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J Nishimura

Publications and source records attributed to J Nishimura.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Perioperative considerations for a holoprosencephaly patient].

We had twelve anesthetic experiences of seven holoprosencephaly patients for the past thirteen years. We classified these seven patients and compared the difficulty in perioperative control in the patients. Seven patients were divided according to two different holoprosencephaly classifications, one is that by DeMyer and the other by Osaka. We studied them retrospectively about airway management, the control of convulsion or instability of body temperature, and so on. Case of abortive type had nothing particular to be considered about, but cases of semilober type which had more severe brain anomaly, required careful respiratory management, due to their immature nasopharyngeal function. Concerning the convulsion or body temperature, cases of semilober type were difficult to control. When we anesthetize these holoprosencephaly patients, we must consider the classification of the anomaly and clinical conditions in each case. Especially, in cases of semilober types, prudent treatment is needed thoughout the perioperative period.

Anesthesia↗
PubMed1998

Mechanisms of vasorelaxation induced by troglitazone, a novel antidiabetic drug, in the porcine coronary artery.

BACKGROUND: Troglitazone (TRO), a novel antidiabetic drug, has been reported to decrease blood pressure and relax vascular strips. The mechanism of relaxation induced by TRO was determined in terms of Ca2+ signaling in smooth muscle cells. METHODS AND RESULTS: Front-surface fluorometry and fura 2-loaded medial strips of porcine coronary artery were used to examine the effects of TRO on cytosolic Ca2+ concentrations ([Ca2+]i) and contractions. The sustained contraction induced by 100 nmol/L U46619 was similar to that induced by 60 mmol/L K+ depolarization (60K+). TRO concentration dependently decreased [Ca2+]i and the force of these contractions. The concentration of TRO required to induce 50% inhibition of U46619-induced force (2.9 micromol/L) was significantly lower than that required in the case of 60K+-induced force (7.3 micromol/L). Replacing extracellular Ca2+ with Mn2+ gradually quenched fluorescence at 360 nm excitation. This decline was accelerated by 100 nmol/L U46619 and 30K+ to a similar extent, indicating a similar activation of Ca2+ influx. TRO completely inhibited U46619-activated influx but partly inhibited depolarization-activated influx. Cumulative applications of extracellular Ca2+ during stimulations with U46619 or 118K+ induced stepwise increases in [Ca2+]i and force. TRO shifted the [Ca2+]i-force relation to the right during both stimulations. CONCLUSIONS: TRO relaxes coronary artery by decreasing [Ca2+]i and Ca2+ sensitivity of contractile apparatus. Inhibition of Ca2+ influx was important in decreasing [Ca2+]i. TRO more effectively inhibits receptor-operated Ca2+ influx than voltage-operated Ca2+ channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

The PIG-A mutation and absence of glycosylphosphatidylinositol-linked proteins do not confer resistance to apoptosis in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder characterized by complement-mediated hemolysis and deficient hematopoiesis. The development of PNH involves an acquired mutation in the X-linked PIG-A gene, which leads to incomplete bioassembly of glycosylphosphatidylinositol (GPI) anchors and absent or reduced surface expression of GPI-linked proteins. The origin and mechanisms by which the PNH clone becomes dominant are not well understood, but recently resistance to apoptosis has been postulated. To test the hypothesis that the PIG-A mutation and absence of GPI-linked surface proteins directly confer resistance to apoptosis, we isolated peripheral granulocytes from 26 patients with PNH and 20 normal controls and measured apoptosis induced by serum starvation. Granulocytes from patients with PNH were relatively resistant to apoptosis (38.8% +/- 14.1%) as compared with granulocytes from controls (55.0% +/- 12.0%, P < .001). However, this resistance to apoptosis was not related to the dominance of the PNH clone because patients with a low percentage of GPI-deficient granulocytes had a similar rate of apoptosis as those with a high percentage of GPI-deficient granulocytes. Similarly, the resistance to granulocyte apoptosis was not influenced by the degree of neutropenia or a prior history of aplastic anemia. To investigate formally the importance of GPI-linked surface proteins in apoptosis, we introduced the PIG-A cDNA sequence into the JY5 GPI-negative B-lymphoblastoid cell line using two different methods: (1) stable transfection of a plasmid containing PIG-A, and (2) stable transduction of a retroviral vector containing PIG-A. We then measured rates of apoptosis induced either by Fas antibody, serum starvation, or gamma-irradiation. With each stimulus, apoptosis of JY5 with stable surface expression of GPI-linked proteins was not statistically different from the parent JY5 cell line or the JY25 (GPI-positive) cell line. Our data confirm that granulocytes from patients with PNH have a relative resistance to apoptosis as compared with normal granulocytes. However, this resistance does not vary with the level of expression of GPI-linked proteins, and stable introduction of PIG-A cDNA with correction of GPI-linked surface expression does not change the rate of apoptosis. Taken together, our data do not support the hypothesis that the PIG-A mutation and absence of GPI-linked surface proteins directly confer resistance to apoptosis in PNH. We conclude that the resistance to apoptosis in PNH is not related to the PIG-A mutation, indicating that other factors must be important in the origin of this phenomenon and the clonal dominance observed in PNH.

