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M Nishimura

Publications and source records attributed to M Nishimura.

At least 685 records · Page 38Linked to original sources
PubMed1995

Electrophysiological demonstration and activation of mu-opioid receptors in the rabbit sinoatrial node.

To investigate the presence of opioid receptors and their physiological role in cardiac pacemaker cells, we studied electrophysiological effects of fentanyl citrate, an activator of the mu-opioid receptors, on the spontaneous action potential (AP) and membrane currents, using small preparations (0.2 x 0.2 x 0.1 mm) of rabbit sinoatrial (SA) node (SAN). Fentanyl (0.1-3 microM) progressively decreased the AP amplitude (APA), maximal rate of depolarization (MRD), and spontaneous firing frequency (SFF) and prolonged the AP duration (APD) and diastolic interval in a concentration-dependent manner. At 1 microM, the spontaneous activity ceased in two of the eight preparations. These actions were blocked by a mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), but were not modified by either kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI), or delta-opioid receptor antagonist ICI-174864. In voltage-clamp experiments using double microelectrode techniques, 1 microM fentanyl reduced the Ca2+ current (ICa) obtained on step depolarization from -40 to 0 mV by 19.9 +/- 9.3% (p < 0.05, n = 5), the fast and slow components of the delayed rectifying K+ current (IKfast, IKslow) tail obtained on repolarization from 10 to -60 mV by 54.7 +/- 4.7 and 41.4 +/- 2.4% (p < 0.05, n = 4), and the hyperpolarization-activated inward current at -90 mV by 12.6 +/- 0.5% (p < 0.05, n = 7), respectively. The gating kinetics of ICa and IKslow were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Genetic regulation of development of thymic lymphomas induced by N-propyl-N-nitrosourea in the rat.

To clarify the linkage between Hbb and Tls-1 (thymic lymphoma susceptible-1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of N-propyl-N-nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6 genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls-1 loci could be demonstrated since WKY rats also developed a high incidence of thymic lymphomas in response to PNU. Nevertheless, thymic lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large tumor growth phenotype, while the [(WKY X BUF) X WKY] backcross generation consisted of rats with either rapidly growing or slowly growing tumors. It was thus concluded that rapid development of thymic lymphomas is determined by a gene, provisionally designated Tls-3. Analysis of the relationship between 6 genetic markers and development of thymic lymphoma in the backcross generation demonstrated that the Tls-3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls-3 may not be identical with Tls-1 and other genes known to be relevant to thymic tumors, but its relationship with Tls-2 remains obscure.

Animals↗
PubMed1995

Establishment of a T-cell line from lymphocytes presumably implicated in posttransfusion graft-versus-host disease.

Posttransfusion graft-versus-host disease (PTGVHD) is known to develop in immunocompetent patients exhibiting clinical symptoms such as erythroderma, fever, liver dysfunction, diarrhea and pancytopenia. It is speculated that transfused blood donors' lymphocytes might recognize the recipients' HLAs as alloantigens. The thus stimulated lymphocytes might proliferate, expand and finally attack the host's immune system or tissues. However, details regarding these expanded donor cells such as: (1) whether they represent one clone or more, (2) the composition of lymphocyte subsets, and (3) the target HLA antigens of recipients, are not clear, since T-cell lines derived from PTGVHD patients have not yet been obtained. The aim of this study is to characterize T-cells responsible for PTGVHD and to identify their target molecules. For that purpose, we attempted to establish T-cell lines derived from a PTGVHD patient. We show that the established T-cell line, proven to be derived from donor lymphocytes, showed a CD4+ phenotype and had cytotoxic activities. Furthermore, we describe that the target of the cytotoxic T-cell line (CTL) is an HLA-DRB1*0405-related molecule of the patient.

Base Sequence↗
PubMed1995

Role of cerebral ATP-sensitive K+ channels in arterial pressure regulation during acute cerebral ischaemia in SHR and WKY rats.

