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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 487 records · Page 27Linked to original sources

Recovery of diaphragmatic function in awake sheep after two approaches to thoracic surgery.

Video-assisted thoracoscopic surgery (VATS) is replacing thoracotomy, but no study has addressed the extent or duration of VATS-induced diaphragmatic alteration. We hypothesized that VATS would impair diaphragmatic function less and return diaphragmatic function faster than thoracotomy. In eight sheep, sonomicrometers were randomly implanted on the right costal diaphragm via VATS or thoracotomy. Diaphragmatic resting length, shortening fraction, and respiratory function were measured weekly during quiet breathing (QB) and CO2 rebreathing for 4 wk. For VATS, shortening fraction was smallest on postoperative days 1 (POD 1) (6.4 +/- 3.4 and 12.9 +/- 8.7% during QB and 10% CO2 rebreathing, respectively) and 7 (6.3 +/- 3.4 and 16.9 +/- 4.0% during QB and 10% CO2 rebreathing, respectively) and recovered by 3 wk (13.2 +/- 1.8 and 28.9 +/- 8.0% during QB and 10% CO2 rebreathing, respectively). For thoracotomy, shortening fraction at 10% CO2 rebreathing was smaller on PODs 1, 7, 14 (15.9 +/- 7.1, 13.6 +/- 5.4, and 19.0 +/- 6.9%) than on POD 28 (29.9 +/- 8.2%), but not during QB on POD 1 or 7 (7.5 +/- 3.8 and 3.4 +/- 2.6%) compared with POD 28 (10.7 +/- 8.7%). Shortening fraction did not differ between surgeries. There was no group difference in minute ventilation, respiratory rate, transdiaphragmatic pressure, or esophageal and gastric pressures. In conclusion, although shortening fraction recovered faster for VATS, this translated into insignificant functional differences.

Animals↗

Continuous versus bilevel positive airway pressure in a patient with idiopathic central sleep apnea.

A 57-yr-old man with idiopathic central apnea is reported. He presented at our hospital complaining of excessive daytime sleepiness. Polysomnography, including esophageal pressure monitoring, confirmed central sleep apnea with an apnea index of 27/h. He had mild non-insulin-dependent diabetes mellitus (NIDDM) but no signs of diabetic neuropathy or other background diseases. The ventilatory responses to hypoxia and hypercapnia tested while he was awake indicated increased respiratory chemosensitivity. We applied nasal continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BPAP) in an attempt to compare the possible difference in therapeutic efficacy. Although nasal CPAP completely reversed central apnea, nasal BPAP adversely affected both apnea length and frequency in an applied pressure-dependent manner. Arterial blood gas analyses while he was being treated indicted alveolar hypoventilation with CPAP and hyperventilation with BPAP. Additionally, administration of a mixed gas containing 5% CO2 through a face mask had a significant effect on the disappearance of central apnea in this patient. These findings support the theory that the arterial PCO2 level is critical in generating idiopathic central apnea and that nasal CPAP therapy may be effective in eliminating central apnea by raising the PaCO2.

Blood Gas Analysis↗

Mutation analysis and expression of the mottled gene in the macular mouse model of Menkes disease.

The gene for Menkes disease, an X-linked disorder of copper transport, has recently been identified and shown to encode a copper-transporting P-type ATPase. The macular mutant mouse has been proposed as an animal model for Menkes disease. In the present study, we report the finding of a missense mutation in the mottled gene of the macular mouse. A single base change, T to C, at nucleotide position 4223, is predicted to result in an amino acid change from serine to proline at residue 1382 in the eighth transmembrane domain. This mutation differs from the 6-bp deletion we find in brindled cDNA. With validation of macular as an animal model of Menkes disease, we compared mottled gene expression in the intestine, kidney, and brain of macular and normal mice. In Northern analyses an 8.3-kb transcript was detected in the intestine, kidney, and brain of both normal and macular mice, with the level of transcript in macular approximately 80% that of normal. In situ hybridization studies revealed that the mottled gene was clearly expressed in intestinal epithelial cells, Paneth cells, and renal proximal tubular cells of both normal and macular mice. In normal brain, mottled gene expression was most intensely observed in the choroid plexus, in Ammon's born and the dentate gyrus in the hippocampus, in Purkinje cells, and the granular layer of the cerebellum. The intensity and localization of the signals in the brain of macular mice were similar to those of the controls. The distribution of expression of mottled is correlated with cells and tissues showing histopathology or abnormal copper sequestration in macular and other mutants.