Adolescent↗
PubMed1998

Mechanism of endothelium-dependent relaxation induced by thrombin in the pig coronary artery.

The mechanism of thrombin-induced endothelium-dependent relaxation was investigated using fura-2 front-surface fluorometry. Thrombin induced an endothelium-dependent relaxation during U46619-induced contractions in pig coronary arterial strips. The relaxation consisted of two components: the early phasic component with a transient decrease in [Ca2+]i of smooth muscle and the subsequent sustained tonic component without [Ca2+]i decrease. The phasic relaxation was inhibited by a combination of N(omega)-nitro-L-arginine and K+-depolarization, while the tonic component was inhibited by either indomethacin or K+-depolarization. Thrombin induced a transient [Ca2+]i increase and nitric oxide (NO) production in pig aortic valvular endothelial cells, which expressed NO synthase as determined by reverse transcription and polymerase chain reaction. Thus, it was concluded that NO and hyperpolarizing factor were involved in the phasic component of thrombin-induced relaxation and that hyperpolarizing factor and prostacyclin were involved in the tonic component.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Previously undescribed spondyloepiphyseal dysplasia associated with craniosynostosis, cataracts, cleft palate, and mental retardation: report of four sibs.

We report on four Japanese sibs (three brothers and one sister) with a previously unreported syndrome of spondyloepiphyseal dysplasia, craniosynostosis, cataracts, cleft palate, and mental retardation. Most clinical manifestations were evident neonatally, but skeletal changes and cataracts became substantial in early childhood. Radiological anomalies comprised coronal synostosis, mild epiphyseal dysplasia, particularly in the distal tibiae, strikingly delayed patellar ossification, mild metaphyseal splaying, hypoplastic ilia with iliac flare, and platyspondyly with ovoid-shaped or posteriorly humped vertebral bodies. The nonconsanguineous parents were mildly mentally retarded, and sibs of both gender were equally affected; thus, inheritance was likely autosomal recessive.

Abnormalities, Multiple↗
PubMed1998

Differential effects of Ca2+ channel blockers on Ca2+ transients and cell cycle progression in vascular smooth muscle cells.

We examined the differential effects of Ca2+ channel blockers on the elevation of the cytosolic Ca2+ concentration ([Ca2+]i) and G0/G1 transition induced by platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells in primary culture. The phase of the cell cycle was determined by an immunocytochemical analysis of cell cycle-specific nuclear antigens. [Ca2+]i was monitored by fura-2 microfluorometry. The efficacy of Ca2+ channel blockers for the inhibition of [Ca2+]i elevation induced by PDGF (NiCl2 > isradipine > verapamil = diltiazem) did not parallel that for the inhibition of cell cycle progression induced by PDGF (verapamil = diltiazem > NiCl2 > isradipine). In addition, no significant correlation was observed between the extent of [Ca2+]i elevation and the extent of G0/G1 transition. We thus conclude that the inhibitory effects of Ca2+ channel blockers on the G0)/G1 transition induced by PDGF are not simply due to their inhibitory action on the [Ca2+]i elevations but instead are due to more complex unknown factors.

Animals↗
PubMed1998

Expression and function of alpha1-adrenoceptor subtypes in the porcine renal artery.

We investigated the expression and function of alpha1-adrenoceptor subtypes in the porcine renal artery. Reverse transcription polymerase chain reaction (RT-PCR) and nucleotide sequencing indicated that the mRNAs for alpha1a- and alpha1b-adrenoceptors were expressed in the porcine renal artery. Chloroethylclonidine, an alpha1B- and alpha1D-adrenoceptor antagonist, partially inhibited the phenylephrine-induced contraction, while 3 nM BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]dec ane-7,9-dione dihydrochloride), an alpha1D-adrenoceptor antagonist, had no effect. In contrast, 5-methylurapidil, an alpha1A-adrenoceptor antagonist, induced a rightward shift of the phenylephrine concentration-response curve. The simultaneous measurement of cytosolic Ca2+ concentration ([Ca2+]i) and tension revealed that chloroethylclonidine pretreatment abolished the phenylephrine-induced increases in [Ca2+]i and tension in the Ca2+-free solution. The application of 5-methylurapidil (3 nM) to the chloroethylclonidine-pretreated strips completely inhibited the 3 microM phenylephrine-induced [Ca2+]i and tension increase in normal PSS. We concluded that both alpha1A- and alpha1B-adrenoceptors mediate the phenylephrine-induced contraction of the porcine renal artery accompanied by an increase in [Ca2+]i, and that alpha1A-adrenoceptors cause Ca2+ influx whereas alpha1B-adrenoceptors mainly mediate Ca2+ release.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1998