1. ATP-sensitive K+ channels (KATP) are activated either by decreased intracellular ATP content or ATP/ADP ratio during ischaemia. We examined the role of a cerebral KATP in arterial pressure regulation during acute cerebral ischaemia using SHR and WKY rats. Thirteen week old male SHR or WKY rats were anaesthetized with urethane, and arterial pressure and heart rate were recorded under an artificial ventilation. 2. Intracerebroventricular (i.c.v.) injections of glibenclamide, a specific inhibitor of KATP, elicited dose-dependent vasopressor responses in WKY with bilateral ligation of carotid arteries, whereas it caused smaller vasopressor responses in SHR than WKY. 3. Systemic administration of AVP V1 receptor antagonist, OPC-21268, abolished the vasopressor responses of i.c.v. injections of glibenclamide in WKY but not in SHR. 4. Intracerebroventricular injections of glibenclamide caused both the increase in plasma concentration of AVP and the decrease in pituitary AVP content in WKY with bilateral ligation of carotid arteries, whereas it elicited no significant change in plasma and pituitary concentration of AVP in SHR with bilateral ligation of carotid arteries. 5. Cerebral KATP may play a role in the protection of excess hypertension by inhibiting AVP release from the pituitary glands during acute ischaemia in WKY, but this mechanism might not work in SHR during acute cerebral ischaemia.

Adenosine Triphosphate↗
PubMed1995

Histochemical localization of copper in various organs of brindled mice after copper therapy.

Copper (Cu) distribution in various organs of brindled mice (BM), an animal model of Menkes disease, was studied histochemically and by atomic-absorption-spectrophotometry 7 months after Cu injections. The results were compared with those of untreated BM. In the treated BM brain, a diffuse reduction in Cu-related staining of neurons and astroglia was still evident, though it had improved to some extent. The reduction was noticeable in the thalamus, brain stem and cerebellum, although intensely stained capillaries were noted occasionally in the retrosplenial and mediobasal temporal areas, including the hippocampus. In the treated BM liver, near normalization of Cu distribution was observed. In the treated BM intestine, the main localization of Cu accumulation was in histiocytes/macrophages in the lamina propria, while in the untreated BM it was in the absorptive and secretory epithelial cells. In the treated BM kidney, there was no clear improvement in Cu distribution. These histochemical results were consistent with the data obtained by the spectrophotometric assay. Electron microscopic histochemistry of affected renal tubular epithelial cells revealed numerous silver grains, which represent Cu++ localization, distributed only within the cytoplasm outside organella and nucleus. This suggests impaired intracellular Cu transport from cytosol to organella, which in the kidney is refractory to the Cu therapy adopted.

Animals↗
PubMed1995

Cerebral ATP-sensitive potassium channels during acute reduction of carotid blood flow.

The ATP-sensitive potassium channels (KATP) are activated either by a decrease in intracellular ATP content or by a lowering of the ATP-ADP ratio such as during stroke. We studied the role of cerebral KATP on arterial pressure during acute reduction of cerebral blood flow in 12-week-old male Wistar rats anesthetized with urethane by recording arterial pressure and heart rate continuously. After bilateral ligation of the common carotid arteries, glibenclamide, a specific blocker of KATP, was injected intracerebroventricularly into the cerebral lateral ventricle. Glibenclamide elicited a sustained vasopressor response in a dose-dependent manner in rats with bilateral carotid artery ligation (10 nmol, +15 +/- 2 mm Hg; 1 nmol, +5 +/- 1 mm Hg, P < .01 versus vehicle), but hemodynamic alterations were barely recorded with glibenclamide in sham-operated control rats. The abdominal sympathetic discharge was not increased significantly enough to explain the pressor mechanism. Similarly, pretreatments with intravenous injections of bunazosin, an alpha 1-adrenoceptor antagonist, did not affect the pressor response of intracerebroventricular glibenclamide. To investigate the vasopressor mechanism further, we measured plasma and pituitary concentrations of arginine vasopressin and determined the effects of vasopressin receptor antagonists. The intracerebroventricular injections of glibenclamide significantly increased the plasma concentration of vasopressin (P < .05) and significantly decreased the pituitary concentration of vasopressin (P < .05) in rats with bilateral carotid artery ligation. Intravenous pretreatment with the vasopressin V1 receptor antagonist OPC-21268 abolished the vasopressor response to intracerebroventricular glibenclamide (+16 +/- 2 versus +1 +/- 1 mm Hg, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1995

Neutrophil elastase associated with alveolar macrophages from older volunteers.

