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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 109 records · Page 6Linked to original sources

Digoxin-like immunoreactivity increases with intravenous infusion of saline in rats.

1. The effects of sodium-loading on releases of endogenous digitalis-like substance were investigated by measuring digoxin-like immunoreactivity (DLI) during intravenous infusions of isotonic (0.15 mol/L) and hypertonic (1 mol/L) saline in anaesthetized rats. Plasma DLI was measured after death by a digoxin-radioimmunoassay. 2. The infusion of isotonic saline and hypertonic saline elevated the central venous pressure to similar levels. The plasma DLI concentration in both the infused groups rose significantly compared with that in the control rat not receiving the intravenous infusion. 3. The difference in the hypothalamic concentrations of DLI was not significant among the three groups, however, there was a significant inverse relationship between the plasma and hypothalamic concentrations of DLI. 4. Results indicate that the central venous pressure, but not sodium concentration, is essentially involved in the release of DLI, possibly from the hypothalamus.

Animals

[A study on the beta-lactamase production for Neisseria gonorrhoeae and the sensitivity to various antibacterial agents].

During the 10-year period from 1980 through 1989 using gonococci isolated in Sapporo, we studied beta-lactamase production capacity and the sensitivity of various antibacterial agents and obtained the following results. 1. The frequency of isolating beta-lactamase producing gonococci (PPNG) displayed a gradual tendency to increase during the first half of the 80's and reached a peak in 1985 of 23.9% (61/255). However, thereafter it tended to decline and in 1989 it was 6.3% (2/32). 2. The sensitivity to penicillin-type antibacterial agents was higher against PPNG than non-PPNG against PCG, ABPC, and AMPC displaying about a 7 level MIC90 so that it was quite sensitive. Against CVA/AMPC, SBTPC it showed a relatively favorable MIC90. Also, the sensitivity of PPNG against AMPC with 1984 as the boundary, thereafter the MIC distribution was observed to decline somewhat. 3. Against the monobactam-type injectable drug, AZT, both non-PPNG and PPNG showed a low MIC distribution and against SPCM both showed a relatively high MIC distribution of 3.13-25 micrograms/ml. 4. In regard to the sensitivity to cephem-type antibacterial agents, against such 3rd generation injectables as CZX, CFTM-PI, etc. it displayed a particularly low MIC distribution. 5. Against tetracycline and macrolide antibacterial agents, it displayed a relatively high MIC distribution. 6. Against new quinolone type antibacterial agents, regardless of being non-PPNG or PPNG, it showed a low MIC.

Anti-Bacterial Agents

The PHO84 gene of Saccharomyces cerevisiae encodes an inorganic phosphate transporter.

The PHO84 gene specifies Pi-transport in Saccharomyces cerevisiae. A DNA fragment bearing the PHO84 gene was cloned by its ability to complement constitutive synthesis of repressible acid phosphatase of pho84 mutant cells. Its nucleotide sequence predicted a protein of 596 amino acids with a sequence homologous to that of a superfamily of sugar transporters. Hydropathy analysis suggested that the secondary structure of the PHO84 protein consists of two blocks of six transmembrane domains separated by 74 amino acid residues. The cloned PH084 DNA restored the Pi transport activity of pho84 mutant cells. The PHO84 transcription was regulated by Pi like those of the PHO5, PHO8, and PHO81 genes. A PHO84-lacZ fusion gene produced beta-galactosidase activity under the regulation of Pi, and the activity was suggested to be bound to a membrane fraction. Gene disruption of PHO84 was not lethal. By comparison of nucleotide sequences and by tetrad analysis with GAL80 as a standard, the PHO84 locus was mapped at a site beside the TUB3 locus on the left arm of chromosome XIII.

Amino Acid Sequence

Tracheal dimensions at full inflation and deflation in adolescent twins.

