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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 271 records · Page 15Linked to original sources
PubMed2000

Optimal level of pressure support ventilation for recovery from diaphragmatic fatigue in rabbits.

OBJECTIVE: To determine whether there is an optimal level of pressure support ventilation (PSV) for recovery from acute diaphragmatic fatigue. DESIGN: Prospective laboratory trial. SETTING: Experimental laboratory. SUBJECTS: Twenty healthy adult New Zealand White rabbits. INTERVENTIONS: Diaphragmatic fatigue was induced with 50 Hz of phrenic nerve stimulation for 30 mins. Recovery was compared between inspiratory load + PSV of 0 cm H2O (L0), inspiratory load + PSV of 60 cm H2O (L60), inspiratory load + PSV of 80 cm H2O (L80), and PSV of 0 cm H2O without inspiratory load (SB) for 90 mins immediately after the end of the fatigue-inducing procedure. To add inspiratory load during the recovery phase, three pressure threshold valves, each having an opening pressure of -20 cm H2O, were used. MEASUREMENTS AND MAIN RESULTS: After the fatigue-inducing procedure, diaphragmatic electromyogram and transdiaphragmatic pressure remained at baseline in both SB and L60, decreased in L80, and increased in L0. Recovery was assessed by abdominal cavity pressure (Pabd) generated by high-frequency (100 Hz) and low-frequency (20 Hz) stimulation. Pabd at 100 Hz recovered to baseline in L60 and SB but not in L0 and L80 (69.1%, 81.3%, 100.3%, and 100.7% of the baseline at 90 mins for L0, L80, L60, and SB, respectively). Pabd at 20 Hz did not differ among ventilatory settings. CONCLUSION: There is an optimal range of PSV assist level to improve recovery from diaphragmatic fatigue. Recovery was hampered not only by inadequate PSV but also by excessive PSV.

Airway Resistance↗
PubMed2000

Artificial ventilation-induced diffuse alveolar damage in rabbits: preliminary study of early detection on expiratory high-resolution computed tomography.

RATIONALE AND OBJECTIVES: To investigate whether expiratory high-resolution computed tomography (HRCT) is more useful than inspiratory HRCT for the detection of early-phase diffuse alveolar damage. METHODS: Eleven anesthetized rabbits were scanned with both inspiratory and expiratory HRCT every 30 minutes during mechanical ventilation. Ten rabbits were killed after the detection of pulmonary abnormalities on both inspiratory and expiratory HRCT. The remaining rabbit was killed when the pulmonary abnormalities appeared only on expiratory HRCT. RESULTS: In four cases (36%), the abnormal findings were detected earlier on expiratory HRCT than on inspiratory HRCT. In seven cases (64%), the abnormalities appeared simultaneously on inspiratory and expiratory HRCT. In all 11 cases, the histopathological changes of areas with abnormal CT findings corresponded to the exudative or proliferative phase of diffuse alveolar damage. CONCLUSIONS: Expiratory HRCT has the potential to detect the abnormalities of diffuse alveolar damage earlier than inspiratory HRCT.

Acute Disease↗
PubMed2000

Purification and characterization of a novel pumpkin short-chain acyl-coenzyme A oxidase with structural similarity to acyl-coenzyme A dehydrogenases.

A novel pumpkin (Cucurbita pepo) short-chain acyl-coenzyme A (CoA) oxidase (ACOX) was purified to homogeneity by hydrophobic-interaction, hydroxyapatite, affinity, and anion-exchange chromatography. The purified enzyme is a tetrameric protein, consisting of apparently identical 47-kD subunits. The protein structure of this oxidase differs from other plant and mammalian ACOXs, but is similar to the protein structure of mammalian mitochondrial acyl-CoA dehydrogenase (ACDH) and the recently identified plant mitochondrial ACDH. Subcellular organelle separation by sucrose density gradient centrifugation revealed that the enzyme is localized in glyoxysomes, whereas no immunoreactive bands of similar molecular weight were detected in mitochondrial fractions. The enzyme selectively catalyzes the oxidation of CoA esters of fatty acids with 4 to 10 carbon atoms, and exhibits the highest activity on C-6 fatty acids. Apparently, the enzyme has no activity on CoA esters of branched-chain or dicarboxylic fatty acids. The enzyme is slightly inhibited by high concentrations of substrate and it is not inhibited by Triton X-100 at concentrations up to 0.5% (v/v). The characteristics of this novel ACOX enzyme are discussed in relation to other ACOXs and ACDHs.

