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Biomedical subjects

Y Goto

Publications and source records attributed to Y Goto.

At least 127 records · Page 7Linked to original sources

Acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension.

OBJECTIVE: To assess acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Cardiopulmonary exercise testing was performed in 20 patients with CTEPH before thromboendarterectomy (baseline), one month after (early phase), and four months after (late phase). Peak oxygen uptake (peak VO(2)) and the ventilatory response to carbon dioxide production (VE-VCO(2) slope) were measured for assessment of exercise capacity and ventilatory efficiency. Right heart catheterisation was performed in all patients before and one month after surgery. RESULTS: Baseline peak VO(2) decreased and VE-VCO(2) slope increased along with the increase in pulmonary vascular resistance in patients with CTEPH. After thromboendarterectomy, the VE-VCO(2) slope decreased greatly from baseline to the early phase (mean (SD), 50 (9) to 37 (7), p < 0.05) and reached a steady level thereafter. In contrast, a continued increase in peak VO(2) was noted from the early to the late phase (16.9 (4.1) to 21.1 (5.0) ml/kg/min, p < 0.05). The decrease in the VE-VCO(2) slope from baseline to the early phase, but not the increase in peak VO(2), correlated strongly with the decrease in pulmonary vascular resistance after surgery (r = 0.75, p < 0.01). CONCLUSIONS: Thromboendarterectomy may cause an immediate improvement in ventilatory efficiency, possibly through its beneficial haemodynamic effects. In contrast, exercise capacity may continue to improve towards the late phase, reflecting peripheral adaptation to exercise.

Acute Disease↗

Triggering the induction of myofibroblast and fibrogenesis by airway epithelial shedding.

Myofibroblasts have been thought to participate in subepithelial fibrosis in asthma, but the mechanism of myofibroblast induction has not been fully understood. In this study we investigated injury-related myofibroblast induction in a coculture system of guinea-pig epithelial cells and fibroblasts cocultured in a human amnion chamber. After pseudostratified epithelial cells were mechanically scraped, migrated flat epithelial cells differentiated into cuboidal appearances on Day 4 and then returned to their original shapes on Day 8. During the course of the epithelial redifferentiation, it was found by Northern blot analysis, immunohistochemistry for alpha-smooth muscle actin, and electron microscopic observation that the myofibroblasts were transiently induced on Day 4. The myofibroblast induction was inhibited by the blocking of transforming growth factor (TGF)-beta1 and thrombospondin (TSP)-1, indicating that the activation of TGF-beta1 by TSP-1 would induce myofibroblasts. This finding was also supported by a transient upregulation of TSP immunoreactivity and TSP-1 messenger RNA (mRNA) in fibroblasts. Interestingly, epithelial injury reduced TGF-beta1 immunoreactivity in the amnion membrane but did not affect TGF-beta1 mRNA in epithelial cells and fibroblasts, indicating that TGF-beta1 supplied from the extracellular matrix can participate in myofibroblast induction. Concurrently with myofibroblast induction, procollagen type I and III mRNAs were upregulated in fibroblasts, and obvious collagen deposition was observed ultrastructurally around the myofibroblasts compared with the fibroblasts. These results indicate that induced myofibroblasts can be functionally more active in producing collagen than are resting fibroblasts. The present study suggests that epithelial injury stimulates TGF-beta1 release from the extracellular matrix and its activation via TSP-1 production, causing collagen synthesis through myofibroblast induction.

Actins↗

Diastereoselective synthesis of (2R,4R)-2-aryl-4-hydroxypyrrolidine: preparation of the side chain of novel carbapenem.

Improved synthesis of the trans-3,5-disubstituted pyrrolidin-3-ylthio side-chain of the novel carbapenem 1 was achieved via stereoselective reduction of the 1-aryl-1-butanone derivative 5 and successive intramolecular cyclization of the resulting chiral alcohol 6. The 1-aryl-1-butanone derivative 5 was obtained by a coupling reaction of protected 4-hydroxy-2-pyrrolidone with aryl-Grignard reagent.

Carbapenems↗

Effects of counter cations of base catalysts on nitrosation mechanisms.

