Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 289 records · Page 16Linked to original sources

PubMed1990

Removal of famotidine by haemodialysis in elderly anuric patients.

The effect of haemodialysis on the pharmacokinetics of oral famotidine has been studied in five elderly anuric patients. Famotidine 20 mg was administered in a cross-over design to patients on and not on haemodialysis. The elimination rate constant of haemodialysis (k) was 4.6-fold larger than the systemic elimination rate constant (ke). Although the mean maximum serum concentration of famotidine during haemodialysis (141.5 ng.ml-1) was not significantly lower than that without haemodialysis (195.6 ng.ml-1), the AUC up to 5 h during haemodialysis was significantly decreased to 58.1% of the value without it. The data suggest that famotidine is dialysable by haemodialysis.

Aged↗

PubMed1990

Leakage of cytoplasmic enzymes from rat heart by the stress of cardiac beating after increase in cell membrane fragility by anoxia.

The effects of spontaneous beating after anoxia and the pumping stress induced by a left ventricular balloon on the leakage of myocardial enzymes from the isolated perfused rat heart were investigated. Beating of the heart was arrested by perfusion with high-K+ medium. When the beating was arrested during reoxygenation after anoxia, the leakage of lactate dehydrogenase (LDH) was significantly lower than during reoxygenation with spontaneous cardiac beating. After changing from K+ arrest to spontaneous beating by perfusion with low-K+ medium during reoxygenation, the leakage of LDH increased markedly. Imposition of left ventricular wall stress on the K(+)-arrested heart by repetitive passive distension during aerobic perfusion and after 20 min and 60 min of anoxia caused LDH leakages of 1.0, 4.6 and 21.0 units/g in 30 min, respectively. Under this mechanical stress, the release of LDH as a percentage of its total myocardial activity coincided well with that of cytoplasmic aspartate aminotransferase (AST), while the percentage release of mitochondrial AST was much less. These results appeared to indicate that the leakage of cytoplasmic enzymes during reoxygenation is accelerated by cardiac beating because of fragility of the cell membranes developing during the preceding anoxia.

Adenosine Triphosphate↗

PubMed1990

Gene deletions in Japanese patients with Duchenne and Becker muscular dystrophy.

Thirty-eight unrelated Japanese patients with Duchenne and Becker muscular dystrophy (DMD and BMD) have been investigated with the DMD cDNA probes. The 14-kb DMD cDNA was subdivided into 6 subclones and HindIII-digested DNAs were analyzed by Southern blotting. Out of 38 unrelated patients, 14 showed a deletion of one or several of the exon-containing HindIII fragments (36.8%). These corresponded to 50% (9/18) of BMD patients and 25% (5/20) of DMD patients, and the position and extent of deletions were mapped and proved to be more heterogeneous in DMD than in BMD. Both ends of deletions detected in probe 1-2a were common to all six BMD patients without the maintenance of reading frame of messenger RNA, and 5' ends of deletions in probe 5b-7 were also common but maintained in frame in three BMD patients. The phenotypic-specific deletion in Japanese BMD patients has existed in the 5' end of the DMD gene, although its apparently similar deletion produced a wide range of clinical courses (BMD phenotype). There was no tight correlation between clinical severity and presence or absence of deletion in DMD or BMD.

Adolescent↗

PubMed1990

A simple method for screening assessment of acute toxicity of chemicals.

We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD50 values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD50 values reported in the literature. Our toxicological data also showed that LD50 values were about 2-2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD50 of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD50 values of chemicals and for screening for necessity for classical full LD50 test using many animals.

Ammonium Sulfate↗

PubMed1990

State dependent and/or direct memory retrieval by morphine in mice.

