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M Nishimura

Publications and source records attributed to M Nishimura.

At least 397 records · Page 22Linked to original sources

Diazepam-induced hyperphagia in mice is sensitive to quinpirole.

The present trial examined the possibility that diazepam (DZP, 1 mg/kg) induces hyperphagia by acting on the dopaminergic system. Quinpirole (QP), dopamine D-2 receptor agonist, was used for this purpose. Mice fasted for 24 hr were treated with QP 1 (QP-1) or 2 (QP-2) mg/kg 30 min prior to termination of the starvation. DZP was given to untreated mice and half of the QP-1 and QP-2 treated mice 10 min before the termination of the starvation. Food consumed during six 30 min intervals (30 min-feeding), food consumed for 3 hr (total feeding), time required to enter the room containing food by passing through a maze with four multiple routes (time to banquet), latent period to commencement of eating food after entering the banquet room (latent period), and feeding frequency for the 30 min intervals as well as for 3 hr were measured. DZP stimulated feeding, shortened the latent period without affecting the time to banquet and increased the feeding frequency. The hyperphagic effect was restricted to the first 30 min interval only. Both QP-1 and QP-2 first reduced, then progressively stimulated, and finally reduced feeding without modifying total feeding, thus making a bell-shaped profile. They also prolonged both the time to banquet and the latent period, and reduced the feeding frequency of the first 30 min interval but not that for 3 hr. Both QP-1 and QP-2 canceled all the effects of DZP. These results imply that dopamine D2 receptor is involved in the induction of hyperphagia by DZP.

Animals↗

Effects of inhaled bronchodilators on pulmonary hemodynamics at rest and during exercise in patients with COPD.

INTRODUCTION: Inhaled anticholinergic drugs are often recommended for use as a first-line therapy for patients with COPD because they provide similar or more effective bronchodilating actions, as well as fewer side effects. It is not known, however, which class of bronchodilators is more advantageous for pulmonary hemodynamics, particularly during exercise. OBJECTIVES: To compare the effects of oxitropium and fenoterol on pulmonary hemodynamics in patients with COPD at rest and during exercise. PATIENTS: The study participants consisted of 20 consecutive male patients with stable COPD, a mean (+/- SD) age of 68+/-8 years old, and an FEV1/FVC ratio of 47.5+/-10.0%. METHODS: Eleven patients inhaled two puffs of oxitropium, and nine patients inhaled two puffs of fenoterol. Seven members of each group performed incremental exercise using a cycle ergometer. The hemodynamic measurements with right heart catheterization were performed by taking the average of three consecutive respiratory cycles before and after the administration of inhaled bronchodilators at rest and during exercise. RESULTS: At rest, despite a similar improvement of spirometric data with the two drugs, fenoterol, not oxitropium, caused significant increases in heart rate and cardiac output, a decrease in pulmonary vascular resistance, and a deteriorated Pao2. During exercise, however, both drugs similarly attenuated elevations in the mean pulmonary arterial pressure (40+/-12 to 38+/-10 mm Hg by oxitropium, and 41+/-9 to 36+/-9 mm Hg by fenoterol), the mean pulmonary capillary wedge pressure, and the mean right atrial pressure. CONCLUSION: Our findings indicate that both classes of bronchodilators are equally beneficial in the attenuation of right heart afterload during exercise in patients with COPD.

Administration, Inhalation↗

Video-assisted thoracoscopic surgery for small indeterminate pulmonary nodules: indications for preoperative marking.

STUDY OBJECTIVE: To determine the indications for preoperative localization of a small indeterminate pulmonary nodule. DESIGN: In this retrospective study, univariate and multivariate analyses were performed by the logistic regression procedure. SETTING: A single National Cancer Center Hospital in Japan. PATIENTS: A series of 92 consecutive patients who underwent video-assisted thoracoscopic surgery (VATS) at our institute between 1993 and 1996. INTERVENTIONS: The frequency and reasons for conversion to thoracotomy were assessed retrospectively. All preoperative CT scans were reviewed for eight radiologic features by two of the authors. These data were entered into univariate and multivariate analyses to identify the significant risk factors for a failure to detect a pulmonary nodule. MEASUREMENTS AND RESULTS: Fifty patients (54%) needed conversion to a thoracotomy. The most common reason for the conversion was failure to localize nodules (46%). Univariate and multivariate analyses of 11 variables revealed one significant risk factor in the failure to detect nodules: distance to the nearest pleural surface (p < 0.05). Tumor size on radiograph remained marginally significant (p = 0.065) in multivariate analyses. If the distance to the pleural surface was > 5 mm in cases of nodules < or = 10 mm in size, the probability of failure to detect a nodule was 63%. CONCLUSIONS: Our results suggested the indications for preoperative localization of a peripheral pulmonary nodule. Preoperative marking for a small indeterminate pulmonary nodule should be considered when the distance to the nearest pleural surface is > 5 mm in cases of lung nodules of < or = 10 mm in size.