Adenosine Triphosphatases↗

Influence of albumin on enantioselective local disposition of BOF-4272, a xanthine oxidase inhibitor with chiral sulfoxide, in rat liver.

8-(3-Methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one (BOF-4272) blocks xanthine oxidase/xanthine dehydrogenase in the liver. BOF-4272 with a sulfoxide chiral center includes R(+)- and S(-)-enantiomers. The enantioselectivity in the global disposition of BOF-4272 can be attributed to that in the local disposition of organs, especially the liver. Thus, the enantioselectivity in the hepatic local disposition of BOF-4272 was compared between R- and S-enantiomers by a hepatic perfusion experiment with a pulse input into the portal vein. The influence of perfusate albumin on the enantioselective local disposition was also investigated. The elution time profile of each BOF-4272 enantiomer from the liver into the hepatic vein was measured at four different bovine serum albumin (BSA) concentrations (0, 0.25, 1.0 and 4.0%) in the perfusate at 37 and 4 degrees C. A crossover test was carried out for R- and S-enantiomers using one rat liver. In the absence of perfusate BSA at 37 degrees C, hepatic extraction ratios (E[H]) of R- and S-enantiomers of BOF-4272 were 75.6 +/- 4.3% and 71.7 +/- 3.3%, respectively, which were statistically the same. In the presence of 4.0% BSA at 37 degrees C, E(H) values of R- and S-enantiomers were 31.7 +/- 4.6% and 19.6 +/- 3.8%, respectively, which demonstrated that E(H) of R-enantiomer was significantly greater than that of S-enantiomer (p < 0.001). In the absence and presence of perfusate BSA at 4 degrees C, there was no significant difference in E(H) between S- and R-enantiomers. An amplification of stereoselectivity with albumin was observed by the perfusion experiment using BOF-4272 enantiomers.

Albumins↗

mRNA expression and cDNA sequences of beta- and gamma-sarcoglycans are normal in cardiomyopathic hamster heart.

In BIO14.6 cardiomyopathic hamster heart, the dystrophin-glycoprotein complex is disrupted and sarcoglycans are greatly reduced in abundance. We examined whether the gene expression of beta- and gamma-sarcoglycans is indeed defective in this hamster. We found that mRNA expression for these proteins and the cDNA sequences of their coding regions are identical in both normal and myopathic hamster cardiomyocytes. The results strongly suggest that defect in a currently unknown sarcoglycan-associated protein(s) is responsible for the deficiency of the sarcoglycan complex that leads to muscle cell necrosis in the myopathic hamster.

Amino Acid Sequence↗

[Effects of phenylalanine and tyrosine on cold acclimation in mice].

The effects of phenylalanine (PHE) and tyrosine (TYR) on cold acclimation were studied in mice of the ddY strain. At 5 weeks of age, mice were maintained at 4 degrees C for 4 weeks. Test groups of mice were supplied with a 0.05% (w/v) solution of PHE or TYR as drinking water in addition to water. We measured changes in body weight, intake of water and food, rectal temperature upon acute exposure to -20 degrees C, weight of interscapular brown adipose tissue (BAT) and the levels of glucose, nonesterified fatty acids (NEFA) and 3H-butyrate in the blood prior to and after exposure to the lower temperature of -20 degrees C. Chronic exposure to cold (4 degrees C) reduced body-weight gain for the first two weeks but weight gain recovered within the next two weeks. PHE and TYR partially inhibited the gain in body weight under exposing to cold. TYR reduced the gain of body weight under room temperature. Exposure to cold stimulated the daily consumption of food. Both PHE and TYR somewhat enhanced the food intake when exposed to cold. Exposure to cold rendered mice resistant to severe cold (-20 degrees C). Both PHE and TYR did not reduce this resistance except in the early state in the case of TYR. Exposure to cold increased the weight of BAT but both PHE and TYR prevented this increase. The effect of TYR was determined in the case fed under room temperature. Cold exposure changed the utilization of glucose, NEFA and 3H-butyrate in the blood when exposed to severe cold (-20 degrees C). Both PHE and TYR prevented the change in NEFA. It remains to be confirmed whether the growth of brown adipocytes is always necessary when mice acclimate to cold.