Reaction of 2-butanone (1) with tert-butyl nitrite (tert-BuONO) was performed using base catalysts (RO-M+: R=CH3, C2H5; M+=Li+, Na+, K+) in alcohols (CH3OH or C2H5OH). In this report, the effects of M+ of RO-M+ on the nitrosation mechanisms were investigated. The yield of E-hydroxyimino compound (5E) increases much better in the reaction using Na+ or K+ as M+ compared with that using Li+. It is also observed that the yield of 5E increases by addition of crown ether as a cation-capturing agent. The experimental results suggested that under the conditions lowering the effects of M+ of RO-M+ on the nitrosation mechanisms, because the reactivity of naked enolate of I increases and the reaction in the C-N bond formation process tends to proceed via open-chain transition state without M+, the yield of 5E tends to increase.

Catalysis↗

Ab initio molecular orbital study of reactivity of active alkyl groups. IV. Nitrosation of acyclic carbonyl compound with methyl nitrite via "open-chain" transition state.

The mechanism of the nitrosation of enolate anion of acetone [CH3COCH2]- (1) with methyl nitrite CH3ONO (2) via an "open-chain" transition state without Na+ in the C-N bond formation process was studied by the ab initio MO method. The complex [CH3COCH2NO(OCH3)]- (C-II) was first formed from the adduct (C-I) of 1 and 2 through the transition state (TSI). Finally, E-1-hydroxyimino-2-oxo-propane CH3COCH=NOH (3E), together with Z-form (3Z), was obtained by way of the elimination process. It has become apparent that 3E is formed when C-II-A is produced in the C-N bond formation process.

Acetone↗

Appropriate indications for the use of a percutaneous cardiopulmonary support system in cases with cardiogenic shock complicating acute myocardial infarction.

Percutaneous cardiopulmonary support (PCPS) is now available for hemodynamic support in patients with cardiogenic shock, but there are no guidelines for its use. The present study determined the appropriate indications for the use of the PCPS in patients with cardiogenic shock complicating acute myocardial infarction (AMI). Sixty-four consecutive patients with cardiogenic shock complicating AMI had hemodynamic support with an intraaortic balloon pump (IABP; n=38) and/or PCPS (n=26). The shock score (0-15) was calculated immediately before starting these support systems to quantify the severity of shock. Multivariate logistic regression analysis determined the clinical factors affecting in-hospital mortality. The relationship between in-hospital prognosis and the shock score was also examined in the 2 groups. The most significant factor related to the in-hospital prognosis was the shock score (p=0.0007; OR 2.16, 95% CI: 1.37-3.39). Another related factor was revascularization; however, this relationship did not reach statistical significance (p=0.069; OR 0.06). Among the 13 cases whose shock score was 4-8 (moderate shock), 5 survived in the PCPS group, but only 1 of 19 patients survived in the IABP group (p<0.05). None of the patients in either group whose shock score was more than 9 survived. The severity of shock is the most reliable independent predictor of in-hospital mortality in patients with cardiogenic shock complicating AMI. Using PCPS in patients with moderate cardiogenic shock may improve their in-hospital survival, but it must be used before the shock becomes severe.

Aged↗

Late reperfusion (6-24 hours after onset) improves left ventricular function in patients with acute myocardial infarction.

The TAMI-6 trial has demonstrated that coronary reperfusion >6h after onset (ie, late reperfusion) in patients with acute myocardial infarction (AMI) does not improve left ventricular (LV) function during the chronic phase of infarction. However, the low patency rate (only 60%) of the infarct-related artery (IRA) during the chronic phase in the TAMI-6 trial raises a new hypothesis that late reperfusion with a higher patency rate may improve LV function during the chronic phase. Forty-four patients with AMI, who were admitted to hospital 6-24h after the symptom onset and in whom emergency coronary angiography revealed a total occlusion of the IRA, were randomly assigned to either the late reperfusion group (n=22) or the non-reperfusion group (n=22). The initial success rate of reperfusion therapy in the late reperfusion group was 86% and the chronic patency rate of the IRA was 91%. The improvements in ejection fraction and chord shortening in the infarct region from the acute phase to the chronic phase were significantly greater in the late reperfusion group than in the non-reperfusion group. Late reperfusion with a high patency rate of the IRA significantly improves LV global and regional function in patients with AMI.

Adult↗

Excessive ventilation after acute myocardial infarction and its improvement in 4 months.

