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Biomedical subjects

Yukio Saito

Publications and source records attributed to Yukio Saito.

16 recordsLinked to original sources

Relation between transcardiac gradient of VEGF and coronary flow response in humans.

BACKGROUND: Angiogenic growth factors, produced in the myocardium and coronary vascular bed, increase myocardial blood flow. This study examined whether plasma levels of vascular endothelial growth factor (VEGF) in coronary circulation may be related to coronary blood flow responses. METHODS: Blood flow responses in the left anterior descending coronary artery to an intracoronary infusion of acetylcholine (ACh) were measured by an intracoronary flow wire technique in 46 consecutive control subjects with normal coronary angiograms and left ventriculograms. Circulating VEGF levels were measured by ELISA in plasma obtained from the aortic root (AO) and anterior interventricular vein (AIV). RESULTS: The transcardiac gradient of VEGF, calculated by the difference in VEGF concentrations between the AIV and AO, showed a positive correlation with the coronary blood flow increase in response to ACh independently of traditional coronary risk factors. In patients with cardiac syndrome X (n=17), defined as a positive exercise stress test with a normal coronary angiograms and left ventriculogram, the transcardiac VEGF gradient was significantly lower than in the risk factors-matched control subjects (n=21). CONCLUSIONS: The transcardiac gradient of plasma VEGF was independently and positively correlated with the coronary blood flow increase in response to ACh. A reduced transcardiac VEGF gradient was present in cardiac syndrome X, a condition with a blunted coronary blood flow response.

Blood Flow Velocity↗

Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study.

BACKGROUND: The aim of this study was to clarify the characteristics of recurrence and the effectiveness of surveillance tools after curative resection for colorectal cancer. METHODS: We enrolled 5230 consecutive patients (stage I, 1367; stage II, 1912; stage III, 1951) who underwent curative resection at 14 hospitals from 1991 to 1996. All patients were followed up intensively, and their outcomes were investigated retrospectively. RESULTS: Of the 5230 patients, 906 developed recurrence. The recurrence rates of stage I, II, and III cancers were 3.7%, 13.3%, and 30.8%, respectively (P < .0001). The curves of the cumulative appearance rate of recurrence in stage II and III patients showed a rapid increase for the first 3 years. Recurrence after 5 years was less than 1% in each stage. Clinical visits combined with measurements of tumor markers detected the majority of recurrences except in the case of lung metastasis. In contrast, 43.4% of hepatic recurrences were detected by liver imaging, and 48.4% of pulmonary recurrences were noted by chest x-ray. The 5-year survival rates after primary colorectal surgery in patients who underwent resection for recurrence were better than in those without resection: 55% vs 11% in hepatic recurrence, 68% vs 13% in pulmonary recurrence, and 48% vs 22% in local recurrence (all P < .001). CONCLUSION: It is useful to take these characteristics of recurrence into account in the management of patients after curative resection for colorectal cancer and in the setting of clinical trial for follow-up after curative resection for colorectal cancer.

Aged↗

Diffusion accelerates and enhances chirality selection.

The diffusion effect on chirality selection in a two-dimensional reaction-diffusion model is studied by Monte Carlo simulations. The model consists of achiral reactants A which turn into either of the chiral products R or S in a solvent of chemically inactive vacancies V . The reaction contains a nonlinear autocatalysis as well as a recycling process, and the chiral symmetry breaking is monitored by an enantiomeric excess (ee) phi. Without dilution a strong nonlinear autocatalysis ensures chiral symmetry breaking. By diluting a diffusionless system, the ee phi decreases and a racemic state is recovered below a critical concentration c(c) . When the diffusion is allowed, the steady value of phi increases and c(c) decreases. As for the relation between the ee phi and the concentration c , a formula interpolating between the diffusionless (D=0) and the homogeneous (D=infinity) limits is proposed by incorporating the diffusional enhancement of the concentrations of chiral species. Diffusion also accelerates the development of the chiral order, and the time required to establish the order in a system of a size L(2) is inversely proportional to the diffusion constant D as L(2)/D .

Journal Article↗

Atorvastatin increases plasma soluble Fms-like tyrosine kinase-1 and decreases vascular endothelial growth factor and placental growth factor in association with improvement of ventricular function in acute myocardial infarction.

