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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 91 records · Page 5Linked to original sources

Stopped-flow investigation of the reaction of vitamin C with tocopheroxyl radical in aqueous triton X-100 micellar solutions. The structure-activity relationship of the regeneration reaction of tocopherol by vitamin C.

A kinetic study of the reaction between vitamin C (L-ascorbic acid, AsH2) and a tocopheroxyl radical (7-tert-butyl-5-isopropyltocopheroxyl) in Triton X-100 micellar solution has been performed using stopped-flow spectrophotometry. The second-order rate constants (k2) obtained showed notable pH dependence with a broad maximum around pH 8. For instance, the k2 values obtained were 26 M-1 S-1 at pH 3, 322 M-1 S-1 at pH 7, and 273 M-1 S-1 at pH 10. A good correlation between the rate constants and the mole fraction of ascorbate monoanion (AsH-) was observed, showing that ascorbate (AsH-) can regenerate the tocopherol from tocopheroxyl in biological systems. Furthermore, the results indicate that reduced ascorbic acid (AsH2) does not have the ability to regenerate the tocopherol in aqueous solution. On the other hand, it was found that AsH2 can reduce the tocopheroxyl to tocopherol in benzene/ethanol (2:1) mixtures, although the rate of reaction is only approximately 15% of that observed in micellar solution at pH 7.

Ascorbic Acid

Genetic expression of Menkes disease in cultured astrocytes of the macular mouse.

The copper concentration was investigated in the cultured astrocytes from macular mice, an animal model of Menkes disease. An excessive amount of copper was accumulated in the astrocytes as copper-metallothionein. These results show that the underlying genetic defect of the macular mouse is expressed in the astrocytes. A similar situation may exist in Menkes disease and cause a failure of copper transport to neurones.

Animals

Multicentric reticulohistiocytosis associated with subclinical Sjögren's syndrome.

A case of multicentric reticulohistiocytosis in a 60-year-old Japanese woman associated with subclinical Sjögren's syndrome is presented. The clinical features along with the light microscopic studies are commented. Partial improvement of the skin lesions and tendon sheath swelling was achieved after treatment with cyclophosphamide but the patient's general condition remained unchanged. Taking the rarity of multicentric reticulohistiocytosis into account, coexistence of these two conditions in the present and previously reported cases suggests that an autoimmune mechanism may play a part in the pathogenesis of multicentric reticulohistiocytosis.

Cyclophosphamide

Respiratory outcome in extremely premature infants following ketamine anaesthesia.

Premature infants are prone to develop postoperative apnoea. The purpose of the present study was to determine if risk factors could be identified to predict which patients would require postoperative tracheal intubation and lung ventilation. Twenty-five extremely premature infants (birth weight: 811 +/- 242 g (mean +/- SD) and operation weight: 1585 +/- 394 g) needing cryotherapy for retinopathy were studied. After surgery the tracheas were extubated if there was no prolonged apnoea, SaO2 greater than 85%, and heart rate greater than 120 bpm. In eight, tracheal extubation in the operating room was unsuccessful. Using multivariate discriminant analysis, four risk factors correlated with the need for pulmonary ventilation-gestational duration, birth weight, postconceptional age, and preoperative aminophylline treatment for seven days. A scoring system using these factors successfully predicted the need for a tracheal tube after surgery in 92% of patients. It is concluded that the system may be clinically useful in the perioperative care of low-birth-weight infants as it identifies important variables for evaluating postoperative prolonged apnoea.

Age Factors

Effect of a cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, on myocardial reperfusion injury.

A new cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, was examined to see whether myocardial reperfusion injury could be reduced in a setting of cardioplegic arrest through its antiaggregation effect on leukocytes. Isolated rabbit heart models with whole blood perfusion were used, and 18 hearts were divided into three groups according to the reperfusion method: control (G-1, n = 5), DN-9693 (G-2, n = 7), and leukocyte depletion (G-3, n = 6). The hearts were subjected to 120 minutes of cold global ischemia under crystalloid cardioplegia followed by 30 minutes of reperfusion. A dose of 20 micrograms.kg-1.min-1 of DN-9693 was administered in G-2, and a leukocyte removal filter was used in G-3 during reperfusion. Ultrastructural changes in mitochondrial injuries, intracellular edema, and capillary injuries of the myocardium showed worse changes in G-1 than in G-2 and G-3. Under microscopic study, the intracapillary leukocyte count was significantly higher in G-1 than in G-2 and G-3. Recovery of rate-pressure product, left ventricular developed pressure, and coronary flow were significantly better in G-2 and G-3 than in G-1. There were no significant differences between G-2 and G-3 for all these indices. These results indicate that reperfusion with leukocyte-depleted blood attenuates reperfusion myocardial injury and DN-9693 has a comparable myocardial protective effect with possible inhibition of leukocyte aggregation.