The relationship between ventilation (VE) and CO2 output (VCO2) is fitted linearly. The steeper gradient implies excessive ventilation. Through an evaluation of the VE-VCO2 slopes, this study investigated whether patients with acute myocardial infarction (AMI) have excessive ventilation and whether it improved in 4 months. The VE-VCO2 slopes were determined in exercise tests at 1 and 4 months in 131 patients with AMI. Patients were divided into 3 groups according to the 1 month VE-VCO2 slope value: (i) normal (<30); (ii) intermediate (30-32); and (iii) excessive (>32). In the normal group (n=76), at 4 months, the slope decreased in 10, increased in 5 and remained unchanged in 61 patients; in the intermediate (n=31) group, 9, 2 and 20; and in the excessive (n=24) group, 15, 3 and 6, respectively, showing that the slope reduction was greater in the excessive group (p<0.01). The slope correlated with age and acute phase heart failure. The percent reduction of the slope did not correlate with these parameters. In conclusion, a substantial fraction of patients with AMI have excessive ventilation that improves in 4 months. The improvement is greater in patients with greater excessive ventilation but is not associated with an improvement in exercise capacity nor hemodynamics.

Acute Disease↗

Is inflammation related to the clinical severity of unstable angina?

The present study determined the white blood cell (WBC) count and the serum C-reactive protein (CRP) level in 27 patients with coronary spastic angina, 16 with Braunwald class IB unstable angina (UA) and 13 with Braunwald class IIIB. The relationship between the clinical presentation of UA and the requirement for emergency percutaneous transluminal coronary angioplasty (PTCA) was examined, and in patients with medically refractory angina, the determining factor among the clinical manifestations of angina was also investigated. In the acute phase, the WBC count and the serum CRP level were significantly higher in patients with Braunwald class IIIB than in those with coronary spastic angina or Braunwald class IB UA (p<0.001). In the Braunwald class IIIB group, a significantly higher rate of patients required emergency PTCA than that of the coronary spastic angina group (p<0.01). Patients with medically refractory angina had a significantly higher WBC count and higher serum CRP level on admission, and the WBC count on admission was independently associated with medically refractory angina by multivariate analysis (p<0.05). Inflammation may play a major pathological role in the rapid development of acute coronary syndrome.

Angina, Unstable↗

Dietary manipulations of body fat-reducing potential of conjugated linoleic acid in rats.

To study whether the body fat-reducing potential of conjugated linoleic acid (CLA) could be increased through dietary manipulations, the effects of the combination of CLA with different proteins, fats, and sesamin were examined in rats. Male rats were fed diets containing 1% CLA or linoleic acid (LA) in combination with different proteins (20% of casein or soybean protein), fats (7% perilla oil or soybean oil) and 0.2% sesamin (SES) for 3 or 4 weeks. When the dietary fat source was soybean oil, CLA, as compared with LA, significantly reduced weights of epididymal and perirenal adipose tissues, irrespective of the dietary protein sources. However, the highest reducing effect was shown when soybean protein was given as a protein source. SES stimulated the reduction of epididymal and perirenal adipose tissue weights in both protein diets. In contrast, CLA increased the weight of brown adipose tissue, and SES further increased it in combination with soybean oil but not with perilla oil. No effect of dietary manipulation was observed on serum leptin and TNF-alpha levels. Thus, the body fat-reducing potential of CLA can be increased by an appropriate combination with food factors that may stimulate fatty acid beta-oxidation.

Adipose Tissue↗

The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese but does not alter the sensitivity to pressor effects of alcohol: the Suita study.

Excessive alcohol consumption is a potent risk factor for high blood pressure. About half of Japanese show an extremely high sensitivity to alcohol, which is due to a genetic deficiency in an isoenzyme of aldehydede-hydrogenase with a low Km (ALDH2). It is possible that the effects of alcohol consumption on blood pressure differ according to the ALDH2 genotype. The purpose of the present study was to assess the influence of the ALDH2 genotype on the pressor effects of alcohol. The influence of the ALDH2 genotype on blood pressure was investigated in a large cohort (4,000 subjects) representing the general population in Japan. The genotype was determined by the TaqMan method. The genotype was significantly associated with alcohol consumption, gamma-GTP level, and HDL cholesterol level in both males and females. The odds ratio for the presence of hypertension for the Glu/Glu genotype in comparison to other genotypes was 1.67 (p< 0.0001, odds ratio=1.37-2.08, 95% confidence interval) among males. In contrast, the ALDH2 genotype had no significant effects on blood pressure among females. To investigate whether the ALDH2 genotype affected the sensitivity to the pressor effects of alcohol, we analyzed the effects of the ALDH2 genotype (Lys/Lys+Lys/Glu=0, Glu/Glu=1) and the level of alcohol consumption on blood pressure values after adjusting for age and BMI (residuals after adjusting for age and BMI). Among males, while the level of alcohol consumption significantly affected systolic, diastolic and pulse pressure, no significant interaction was observed between the ALDH2 genotype and the level of alcohol consumption in determining blood pressure levels. These results suggest that the Glu/Glu genotype is a potent risk factor for hypertension among males mainly through its association with the level of alcohol consumption, and that the ALDH2 genotype does not affect the sensitivity to the pressor effects of alcohol.