Acclimatization↗

[Effects of adenosine and adenine on cold acclimation in mice].

The effects of adenosine (ADO) and adenine (ADE) on cold acclimation were studied in mice of the ddY strain. At 5 weeks of age, mice were maintained at 4 degrees C for 4 weeks. Test groups of mice were supplied with a 0.05% (w/v) solution of ADO or ADE as drinking water in addition to water. We measured changes in body weight, intake of water and food, rectal temperature upon acute exposure to -20 degrees C, weight of interscapular brown adipose tissue (BAT) and the levels of glucose, nonesterified fatty acids (NEFA) and 3H-butyrate in the blood prior to and after exposure to the lower temperature of -20 degrees C. Chronic exposure to cold (4 degrees C) reduced body-weight gain for the first two weeks but weight gain recovered within the next two weeks. ADO partially but selectively inhibited the gain in body weight. This effect was marked in mice maintained at room temperature. Such an inhibitory effect was the case of ADE in the room temperature. Exposure to cold stimulated the daily consumption of food. ADO further and selectively enhanced food intake, but ADE enhanced that in room temperature. Cold increased in daily intake of water. Both ADO and ADE accelerated the intake of water. This effect was marked in mice maintained at 4 degrees C and the effect of ADE was considerable. Mice chose to drink the water that contained ADO, while the choice of water that contained ADE was apparent only during exposure to cold. Exposure to cold rendered mice resistant to severe cold (-20 degrees C). ADO and ADE partially reduced this resistance. Exposure to cold increased the weight of BAT but ADO selectively prevented this increase. Cold did not change the levels of the various compounds measured in the blood. In mice exposed to 4 degrees C for 4 weeks, acute exposure to severe cold decreased the glucose level and increased the levels of NEFA and 3H-butyrate. ADO selectively prevented the changes in the levels of NEFA and 3H-butyrate. It remains to be confirmed whether the growth of brown adipocytes is always necessary when mice acclimate to cold.

Acclimatization↗

Restriction of dietary sodium may enhance nitric oxide production in rats.

To clarify the precise relationship between sodium and nitric oxide (NO), we studied the effects of altered sodium intake on NO production. Male Wistar rats were maintained on a low-sodium (0.2% NaCl), normal-sodium (2% NaCl), or high-sodium (8% NaCl) diet for 10 days or 8 weeks; 24-h urine was collected at those times for assay of nitrate ion (NO3-), a stable metabolite of NO, and of cyclic GMP. Urinary excretion of NO3- and cyclic GMP was increased on the 10th day in the low-sodium group, as compared with the normal- and high-sodium groups. The urinary excretion of cyclic GMP was increased at the 8th week, and NO3- showed a tendency to increase in the low-sodium group, as compared with the high-sodium group. An up-regulation of NO production may explain, at least in part, the antihypertensive effect of sodium restriction.

Animals↗

Spontaneous skin lesions in beige rats (Chediak-Higashi syndrome of rats).

Beige rats, a model animal of Chediak-Higashi syndrome (CHS), frequently developed the skin lesions consisting of crust formations and alopecia in the skin around the neck from about 4 months of age. Erosion and ulceration were also observed in advance of the skin lesions. In severe cases, the lesions spread to all of the dorsum of the trunk. Skin tissues with or without lesions were studied histopathologically in 41 beige rats comparing with normal skin from 26 age-matched DA rats. Microscopically, epidermal lesions consisted of spongiosis, pustules and erosions with crust. Inflammatory cells in pustules consisted predominantly of eosinophil, and colonization of gram-positive cocci was occasionally observed in the surface area. Mites on the epidermis were also seen in some cases. Dermal lesions were superficial perivascular inflammatory cell infiltrations of eosinophils, neutrophils and mastocytes, and edema under the epidermal lesions. Follicles in the alopecic area showed resting stage and atrophic hair germ, but inflammatory changes were slight. Morphologic characters were very similar to those of chronic eosinophilic dermatitis or spongiotic dermatitis.