We focused on the role of neutrophil elastase (NE) in alveolar macrophages (AMs), and evaluated the esterolytic activity using an NE-sensitive substrate, methoxysuccinyl-alanyl-alanyl-prolyl-valyl paranitroanilide (MEOSAAPVNA) in AMs from 36 older healthy volunteers (61 +/- 2 yr mean age +/- standard error) and examined the relationship to chronic effects of cigarette smoking and also to the presence of low attenuation areas (LAAs) on the computed tomographic (CT) scans. The AMs from the subjects with LAAs showed significantly higher activity than those from the current smokers without LAA (1.16 +/- 0.40 versus 0.34 +/- 0.07 nM, respectively, p < 0.05). Although the study of inhibitory profile revealed that the esterolytic activity could not be attributed to NE alone, the NE activity seemed to dominate in AMs at least from some who had higher esterolytic activity. We then examined the releasability of NE from cultured AMs in 10 subjects. The immunologic NE complex with alpha 1-protease inhibitor (alpha 1-PI) was released significantly higher in the LAA(+) group than in the LAA(-) group (17.4 +/- 6.5 versus 1.8 +/- 0.6 micrograms/L, respectively, p < 0.05). These data suggest that NE in AMs may play a role in the development of emphysematous changes in susceptible smokers.

Adult↗
PubMed1995

Dependency on the rate of change in PaO2 of the ventilatory response to progressive hypoxia.

The biphasic nature of the ventilatory response to sustained hypoxia (< 1 h) is thought to occur as a result of combined effects of stimulation and depression with hypoxia. If the depressant effect of hypoxia on ventilation occurs later than the stimulatory effect, the magnitude of the ventilatory response to progressive hypoxia may be different according to the time required for a given fall in PaO2 during the test. In this study, we measured, in 10 healthy adult volunteers, ventilatory responses to isocapnic progressive hypoxia (HVR) using three different protocols (4 min, 6 min, and 15 min for SaO2 to decrease from the baseline to 80%) with or without pretreatment using theophylline (300 mg twice a day), an adenosine receptor antagonist, in a 2-d, single-blind crossover design. The slope values of HVR with the placebo were 0.31 +/- 0.04 (SE) (L/min/% fall of SaO2) in the 4-min protocol, 0.26 +/- 0.04 in the 6-min protocol, and 0.18 +/- 0.04 in the 15-min protocol. The HVR for the 15-min protocol was significantly lower than that for the 4-min or 6-min protocol. The HVR with theophylline was 0.46 +/- 0.08 for the 4-min protocol, 0.54 +/- 0.09 for the 6-min protocol, and 0.66 +/- 0.11 for the 15-min protocol, among which there were no significant differences. The dependency of HVR on the rate of change in PaO2, that was seen with a placebo run, disappeared after pretreatment with theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1995

Gender effect on prognosis of patients receiving long-term home oxygen therapy. The Respiratory Failure Research Group in Japan.

Although long-term home oxygen therapy (LTOT) certainly prolongs survival, it is not known whether this advantageous effect is similar for both sexes. In this study, we analyzed sex-related differences in survival based on a very large population that had received LTOT from 1986 to 1993. A total of 9,759 patients with chronic obstructive pulmonary disease (COPD), sequelae of tuberculosis (TBsq), and chronic interstitial pneumonia (IP) were selected in 1,212 medical institutions for analysis of survival rates. The survival rates of both sexes were compared with each other using the Cutler-Ederer Method. Despite higher PaCO2 at the beginning, the survival rate of women was significantly better than that of men in these three disease categories. Cox's proportional hazards analysis further confirmed the gender effect on survival by eliminating the effects of age, PaO2, PaCO2, %VC, and FEV1/FVC. The mean survival periods of the women who died during follow-up periods were also significantly longer than those of men (0.41 yr in COPD, 1.84 yr in TBsq, and 0.78 yr in IP). From these findings, we conclude women have a better prognosis than men when they start receiving LTOT, regardless of the cause of respiratory failure.

Female↗
PubMed1995

The response of flow-triggered infant ventilators.

Patient-triggered ventilation (PTV) has not been feasible for infants because of large trigger pressures and long delay times with pressure-triggered systems. Recently, four infant ventilators with flow triggering have become available. We questioned if delay times, trigger pressures, and trigger work with these ventilators would be acceptable for PTV in infants. All ventilators were attached via 3-, 4-, and 5-mm endotracheal tubes to a spontaneously breathing infant lung model. The lung simulator was set at an inspiratory time of 0.65 s, tidal volume of 15, 30, and 45 ml, and 0 and 5 cm H2O positive end-expiratory pressure (PEEP). Delay time, trigger pressure, and trigger work were determined from pressure measured at the proximal airway, trachea, and alveolus. There were significant differences between the endotracheal tube sizes, sites of measurement, ventilatory demand and ventilator brand at each PEEP level for delay time, trigger pressure, and trigger work (p < 0.001). Delay time was greatest with the 3-mm endotracheal tube at high ventilatory drive (maximum 138.2 +/- 2.1 ms). Both trigger pressure (minimum 0.23 +/- 0.02 cm H2O) and trigger work (minimum 0.05 +/- 0.01 g.ml) increased with decreasing endotracheal tube size, increasing ventilatory demand, use of PEEP, and site of measurement: alveolus > trachea > airway (maximum: trigger pressure 5.04 +/- 0.02 cm H2O; trigger work 114.48 +/- 0.88 g.ml). PTV may not be appropriate under conditions of increased ventilatory drive and small endotracheal tube size in infants.