Acyl-CoA Dehydrogenase↗
PubMed2000

Salivary gland MALT lymphoma associated with Helicobacter pylori infection in a patient with Sjögren's Syndrome.

We report a case of salivary gland MALT lymphoma in Sjögren's syndrome associated with localized H. pylori infection. A 76-year-old woman had a history of bilateral cheek masses for two years. Histologically, the parotid glands were invaded by numerous centrocyte-like cells to form lymphoepithelial lesions. The tumor cells showed immunohistological differentiation into B cells. Southern blotting demonstrated immunoglobulin gene rearrangement. These results indicated that the tumors were MALT lymphoma. H. pylori, as assessed by the urease test (CLO test; BML Ltd., Tokyo, Japan), was positive in the tumor specimen. After wide local excision of the tumors followed by radio therapy and oral administration of antibiotics and proton pump inhibitor, no evidence of recurrence was found during the 24-months of follow up. H. pylori infection in the salivary gland is rare, although the source of infection and transmission of H. pylori organisms has been thought to be the oral cavity. We discussed the association between H. pylori infection and salivary gland MALT lymphoma. The microorganism may play a role as an additional antigenic stimulus for the development of salivary gland MALT lymphoma as well as for the development of gastric MALT lymphoma. This means that H. pylori can play a role in lymphoma progression as booster of B cell lymphoproliferation.

Aged↗
PubMed2000

A case of uterine endometrial carcinoma 15 months post-partum.

A case of uterine endometrial carcinoma 15 months post-partum, who did have none of typical risk factors of uterine endometrial carcinoma, is presented. The occurrence of post-partum uterine endometrial carcinoma is extremely rare condition probably due to anti-carcinogenic effects of progesterone. Progesterone refractory cells in the uterine endometrium, which could be an origin of the endometrial carcinoma, might have existed.

Adenocarcinoma↗
PubMed2000

Biological characteristics of the leukemia-associated transcriptional factor AML1 disclosed by hematopoietic rescue of AML1-deficient embryonic stem cells by using a knock-in strategy.

AML1 is one of the most frequently mutated genes associated with human acute leukemia and encodes the DNA-binding subunit of the heterodimering transcriptional factor complex, core-binding factor (CBF) (or polyoma enhancer binding protein 2 [PEBP2]). A null mutation in either AML1 or its dimerizing partner, CBFbeta, results in embryonic lethality secondary to a complete block in fetal liver hematopoiesis, indicating an essential role of this transcription complex in the development of definitive hematopoiesis. The hematopoietic phenotype that results from the loss of AML1 can be replicated in vitro with a two-step culture system of murine embryonic stem (ES) cells. Using this experimental system, we now demonstrate that this hematopoietic defect can be rescued by expressing the PEBP2alphaB1 (AML1b) isoform under the endogenous AML1-regulatory sequences through a knock-in (targeted insertion) approach. Moreover, we demonstrate that the rescued AML1(-/-) ES cell clones contribute to lymphohematopoiesis within the context of chimeric animals. Rescue requires the transcription activation domain of AML1 but does not require the C-terminal VWRPY motif, which is conserved in all AML1 family members and has been shown to interact with the transcriptional corepressor, Groucho/transducin-like Enhancer of split. Taken together, these data provide compelling evidence that the phenotype seen in AML1-deficient mice is due solely to the loss of transcriptionally active AML1.

Animals↗
PubMed2000

Genetic mapping of quantitative trait loci influencing left ventricular mass in rats.