3',5'-Cyclic-AMP Phosphodiesterases

Cerebral angio- and neuro-Behçet's syndrome: neuroradiological and pathological study of one case.

Cerebral angio-Behçet's syndrome is extremely rare and pathological studies are scarce. We describe a 63-year-old man who developed left homonymous hemianopsia and hemiparesis 16 years after the onset of cardinal symptoms of Behçet's syndrome. CT, MRI and PET studies disclosed cerebral lesion with reduced neuronal metabolism in the right hemisphere, which was resolved by glucocorticoid therapy. Cerebral angiography showed no filling of the right Rolandic, anterior and posterior parietal and angular arteries. The postmortem study revealed: (a) occlusive panarteritis of some medium-sized pial branches of the right middle cerebral artery, considered as angio-Behçet's pathology, and small infarctions due to the vascular occlusion; (b) patchy or confluent demyelinated foci with perivascular lymphocytic infiltration in the bilateral brain basis, predominantly in the right retro- and sublenticular structures, being equivalent to neuro-Behçet's pathology. Cerebral angio- and neuro-Behçet's syndromes could have occurred and progressed concomitantly, which suggests a close relationship between the two subclassified processes.

Arterial Occlusive Diseases

Oxygen consumption stimulated by increases in permeability of Na+ of mouse diaphragm muscle in vitro.

1. The effects on oxygen consumption of agents that modify Na(+)-permeability were examined in mouse diaphragm muscle perfused with a bathing solution that contained (+)-tubocurarine in a flow-through mode. Twitch tension and levels of Na+ and K+ in the muscle were also measured. 2. Unstimulated preparations decreased the concentration of oxygen in the bathing solution, indicating a basal level of oxygen consumption. Electrical stimulation of the muscle further decreased the concentration of oxygen. Potassium cyanide eliminated both the basal and the stimulated consumption of oxygen. 3. Veratridine facilitated the effect of stimulation at 0.1 Hz on both the consumption of oxygen and the twitch tension. Ouabain antagonized those effects. 4. Twitch contractions were blocked in the presence of dantrolene sodium or by pretreatment with ethylene glycol. Electrical stimulation of such preparations still caused a residual but considerably decreased consumption of oxygen. Ouabain and tetrodotoxin reduced the residual consumption of oxygen. 5. Ouabain significantly increased the levels of Na+ in the tissue, while veratridine alone did not. The effect of ouabain was further potentiated by the simultaneous presence of veratridine. 6. These results indicate that the enhancement of the sarcolemmal permeability to Na+ increases the rate oxygen consumption. This concept supports the hypothesis that Na+ homeostasis depends on energy consumption.

Animals

Evaluation of a new finger-type intraoperative epicardial echocardiographic probe for infants and small children.

A new finger-type epicardial echocardiographic probe was evaluated in 26 children with complex cardiac anomalies during open heart surgery. The probe is a small 3.75 MHz phased array transducer for 2-dimensional echo and color Doppler imaging. The tip is slightly angled to facilitate the apical approach through a median sternotomy. The patients included 4 neonates and 8 infants, and the major cardiac lesions were complete atrioventricular (AV) canal, transposition of the great arteries, double outlet right ventricle, and others. The intraoperative study was possible in most of the patients facilitating various approaches for the assessment of left-sided AV valve function, left ventricular outflow obstruction, residual shunt and intraatrial anatomy. Four patients received subsequent operative procedures after the assessment. This transducer appears to be useful in the intraoperative study during surgery for complex cardiac anomalies in neonates and small infants.

Child

Changes of copper level and cytochrome c oxidase activity in the macular mouse with age.

The macular mouse is an animal model of Menkes disease. The neurological degeneration is caused by decreased cuproenzymes activity, such as cytochrome c oxidase (CCO), associated with copper deficiency in the brain. We investigated the age-related changes in copper concentration and CCO activity in the brain of macular mice which were given a single injection of cupric on postnatal day 7. The copper concentration in the brain of macular mice was always about 40% of that of the age-matched controls. However, the copper concentration of both macular and control mice increased with age gradually. The CCO activity in the brain of macular mice was significantly lower than that of controls at the age of 8 days. However the activity in macular mice increased with growth and reached a level equal to the controls at 180 days. These results suggest that the improvement of CCO activity in the brain of macular mice is due to the brain copper concentration which increased with age. Therefore, parenteral administration of copper is recommended especially during infancy in patients with Menkes disease.

Aging

Chronic intracerebroventricular infusions of endothelin elevate arterial pressure in rats.