Animals↗

Performance characteristics of bilevel pressure ventilators: a lung model study.

Bilevel pressure ventilators are being used increasingly to provide noninvasive ventilatory support in the management of obstructive sleep apnea, chronic ventilatory failure, and acute respiratory failure. However, the ability of these ventilators to respond to inspiratory demand without imposing expiratory loads has not been evaluated extensively. We evaluated the performance of nine bilevel pressure ventilators in a lung model, as compared with the Nellcor Puritan-Bennett 7200ae adult critical care ventilator. All ventilators were set to provide pressure support ventilation (PSV) and positive end-expiratory pressure (PEEP) at a rate of 10 breaths/min with an inspiratory time of 1.0 s. Simulated pleural pressure, airway pressure, and flow at airway opening were continuously monitored. We studied the effects of three PSV levels (5, 10, and 15 cm H2O) with 5 cm H2O PEEP at two lung compliances (50 and 80 mL/cm H2O) and four peak inspiratory flow demands (20, 40, 60, and 80 L/min) on seven dependent variables: inspiratory delay time (D-I), inspiratory trigger pressure (P-I), inspiratory area percent (Area I%), expiratory delay time (D-E), supraplateau expiratory pressure change (P-E), expiratory area (Area E), and ventilator peak flow (VPF). Most ventilators performed as well as or significantly (p<0.05) better than the 7200ae in all studied variables. Compliance did not significantly affect ventilator performance. Increasing inspiratory flow demand significantly (p<0.05) increased D-I, P-I, P-E, and VPF and decreased Area I% with most ventilators. As ventilatory demand increased, D-E and Area E significantly (p<0.05) changed. With some units, D-E and Area E increased, while with others they decreased. Most bilevel pressure ventilators evaluated were able to respond to high ventilatory demands and outperformed the Nellcor Puritan-Bennett 7200ae ventilator.

Calibration↗

[A clinical study on combination therapy of antimicrobial agents for complicated urinary tract infection--with special reference to combination with clarithromycin].

PURPOSE: To confirm the clinical efficacy of the combined therapy to complicated urinary tract infection (UTI), we conducted a comparative clinical study of the combined therapy with ciprofloxacin (CPFX) and clarithromycin (CAM) acting an biofilm elimination or CPFX alone in patients with complicated UTI. PATIENTS AND METHODS: The study was carried out in patients with complicated UTI having WBCs with 5/hpf or more in urinary sediment and bacteriuria at least 10(4) CFU/ml. The combined therapy was CPFX and CAM, each 600 mg/day, for 14 days, and the single therapy group CPFX, 600 mg/day, for 14 days. On Day 7 and 14, the eradication rate and efficacy rate (according to the criteria of the Japanese UTI committee) were determined. In the patients with indwelling catheter, the surface of the catheter tip was observed under a scanning electron microscope (SEM) on Day 14. RESULTS: In both cases with and without catheters, clinical efficacy was higher in the combined therapy group than in the single therapy group. In particular, the efficacy rates at 14 Day were significantly higher in the former group. Furthermore, we investigated the therapeutic effect in the below MIC breakpoint of CPFX in complicated UTI. The combined therapy group showed a higher clinical efficacy in both cases with and without indwelling catheter than the single therapy group, although there was not statistically significant. Biofilm on the surface of the catheter tip was eliminated in 75% of the combined therapy group. However, none of the biofilm was eliminated in the single therapy group. CONCLUSION: From the above results, we surmise that the combined use of CPFX and CAM will show some degree of efficacy in eliminating both the causative organism and its biofilm in the complicated UTI.

Adult↗

[Is reduced left ventricular volume related to mechanisms of dynamic mid-ventricular obstruction provoked by dobutamine infusion?].