High blood pressure is the leading cause of left ventricular hypertrophy (LVH); however, not all hypertensive patients develop LVH. Genetic factors are important in the development of LVH. With the use of F2 male rats from spontaneously hypertensive rats and Lewis rats, we performed a study to identify the quantitative trait loci (QTL) that influence left ventricular mass (LVM). Mean arterial pressure (MAP) was measured by the direct intra-arterial method in conscious animals, and LVM was determined at 24 wk of age. QTL analysis was done using 160 microsatellite markers for a genome-wide scan. Two loci that influenced body weight-adjusted LVM with logarithm of the odds scores >3.4 were found. One locus on chromosome 17 influenced LVM independently of MAP. Another locus on chromosome 7 influenced LVM and MAP. These findings indicate not only the existence of a gene on chromosome 7 that influences LVM in a manner dependent on blood pressure but also the existence of a gene on chromosome 17 that influences LVM independently of blood pressure.

Animals↗
PubMed2000

Decline in FEV(1) in community-based older volunteers with higher levels of neutrophil elastase in bronchoalveolar lavage fluid.

BACKGROUND: Neutrophil elastase (NE) is thought to be one of the key proteinases in the development of chronic obstructive pulmonary disease (COPD). Previously, we have shown that the NE-alpha1-proteinase inhibitor (NE-alpha1PI) complex in bronchoalveolar lavage (BAL) fluid was markedly elevated in asymptomatic smokers who had subclinical emphysema on CT scans. We proposed that excessive NE-alpha1PI complex in BAL fluid was a factor which might differentiate smokers who were developing emphysema from others. OBJECTIVE: In this study, we addressed the question of whether elevated levels of the NE-alpha1PI complex in BAL fluid are linked to the accelerated decline in pulmonary functions in those subjects. METHODS: We conducted a follow-up study to analyze the decline in FEV(1) for 4.3 years on average for 26 community-based volunteers who had received pulmonary function tests, CT scans and BAL. The levels of the NE-alpha1PI complex in BAL fluid and in plasma was measured. RESULTS: Neither pulmonary function measurements nor the presence of emphysema on CT scans could predict the decline in FEV(1). The number of inflammatory cells in BAL fluid was also not an indicator of progression. By contrast, subjects with higher levels of the NE-alpha1PI complex in BAL fluid had a significantly accelerated decline in FEV(1) compared to those with lower levels. CONCLUSION: These data seem to support the hypothesis that NE in the lung is related to the onset and/or progression of COPD.

Aged↗
PubMed2000

Exhaled nitric oxide--is it really a good marker of airway inflammation in bronchial asthma?

BACKGROUND: The concentration of exhaled nitric oxide ([NO]) has been reported to reflect the inflammatory process of airways in patients with bronchial asthma, particularly when they are steroid naive. However, it is not fully understood whether it equally reflects the degree of airway inflammation in patients receiving inhaled corticosteroids, but whose symptoms are not necessarily well controlled. OBJECTIVE: To examine whether the exhaled [NO] really reflects airway inflammation in patients with bronchial asthma, regardless of treatment with inhaled steroids. METHODS: Exhaled [NO] was measured in patients with bronchial asthma (43 steroid treated and 32 steroid naive), chronic obstructive pulmonary disease (COPD) (n = 36), bronchiectasis (n = 10) and in control subjects (n = 26). We examined in each asthmatic group whether the exhaled [NO] correlated with parameters reflecting airway inflammation. RESULTS: Exhaled [NO] was significantly correlated with symptom score, clinical severity, circulating eosinophil count, and the percentage of eosinophils in induced sputum in the steroid-naive asthmatics, but not in the steroid-treated asthmatics, although airway inflammation in this group was not well controlled, as evidenced by clinical symptoms and the higher percentage of eosinophils in induced sputum. Exhaled [NO] from the patients with COPD (6.2 +/- 0. 7 ppb) or bronchiectasis (5.4 +/- 1.3 ppb) was not significantly increased compared with the controls (6.0 +/- 1.0 ppb), and was significantly lower than in the asthmatic patients as a whole (19.0 +/- 2.0 ppb). CONCLUSIONS: Although exhaled [NO] is a useful marker of airway inflammation for differential diagnosis and evaluation of severity in steroid-naive patients with bronchial asthma, it may not be as useful in steroid-treated patients.

