Biomedical subjects

J Nishimura

Publications and source records attributed to J Nishimura.

At least 127 records · Page 7Linked to original sources

PubMed1989

Direct regulation of smooth muscle contractile elements by second messengers.

The effects of adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP) and phorbol 12,13 dibutyrate (PDBu) on the Ca2+ sensitivity of the contractile elements in the rat mesenteric artery were investigated, using a method of permeabilizing smooth muscle with Staphylococcal alpha-toxin. Both cAMP and cGMP relaxed the permeabilized rat mesenteric artery at the intracellular Ca2+ concentrations [( Ca2+]i) held constant with Ca2+ EGTA buffer and Ca2+ ionophore, ionomycin. In addition, forskolin and sodium nitroprusside which activate adenylate and guanylate cyclases, respectively, also induced relaxation at a fixed [Ca2+]i. In contrast PDBu which stimulates protein kinase C caused an increase in force at a constant [Ca2+]i which could be partially reversed by cAMP or cGMP. These results indicate that second messengers exert direct control over smooth muscle Ca2+ sensitivity of the contractile elements, which is of physiologic and pharmacologic importance.

Animals↗

PubMed1989

New galactosyllactose containing alpha-glycosidic linkage isolated from ovine (Booroola dorset) colostrum.

Three trisaccharides, tetra-, penta-, hexa- and certain higher oligosaccharides were obtained from ovine colostrum as free forms. The chemical structure of the three trisaccharides were determined by methylation and 13C-NMR analyses to be as follows: Gal alpha 1-3Gal beta 1-4Glc, Gal beta 1-3Gal beta 1-4Glc (3'-galactosyllactose) and Gal beta 1-6Gal beta 1-4Glc (6'-galactosyllactose). Gal alpha 1-3Gal beta 1-4Glc, which had been confirmed as the oligosaccharide portion of a glycolipid prepared biosynthetically from rat spleen or bone marrow, has been identified for the first time from natural sources as a free form. The trisaccharide containing alpha-galactosyl unit is a novel compound in mammalian milk.

Animals↗

PubMed1989

Down-regulation of a Mr 90,000 heat shock cognate protein during granulocytic differentiation in HL-60 human leukemia cells.

Modulation of the synthesis of heat shock proteins in HL-60 human promyelocytic leukemia cells during differentiation was studied by metabolic labeling with [35S]methionine and Northern blot analysis. HL-60 cells were found to synthesize constitutively a high level of a Mr 90,000 protein (heat shock cognate protein, hsc90), which was very closely related to Mr 90,000 heat shock protein, hsp90, as far as molecular weight, isoelectric point, peptide maps, immunoreactivity, and encoded mRNA were concerned. Differentiation induction by dimethyl sulfoxide markedly decreased the level of the hsc90 expression, but preserved the ability to preferentially express hsp90 in response to heat stress. These results suggest distinct regulatory mechanisms of the synthesis between hsc90 and hsp90 although they are indistinguishable by conventional protein or mRNA analysis, and indicate that hsc90 has some role in cell growth and differentiation.

Cell Differentiation↗

PubMed1989

Rejoining between 9q+ and Philadelphia chromosomes results in normal-looking chromosomes 9 and 22 in Ph1-negative chronic myelocytic leukemia.

Rearrangement of the breakpoint cluster region (bcr) and the chromosomal location of c-abl and 3'-bcr were studied in two patients with Philadelphia chromosome (Ph1)-negative chronic myelocytic leukemia (CML). One patient (patient 1) had a normal karyotype and the other (patient 2), 46,XY,inv(3)(q21q26). Both patients showed the bcr rearrangement by Southern blot analysis with a 1.2kb 3'-bcr probe. In situ hybridization studies demonstrated the location of the homologous sequences of bcr on chromosome 22 in patient 1, and on chromosomes 9 and 22 in patient 2. These findings indicate that the morphologically normal-looking chromosomes 9 and 22 in patient 2 are the result of a retranslocation between chromosomes 9q+ and 22q-, abnormalities which were first formed by a standard Ph1 translocation.

Adult↗

PubMed1989

Histamine-induced calcium transients in vascular smooth muscle cells: effects of verapamil and diltiazem.

We investigated the effects of verapamil and diltiazem on histamine-induced Ca2+ transients in vascular smooth muscle. 1) With the use of quin2 microfluorometry, cytosolic Ca2+ concentrations were directly measured in cultured vascular smooth muscle cells of the rat aorta. In the presence of extracellular Ca2+, histamine induced an elevation of cytosolic Ca2+ concentrations of a peak and plateau type. The peak component is due to a release of Ca2+ from cellular store sites, and the plateau component depends on extracellular Ca2+. Verapamil and diltiazem inhibited the plateau component, and the 50% inhibitive concentration (IC50) of verapamil and diltiazem for 10 microM histamine was 0.09 and 0.18 microM, respectively. Only at high concentrations did verapamil (IC50 = 8.7 microM) and diltiazem (IC50 = 95.7 microM) inhibit the Ca2+ release from the cellular store sites, as induced by 10 microM histamine. 2) Histamine, verapamil, and diltiazem competed with [3H]mepyramine for binding to the porcine aortic membranes, the order of potency being verapamil (Ki = 7.1 microM) greater than histamine (Ki = 18 microM) greater than diltiazem (Ki = 114 microM). From these results, we conclude that verapamil and diltiazem strongly inhibit the histamine-mediated, extracellular Ca2+-dependent intracellular [Ca2+] increase. In addition, verapamil and diltiazem seem to inhibit the release of Ca2+ from intracellular store sites, only at high concentrations, and probably by competing with histamine for binding to the H1-receptor. The inhibitory effects of Ca2+ antagonists on the histamine-induced contraction or spasm of vascular smooth muscle may well relate to these mechanisms.

Aminoquinolines↗

PubMed1989

Bone marrow stromal cells in myeloproliferative disorders.

The number of bone marrow-derived fibroblastoid colony-forming cells (CFU-F) and the production of colony-stimulating activity (CSA) by bone marrow stromal cells were studied in 71 patients with myeloproliferative disorders (MPD). The numbers of CFU-F in chronic-phase chronic myelogenous leukemia (CML), polycythemia vera (PV) and essential thrombocythemia (ET) were not different from those in normal subjects. However, the number of CFU-F in acute-phase CML was markedly decreased. Bone marrow adipocyte colony-forming capacity (adipo-CFC), which was previously shown to reflect both the number of preadipocytes and the stromal cell function in vivo, was increased in patients with chronic-phase CML, PV and ET, but was absent in acute-phase CML patients. The production of CSA by marrow stromal cells of MPD patients, however, was not different from that of normal subjects. These results suggest that the characteristics of marrow stromal and its precursor cells of chronic-phase MPD patients were not different from those of normal subjects, however, they became changed in acute-phase CML patients.

Adipose Tissue↗

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↗