Mice were trained in step-down and step-through type passive avoidance learning tasks and given retention tests. Pre-training administration of morphine impaired retention, the effect recovering completely after an additional injection of the same dose of morphine given 30 min before the retention test. Amnesia produced by scopolamine, cycloheximide and electroconvulsive shock was also reversed by pre-test morphine. Pre-test saline also reversed the morphine-induced memory impairment to some extent, indicating that the recovery may partially be due to the state dependent effect. Thus, it is demonstrated that pre-test morphine not only state dependently but also directly reversed memory impairment in mice.

Amnesia↗

PubMed1990

An immunohistological study of breast cancer--with special reference to the expression of carbohydrate antigens and estrogen receptor status.

An investigation carried out on 100 cases of primary breast cancer, both clinicopathologically and immunohistologically, revealed estrogen receptor (ER)-positive cases to be found significantly more often in early stage cancer than advanced stage cancer. On the other hand, ER negative cases were found to have a greater incidence of high-grade lymph node metastasis and were seen significantly more frequently in large tumors. Span-1, CA19-9, and SLEX antigens were detected in 33 per cent, 38 per cent, and 64 per cent of the total cases, respectively and the ratio of ER negative cases was significantly higher in each antigen positive group. Irrespective of the presence or absence of lymph node metastasis, ER negative cases were found significantly more often in antigen-positive groups than in their counterparts and tumor size tended to be greater in the antigen-positive cases. The results of this study thus indicated that the disease progression in breast cancer appears to be correlated with ER status and carbohydrate antigen expression.

Antigens, Neoplasm↗

PubMed1990

Recovery of the slow inward current from Ca2(+)-mediated and voltage-dependent inactivation in the rabbit sinoatrial node.

The process of recovery from inactivation of the slow inward current (isi) in the rabbit sinoatrial (S-A) node was evaluated by voltage clamp experiments using double microelectrode method. Double pulse experiments were carried out on preparations loaded with Cs+ using nystatin. The rate of the rapid isi inactivation depended on the amplitude of isi rather than the membrane potential. After a 50 ms depolarizing prepulse isi rapidly recovered from inactivation at -40 mV with a time constant of 84 +/- 25 ms, whereas after a longer prepulse, an additional slow recovery phase with a time constant of 1 to 2 s was observed. The amount of isi during the fast recovery phase following a 300 ms prepulse to -20 mV was smaller than that following a prepulse to +20 mV, as predicted by a Ca2(+)-mediated inactivation mechanism. Conversely, a prepulse to +20 mV caused a greater inactivation in the slow recovery phase, suggesting a voltage-dependent mechanism. The inactivation curve obtained during the fast recovery phase using 50 ms prepulses was U-shaped, indicating a predominant role of the Ca2(+)-mediated mechanism, whereas that obtained during the slow recovery phase resembled previously reported voltage-dependent steady state inactivation (f infinity) curve. These results indicate that the fast and slow phases of recovery represent the removal of Ca2(+)-mediated and voltage-dependent isi inactivation, respectively. The presence of Ca2(+)-mediated inactivation via steady state Ca2+ inflows was also suggested.

Animals↗

PubMed1990

Chronic progressive spinobulbar spasticity with disturbance of voluntary eyelid closure. Report of a case with special reference to MRI and electrophysiological findings.

We describe a 56-year-old man who had a progressive pseudobulbar palsy, spastic tetraparesis, forced laughing and disturbance of voluntary eyelid closure, and was clinically compatible with chronic progressive spinobulbar spasticity. Magnetic resonance images (MRI) revealed atrophy of the bilateral motor cortices and single photon emission tomography after intravenous injection of N-isopropyl-p-iodoamphetamine iodine-123 (IMP-SPECT) showed hyporadioactivity in the same regions. Electrophysiological studies on supranuclear paralysis of eyelid closure demonstrated that so-called apraxia and motor impersistence coexisted and that in attempts to keep the eyelid closed the inhibition of basal activity of the levator palpebrae superioris muscle and activation of the orbicularis oculi muscle were insufficient, indicating the impaired reciprocity of these ocular muscles. The corresponding lesion of these eyelid symptoms was considered to be the bilateral motor cortices.