Adrenal Cortex Hormones↗
PubMed2000

Enhanced expression of osteopontin in human diabetic artery and analysis of its functional role in accelerated atherogenesis.

We have previously reported that high glucose stimulates osteopontin (OPN) expression through protein kinase C-dependent pathways as well as hexosamine pathways in cultured rat aortic smooth muscle cells. The finding prompted us to study in vivo expression of OPN in diabetes mellitus. In the present study, we found by immunohistochemistry that medial layers of the carotid arteries of streptozotocin-induced diabetic rats and the forearm arteries of diabetic patients stained positively for OPN antibodies, whereas the staining from arteries of control rats and nondiabetic patients was negative. We also found that OPN stimulated the migration and enhanced platelet-derived growth factor (PDGF)-mediated DNA synthesis of cultured rat aortic smooth muscle cells. OPN and PDGF synergistically activated focal adhesion kinase as well as extracellular signal-regulated kinase; this finding seems to explain the OPN-induced enhancement of PDGF-mediated DNA synthesis. Taken together, our present results raise a possibility that OPN plays a role in the development of diabetic vascular complications.

Adult↗
PubMed2000

Role of FMRFamide-activated brain sodium channel in salt-sensitive hypertension.

FMRFamide, a cardioexcitatory neuropeptide, directly activates a newly cloned amiloride-sensitive sodium channel that is expressed specifically in the brain and blocked by benzamil hydrochloride. In the present study, we investigated the effects of short- and long-term intracerebroventricular infusion of FMRFamide on arterial pressure, sympathetic activity, vasopressin release, and brain renin-angiotensin system genes in rats and studied the role of FMRFamide-activated brain sodium channels in salt-sensitive hypertension. The intracerebroventricular preinjection of FMRFamide and subsequent intracerebroventricular infusion of 0.15 mol/L NaCl increased mean arterial pressure (FMRFamide: 30 nmol/kg +13+/-2.6 mm Hg, P<0.01; 100 nmol/kg +21+/-1.8 mm Hg, P<0.01), heart rate, abdominal sympathetic activity, and plasma vasopressin concentration compared with vehicle. The intracerebroventricular copreinjection with either benzamil or CV-11974 abolished these increases. In rats administered a high-salt diet (8% NaCl), the continuous intracerebroventricular infusion of FMRFamide (50 and 200 nmol. kg(-1). d(-1)) for 5 days increased mean arterial pressure, heart rate, urinary excretion of vasopressin and norepinephrine, and mRNAs of renin, angiotensin I-converting enzyme, and angiotensin II type 1 receptor in hypothalamus and brain stem compared with vehicle. These increases were abolished by intracerebroventricular coinfusion of benzamil. In rats administered a low-salt diet (0.3% NaCl), however, increases in these variables were smaller than those in rats receiving a high-salt diet. Together, these findings suggest that brain FMRFamide-activated sodium channels may be involved in the mechanism of salt-sensitive hypertension through regulation of the brain renin-angiotensin system.

Amiloride↗
PubMed2000

Prevalence of renal artery stenosis in autopsy patients with stroke.

BACKGROUND AND PURPOSE: Atherosclerotic renal artery stenosis commonly exists as one manifestation of more generalized atherosclerosis. It is a progressive but potentially curable disorder. Thus, information on renal artery involvement in atherosclerotic diseases could be important. We investigated the prevalence of renal artery stenosis in autopsied patients with stroke over 40 years of age. METHODS: From 2167 consecutive autopsy patients who died between 1980 and 1997, we studied 346 cases of mean age of 69+/-11 years with clinical evidence of stroke. RESULTS: Atherosclerotic renal artery stenosis (>/=75% luminal area narrowing) was found in 36 patients (10.4%). Patients with renal artery stenosis were older and had worse renal function. Renal artery stenosis was found in 14.7%, 28.6%, and 23.9% of patients with hypertension, renal insufficiency, and aortic aneurysm, respectively. Extracranial carotid artery stenosis (>50% luminal area narrowing) was found in 101 patients (29.2%). Of the 346 stroke patients, 256 had a history of brain infarction. In patients with brain infarction, renal artery stenosis was found in 31 (12.1%) and carotid stenosis was found in 81 (33.6%). Patients with carotid artery stenosis were more likely to have renal artery stenosis than patients without carotid artery stenosis (24.4% versus 5.9%, P<0.0001). Multiple logistic regression analysis identified renal insufficiency, hypertension, female gender, and presence of carotid artery stenosis as independent predictors of renal artery stenosis in patients with brain infarction. CONCLUSIONS: These data reveal that atherosclerotic renal artery stenosis is common in patients with stroke, especially in those with brain infarction.