Adolescent↗

Effect of mild hypoxia on airway responsiveness to methacholine in subjects with airway hyperresponsiveness.

STUDY OBJECTIVES: The inhalation of hypoxic gas has been reported to enhance the airway responsiveness to methacholine in some animal models. However, the data on humans have so far been conflicting. We attempted to examine the effect of hypoxic gas inhalation on the airway responsiveness to methacholine. DESIGN: We evaluated the airway responsiveness to methacholine by continuously measuring respiratory conductance with the forced oscillation method under normoxia or hypoxia in a single-blind, randomized, crossover fashion (2 days for each). PARTICIPANTS: Twelve asymptomatic male volunteers (mean +/- SD age, 27 +/- 4 years) with airway hyperresponsiveness to methacholine. Two of the 12 volunteers had a history of bronchial asthma. SETTING: The participants inhaled either normoxic or hypoxic gas with continuous inhalation of aerosolized methacholine in incremental doses with a sustained respiratory rate of 15 breaths/min. The arterial oxygen saturation was kept to 90% on the hypoxic days. RESULTS: There were no significant differences in any indexes of airway responsiveness to methacholine (the cumulative dose of methacholine at the threshold and the point of 35% decrease of the respiratory conductance, and the slope factor of the dose-response curve) between the hypoxic days and the normoxic days. CONCLUSION: The inhalation of mildly hypoxic gas does not enhance the airway responsiveness to methacholine in humans with airway hyperresponsiveness.

Adult↗

Isolation of two novel alternative splicing variants of allograft inflammatory factor-1.

Allograft inflammatory factor-1 (AIF-1) was initially cloned from rat cardiac allografts undergoing chronic rejection. AIF-1, possessing an EF-hand-like motif, is thought to be a Ca2+ binding protein. In this study, we identified two novel alternatively spliced variants of AIF-1 by reverse-transcription polymerase chain reaction. One variant encodes an AIF-1 protein that lacks 14 amino acids corresponding to one exon. The other variant encodes a truncated AIF-1 protein due to a frameshift introduced by an 85-bp insertion, and its C-terminal region differs from that of AIF-1. Interestingly, these variants have incomplete and no EF-handlike motifs, respectively. The expression level of the latter variant is high in peripheral blood leukocytes, and it is selectively expressed in macrophage-like cell lines.

Alternative Splicing↗

[Chronic pulmonary thromboembolism diagnosed on the basis of characteristic mosaic patterns on lung computed tomograms].

We report on a 59-year-old woman who presented with characteristic findings on lung computed tomographic (CT) scans and was therefore suspected to have chronic pulmonary thromboembolism. She visited our hospital because of worsening exertional dyspnea over the preceding year, and because she was dissatisfied with an earlier diagnosis made by another institution. Chest roentgenograms disclosed nonhomogeneous hyperlucency in both lungs associated with linear and bundle shadows, dullness of the right costophrenic angle, and dilatation of the descending branch of the right pulmonary artery. The patient experienced moderate hypoxemia even at rest. Pulmonary function tests demonstrated a restrictive ventilatory pattern associated with reduced diffusion capacity. The lung CT scans disclosed a mosaic pattern of attenuation in the lung parenchyma, which probably reflected scattered areas of low perfusion. The unique characteristics of such CT findings drew our attention to chronic pulmonary thromboembolism as a possible diagnosis. We eventually confirmed the diagnosis on the basis of enhanced CT scans, pulmonary perfusion and ventilation scintigrams, and digital subtraction angiography. In our view, chronic pulmonary thromboembolism should be kept in mind as a possible differential diagnosis of the mosaic patterns of attenuation on lung CT scans.

Chronic Disease↗

[Efficacy and indications of home oxygen therapy for patients with chronic obstructive pulmonary disease].

Efficacy of home oxygen therapy (HOT) is well established for patients with chronic obstructive pulmonary disease who fall into chronic respiratory failure. We should consider now how the quality of life improves with HOT in those patients. According to the guideline of the Japanese Respiratory Society, indications of HOT are as follows: 1) A PaO2 of less than 55 Torr at rest while breathing room air, 2) A PaO2 between 55 Torr and 60 Torr in the presence of clear evidence of cor pulmonale, pulmonary hypertension, or a long history of severe hypoxemia during sleep or during exercise. Further studies are definitely required to pick up the patients who do not necessarily meet these indications but who may benefit from HOT.

Home Care Services↗

[Creatinine].

Explore the source record for details and available documents.

Adult↗

[An analysis of nutritional status and pulmonary hypertension in patients with sequela of pulmonary tuberculosis and chronic obstructive pulmonary disease].