Blinking↗

PubMed1990

The role of Na,K-ATPase inhibitor on pressor responsiveness in patients with benign essential hypertension.

To clarify the role of Na,K-ATPase inhibitor in the enhanced pressor response to infused noradrenaline (NA-R) in patients with benign essential hypertension (EHT), NA-R, plasma noradrenaline concentration (PNA), and blood ionized calcium (Ca2+) were investigated before and after intravenous injection of ouabain in 15 normotensive subjects (NT) and 13 EHT. NA-R was enhanced by ouabain in both NT and EHT. The augmentation of NA-R following ouabain injection (delta NA-R) and % delta NA-R were significantly lower in EHT than in NT. Following ouabain injection, no significant change in PNA and blood Ca2+ was observed in both NT and EHT. NA-R negatively correlated with PNA and blood Ca2+, which were estimated just prior to noradrenaline infusion, before ouabain injection as well as after. After ouabain, the regression line between NA-R and PNA or blood Ca2+ shifted toward higher NA-R level in NT, unlike in EHT. These results suggest that an exogenous Na,K-ATPase inhibitor brings about a blunted enhancement of NA-R in EHT consistent with the presence of an endogenous Na,K-ATPase inhibitor in EHT.

Adult↗

PubMed1990

Diabetic strain (WBN/Kob) of rat characterized by endocrine-exocrine pancreatic impairment due to distinct fibrosis.

A spontaneously developed endocrine-exocrine pancreatic dysfunction was observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. Nonobese male WBN/Kob rats developed glycosuria and hyperglycemia at around 9 months of age. Cumulative incidence of diabetes in male rats was 43% (33 of 76) at 12 months of age and reached 90% at the age of 21 months. In contrast, female rats did not become diabetic. Urinary excretion of amylase in WBN/Kob rats was significantly increased in comparison with control Wistar rats. Moreover, the exocrine pancreatic function test was impaired in WBN/Kob rats. Pathological examination of pancreata revealed infiltration of inflammatory cells, hemorrhage, deposition of hemosiderin, and fibrinous exudation around pancreatic ducts and blood vessels at 3 months of age. A gradual increase of fibrous tissue into the exocrine tissue and islets was observed with advancing age. The extremely enlarged interlobular lymph nodes were also observed. At the age of 12 months, the fibrous tissue replaced extensive areas of the pancreas and involved islets. The amylase content of pancreata in WBN/Kob rats was markedly decreased in comparison with that in Wistar rats at 12 months of age. Islets composed of few endocrine cells were detected. Immunohistochemical staining for insulin and glucagon showed a decreased number of not only B cells but also A cells. Moreover, both the pancreatic insulin and glucagon contents were markedly decreased in WBN/Kob rats in comparison with Wistar rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

PubMed1990

Intracerebroventricular infusions of insulin increase vasopressin release in rats.

1. The role of cerebral insulin or insulin-like immunoreactive substance (ILI) on arginine-vasopressin (AVP) release using rats was investigated. Feeding rats with a high salt diet for 4 weeks significantly decreased the contents of ILI in both the hypothalamus and pituitary gland. Intracerebroventricular infusions of insulin (4 and 40 micrograms/min for 30 min) increased plasma AVP concentrations dose-dependently without hypoglycaemia, but decreased hypothalamic and pituitary contents of AVP. 2. These results indicate that ILI in the brain may play a role in the secretion of AVP, and that this mechanism could be operated to control a water-sodium balance.

Animals↗

PubMed1990

A histopathological study on senile changes in the human olfactory bulb.