Age Factors↗
PubMed1995

Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema.

In an attempt to further evaluate the role of neutrophil elastase (NE) in the development of emphysema, we examined the immunologic quantity of NE bound to alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF) supernatant from 36 community-based older volunteers. They were classified into three groups: 10 current smokers with low attenuation areas (LAAs) on the lung computed tomography (CT) scans who were considered to have subclinical emphysema, 13 current smokers who had a comparable smoking history but no LAA, and 13 noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was significantly increased in the subjects with subclinical emphysema when compared not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52 +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory activity measured by a spectrophotometric method using methoxysuccinyl-alanyl-alanyl-prolyl-valyl-paranitroanilide did not show any significant difference between the two groups of current smokers. There was no difference in the pattern or density of native and proteolysed alpha 1-PI bands between the three groups by Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that may differentiate smokers who are potentially developing emphysema from those who are not.

Aged↗
PubMed1995

Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.

To clarify the role of PDGF A-chain in hypertensive vascular hypertrophy of spontaneously hypertensive rats (SHRs), we studied levels of PDGF A-chain gene expression and transcription factors related to the gene in vascular smooth muscle cells (VSMCs) of SHRs in vivo. RNase protection assay and in situ hybridization showed that PDGF A-chain mRNA levels in VSMCs of SHRs were twofold higher than in those of normotensive Wistar-Kyoto rats. Gel retardation assays showed that levels of Sp1 and AP-2 in VSMCs of SHRs were twofold more abundant than in those of Wistar-Kyoto rats. Treatment with four pharmacologically different species of antihypertensive drugs for 2 wk decreased the levels of both PDGF A-chain mRNA and Sp1, but not AP-2 level in VSMCs of SHRs with regression of aortic hypertrophy, indicating that increases in levels of both PDGF A-chain mRNA and Sp1 in VSMCs of SHRs were associated with high blood pressure. These results suggest that high blood pressure is a stimulus which upregulates PDGF A-chain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular hypertrophy, and that the activation of the gene may be mediated through increases in Sp1 in these cells.

Animals↗
PubMed1995

No association of the 11778 mitochondrial DNA mutation and multiple sclerosis in Japan.

Leber's hereditary optic neuropathy (LHON), a maternally inherited disease causing severe bilateral visual loss in young men, is linked to 12 point mutations in mitochondrial DNA, the most common of which is at the nucleotide position 11778. The 11778 point mutation has also been detected in several patients with possible multiple sclerosis (MS), especially women with severe visual loss in both eyes. Because frequent and severe optic neuropathy is a feature of MS in Japan, we screened 80 Japanese MS patients for the presence of the 11778 mutation by mutation-specific polymerase chain reaction. Eighteen women with MS had bilateral optic neuropathy, but none had the mutation at 11778. There is no association between Japanese MS and the 11778 mitochondrial DNA mutation.

Base Sequence↗
PubMed1995

Effect of temperature in perfusate on local hepatic disposition of BOF-4272, a new xanthine oxidase inhibitor.

The effect of temperature on the local hepatic disposition of BOF-4272 [(+/-)-8-(3-methoxy-4-phenylsulfinyl-phenyl)pyrazolo[1,5-a]-1,3,5- triazine-4-olate], a new drug used to treat hyperuricemia, was investigated by means of a perfusion experiment following the pulse input into the portal vein of rat, in which the temperature of the perfusate was changed from 37 degrees C down to 4 degrees C. The same perfusion experiment was also attempted using bovine serum albumin (BSA) as a reference substance to compare with the hepatic disposition of BOF-4272. The elution time profiles of BOF-4272 and BSA from the liver into the hepatic vein were evaluated by moment analysis. The recovery ratio (FH) and the mean transit time (tH) of BOF-4272 were 22.8 +/- 3.3% and 0.111 +/- 0.008 min at 37 degrees C, respectively. Both FH and tH significantly increased with the decrease in the temperature of the perfusate, 3 times and 2 times greater at 4 degrees C than at 37 degrees C, respectively. The FH and tH of BSA were 98.3 +/- 4.5% and 0.129 +/- 0.013 min at 37 degrees C, respectively. These parameters of BSA were independent of temperature, while those of BOF-4272 showed a definite dependency on temperature. A new estimation method for the elimination rate constant (kc) and the partition ratio (k') in the dispersion model was developed by rearranging the theoretical equations of FH and tH. The index for the elimination (ke) of BOF-4272 decreased with the decrease in temperature, while the index for the distribution (k') increased with the decrease in temperature. This result shows that the metabolism (or the biliary excretion) decreased and the distribution increased with a decrease in temperature, indicating that the hepatic metabolizing pathway which is presumably temperature-dependent is blocked, and the blocked portion of BOF-4272 thus returns back to the perfusate at the low temperature.