Aged↗
PubMed2000

Tumor necrosis factor microsatellite polymorphism influences the development of insulin dependency in adult-onset diabetes patients with the DRB1*1502-DQB1*0601 allele and anti-glutamic acid decarboxylase antibodies.

Recently, several studies have demonstrated that tumor necrosis factor microsatellite polymorphism (TNFalpha) contributes to the susceptibility of type 1 diabetes. This study investigates the influence of TNFalpha on the predisposition to insulin dependency in adult-onset diabetic patients with type 1 diabetes-protective human leukocyte antigen haplotypes. The TNFalpha of three groups of DRB1*1502DQB1*0601-positive diabetic patients who had initially been nonketotic and noninsulin dependent for more than 1 yr was analyzed. Group A included 11 antibodies to glutamic acid decarboxylase (GADab)-positive patients who developed insulin dependency within 4 yr of diabetes onset. Group B included 11 GADab-positive patients who remained noninsulin dependent for more than 12 yr. Group C included 12 GADab-negative type 2 diabetes, and a control group included 18 nondiabetic subjects. In the group C and control subjects, DRB1*1502-DQB1*0601 was strongly associated with the TNFalpha13 allele. DRB1*1502-DQB1*0601 was strongly associated with the TNFalpha12 allele among the group A patients, but not among the group B patients. Interestingly, sera from all patients with non-TNFalpha12 and non-TNFalpha13 in group B reacted with GAD65 protein by Western blot. These results suggest that TNFalpha is associated with a predisposition to progression to insulin dependency in GADab/DRB1*1502DQB1*0601-positive diabetic patients initially diagnosed with type 2 diabetes and that determination of these patients' TNFalpha genotype may allow for better prediction of their clinical course.

Adult↗
PubMed2000

Evaluation of the pharmacological actions and pharmacokinetics of BOF-4272, a xanthine oxidase inhibitor, in mouse liver.

BOF-4272 (+/-)-8-(3-methoxy-4-phenylsulphinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4-(1H)-one, a new synthetic anti-hyperuricaemic drug, which has a chiral centre and exists as racemates, is a potent inhibitor of xanthine oxidase/dehydrogenase in the purine catabolism pathways. The present studies using mice demonstrated that BOF-4272 was specifically distributed in the liver, which is the main organ of uric acid production. Therefore, a decrease in uric acid concentration in the liver, rather than the plasma, was identified as a pharmacological action of BOF-4272. The ratio of liver to plasma concentrations of BOF-4272 increased from 2.5 to 6.3 over time, up to 8 h after oral administration. The elimination half-life of BOF-4272 in the liver was 5-1-fold longer than that in the plasma. High concentrations of BOF-4272 were observed in the liver up to 8 h after oral administration. Furthermore, the influx of BOF-4272 into hepatocytes occurred in a temperature-dependent manner. The liver concentrations of uric acid from 1 h to 8 h after the oral administration of BOF-4272 (0.34-0.75 microg (g tissue)(-1)) were significantly lower than those in control animals (5.03-10.96 microg (g tissue)(-1)). BOF-4269 (the sulphide metabolite of BOF-4272) was the only metabolite detected in plasma or faeces after intravenous or oral administration. BOF-4269, which has no inhibitory action on the uric acid biosynthesis system, is generated by the metabolism of BOF-4272 in the intestinal tract. In conclusion, this work using the liver as the target organ has allowed us to identify the pharmacological actions of BOF-4272 in mice. The long-lasting effect of BOF-4272 in reducing levels of hepatic uric acid was consistent with the prolonged high BOF-4272 concentrations in the liver. These results also demonstrate that the mouse is a suitable animal species for evaluating the clinical pharmacology and pharmacokinetics of BOF-4272.