Adult↗

Isolation of Pasteurella multocida during an outbreak of infectious septicemia in Japanese quail (Coturnix coturnix japonica).

In May 1994, about fifty Japanese quails out of ninety being bred for experimental purposes at Miyazaki University died of acute septicemia within a few days. At autopsy, there were no gross pathological lesions, however, severe bacteremia was observed in all cases. Bacterial examination revealed the presence of Pasteurella multocida in blood and several organs in pure culture and they were of Carter's capsular type A, Heddleston's type 3-4 and Namioka's type O-8-9. The LD50 of bacteria in quails and mice were 4.3 x 10(4) cfu and 3.9 x 10(2) cfu, respectively. All of the three chickens experimentally infected with 4 x 10(4) of the isolate died within 20 hr after the infection and several bacteria were recovered from their blood and organs. This, to our knowledge, is the first report on an outbreak of fowl cholera in Japanese quails in Japan.

Agglutination Tests↗

Localization of extracellular matrix receptors in ICGN mice, a strain of mice with hereditary nephrotic syndrome.

Fibrotic degeneration was examined in the kidneys of ICR-derived glomerulonephritis (ICGN) mice, a novel inbred mouse line with a hereditary nephrotic syndrome of unknown etiology considered to be a good model of human idiopathic nephrotic syndrome. In the present study, we histochemically revealed changes in accumulation of extracellular matrix (ECM) components and in localization of integrins, cellular receptors for ECM, in the kidneys of ICGN mice with the progression of renal failure. Excessive accumulation of basement membrane (laminin and collagen IV) and interstitial (type III collagen) ECM components were demonstrated in the glomeruli and tubulointerstitum of ICGN mice. Marked deposition of type I collagen and tenascin was seen only in the glomeruli of ICGN mice but not in those of ICR mice as normal controls. Increased expression of integrin alpha1-, alpha2-, alpha5- and beta1-subunits in glomeruli with fibrotic degeneration and abnormal distribution of alpha6-subunit were noted in the kidneys of ICGN mice. Excessive laminin, a ligand of alpha6beta1-integrin, was demonstrated on the tubular basement membrane, but alpha6-subunit diffusely disappeared on the basal side of the tubular epithelial cells. We presumed that abnormal integrin expression in renal tubules causes epithelial cell detachment, and consequently tubular nephropathy, and results in disorder of ECM metabolism causing excessive accumulation of ECM components in the kidneys of ICGN mice.

Albumins↗

Increase in plasma lipid peroxide in cats fed a fish diet.

Plasma lipid peroxide levels were examined in cats. Plasma lipid peroxide levels in 3 of 4 clinical cases which had been fed raw fish were higher than those in normal cats. When healthy cats were put on a raw fish diet in controlled conditions, a remarkable increase in plasma lipid peroxide was observed. This increase occurred within 1 to 3 weeks in cats without obvious clinical disorders. We also showed that a continuous raw fish diet is necessary to cause the increase, but the increase was transient and restored in spite of a continuous raw fish diet, indicating the development of an unidentified antioxidant process. Our results clearly indicate that intake of foods high in polyunsaturated fatty acid can induce oxidative stress in cats.

Animal Feed↗

Lymphoproliferative responses in pigs infected with Mycobacterium avium.

Naturally infected cases of swine mycobacteriosis were divided into two groups, localized infection (LI) and disseminated infection (DI). Lymphoproliferative response (LPR) was then examined to estimate their immunological states. Both control and LI groups showed strong response to Concanavalin A (Con A) and phytohemagglutinin (PHA) in the LPR, and lymphocytes recovered from the LI responded well to purified protein derived from M. avium (PPD). On the other hand, the DI group showed weak response to both Con A and PHA, despite their strong response to PPD stimulation. These data suggest that the low LPR to Con A and PHA observed in the DI groups was probably not due to the general unresponsiveness of T-cells.

