding to alpha-adrenoceptors in the porcine aortic membranes were investigated using [3H]prazosin and [3H]yohimbine binding assays to identify alpha 1- and alpha 2-adrenoceptors, respectively. The extent of the inhibition (Ki values) of [3H]prazosin binding to alpha 1-adrenoceptors induced by bunazosin was 0.29 nmol/l and about the same as that induced by prazosin (Ki = 0.10 nmol/l). The Ki value of bunazosin inhibition of [3H]yohimbine binding to alpha 2-adrenoceptors was 350 nmol/l. There was over a 1000-fold difference in Ki value for bunazosin between alpha 1-and alpha 2-adrenoceptors. Thus, bunazosin is a highly alpha 1 selective agent in vascular smooth muscle.

Adrenergic alpha-Antagonists↗

PubMed1989

[Rapid bone marrow dissemination of gastrointestinal lymphomas after surgical resection].

We describe two cases of gastrointestinal lymphoma associated with rapid bone marrow dissemination after surgical resection. Case 1: A 73-year-old male was diagnosed as having malignant lymphoma originating from ileocaecal region (diffuse medium-sized, B cell type). Tumor (8 x 8 cm) was resected but infiltrated to the peritoneum and curative operation could not be done. Two weeks after operation, elevation of LDH, pancytopenia and bone marrow infiltration of lymphoma cells developed and he died of respiratory failure. Case 2: A 69-year-old female was diagnosed as having remnant gastric lymphoma (diffuse large, B cell type). Tumor size was 5 x 4 cm and swelling of the third lymph nodes was found, so curative operation could not be done. Two months after operation bone marrow infiltration of lymphoma cells was observed and she is now undergoing chemotherapy. Surgical resection is performed in the majority of patients with localized gastrointestinal lymphoma. But the operation of the advanced case must be carefully done, because the operative procedure may sometimes facilitate growth and metastasis of tumor.

Aged↗

PubMed1989

[Appearance of chromosomally normal hemopoiesis during busulfan-induced remission in a case of Ph1 positive chronic myelogenous leukemia].

A 33-year-old female was admitted to St. Marianna University hospital in April 1983 for the purpose of examination for leukocytosis. Physical examination revealed a marked splenomegaly. The white cell count was 174 x 10(9)/l. The hemoglobin was 9.0 g/dl and the platelet was 790 x 10(9)/l. Microscopical examination of aspirated specimen of bone marrow revealed hypercellularity with granulocytic hyperplasia. The chromosomal analysis of bone marrow cells showed Philadelphia chromosomes in all metaphases analyzed. The neutrophil alkaline phosphatase activity was reduced. A diagnosis of CML was made. She was treated with busulfan in a dose of 2 mg/day until the white cell count was 14.5 x 10(9)/l. She has been followed without any therapy and clinical remission state has been continued. In April 1985, the chromosomal analysis of bone marrow cells revealed the recovery of normal karyotype hemopoiesis in 57% of metaphases analyzed. These findings of this case suggest that some of Ph1-positive cells may reduce their growth advantage over normal cells without any bone marrow hypoplasia.

Adult↗

PubMed1989

[Adult T-cell leukemia with vertebral bone tumor and acute transverse myelopathy].

We describe a case of adult T-cell leukemia (ATL) with vertebral bone invasion, who developed acute paraplegia and responded well to irradiation and combined chemotherapy. A 36-year-old man born in Tsushima Island was admitted to our hospital in May 1987, because of a sudden onset of paraplegia, hypesthesia below the level of 7th thoracic vertebra and vesicorectal disturbance. The white blood cell count was 9,500/microliter with 16% of abnormal lymphocytes showing lobulated nuclei. The surface marker analysis revealed that CD3, CD4, CD8 and CD25 positive cells were 88.1, 83.9, 6.4 and 1.3% of the peripheral mononuclear cells, respectively. Anti-ATLA antibody was positive. Serum calcium level was elevated. Bone scintigraphy showed multiple vertebral bone lesions. Vertebral bone mass and a compressed spinal cord in the 7th thoracic level were confirmed by CT scanning and MR imaging. Cerebral spinal fluid was negative for tumor cells. A diagnosis of ATL was made. Irradiation and combination chemotherapy improved bone lesions and neurological signs and the disease was well controlled by maintenance chemotherapy up to the present (August, 1988).