Tracheal dimensions at total lung capacity (TLC) and residual volume (RV) were analyzed roentgenographically in 17 pairs of male adolescent twins (mean age 16.3 yr; 12 monozygotic pairs and 5 dizygotic pairs). Genetic factors dominated environmental traits in intra- as well as extrathoracic tracheal width at RV. Extrathoracic tracheal width at TLC was also governed by genetic components. Intrathoracic tracheal depth (anteroposterior diameter), length, and cross-sectional area did not seem to be genetically controlled at TLC and RV. Intrathoracic tracheal cross-sectional area increased by 14.4% and became more elliptical from RV to TLC, owing mainly to an increase in tracheal depth (16.7%). Increments from RV to TLC in tracheal depth but not width correlated with increases in lung width, depth, and height. Intrathoracic trachea was elongated 14% in association with increase in lung height from RV to TLC. At TLC, extrathoracic tracheal width was larger than intrathoracic tracheal width, but this dimension did not differ at RV. These results indicate that genetic factors influence, at least at RV, the tracheal rings more strongly than membranous parts. Intrathoracic tracheal depth but not width increases during inspiration in accordance with increase in lung volume. Extrathoracic tracheal width widens more than intrathoracic trachea from RV to TLC.

Adolescent

Comparison of hemin enhancement of burst-forming units-erythroid clonal efficiency by progenitor cells from normal and HIV-infected patients.

The ability of peripheral-blood hematopoietic progenitor cells from AIDS patients and normal controls to respond to erythropoietin (Epo) was assessed for burst-forming units-erythroid (BFU-E). BFU-E colony formation from AIDS patients' peripheral blood responded to a wide range of Epo concentrations (0.5-4 U) in a similar manner as erythroid progenitors obtained from normal peripheral blood. The optimum dose response of BFU-E to Epo was 2 U which resulted in generation of 71 +/- 4 BFU-E in AIDS patients (n = 10), as compared to 77 +/- 5 BFU-E in normal donors (n = 3). The optimum concentration range of hemin enhancement of erythroid progenitor BFU-E was 10-50 microM. In all instances, Epo was essential for BFU-E growth. Inclusion of hemin at a concentration of 10 microM in AIDS patients' peripheral-blood erythroid progenitor cells resulted in enhancement of BFU-E by 136-215%. Similarly, inclusion of hemin (10-100 microM) in normal bone marrow erythroid progenitor cell cultures resulted in enhancement of BFU-E. Inclusion of an equivalent amount of iron or tin protoporphyrin to progenitors cells from AIDS patients' peripheral blood had no effect on the number of colonies observed. On the other hand, inclusion of another heme analogue, zinc protoporphyrin, in AIDS or normal cultures resulted in a 50% suppression of BFU-E colony formation. These results demonstrate that peripheral-blood mononuclear cells from AIDS patients retain the capacity to generate erythroid precursors such as BFU-E in the presence of Epo, and that hemin has a specific enhancement effect on growth of BFU-E colony formation obtained from peripheral blood or bone marrow cells.

AIDS-Related Complex

Longitudinal analyses of respiratory chemosensitivity in normal subjects.

To evaluate relative contributions of inherent versus extrinsic factors to respiratory chemosensitivity, ventilatory responses to isocapnic progressive hypoxia and normoxic progressive hypercapnia were examined at intervals of 8 to 10 yr in 32 healthy male volunteers aged 42.2 +/- 1.4 yr (SEM) in the final examination. The volunteers included 22 sons of patients with chronic obstructive pulmonary disease. The mean value for the slope factor of the end-tidal PO2-ventilation hyperbola (A) significantly decreased from 98.3 +/- 12.2 to 77.4 +/- 10.3 L/min mm Hg (p less than 0.05), but that for the end-tidal PCO2 ventilation line (S) did not change over the years. The individual values for the hypoxic ventilatory response were significantly correlated (r = 0.63, p less than 0.001) between the initial and final examinations but not so for the hypercapnic ventilatory response (r = 0.23, NS), suggesting that the latter is more subject to influence from extrinsic factors than the former in the long term. The reproducibility of both tests expressed as coefficients of variation was similar or rather small for the hypercapnic ventilatory response, which was determined by three consecutive measurements at 1 wk intervals in a different group of six subjects. From these data we conclude that hypoxic chemosensitivity is more determined by factors inherent to the individual than hypercapnic chemosensitivity and that it is more systematically influenced by temporal factors, as demonstrated by the systematic decrease over the years.