Animals↗

Marked improvement of neuropsychological impairment in a patient with chronic obstructive pulmonary disease after lung volume reduction surgery.

This paper reports a case of a 71-year-old pulmonary emphysema patient with neuropsychological impairments that were markedly improved 6 months after he underwent lung volume reduction surgery (LVRS). He also underwent pulmonary rehabilitation before and after surgery. He was suspected of having memory impairment and attention disorder when he was referred for rehabilitation. The neuropsychologic test showed a general cognitive impairment, attention disorder, and verbal memory impairment. Magnetic resonance imaging showed moderate atrophy of the left hippocampal area, cortex, and lacunae infarction in the periventricular area. Interestingly, scores of the neuropsychologic test, as well as severity of dyspnea and lung function, remarkably improved 6 months after LVRS. These results suggested that the neuropsychological impairments in pulmonary emphysema patients can be improved after lung reduction surgery.

Aged↗

Population pharmacokinetics of digoxin in Japanese patients: a 2-compartment pharmacokinetic model.

OBJECTIVE: To clarify the observed variability of digoxin disposition by performing a population pharmacokinetic analysis in a Japanese population. DESIGN: Retrospective analysis of clinical pharmacokinetic data. PATIENTS AND PARTICIPANTS: Data were obtained from 106 patients with heart failure and atrial fibrillation (43 males and 63 females). METHODS: Digoxin concentrations in serum were measured by fluorescence polarisation immunoassay. Population pharmacokinetic analysis was performed using a 2-compartment open pharmacokinetic model with the computer program NONMEM. RESULTS: 246 serum concentrations were obtained. Final pharmacokinetic parameters were: CL (L/h) = (0.036 x TBW + 0.112 x CL(CR)) x 0.77SPI x 0.784CCB, V1 = 1.83 L/kg, V2 = 22.6 L/kg and Q = 0.629 L/h/kg, where CL is total body clearance, V1 and V2 are the apparent volumes of distribution in the central and peripheral compartments, Q is intercompartmental clearance, TBW is total bodyweight (in kg), CL(CR) is creatinine clearance (in ml/min), SPI = 1 for concomitant administration of spironolactone (and zero otherwise) and CCB = 1 for concomitant administration of calcium antagonists (and zero otherwise). Concomitant administration of digoxin and spironolactone resulted in a 23% decrease in digoxin clearance. Concomitant administration of digoxin and calcium antagonists (diltiazem, nicardipine, nifedipine or verapamil) resulted in a 21.6% decrease in digoxin clearance. CONCLUSIONS: The estimated population parameter values may assist clinicians in the individualisation of digoxin dosage regimens.

Cardiotonic Agents↗

[The developmental effects of an early intervention program for very low birthweight infants].

We assessed the efficacy of an early intervention program (EIP) designed to promote the neonatal behavioral organization and developmental progress in infants born prematurely. The study subjects consisted of 48 very low birthweight infants (< or = 1,500 gms) who received care in NICU of Nagasaki University Hospital, Nagasaki, Japan. During 1993-1996, the experimental group (n = 30) received the NBAS (Neonatal Behavioral Assessment Scale) based intervention combined with a therapeutic program (EIP), for 44 weeks starting from 38 weeks of postmenstrual age. The control group (historical control, n = 18) received the standard medical-nursing care without EIP during 1990-1992. Developmental outcome was assessed in both groups using the NBAS examination after EIP at 44 weeks of postmenstrual age, and the Bayley Scales at 12 months corrected age. Multivariate analyses were performed to adjust for baseline variables that might be associated with the developmental outcome: sex, appropriate or light for dates infant, birthweight, gestational age, Apgar score at 1 minute, duration of intubation, and NBAS cluster score before EIP. In the NBAS examination after EIP, the experimental group achieved significantly higher scores in orientation, motor performance, state range and state regulation tasks than the control group. Furthermore, the experimental group showed significantly higher Bayley Mental and Psychomotor Developmental Indices compared with the control group. These results suggested that EIP was effective in promoting the neonatal neurobehavioral development of very low birthweight infants.

Child Development↗