Senile changes in the human olfactory bulb were studied histopathologically in 133 individuals ranging in age from 40 to 91 years with a mean age of 64.3 years. Neurofibrillary tangles (NFTs) in the olfactory bulb were observed in 47 subjects aged over 50 years. The frequency of NFTs was 35.3% (47/133) in total and 40.5% (47/116) among subjects 50 years of age or older. The frequency of individuals with NFTs increased linearly with age. Senile plaques (SPs) were observed in 5 individuals over 60 years old at a frequency of 3.8% (5/133) in total and 5.7% (5/88) among individuals 60 years old or more. Granulovacuolar degeneration was rarely seen, and amyloid angiopathy was not recognized. Senile changes in the hippocampus and parahippocampal gyrus were also examined. In some cases, the frequencies of NFTs and SPs in the hippocampal region were not identical to those in the olfactory bulb. However, it was not apparent whether senile changes first appear in the olfactory bulb or in the hippocampal region.

Adult↗

PubMed1990

Chronological observations of histological changes, cytochrome oxidase activity and copper level in the brain of the postnatal brindled mouse.

Neuropathological and enzyme-histochemical studies were performed on brindled mouse hemizygotes (BMs) and normal littermates at the age of 2 days, 7 days, 11 days and 14 days, together with an investigation of their tissue copper levels. A greatly increased copper concentration was confirmed in the kidney and intestine and a greatly reduced concentration in the liver and brain of BMs. The copper concentration in the brain increased gradually with age in the normal littermates, whereas this did not occur in BMs. There was no significant difference in the tissue copper concentration between the cerebrum and the cerebellum-brainstem in BMs or in normal littermates. Light and electron microscopy of the BM brain revealed progressive neuronal degeneration in association with increased mitochondrial changes (ballooning and crista disintegration). Enzyme histochemical examinations demonstrated a progressive comparative decrease (i.e., an increased difference from normal) of cytochrome oxidase activity in the BM brain. These data suggest that progressive degeneration of the brain in Menkes' disease is attributable to mitochondrial degeneration caused by a comparative decrease of both copper concentration and cytochrome oxidase activity in the brain.

Animals↗

PubMed1990

Role of dopaminergic mechanisms in the kidney for the pathogenesis of hypertension.

1. To estimate the role of renal dopaminergic mechanisms in the pathogenesis of hypertension, patients with essential hypertension and animal models of hypertension were investigated. 2. Impaired dopaminergic activity in kidneys for natriuresis was observed in patients with 'salt-sensitive' hypertension and with low-renin hypertension. 3. Decreased dopaminergic activity in kidneys was observed in the Dahl S-rats without salt loading. 4. In spontaneously hypertensive rats, renal dopamine synthesis was enhanced whereas there was a decrease of adenylate cyclase activity in renal tubules. 5. Demonstration of impaired dopaminergic mechanisms in kidneys of human and animal hypertension suggests that renal dopaminergic mechanisms play an important role in development of hypertension.

Animals↗

PubMed1990

Ryanodine facilitates calcium-dependent release of transmitter at mouse neuromuscular junctions.

1. Quantal release of transmitter was measured intracellularly at mouse neuromuscular junctions in the presence and absence of ryanodine (Rnd). 2. Rnd at concentrations up to 1 microM did not significantly alter the frequency of miniature endplate potentials (m.e.p.ps) in the presence or absence of Ca2+, suggesting that Rnd is unlikely to alter the internal concentration of Ca2+ ([Ca2+]i) at rest. 3. In a high-K+ (10 mM) bathing solution, Rnd further potentiated the facilitatory effect of Ca2+ on the frequency (F, s-1) of m.e.p.ps. Rnd shifted the relationship between 1n(F) and 1n[Ca2+]o to lower concentrations. 4. In a high-Mg2+ bathing solution, Rnd did not affect the frequency of m.e.p.ps at any value of [Ca2+]o. However, Rnd slightly but significantly increased the quantal content (m) of e.p.ps. It shifted the relationship between 1n(m) and 1n[Ca2+]o to lower concentrations. These results suggest that Rnd potentiates the quantal release of transmitter after depolarization of the membrane or nerve impulse, in keeping with the cooperativity of Ca2+ at the active site. 5. A series of two closely spaced nerve impulses produced a facilitation of transmitter release, as judged by the quantal content (m2) of the second response in relation to that of the first one (m1), m2/m1. Rnd did not change the ratio m2/m1. Thus Rnd is unlikely to affect the rapid phase of the sequestration of Ca2+ inside the nerve terminal. 6. High levels of K+ (5 mM) and caffeine (2 mM) potentiated both modes of transmitter release, in a manner dependent on [Ca2+]o. Caffeine did not potentiate facilitation of transmitter release. 7. These results indicate that Rnd facilitates the quantal release of transmitter presumably via an increase in [Ca2 ]i by a manner different from that of high-K+ or caffeine. The results suggest that Rnd probably affects calcium turnover in neuronal cells.