The prognostic value of hypercapnia and/or pulmonary hypertension differs in patients with sequela of pulmonary tuberculosis (TBseq) and those with chronic obstructive pulmonary disease (COPD) who are receiving home oxygen therapy (HOT). In an attempt to identify the factors, if any, that might explain this difference, we first compared nutritional status, respiratory function test results, dyspnea indexes, and other data for hypercapnic patients (PaCO2 > or = 45 Torr) and normocapnic patients (PaCO2 < 45 Torr) receiving HOT. Second, we examined the relationship between the degree of pulmonary hypertension and several respiratory function parameters for patients in each disease category. In 44 patients with TBseq, nutritional status estimated by body mass index and serum albumin was significantly better in the hypercapnic patients than in the normocapnic patients. However, this difference was not observed in 37 patients with COPD. In 30 patients with TBseq, the degree of pulmonary hypertension correlated significantly only with PaO2; in 32 patients with COPD, however, significant correlations were observed not only with PaO2 but also with PaCO2, %VC, and FEV1. These differences distinguishing groups of patients with the 2 diseases may provide an explanatory basis for the difference in prognostic value of hypercapnia and/or pulmonary hypertension in patients receiving HOT.

Aged↗

[Evaluation of mortality of patients admitted to ICU for the last 12 years].

We evaluated mortality of 2689 patients admitted to the Intensive Care Unit, Osaka University Hospital from January, 1987 to December, 1998. The patients were divided into 3 groups. Group A consisted of 1408 patients who underwent cardiovascular surgery, group B, 1082 patients who underwent other surgical procedures and group C, 199 patients who were transferred from the department of medicine. We studied mortality rate, causes of death, correlation between length of ICU stay and mortality rate, and mortality rate among age groups for 12 years. The main causes of death were cardiac failure and sepsis in group A, and respiratory failure and sepsis in group B and C. Mortality rate in each group showed no significant change for the last 12 years. Those who stayed more than 2 weeks in ICU showed a significantly higher mortality rate (p < 0.0001). Thus, length of ICU stay and mortality rate showed a positive correlation (p < 0.0001). The youngest group (age 0-1) showed a significantly higher mortality rate than other age groups (p < 0.0001). As sepsis was the most important cause of death in all the groups, the prevention and treatment of infection are the most important issue in our ICU to reduce mortality rate.

Adolescent↗

Low frequency of Ras gene mutation in spontaneous and gamma-ray-induced thymic lymphomas of scid mice.

Scid mice, which have a defect in the capacity to repair DNA double-strand breaks, were highly prone to the induction of thymic lymphomas after exposure to ionizing radiation; approximately 70% of mice developed lymphomas within 1 year after exposure to 1-3 Gy, whereas approximately 20% of unirradiated control mice developed lymphomas. To gain information on the possible role of Ras activation in development of thymic lymphomas in scid mice, we have examined both the frequency and the spectrum of Kras and Nras mutations in spontaneous and radiation-induced lymphomas. Neither activated Kras nor Nras genes were detected in spontaneous lymphomas, while Kras mutations increased in a dose-dependent manner in radiation-induced lymphomas. However, Kras mutations were infrequent (6% in lymphomas in mice exposed to 1 Gy, 12.5% in those exposed to 2 Gy, 16.7% in those exposed to 3 Gy), and no mutations were detected in Nras genes, suggesting that Ras mutation was not significantly involved in the development of thymic lymphomas in scid mice. Analysis of the spectrum of Kras mutations demonstrated unique mutations in both codons 13 (GGC to GAC) and 61 (CAA to CTA) in addition to the commonly identified substitution of GAT for GGT in codon 12 of Kras.

Animals↗

HLA-DRB1 and tumor necrosis factor gene polymorphisms in Japanese patients with multiple sclerosis.

We studied genetic polymorphisms in the tumor necrosis factor (TNF) region as well as HLA-DRB1 of 42 patients with Western-type multiple sclerosis (MS) and 38 with Asian-type MS in Japan. The sex ratio (Female:Male) was significantly higher in Asian than in Western type MS (3.8 vs. 1.3, P = 0.038). The frequency of HLA-DRB1 * 1501 allele in the Western-type MS group increased significantly compared with the control group, while Asian-type MS and control groups showed similar distribution in the frequencies of HLA-DRB1 alleles. No significant differences existed in the TNF region, however, including TNF-a microsatellite alleles. The results suggest that MS in Asians may present two different clinical and immunogenetic manifestations.

Adult↗

In vivo transfer of a beta 2-adrenergic receptor gene into the pressure-overloaded rat heart enhances cardiac response to beta-adrenergic agonist.