Acute Disease↗

PubMed1988

Norepinephrine and GTP-gamma-S increase myofilament Ca2+ sensitivity in alpha-toxin permeabilized arterial smooth muscle.

A new method for preparing permeabilized smooth muscle fibers from rabbit mesenteric artery has been developed using alpha-toxin, a transmembrane pore-making exo-protein produced by Staphylococcus aureus. After alpha-toxin treatment the fibers developed tension as a function of Ca2+ concentration (EC50 = 890 nM). But they could not contract without added ATP, indicating ATP is permeable. When the sarcoplasmic reticulum was loaded with 5 X 10(-7) M Ca2+ solution, NE induced a transient contraction in 2 mM EGTA 0 M Ca2+ solution and a transient and maintained contraction in 5 X 10(-7) M Ca2+ solution. GTP-gamma-S, a non-hydrolyzable analogue of GTP, substituted for NE in producing these contractile effects. The analysis of the relationship between Ca2+ and maintained tension revealed that NE and GTP-gamma-S cause increases in Ca2+ sensitivity of myofilament shifting the EC50 to 280 nM and 160 nM, respectively. We conclude that NE or GTP-gamma-S causes an increase in myofilament Ca2+ sensitivity and that G protein may be involved in receptor signal transduction system. alpha-Toxin is a useful tool to permeabilize the smooth muscle tissue to ions and small molecules without any damage of receptor and signal transduction system.

Animals↗

PubMed1988

Regulation of biosynthesis and phosphorylation of P210bcr/abl protein during differentiation induction of K 562 cells.

The changes of P210bcr/abl and other tyrosine phosphorylated proteins in K562 cells during growth and differentiation were studied by metabolic labeling with 32PO4 and immunoprecipitation with anti-phosphotyrosine sera. The anti-phosphotyrosine sera recognized P210bcr/abl and other phosphoproteins with mol wt of 150, 115, 100, 70 and 64 kD. The 2-day incubation of K562 cells with inducers for differentiation, hemin, sodium butyrate and TPA, decreased the level of P210bcr/abl protein and other phosphoproteins. Inhibitors of tyrosine protein kinase, amiloride and genistein, also reduced the phosphorylation of P210bcr/abl protein and other substrates, but did not induce differentiation of the cells. Although most of these additives inhibited the cell growth, cytotoxic agents such as adriamycin, vincristine and Ara-C did not affect the level of P210bcr/abl protein. The experiments using 35S-methionine labeled cells and the immunoprecipitation with anti-abl sera suggested that reduced biosynthesis but not dephosphorylation of P210bcr/abl protein mainly accounted for the reduction of P210bcr/abl protein reacting to anti-phosphotyrosine sera in differentiation-induced cells. These results indicate that the reduction of P210bcr/abl protein synthesis plays some roles in cellular differentiation of K562 cells.

Cell Differentiation↗

PubMed1988

Difference of bone marrow adipocyte colony-forming capacity between aplastic anemia and iron deficiency anemia.

The bone marrow adipocyte colony-forming capacity (Adipo-CFC) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) and iron deficiency anemia (IDA) was studied. Before treatment, Adipo-CFC in IDA was higher than that in AA and MDS. After treatment, Adipo-CFC decreased in IDA, but it increased in AA and MDS only at the responsive stage. In this context, it is suggested that increase of Adipo-CFC occurs during not only regenerating hemopoiesis but also accelerated erythropoiesis such as severe IDA. Colony-stimulating activity (CSA) production by marrow stromal cells (MSC) in AA was lower than that in normal subjects. Low Adipo-CFC and defective CSA production by MSC may explain in part the pathogenesis of microenvironmental defect in AA.

Adipose Tissue↗

PubMed1988

Hematopoietic growth factors (BPA and Epo) induce the expressions of c-myc and c-fos proto-oncogenes in normal human erythroid progenitors.