Animals↗
PubMed1995

Mechanism of hypertension induced by chronic inhibition of nitric oxide in rats.

In order to clarify the mechanism of hypertension induced by a nitric oxide (NO) synthase inhibitor, L-NG-nitro-L-arginine (LNNA), metabolites of NO, catecholamines, and hemodynamic parameters were measured during 7 days of oral administration of LNNA in rats. Control rats received either L-arginine (L-Arg) or the vehicle. systolic blood pressure, measured by the tall-cuff method was elevated throughout the period of LNNA administration, but that in the two control groups was not influenced by treatment. Heart rate decreased on the second day only in LNNA-treated rats. Although L-Arg treatment had no influence, LNNA markedly decreased the plasma level and the urinary excretion of nitrate ions (NO-3). Urinary excretion of noradrenaline was significantly decreased on the second day of LNNA administration and returned to the control level thereafter. When hemodynamic changes were measured by using radioactive microspheres, LNNA was found to increase blood pressure by markedly increasing total peripheral resistance. Cardiac output was decreased by LNNA. L-Arg, again, did not influence the hemodynamic variables as compared with the vehicle control group. The regional vascular resistance index was increased by LNNA in many tissues and organs, except the brain and the heart. Regional blood flow, on the other hand, was significantly decreased only in the liver and skin by LNNA. The marked reduction in NO3- in urine by LNNA-treatments may indicate that the measured NO3- is exclusively of endogenous origin, and that inhibition of NO production causes elevation of blood pressure by constricting peripheral arteries. Sympatholytic responses by the baroreceptor reflex were thereby evident only on the second and the third days, which was indicated by bradycardia and suppression of noradrenaline excretion into urine. These results indicate that the inhibition of NO synthase actually decreases production of endogenous NO, and that the hypertension caused by decreases in NO production is due to elevation of total peripheral vascular resistance.

Animals↗
PubMed1995

Does dopamine act on myocardial cells?

We examined the electrophysiological effects of dopamine on the single myocardial cells isolated from the rat and rabbit heart. Dopamine at a concentration of 1 or 10 microM did not affect the L-type Ca2+ current (ICa) or the transient outward current (ITO) in rat ventricular, rabbit atrial, ventricular, and sinoatrial node cells. It did not induce any detectable change in the action potential configuration of the rabbit ventricular cells either. We conclude that dopamine does not directly act on myocardial cells at least in terms of the electrophysiological properties.

Action Potentials↗
PubMed1995

Urinary excretion of free dopamine and digoxinlike substances correlates with endogenous secretion of insulin in normotensive adults, but not in hypertensive subjects.

We investigated whether urinary excretion of free dopamine is related with the humoral factors which affect Na+, K+ ATPase activity in the kidneys. Subjects were 51 adults admitted in a hospital without renal insufficiency: they were divided into normotensive (n = 36, 60 +/- 3 years old, 122 +/- 3/73 +/- 2 mmHg) and hypertensive groups (n = 15, 65 +/- 5 years old, 157 +/- 6/91 +/- 2 mmHg). Urinary excretion of free dopamine was significantly and positively correlated with urinary excretion of C-peptide immunoreactivity of insulin (CPR) (r = 0.451, p = 0.014) in normotensive subjects, but not in hypertensive subjects (r = 0.155, p = 0.668). Urinary excretion of endogenous digoxinlike substances (EDLS) was also significantly and positively correlated with urinary CPR (r = 0.500, p = 0.006) in normotensive subjects, but not in hypertensive subjects (r = 0.275, p = 0.363). In normotensive subjects, urinary excretion of free dopamine and EDLS may be regulated at least in part by insulin secreted endogenously. In hypertensive subjects, however, this regulatory mechanism of the diuretic factors, such as insulin, EDLS and dopamine, is thought to be deranged, which might result in decompensation of a diuretic and antidiuretic balance leading to blood pressure elevation.

Adult↗