Establishment of a novel B cell clonality analysis using single-strand conformation polymorphism of immunoglobulin light chain messenger signals.

The remarkable diversity of the complementarity determining region (CDR) 3 of the immunoglobulin (Ig) heavy (H) chain gene rearrangements has been exploited to identify the clonal populations of B cells in B cell malignancies. However, when B cell malignancies of different categories were examined, the overall detection rate was found to be approximately 70%. The development of a simple clonality analysis using Ig light (L) chain CDR3 diversity has been hampered due to the sparseness of knowledge regarding the sequence of Vkappa and Vlambda gene segments and the restriction of L chain CDR3 length. Based on the recently reported Vkappa and Vlambda gene sequences, we designed Vkappa and Vlambda framework 3 consensus primers. We combined the reverse transcriptase polymerase chain reaction (RT-PCR) of IgL chain transcripts with a single-strand conformation polymorphism (SSCP) analysis and then analyzed samples from patients with B cell malignancies. Clonal B cell populations were detected as discrete bands, and identical clones showed a similar mobility in a RT-PCR SSCP analysis. This method was thus found to be a useful supplement to the previously described approach of VH gene amplification for detecting clonal B cell populations. By using SSCP, we were able to determine the clonal identities of B cell expansion in different samples.

Arthritis, Rheumatoid↗
PubMed1998

Expression of beta3-adrenoceptors in rat detrusor smooth muscle.

PURPOSE: To investigate the expression of beta-adrenoceptor (AR) subtypes responsible for detrusor smooth muscle relaxation. MATERIALS AND METHODS: Isolated rat detrusor smooth muscle was examined by tension measurement and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Norepinephrine (NE), epinephrine (EP) and isoproterenol (ISO) were found to relax the detrusor muscle pre-contracted by 6 x 10(-7) M carbachol in the presence of 10(-6) M phentolamine. NE relaxed the detrusor muscle as potently as EP. This potency order (NE=EP) thus indicated the beta-ARs of the rat detrusor muscle to possibly be a beta1 subtype. However, in the presence of 10(-6) M propranolol, beta1- and beta2- but not beta3-AR antagonist, NE showed a more potent relaxation than EP. This observation indicated that the rat detrusor muscle also possesses beta3-AR. RT-PCR revealed all three subtypes of beta-AR mRNA, namely beta1-, beta2- and beta3-AR mRNA, to be expressed in rat detrusor smooth muscle cells. CONCLUSION: We concluded that beta3-ARs exist in rat detrusor smooth muscle based on both pharmacological and molecular biological studies. Based on these findings, beta-ARs of rat detrusor smooth muscle are considered to be mixed populations consisting of three subtypes which play an important role in relaxing smooth muscle in response to catecholamines.

Animals↗
PubMed1998

Mechanisms of galanin-induced contraction in the rat myometrium.