BACKGROUND: In the failing heart, the density and affinity of beta-adrenergic receptors in the myocardium both tend to decrease as the severity of cardiac dysfunction increases. If this suppression of beta-adrenergic receptors could be prevented or reversed, this could serve as a fundamental form of treatment for the failing heart. We report here a possible new therapeutic approach for the failing heart involving the transfer of the beta 2-adrenergic receptor (B2AR) gene. METHODS AND RESULTS: The B2AR cDNA was transfected in vivo to the concentric hypertrophied rat heart by intracoronary infusion with a hemagglutinating virus of Japan liposome method, and the transfected heart was transplanted into the abdomen of another rat. Four days after transfection, the sarcolemma of the cardiomyocytes was well labeled by immunohistochemical labeling. An overexpression of BAR of approximately 5 times in the heart (140 +/- 35 versus 24 +/- 3 fmol/mg protein for the transfected versus control hearts) was demonstrated by a ligand binding assay. The cardiac response of the transfected heart to isoproterenol was shown to be enhanced in a Langendorff perfusion system: After isoproterenol, developed pressure and maximal derivative of the left ventricle were greater than in the control heart (260 +/- 20 versus 230 +/- 10 mm Hg and 5500 +/- 300 versus 4500 +/- 300 mm Hg/s), and the minimal derivative of the left ventricle was remarkably smaller (-4500 +/- 300 versus -3300 +/- 200 mm Hg/s). CONCLUSIONS: These results indicate that in vivo transfection of the gene for B2AR enhances the cardiac response to isoproterenol in the pressure-overloaded rat heart (in which the disease causes a decrease in receptor density), suggesting that transfer of this gene by intracoronary infusion during cardiac arrest has potential as a novel therapeutic approach for failing hearts.

Adrenergic beta-Agonists↗

Endogenous nitric oxide inhibits glucose-induced insulin secretion by suppression of phosphofructokinase activity in pancreatic islets.

The physiological role of nitric oxide (NO) on the mechanism of insulin secretion is unknown, but some studies suggest that NO affects glucose metabolism in pancreatic beta-cells. We have aimed at clarifying the physiological role of endogenous NO and its target in the glucose metabolism of beta-cells. The expression of brain-type NO synthase (bNOS) was detected in pancreatic islets by Western blotting. Under the condition of elevated intracellular Ca2+ concentration induced in the beta-cells by high glucose and forced depolarization by 40 mM K+, the generation of NO from the islets was enhanced. This increase was suppressed by the NOS blockers, N-iminoethyl-l-ornithine (L-NIO), and exposure to Ca2+-free extracellular solution. In addition, the NOS blockers L-NIO and 7-nitro indazole (7-NI) enhanced glucose-induced but not glyceraldehyde- or KIC-induced insulin secretion. In an in vitro enzyme study, the NO donor sodium nitroprusside (SNP) suppressed phosphofructokinase activity and activated glucokinase and glucose-6-phosphate isomerase activity, but SNP significantly inhibited the combined activity of the enzymes. This suggests that endogenous NO has an inhibitory role on insulin release induced by glucose and that its underlying mechanism is the suppression of phosphofructokinase activity in glycolysis.

Animals↗

Vasculitis-susceptible genes in mice with a deficit in Fas-mediated apoptosis.

Autoimmune diseases show complex pathological manifestations, which frequently involve systemic vasculitis. This complication is understood to be a manifestation of advanced disease, or to represent distinct entities, restricted by genetic and/or environmental factors. An MRL/Mp strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop systemic vasculitis coincidentally with glomerulonephritis, arthritis and sialoadenitis, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. Thus, this is a suitable model for analyzing the genetic basis of vasculitis in autoimmune diseases. To genetically dissect these complex pathological manifestations, a linkage analysis of each lesion with polymorphic microsatellite markers was performed by using MRL/lpr x (MRL/lpr x C3H/lpr)F1 backcross mice. Vasculitis-susceptible gene loci were mapped on chromosomes 3 and 4, which were not associated with glomerulonephritis, arthritis and sialoadenitis. These results indicate that systemic vasculitis in MRL/lpr mice may be under the control of host genes which are different from those for other autoimmune diseases.

Animals↗

Ouabain suppresses ATP elevation in response to fuel secretagogues in pancreatic islets.

The alterations of the ATP concentration in response to fuel secretagogues such as glucose, glyceraldehyde, and ketoisocaproate (KIC) were investigated in a single islet. The intraislet ATP concentration was transiently elevated and then decreased to a level slightly higher than basal. To asses the ATP content under conditions of reduced ATP consumption, the Na-K pump blocker ouabain was used. The elevation of ATP concentration was found unexpectedly to be suppressed under ouabain in the islet, even when incubated with any of the secretagogues. High glucose did not elevate the intracellular creatine phosphate during incubation with ouabain. Since the suppression rate for the intraislet ATP elevation was considerably smaller with KIC than with glyceraldehyde and glucose, we conclude that ouabain inhibits ATP production, at least in part, in the glycolytic pathway through a feedback mechanism.

Adenosine Triphosphate↗