Adult

Changes in beta-tubulin isoforms and their RNA level in synchronized tobacco cells.

Tobacco BY-2 cells were synchronized by an aphidicolin treatment, and their beta-tubulin isoforms and their mRNA were analyzed by Western, Northern and dot blottings. The relative ratio of the beta-tubulin isoforms changed with the progress of cell cycle stage. By Northern blot hybridization of poly(A)+RNAs with a cloned carrot beta-tubulin cDNA probe, a single band of about 1.6 kb was detected throughout the cell cycle. Dot blot hybridization showed that beta-tubulin mRNA existed in all stages in the cell cycle at a relatively constant level, though it accumulated slightly more than average at M phase and decreased during G1 phase.

Aphidicolin

Nicorandil (2-nicotinamidoethyl nitrate) inhibits both vaso-dilating and -constricting effects of endothelin in a vascularly isolated hind-limb preparation in rats.

Effects of nicorandil (2-nicotinamidoethyl nitrate), a nitrate derivative with a K+ channel-opening action, on endothelin-1 (ET)-induced effects on peripheral blood vessels were studied using a hind-limb perfusion preparation in rats. ET injected into this circuit increased the perfusion pressure for more than 30 min following a transient, initial vasodepression of the perfusion system. The magnitude of both responses was dose-dependent. Pretreatments with nicorandil infused into this preparation significantly attenuated both the initial vasodilation and the sustained vasoconstriction caused by ET. The initial vasodepression caused by ET could be mediated by the release of endothelium-derived relaxing factor (EDRF). The sustained phase would be due to increased intracellular calcium elicited by ET. Nicorandil inhibited both the initial and the sustained phase of the ET-responses, probably by inhibition of intracellular phosphoinositide metabolism in both endothelium and vascular smooth muscle cells.

Analysis of Variance

[Pharmacological action of SN-408, a novel long-acting selective beta 2-adrenoceptor agonist].

The bronchodilating effect and other related pharmacological properties of SN-408 were studied in comparison with those of isoproterenol, salbutamol and procaterol. SN-408 caused concentration-dependent relaxation of isolated guinea pig trachea via the beta 2-adrenoceptor. The order of relaxation potency was: procaterol greater than SN-408 greater than or equal to isoproterenol greater than salbutamol, but the duration of the action of SN-408 was far longer than those of other beta-agonists. Positive chronotropic and inotropic actions of SN-408 in isolated guinea pig right atria and left atria were less potent than those of other beta-agonists. In isolated guinea pig lung tissues, SN-408 increased cyclic AMP contents. Also in vivo, SN-408 showed dose-dependent bronchodilating action by i.v. administration in anesthetized guinea pigs and by inhalation in conscious guinea pigs. Bronchodilating actions of SN-408 were less potent than those of procaterol and isoproterenol, but the duration of action of SN-408 was far longer than those of other beta-agonists. SN-408 showed no evidence of the development of tolerance to the bronchodilating action. SN-408 caused small tachycardia in guinea pigs by i.v. and inhalation. SN-408 given i.v. suppressed vascular permeability in mice. These results indicate that SN-408 is a long-acting and selective beta 2-stimulant bronchodilator.

Adrenergic beta-Agonists

Peripheral chemosensitivity assessed by the modified transient O2 test in female twins.

To evaluate genetic influence on the control of breathing in adult women, we measured, in healthy female twins, ventilatory responses to isocapnic progressive hypoxia and hyperoxic progressive hypercapnia, and the withdrawal response (the modified transient O2 test) which is considered to selectively reflect peripheral chemoreceptor activity. The withdrawal response was obtained as the magnitude of initial depression in ventilation induced by two breaths of O2 from steady-state hypercapnic hypoxia. Nine monozygotic twin pairs, aged 44 +/- SD17 years, and 7 dizygotic twin pairs, aged 39 +/- 8 years, were studied. Mean values for ventilatory responses to hypoxia and hypercapnia, and the withdrawal response were not different between MZ and DZ. The within-pair variance ratio (VDZ/VMZ) for the withdrawal response was significantly greater than one (p less than 0.05), although neither VDZ/VMZ for the hypoxic response nor that for the hypercapnic response was greater than one. These observations suggest that the peripheral chemosensitivity is influenced by genetic factors even in adult women, including aged subjects, when genetic influence is not apparent in the ventilatory responses to progressive hypoxia and hypercapnia.