Forty-seven patients with unexplained chest pain and normal resting echocardiograms were examined to see whether dynamic mid-ventricular obstruction (MVO) is induced by dobutamine infusion. Dynamic MVO was provoked in 17 patients (MVO group), but not in the other 30 patients (Non-MVO group). Before dobutamine infusion, the blood pressure in the MVO group was higher than that in the Non-MVO group (p < 0.05), but end-diastolic volume index (p < 0.001), end-systolic volume index (p < 0.01), stroke volume index (p < 0.001), cardiac index (p < 0.001), end-diastolic volume (p < 0.01) and end-systolic volume (p < 0.05) of the apical territory of the left ventricle in the MVO group were significantly less than those in the Non-MVO group. The left atrial function, left ventricular ejection fraction and ejection fraction of the apical territory of the left ventricle did not differ between the groups. Seven patients in the MVO group were re-examined by dobutamine stress echocardiography after beta-blocker administration, showing that the dynamic MVO was completely suppressed. The end-diastolic volume tended to increase after beta-blocker administration, but no significant difference was found in any other variables except heart rate. The results suggest that a smaller left ventricle and higher blood pressure are important characteristics in patients with dobutamine-induced dynamic MVO, and additionally, the difference in local myocardial contractility may be an important cause of the induction of dynamic MVO.

Adrenergic beta-Agonists↗

Cardiovascular regulation by L-arginine in the brain of rats: role of the brain renin-angiotensin system and nitric oxide.

The effect of brain L-arginine on arterial pressure was investigated by injecting L- or D-arginine into the cerebral ventricles of male Wistar rats that were anesthetized with urethane. Intracerebroventricular (I.C.V.) injection of 1 micromol L-arginine reduced the arterial pressure and the abdominal sympathetic nervous activity (SNA), whereas the injection of 10 micromol L-arginine induced a transient pressor response and reduced both the heart rate and SNA. Although I.C.V. injection of 1 micromol D-arginine had no effect on cardiovascular function or SNA, injection of 10 micromol of this enantiomer elicited a transient pressor response, similar to that induced by 10 micromol L-arginine, followed by a persistent increase in arterial pressure and a corresponding increase in SNA. I.C.V. pretreatment with the nitric oxide synthase inhibitor N(G)-monomethyl L-arginine abolished the vasodepressor response and reduced the inhibition of SNA induced by I.C.V. injection of 1 micromol L-arginine; such pretreatment increased the arterial pressure, heart rate, and SNA measured 30 min after I.C.V. injection of 10 micromol L-arginine. I.C.V. pretreatment with the angiotensin II type 1 receptor antagonist CV-11974 inhibited the pressor response to 10 micromol L-arginine and the first phase of the pressor response to 10 micromol D-arginine. Intravenous pretreatment with the alpha1-adrenoceptor blocker bunazosin hydrochloride abolished the pressor response to 10 micromol L-arginine and both phases of the pressor response to 10 micromol D-arginine. Brain L-arginine thus appears to exert pressor actions through stimulation of the brain renin-angiotensin system and peripheral SNA. However, these actions may be attenuated by L-arginine-derived nitric oxide.

Animals↗

Intravascular lymphomatosis diagnosed by transbronchial lung biopsy.

Intravascular lymphomatosis is a rare lymphoma presenting a variety of symptoms due to proliferation of tumour cells within blood vessels in the brain, the skin and other organs. This disease is generally considered to be highly malignant, but to be relatively susceptible to combined chemotherapy, when diagnosed in the early stage. We describe a case of intravascular lymphomatosis, presenting with diffuse interstitial shadows on chest radiographic image, which could be diagnosed by transbronchial lung biopsy. The patient showed a good response to combined chemotherapy. We propose that transbronchial lung biopsy is a useful procedure for the diagnosis of intravascular lymphomatosis.

Antineoplastic Combined Chemotherapy Protocols↗

[Type III procollagen N-peptide and hyaluronate in serum and dialysate of CAPD patients].