A neuropeptide, galanin, regulates the reproductive process and directly induces myometrial contraction. The aim of this study was to determine the mechanism of galanin-induced myometrial contraction. For this purpose, we simultaneously measured intracellular Ca2+ concentration ([Ca2+]i) and tension using fura-PE3-fluorometry and the rat longitudinal myometrium. The effect of galanin on the Ca2+ sensitivity of the contractile apparatus was examined in beta-escin permeabilized strips. The expression of galanin and the galanin receptors mRNAs in the rat myometrium were determined by reverse transcription polymerase chain reaction (RT-PCR). Galanin (10-300 nM) induced phasic contraction with or without oscillation in the pregnant rat myometrium in a concentration-dependent manner. The maximal response was obtained at 100 nM. There was no significant difference either in the maximal responses or EC50 values for galanin-induced myometrial contractions among myometriums from non-pregnant and pregnant (day 4, day 11, day 20, day 22) rats. In the day 20 and 22 pregnant myometriums, assigning the levels of [Ca2+]i and tension at 40 mM K+-depolarization to be 100%, galanin increased the [Ca2+]i and tension to 126.9+/-2.9% and 116.3+/-2.7%, respectively. Diltiazem (10 microM) inhibited the galanin-induced elevation of [Ca2+]i and tension to 71.9+/-2.4% and 16.2+/-0.7%, respectively. Ni2+, by itself, decreased the basal [Ca2+]i to -50.2+/-3.9% without affecting resting tension. After Ni2+ treatment, galanin-induced increases in [Ca2+]i and tension were -19.6+/-3.4% and 0.9+/-0.1%, respectively. In myometrium treated with diltiazem, no oscillation in [Ca2+]i and tension was observed. In Ca2+-free solution with 0.1 mM EGTA, galanin increased [Ca2+]i from -40.2+/-2.7% to -18.0+/-2.6% and induced transient contraction (3.6+/-0.8%). In beta-escin permeabilized myometrium, galanin enhanced the contraction induced by 0.3 microM Ca2+ in the presence of GTP. In the presence of GDPbetaS (1 mM) instead of GTP, galanin failed to increase the Ca2+ sensitivity of the contractile apparatus. RT-PCR revealed that galanin mRNA was hardly expressed in the non-pregnant rat myometrium and increased to reach a maximal level at mid pregnancy (day 11), but decreased to the same level as in the non-pregnant myometrium at term (day 22). Type 2 galanin receptor (GALR2) mRNA was found to be expressed in the rat myometrium whereas type 1 galanin receptor (GALR1) mRNA expression was not detected. In conclusion, galanin induces contraction of the rat myometrium by increasing [Ca2+]i as well as by increasing Ca2+ sensitivity of the contractile apparatus. Galanin-induced increases in [Ca2+]i are caused by both intracellular Ca2+ release and Ca2+ influx from extracellular space. The responsiveness of the rat myometrium to galanin does not change during pregnancy. The galanin mRNA is expressed in the rat myometrium and it is upregulated during mid-pregnancy. Rat myometrium expresses GALR2 but not GALR1 mRNA. By changing mRNA expression in the myometrium during pregnancy, galanin may act as a paracrine or autocrine mediator in the regulation of myometrial contractility.

Animals↗
PubMed1998

[Partial splenic embolization as a preoperative treatment for refractory idiopathic thrombocytopenic purpura].

A 53-year-old woman presented with idiopathic thrombocytopenic purpura (ITP) that was refractory to corticosteroid therapy. Her bleeding had worsened gradually due to prolonged thrombocytopenia, but her low platelet count after high-dose intravenous gamma globulin therapy contraindicated a splenectomy. We therefore decided to perform a partial splenic embolization (PSE). The patient's platelet count increased gradually thereafter, allowing us to safely perform a splenectomy. We concluded that PSE is a useful preoperative procedure, especially for patients with ITP that is refractory to high-dose intravenous gamma-globulin therapy. Moreover, it is possible to predict the effects of a splenectomy preoperatively if the PSE procedure is used.

Embolization, Therapeutic↗
PubMed1998

[Basophilia].

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Basophils↗
PubMed1998

[Basophilopenia].

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Basophils↗
PubMed1998

Paroxysmal nocturnal hemoglobinuria: molecular pathogenesis and molecular therapeutic approaches.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic stem cell disorder classified as an intravascular hemolytic anemia. Abnormal blood cells are deficient in glycosylphosphatidyl inositol (GPI)-anchored proteins. Deficiencies of GPI-anchored complement regulatory proteins, such as decay accelerating factor (DAF) and CD59, render red cells very sensitive to complement and result in complement-mediated hemolysis and hemoglobinuria. In the affected hematopoietic cells from patients with PNH, the first step in biosynthesis of the GPI anchor is defective. Three genes are involved in this reaction step and one of them, an X-linked gene termed PIG-A, is mutated in affected cells. Granulocytes and lymphocytes from the same patient have the same mutation, indicating that a somatic PIG-A mutation occurs in hematopoietic stem cells. The PIG-A gene is mutated in all patients with PNH reported to date. We review these recent advances in the understanding of the molecular pathogenesis of PNH. Furthermore, we present an hypothesis regarding the predominance of the PNH clone, caused by positive selection by hematopoietic suppressive cytokines, such as transforming growth factor (TGF)-beta. In addition, we discuss the possibility of cure for PNH through molecular therapeutic strategy using gene transfer techniques. (Key words: paroxysmal nocturnal hemoglobinuria, glycosylphosphatidylinositol-anchored proteins, PIG-A, clonal dominance, growth advantage, transforming growth factor-beta, gene therapy, molecular therapeutic approach).

Hemoglobinuria, Paroxysmal↗