Adult

Treatment of neuroleptic malignant syndrome with direct hemoperfusion.

Neuroleptic malignant syndrome (NMS) is an uncommon but serious and fatal idiosyncratic reaction to neuroleptics. It is difficult to correct this abnormalities successfully. There has been several reports on the treatment of NMS with dantrolene and/or bromocriptine. But these therapy are not effective in every cases. We have experienced ten cases of NMS. Six of them were presented with respiratory distress. Seven patients were treated with direct hemoperfusion and the remainder were managed by dantrolene, bromocriptine and other drugs. Patients treated with direct hemoperfusion two to four times could got a good improvement within several days and recovered. As to the patients treated by drugs. One of them who was not serious recovered with bromocriptine after twenty days. Two patients needed hemodialysis. NMS is occur not only by the use of neuroleptics but also by the break of them. So, this syndrome is do not develop by the high concentration of neuroleptics merely. NMS differed from ordinary drug intoxication. The etiology of NMS has unknown. But two major theories are present. One is dopaminergic blockade theory the other is direct toxic effect on skeltal muscles. We speculate that direct hemoperfusion remove metabolites of neuroleptics or normalize the alteration in the central nervous system.

Adult

[A case report of mediastinal paraganglioma and a review of the literature in Japan].

Paraganglioma is a tumor arising from the extra-adrenal paraganglion system and is rarely observed in the mediastinum. The authors experienced a case of nonfunctioning paraganglioma of the upper posterior mediastinum. The patient was a 40-year-old female in whom abnormal shadows were noted in chest X-ray films taken in March, 1989. She was examined at our hospital with a diagnosis of mediastinal tumor in June of the same year. CT of the chest revealed a tumor in the upper posterior mediastinum and it was shown to be hypervascular by a DSA study. Urinary hormone levels were normal. The tumor was resected in May, 1990. The tumor, measuring 6.8 X 4.0 X 3.5 cm, was encapsulated, appeared dark red and had relatively clear borders. A histopathologic diagnosis of paraganglioma was made. The patient remains disease-free at present, 6 months after operation. Problems concerning diagnosis and treatment of mediastinal paraganglioma were evaluated with a review of cases reported in Japan.

Adult

[Clinicopathological and histochemical studies of linitis plastica type gastric cancer with special reference to early gastric cancer in the region of the fundic gland].

Early gastric cancer in the region of the fundic gland was found to occur predominantly in women. Many lesions of this type were identified in the posterior wall of the middle portion of the stomach. Histologically, the lesions were classified as poorly differentiated carcinomas in all cases of early cancer. In 9 patients with cancer of linitis plastica type having IIc lesions located in the region of the fundic gland, the tumor focus was also in posterior wall of the middle portion of the stomach. Giant folds were present diffusely in all other portions of the gastric mucosa in these latter cases. These cases also had diffuse infiltration of cancer cells into the submucosa, muscle layer and extraserosal regions. Histologically, the lesions were classified in all cases of linitis plastica type as poorly differentiated carcinomas including signet ring cells. Acid mucopolysaccharides (AMPS) and sialic acid were histochemically detected in the interstitial tissues of early gastric carcinomas and linitis plastica type gastric cancers. The AMPS digestion rates were higher for early cancer tissue. The present results support the hypothesis that early gastric cancer in the region of the fundic gland may occur in conditions favoring tumor growth and may develop into cancer of linitis plastica type.

Adenocarcinoma, Mucinous

Validity of salivary thiocyanate as an indicator of cyanide exposure from smoking.