OBJECTIVES: This study examined whether atorvastatin increases plasma levels of soluble Fms-like tyrosine kinase 1 (sFlt-1) and reciprocally decreases vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels in patients with acute myocardial infarction (AMI). BACKGROUND: Statins exert cardioprotective actions partly through anti-inflammatory actions. By capturing VEGF and PlGF in plasma, sFlt-1 acts as a natural inhibitor of VEGF and PlGF, which have proinflammatory properties. METHODS: Left ventriculography and enzyme-linked immunosorbent assay of plasma levels of sFlt-1, VEGF, and PlGF were repeated after AMI in 50 consecutive patients with a first AMI. Patients were randomized to treatment with atorvastatin (10 mg/day; n=25) or placebo (n=25) within 3 days after AMI, and therapy was continued for 6 months. RESULTS: The sFlt-1 levels were low in the acute phase, followed by an increase at 2 weeks after AMI, whereas free VEGF and PlGF levels were high in the acute phase, followed by a decrease at 2 weeks. Atorvastatin increased sFlt-1 levels and reciprocally decreased VEGF and PlGF levels at 6 months compared with placebo. The increase in sFlt-1 levels and the decrease in VEGF and PlGF levels were correlated with improvement of left ventricular ejection fraction during the follow-up period. CONCLUSIONS: There was a reciprocal relationship between changes in sFlt-1 levels and changes in VEGF and PlGF levels after AMI; and atorvastatin increased sFlt-1 levels while decreasing VEGF and PlGF levels. These changes were associated with late improvement of post-MI ventricular function, and may represent an additional benefit of statin therapy.

Atorvastatin↗

Role of adiponectin receptors in endothelin-induced cellular hypertrophy in cultured cardiomyocytes and their expression in infarcted heart.

Adiponectin, an adipocyte-derived protein, has cardioprotective actions. We elucidated the role of the adiponectin receptors AdipoR1 and AdipoR2 in the effects of adiponectin on endothelin-1 (ET-1)-induced hypertrophy in cultured cardiomyocytes, and we examined the expression of adiponectin receptors in normal and infarcted mouse hearts. Recombinant full-length adiponectin suppressed the ET-1-induced increase in cell surface area and [(3)H]leucine incorporation into cultured cardiomyocytes compared with cells treated with ET-1 alone. Transfection of small interfering RNA (siRNA) specific for AdipoR1 or AdipoR2 reversed the suppressive effects of adiponectin on ET-1-induced cellular hypertrophy in cultured cardiomyocytes. Adiponectin induced phosphorylation of AMP-activated protein kinase (AMPK) and inhibited ET-1-induced ERK1/2 phosphorylation, which were also reversible by transfection of siRNA for AdipoR1 or AdipoR2 in cultured cardiomyocytes. Transfection of siRNA for alpha(2)-catalytic subunits of AMPK reduced the inhibitory effects of adiponectin on ET-1-induced cellular hypertrophy and ERK1/2 phosphorylation. Effects of globular adiponectin were similar to those of full-length adiponectin, and siRNA for AdipoR1 reversed the actions of globular adiponectin. Compared with normal left ventricle, expression levels of AdipoR1 mRNA and protein were decreased in the remote, as well as the infarcted, area after myocardial infarction in mouse hearts. In conclusion, AdipoR1 and AdipoR2 mediate the suppressive effects of full-length and globular adiponectin on ET-1-induced hypertrophy in cultured cardiomyocytes, and AMPK is involved in signal transduction through these receptors. AdipoR1 and AdipoR2 might play a role in the pathogenesis of ET-1-related cardiomyocyte hypertrophy after myocardial infarction.

Adiponectin↗

Fecal pancreatic elastase: a reproducible marker for severe exocrine pancreatic insufficiency.

BACKGROUND: In order to apply fecal pancreatic elastase for follow-up of exocrine pancreatic function in chronic pancreatitis and cystic fibrosis, we examined the sensitivity, specificity, and long-term variability of a new polyclonal antibody-based enzyme-linked immunosorbent assay (ELISA). METHODS: Patients with definite chronic pancreatitis (n = 23), probable or possible chronic pancreatitis (n = 14), autoimmune pancreatitis (n = 7), or acute pancreatitis (n = 11), and 51 healthy subjects and 11 healthy infants participated in this study. Pancreatic function was graded as normal (n = 3), mild (n = 18), moderate (n = 9), or severe (n = 18) exocrine insufficiency on the basis of secretin tests. Fecal pancreatic elastase was measured by a new ELISA. RESULTS: Fecal pancreatic elastase concentration in control subjects varied widely, with a median of 478 microg/g. The specificity of this test was 90.2% with a cutoff value of >200 microg/g. The sensitivities were 60.9% for detecting definite chronic pancreatitis, 76.5% for calcifying pancreatitis, 71.4% for autoimmune pancreatitis, and 7.1% for probable or possible chronic pancreatitis. The sensitivities were 16.7% for mild, 12.5% for moderate, and 72.2% for severe exocrine pancreatic insufficiency. Forty patients were reexamined after a median interval of 347 days. The fecal pancreatic elastase levels between the first and second tests were not significantly different. Two infants, 4.5 and 5 months old, had abnormally low values, but after a median of 304 days all infants showed normal levels (median, 444 microg/g). CONCLUSIONS: Fecal pancreatic elastase is a reproducible marker for severe exocrine pancreatic insufficiency. This test is valuable for longitudinal follow-up of exocrine pancreatic function.

Adult↗

Tumor invasion of lymph node capsules in patients with Dukes C colorectal adenocarcinoma.