We investigated serial expressions of eight proto-oncogenes during in-vitro differentiation of normal human burst-forming unit, erythroid (BFU-E), and found that c-myc and c-fos are expressed in progenies of BFU-E. The expressions of the two proto-oncogenes correlated to the replating efficiency and adversely to erythroid differentiation. The absence of hematopoietic growth factors decreased the expressions, but the addition of erythropoietin together with burst promoting activity induced a re-expression of the c-myc and c-fos after 2 h of incubation. These observations suggest that the c-myc and c-fos proto-oncogenes have a physiological role in the proliferation of erythroid progenitors and that activations of the two proto-oncogenes are early cellular events after the stimulation by hematopoietic growth factors.

Cell Differentiation↗

PubMed1988

Specific phosphorylation of 22-kD proteins by various inducers for granuloid differentiation in myeloid leukemic cells.

We studied the changes of protein phosphorylation in human leukemic cells by granuloid inducers, using two-dimensional electrophoresis. The phosphorylation of 22 kD, pI 6.0 and 5.8 proteins (pp22) in HL-60 cells or myeloid leukemic cells from patients, was enhanced by treatment with granuloid inducers such as retinoic acid, dimethyl sulfoxide or G-CSF, in common with prostaglandin E2 and theophylline, or dibutyryl c-AMP, which increased intracellular c-AMP. In contrast, pp22 phosphorylation was not induced by the monocytes/macrophages inducer in HL-60 cells, or by the granuloid inducers in lymphoid cells. This phosphorylation occurred within 30 min and continued for more than 48 h. These pp22 proteins were present in the cytosol and phosphorylated on the serine residues. We now present a possibility that granuloid differentiation in myeloid cells is closely linked with these pp22 phosphorylation.

Cell Differentiation↗

PubMed1988

Possible mechanism of ineffective erythropoiesis by an altered transferrin receptor cycle in erythroleukemia.

Involvement of the transferrin receptor cycle was noted in erythroblasts from a patient with erythroleukemia (FAB classification M6). The kinetics of transferrin receptor cycle in bone marrow erythroblasts was obtained by pulse-chase experiments before the initiation of therapy. Internalization of transferrin was impaired and resulted in a delayed peak of internalized transferrin, as compared with the kinetics pattern seen in healthy subjects. The subsequent exocytosis of the internalized ligand was also delayed. Thus, transferrin receptor cycle seems to be influenced all along the transferrin pathway, hence transferrin travels more slowly in erythroblasts in erythroleukemia. The altered transferrin receptor cycle led to a diminished iron uptake per surface transferrin receptor (approximately 30% of that in healthy subjects), and the incorporation of iron into heme was greatly reduced. Our observations suggest a possible role for the altered transferrin receptor cycle in the pathogenesis of defective heme synthesis and ineffective erythropoiesis in erythroleukemia.

Endocytosis↗

PubMed1988

Hydrocortisone modulates colony-stimulating activity produced by human bone marrow-derived adherent cells.

In an attempt to clarify the significance of hydrocortisone (HC) in human long-term bone marrow cultures, the production of colony-stimulating activity (CSA) and colony-enhancing activity (CEA) by human bone marrow-derived adherent cells (MDAC) and the modulation by HC were examined. The CSA production by MDAC was demonstrated using bilayer agar cultures. After treatment of MDAC with 10(-6) mol/l HC, the CSA production was markedly enhanced, and after treatment of macrophages with 10(-6) mol/l HC, the CSA production was inhibited. When added to a granulocyte-macrophage precursor cells (CFU-GM) assay system, HC inhibited colony formation. These results suggest that HC treatment directly stimulates CSA production by nonmacrophage cells of MDAC. The conditioned medium of the confluent layer of MDAC contained CEA, which was not influenced by the HC treatment of MDAC. Thus, HC plays an essential role in granulopoiesis in vitro, enhancing the CSA production by MDAC and inhibiting the differentiation of CFU-GM.

Bone Marrow↗