We investigated the effects of intracerebroventricular infusions of endothelin on cardiovascular and endocrinological responses using conscious, unrestrained rats. Chronic intracerebroventricular infusions of endothelin, 10 pmol/h for 7 days, elevated arterial pressure significantly on days 5, 6 and 7 of the infusion, compared with intracerebroventricular infusions of the vehicle. Heart rate decreased from day 1 of the infusion of endothelin until the end of the experiment. The urinary excretion of norepinephrine increased on day 3 and epinephrine increased on days 3, 4 and 5 of endothelin infusion. The urinary excretion of arginine vasopressin increased on day 5, 6 and 7 of the infusion. These findings suggest that chronic intracerebroventricular infusions of endothelin elicit elevations in arterial pressure and that the initiation of blood pressure rises can be related to sympathetic activation although the actual role for the pressor responses has been played by the released arginine vasopressin.

Animals

The effects of insulin and insulin-like materials in the brain on central cardiovascular regulation: with special reference to the central effects of sodium chloride.

The present study investigated the roles of insulin on central cardiovascular regulation. When rats were fed with a high-salt diet for 4 weeks, hypothalamic and pituitary contents of insulin-like immunoreactive substance (ILI) significantly decreased. The plasma concentration of ILI remained unaltered, however. Intracerebroventricular injections of insulin significantly decreased both the blood pressure and the heart rate, with corresponding decreases in renal sympathetic nervous activity in urethane-anesthetized rats. Microinjections of insulin into the ventromedial nucleus in the hypothalamus caused greater vasodepression and bradycardia compared with the intracerebroventricular injections. Intracerebroventricular infusions of insulin inhibited the pressor effects of simultaneously-infused hypertonic saline, and the digitalis-like immunoreactivity in both the plasma and the hypothalamus were significantly decreased by the insulin. These results indicate that ILI in the brain affects the central cardiovascular regulation through the suppression of both sympathetic nervous system activity and the release of digitalis-like substances. These mechanisms may operate particularly during a sodium load.

Animals

Effects of intracerebroventricular and intravenous injections of endothelin-1 on blood pressure and sympathetic activity in urethane-anesthetized rats.

Because endothelin-1 (ET-1) is believed to be an endogenous calcium-channel agonist, it was thought that it may affect not only vascular smooth muscle cells but also nerve activity. Intravenous injections of ET-1 (0.01 nmol) did not affect cardiovascular parameters or renal sympathetic activity. ET-1 (1 nmol) initially decreased blood pressure for a few minutes, and then caused an increase for 5-10 min. Blood pressure then returned to baseline but later there was a rise in pressure for more than 60 min. Sympathetic activity was markedly suppressed during the initial hypertensive phase but increased during the later phase. Intracerebroventricular injections of ET-1 increased blood pressure even with the small dose (0.01 nmol). The increase was maintained for about 10 min, and returned to baseline. It then decreased abruptly with marked bradycardia, and finally returned to the baseline 60-90 min later. These results indicate that ET-1 affects not only the vascular smooth muscle but also the autonomic nervous system to influence cardiovascular functions.

Anesthesia

Chalazion coexisting with dacryolithiasis.

A 41-year-old woman presented with a painless hard subcutaneous nodule in the right upper eyelid. The lesion was diagnosed clinically as pilomatricoma and removed surgically. Histological examination disclosed a granulomatous lesion composed mainly of mononuclear cells with a foamy appearance and multinucleated giant cells with some admixture of granulocytes, plasma cells, and lymphoid cells. Lipid droplets and dilated ductal structures containing an eosinophilic fibrillar substance were observed in and around the granulomatous lesion. In addition, an intraductal dacryolith was seen near the granulomatous lesion. We finally diagnosed this case as chalazion; the coexisting dacryolithiasis was considered to be involved in the pathogenesis of chalazion.

Adult

Gene deletions in Japanese patients with Duchenne and Becker muscular dystrophies: deletion study and carrier detection.

Fifty unrelated Japanese patients with Duchenne and Becker muscular dystrophy (DMD and BMD) have been studied through use of the dystrophin cDNA probes. The 14-kb dystrophin cDNA was subdivided into six subclones, and Hind III-digested DNAs were analyzed by Southern blotting. Of 50 unrelated patients, 20 showed a deletion of one or several of the exon-containing Hind III fragments (40.0%). These corresponded to 50% (11/22) of BMD patients and 32.1% (9/28) of DMD patients, and the position and extent of deletions were mapped and proven to be more heterogeneous in DMD than in BMD. Both ends of deletions detected by probe 1-2a were common to all six BMD patients, and the 5' ends of deletions in probe 5b-7 were also common to four BMD patients. The phenotypic-specific deletion in Japanese BMD patients existed in the 5' end of the DMD gene, although an apparently similar deletion produced a wide range of clinical courses (BMD phenotype). Three out of eight females in DMD/BMD families were diagnosed as carriers through use of the junctional fragment and dosage analyses of dystrophin cDNA.

Adolescent