Alkaloids↗

PubMed1990

High ratio of HTLV-1-infected cells in HTLV-1 associated myelopathy (HAM).

Sixteen patients with HTLV-1 associated myelopathy (HAM) were examined for the presence of HTLV-1 provirus genome by Southern blot analysis of genomic DNA from peripheral blood mononuclear (PBM) cells. Random integration of the provirus was detected in 14 of 16 HAM patients. By contrast, the provirus genome could not be detected in 6 non-HAM HTLV-1 carriers, HAM patients were found to have significantly higher antibody titer to HTLV-1 in the sera compared with carriers. These features of HAM patients, i.e., detectable levels of provirus integration in PBM cells and high antibody titer to HTLV-1 in the sera, were noted in 2 wives of HAM patients with neurological signs and abnormalities. High anti-HTLV-1 antibody titer and detection of the provirus genome by Southern hybridizations may be useful for screening subclinical HAM cases and elucidating pathogenesis.

Adult↗

PubMed1990

Extramammary Paget's disease: comparative histopathologic studies of intraductal carcinoma of the breast and apocrine adenocarcinoma.

We examined 32 cases (38 lesions) of extramammary Paget's disease (EMPD) in relation to comparative studies on intraductal carcinoma of the breast (ductal carcinoma in situ, DCIS) and apocrine adenocarcinoma (AAC). Lesions included scrotum (18 lesions), vulva (8), axilla (6), groin (3), penis (2) and chest wall (1), and the distribution was compatible with that of apocrine or supernumerary mammary glands. Histologically, extra-mammary Paget's and DCIS cells exhibited a large amount of a pale-stained cytoplasm. The cytoplasm of AAC cells frequently contained granules, was eosinophilic and differed from that of Paget's or DCIS cells. Immunohistochemical studies revealed positive reactions for polyclonal and monoclonal antibodies to carcinoembryonic antigen in all EMPD and most DCIS, but not in AAC. Recent studies have shown that extramammary Paget's cells exhibit characteristics of glandular epithelial cells and that most cases of EMPD are not accompanied by an underlying carcinoma. The results obtained in this study, coupled with data on the frequency of the supernumerary breasts, lead to the speculation that extramammary Paget's cells originate from ectopic mammary glands or from pluripotential germinative cells in the epidermis, capable of differentiating toward the mammary glands.

Adenocarcinoma↗

PubMed1990

[An in vitro study on the treatment of complicated cystitis using an automatic simulator].

A computer simulation of a Kidney-bladder model was prepared for automatic control of the urine concentration of antibacterial drug administrated. The following results were obtained in an investigation of the problems of complicated cystitis in vitro using ofloxacin. 1) It was suggested that the time required for elimination of the bacteria was prolonged as the level of complication of the disease state in the urinary tract increased. 2) In the model of highly complicated cystitis caused by urinary flow stagnation, recurrences were observed in vitro even with administration of a large dose of ofloxacin. 3) The time required for a elimination of bacteria tended to become shorter as the dose of the antibacterial agent increased. 4) The time until the start of regrowth of the bacteria tended to be prolonged as the dose of the antibacterial agent increased. 5) It was suggested by our in vitro experiment that if the background disease became more complicated, it would be more difficult to treat, as in the case of complicated cystitis.

Computer Simulation↗