Long-term CAPD may develop peritoneal fibrosis, which is thought to be related to permanent loss of ultrafiltration capacity and sclerosing peritonitis. In CAPD patients, we examined the serum (P-) and effluent (D-) levels of type III procollagen N-peptide (P III P) and hyaluronate (HA), which are expected to change concomitantly with a local increase in submesothelial extracellular matrix of the peritoneum. We selected 40 CAPD patients (age: 46.3 +/- 11.3 years, time on CAPD: 33.6 +/- 26.2 months), who were not suffering from chronic liver disease, any inflammatory disease, nor peritonitis during the previous month. P-P III P, P-HA, D-P III P, and D-HA were measured by PET (values after 4-hour dwelling). D/P ratios (P III P 0.330 +/- 0.137, HA 5.68 +/- 6.44) suggested that their source was from the peritoneum. Although neither P-P III P nor log P-HA value had a significant correlation with age nor time on CAPD, both had significantly positive correlations (p = 0.0009, 0.0005, respectively) with time on total dialysis (including hemodialysis). D-P III P did not have a significant correlation with age nor time on total dialysis but had a significantly positive correlation (p = 0.0098) with D/P-creatinine. Although log D-HA had significantly positive correlations with time on CAPD and time on total dialysis (p = 0.0007, 0.0051, respectively), time on CAPD was first entered (F = 16.5) and time on total dialysis was removed (F to enter: 4) by stepwise regression analysis. In conclusion, a local increase in extracellular matrix of the peritoneum in CAPD patients, indicated by increases in P III P and HA in the effluent, may be related to higher peritoneal permeability and a longer duration of PD.

Adult↗

[A case of primary antiphospholipid antibody syndrome with severe nephrotic syndrome showing remarkable endothelial cell damage in the capillary lumen].

A 25-year-old woman complained of anasarca and was admitted to Sakura National hospital on the presumptive diagnosis of nephrotic syndrome with 10.7 g of 24-hour urinary protein. At first, lupus nephritis with antiphospholipid antibody syndrome was suspected because of prolongation of APTT, existence of lupus anticoagulant and elevation of serum anticardiolipin antibody titer (IgM) in addition to positive ANA, lymphocytopenia and the biologically false positive test for syphilis (BFPTS). On day 28 of hospitalization, renal biopsy findings revealed severe endocapillary cell damage, such as swelling and proliferation of endothelial cells, fragmentation and double contour of the basement membrane walls, which were located only in the capillary lumens with a few thrombi. Immunofluorescent micrography revealed the absence of specific immunoglobulin or complement deposit. Therefore, the diagnosis of lupus nephritis was negated as these findings were suggestive of characteristic glomerulopathy due to primary antiphospholipid antibody syndrome. She was treated initially with oral prednisolone 60 mg and intravenous infusion of heparin 20,000 units daily. Moreover, cyclophosphamide 750 mg was administered intravenously as pulse therapy on day 13 as her serum level of CH50 had fallen suddenly, and hemodialysis was necessary because her renal function had deteriorated and she was suffering from cough and orthopnea with overhydratin. After the combined therapy, BFPTS disappeared and APTT returned to the normal range: dialysis treatment was not required further after the 4th hemodialysis. Thereafter, renal function improved and complete remission of nephrotic syndrome was obtained. This patient was a case of primary antiphospholipid antibody syndrome in which endothelial cell damage was located exclusively in the capillary lumens and pulse cyclophosphamide therapy in addition to prednisolone and anticoagulant was effective. We present this instructive case to promote understanding of the pathogenesis of primary antiphospholipid antibody syndrome.

Adult↗

[Possible involvement of donor-derived B cells in development of post-transfusion graft-versus-host disease].

Post-transfusion graft-versus-host disease(PT-GVHD) is one of the most severe side effects of blood transfusion. To clarify the mechanism of development PT-GVHD, we characterized possible effector lymphocyte clones, presumably involved in the occurrence of PT-GVHD. By lymphocyte cloning from peripheral blood of a PT-GVHD patient, not only donor-derived cytotoxic T cell clones but also donor-derived B cell clones were established. The B cell clones produce cytotoxic IgG, directed against the patient's class II HLA. It was strongly suggested that donor-derived B cells, through production of cytotoxic IgG directed against the patient's HLA, were involved in the pathogenesis of the PT-GVHD in this case.

B-Lymphocytes↗