Animals↗
PubMed2000

Association of human hepatocyte growth factor with hemodialysis hypotension.

Hypotension is a major cardiovascular complication of hemodialysis, and enhanced production of nitric oxide (NO) may be involved in hemodialysis hypotension. Human hepatocyte growth factor (hHGF), which induces endothelial proliferation, causes NO-mediated hypotension in animals. Because heparin, which is routinely used during hemodialysis, increases circulating hHGF concentration in humans, circulating hHGF may be involved in hemodialysis hypotension via increased NO production. To investigate the involvement of hHGF in NO production and hypotension in hemodialysis patients, we measured concentrations of serum hHGF and plasma NO3-, an index of endogenous NO production, in 114 patients undergoing maintenance hemodialysis. The mean serum hHGF concentration before dialysis was greater (p<0.01) in subjects with lower blood pressure (BP) (mean BP before dialysis < or =75 mmHg, n=16, 0.251+/-0.050 ng/ml) than in those with middle BP (mean BP before dialysis 76 to 109 mmHg, n=75, 0.143+/-0.016 ng/ml) or higher BP (mean BP before dialysis > or =110 mmHg, n=23, 0.088+/-0.017 ng/ml). The mean serum hHGF concentration after dialysis was higher in subjects with lower BP (1.854+/-0.242 ng/ml) than in those with middle BP (1.280+/-0.120 ng/ml) or higher BP (0.688+/-0.130 ng/ml). Serum hHGF concentration was positively correlated with plasma NO3- concentration (r=0.608, p=0.0001, n=114). Circulating hHGF may participate in the mechanism of chronic hemodialysis hypotension by affecting endogenous NO production.

Blood Pressure↗
PubMed2000

Performance of transport ventilator with patient-triggered ventilation.

OBJECTIVES: Transport ventilators with inspiratory triggering functions and pressure support-control modes have recently become commercially available. We evaluated these ventilators in comparison with a standard ICU ventilator. STUDY DESIGN: Laboratory study with a mechanical lung model. METHODS: We compared the performance of four transport ventilators (model 740, Mallinckrodt, Pleasanton, CA; TBird, Bird Products Corp, Palm Springs, CA; LTV1000, Pulmonetic Systems, Colton, CA; Esprit, Respironics, Vista, CA) with a standard ICU ventilator (model 7200ae; Mallinckrodt) using a test lung that simulated spontaneous breathing (compliance, 46.8 mL/cm H(2)O; resistance, 5 cm H(2)O/L/s). The settings of ventilators were positive end-expiratory pressure (PEEP) of 0 or 5 cm H(2)O, and pressure support (PS) of 0 or 10 cm H(2)O. The settings of the test lung were inspiratory time of 1 s, respiratory rate of 10/min, peak inspiratory flow of 40, 60, and 80 L/min. To evaluate inspiratory function at each setting, we measured the inspiratory delay time (DT), inspiratory trigger pressure (P-I), and the time for airway pressure to rise from the baseline pressure to 90% of the end-inspiratory pressure (T(90%)); for expiratory function, supraplateau expiratory pressure (P-E) and the time constant (taue) for pressure decrease during exhalation were evaluated. Oxygen requirement was assessed as the time required to empty a 3.5-L oxygen tank. RESULTS: For inspiratory triggering, four transport ventilators had DT < 100 ms, which is considered clinically satisfactory, in all the settings except for PS 0 cm H(2)O, PEEP 0 cm H(2)O, and inspiratory flow of 80 L/min with LTV1000. P-I increased only in LTV1000 when PEEP was increased from 0 to 5 cm H(2)O. taue for the transport ventilators was > 50% shorter than for the ICU ventilator except for PS 0 cm H(2)O and PEEP 5 cm H(2)O with TBird. Oxygen requirement was lowest for the Esprit, followed by the 740, LTV1000, and TBird. CONCLUSION: The newer Food and Drug Administration-approved transport ventilators have performance indexes comparable to the ventilator currently used in ICUs and can probably be recommended for clinical use.

Equipment Design↗