The purpose of this study was to evaluate the validity of salivary thiocyanate as an indicator of cyanide exposure from smoking. The salivary thiocyanate level showed wide variation, and the largest source of thiocyanate was hydrogen cyanide from cigarette smoke. Hydrogen cyanide in the mainstream of cigarette smoke was as high as 40-70 ppm, which is beyond the threshold limit value for occupational health (10 ppm). The hydrogen cyanide level in the sidestream smoke was lower less than 5 ppm. Thus the amount of cyanide intake was larger in active smokers than in passive ones. The correlation between the thiocyanate level in saliva and plasma was statistically significant. Thiocyanate levels in both plasma and saliva increased with the amount of cigarette smoke, and the discriminant powers (smoker versus non smoker) of thiocyanate levels in both plasma and saliva were quite similar. The smoker/non smoker ratio for salivary thiocyanate was 3.04 and that of plasma thiocyanate was 1.73. The result indicated that smoking status could be reflected more by the thiocyanate level in saliva than in plasma. The biological half life of salivary thiocyanate was estimated to be as long as 9.5 days from the changes salivary thiocyanate after stopping smoking. From the results of this study, it was concluded that salivary thiocyanate was a suitable indicator of habitual smoking exposure.

Humans

Possible role of the hormonal form of vitamin D3 in the granuloma-associated angiotensin-converting enzyme activity.

We studied effects of the hormonal form of vitamin D3 on the angiotensin-converting enzyme (ACE) activity of hepatic granulomas in mice infected with Schistosoma mansoni. During 7 to 11 weeks after infection, mice were given orally 0.1 or 1.0 microgram/kg of 1 alpha (OH)D3 or only medium solution every other day. Granulomatous livers were removed at 7, 9 and 11 weeks after infection, and ACE activity was measured in the granulomas isolated from each liver tissue using a fluorometric method. Oral administration of 0.1 or 1.0 microgram/kg/2 days of 1 alpha (OH)D3 for 4 weeks significantly enhanced ACE activity in the granuloma tissue. Since the DNA content relative to a unit weight of protein in the granulomas did not change with the 1 alpha (OH)D3 treatment, it is suggested that the elevated tissue ACE activity is due to an actual increase of the enzyme activity in each granuloma cell. The present observation may have relevance to sarcoid granulomas characterized by an increased tissue ACE activity, since macrophages from patients with sarcoidosis synthesize a biologically active hormonal form of vitamin D3. Namely hormonal form of vitamin D3 locally produced by macrophages is involved not only in systemic Ca++ metabolism but also in the stimulation of macrophages themselves to produce ACE in the granulomas.

Animals

[Immunohistochemical study of glial cytoplasmic inclusion in multiple system atrophy].

Recently, glial cytoplasmic inclusion (GCI) has been demonstrated to be argyrophilic cytoplasmic body by silver staining in the oligodendroglia of patients with multiple system atrophy. We observed such GCIs in all 20 cases of multiple system atrophy. No GCI was noticed in all 6 cases of hereditary spinocerebellar degenerations. Immunohistochemically, GCI was stained positively with antibodies to ubiquitin, alpha-tubulin, and beta-tubulin, of which characteristics is consistent with previous reports. In addition, GCI was first demonstrated to react with an antibody to microtubule-associated protein-1B(5), which is one of the proteins of cytoskeleton organization and a component of cross-bridges between microtubular assembly. The result suggests strong relationship between the formation of the OCI and immunohistochemical expression of MAP-1B(5).

Antibodies, Monoclonal

[A cohort study on deaths from SMON in Japan].

Causes and risk factors of deaths from subacute myelo-optico neuropathy (SMON) were studied in a prospective cohort of 4,329 SMON patients followed for 3 years and 7 months (Sept. 1985-March 1989) with the following findings: (1) Recent excess deaths of SMON patients was estimated as 4% from ratio of O/E (SMR = 104) and deaths due to SMON itself was 6.4%. (2) The ratio of O/E was significantly higher for deaths from cancer of colon/rectum in females, cancer of pancreas in males, hypertension in males, pneumonia/influenza in females, chronic obstructive pulmonary diseases in males, tuberculosis and intestinal obstructive disease in males and females. (3) The ratio of O/E was 1.8 times or greater for those SMON patients with complications of cerebrovascular disease, severe blindness, complete loss of ambulation, and who were bedridden, and who are unable to receive home care from family members or trained home helpers.

Cause of Death