PURPOSE: The objective of this study was to investigate the correlation between the microscopic findings of positive lymph nodes, especially focusing on capsular invasion, and the outcome after curative surgical resection of colorectal cancer. METHODS: We analyzed 480 positive lymph nodes from 155 consecutive patients with Stage III colorectal cancer to determine the frequency and significance of lymph node capsular invasion. Recurrence-free and cancer-specific survival rates were assessed in the patients with and without lymph node capsular invasion. RESULTS: Between April 1995 and December 2000, 406 consecutive patients with primary colorectal cancer underwent curative resection. Regional lymph node metastases were present in 155 cases (38.2 percent). During the median follow-up period of 4.8 years, 41 patients (26.5 percent) developed recurrent disease and 28 patients died of cancer. Lymph node capsular invasion was detected in one or more lymph nodes from 75 cases (48.3 percent). The five-year recurrence-free rate was 56.1 percent in this group, whereas in the 80 patients without lymph node capsular invasion the rate was 88 percent (P<0.01). Features that were associated with recurrent disease were greater number of positive lymph nodes, venous invasion in primary tumor, infiltrative growth pattern of intranodal tumor, and presence of lymph node capsular invasion. Multivariate analysis identified lymph node capsular invasion as the only significant prognostic factor for recurrence. In multivariate analysis with regard to survival, lymph node capsular invasion, venous invasion, and number of positive nodes remained as significant prognostic factors. CONCLUSIONS: Lymph node capsular invasion, determined by routine hematoxylin-eosin staining, is a potent prognostic factor in Stage III colorectal cancer.

Adenocarcinoma↗

Permeation flux of organic molecules through silica-surfactant nanochannels in a porous alumina membrane.

The permeation fluxes of phenol, benzene sulfonate (BS) and benzene disulfonate (BDS) through a porous anodic alumina membrane with the perpendicularly oriented silica-surfactant nanochannel assembly membrane (NAM) were measured in water-ethanol mixture media. The permeation flux depended on solute charges and on solvent composition. As the ethanol ratio increased, the fluxes of BS and BDS increased and the flux of phenol decreased. The results of extraction/elution experiments also depended on the solute charges and the solvent composition. Chromatographic experiments in n-hexane showed that dipole and hydrophobic interactions affect the retention of solutes. Permeation of the solute across the NAM in water-ethanol mixture is likely to be determined by various factors such as dipole interaction, hydrophobic interaction, solvation, and anion-exchange efficiencies.

Aluminum Oxide↗

Endothelial vasomotor dysfunction in the brachial artery is associated with late in-stent coronary restenosis.

OBJECTIVES: This study examined whether endothelial dysfunction in the brachial artery might be associated with late in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). BACKGROUND: Simple and noninvasive identification of late ISR might help to select patients who require further angiographic evaluation. METHODS: Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was measured before (initial FMD) and at six months (follow-up FMD) after PCI in 141 consecutive patients who had elective and successful PCI with bare metal stents in de novo lesions of native coronary arteries for symptomatic coronary artery disease. Follow-up angiography was performed at six months after PCI in all patients. RESULTS: With multivariate logistic regression analysis, the impairment (< or = 4.8% dilation from baseline diameter) of FMD at follow-up showed the strongest association with late ISR (defined as > 50% diameter stenosis, n = 46) independently of other clinical and angiographic variables known to be associated with ISR (odds ratio 7.4, 95% confidence interval 2.8 to 19.2, p < 0.001), whereas the initial FMD did not have the association. The sensitivity of impaired FMD at follow-up (69%) in detecting ISR was higher than chest pain during the follow-up period (45%), with comparable specificity. The impaired FMD in combination with the chest pain increased the sensitivity to 90%. CONCLUSIONS: The impairment of FMD in the brachial artery at the time of follow-up was independently and closely associated with late ISR in native coronary arteries. The noninvasive assessment of FMD at the time of follow-up might be useful for identification of late ISR.

Aged↗

Increased ambulatory pulse pressure is a strong risk factor for coronary endothelial vasomotor dysfunction.

OBJECTIVES: This study was aimed to determine the relationship between pulse pressure (PP) and coronary vasomotor dysfunction, a predictor of coronary events. BACKGROUND: Pulse pressure is a strong risk factor for coronary artery disease (CAD). However, the mechanisms by which an increase in PP affects the pathogenesis of CAD are unclear. METHODS: Ambulatory blood pressure (BP) monitoring for 24 h was performed in 103 consecutive patients with normal coronary angiograms (51 hypertensive and 52 normotensive; age 42 to 70 years). The relationship between changes in coronary arterial diameter and blood flow during an intracoronary infusion of acetylcholine (ACh) (5, 10, 50 microg/min), and BP parameters, and other traditional risk factors was evaluated using univariate and multivariate linear regression analyses. RESULTS: With multivariate analyses, the 24-h PP showed an inverse correlation with the epicardial coronary dilator response to ACh independently of other covariates including age, smoking, and 24-h systolic BP in normotensive as well as hypertensive patients. Furthermore, multivariate analysis showed that the 24-h PP was inversely and independently correlated with the increase in coronary blood flow in response to ACh. The dilator response of epicardial coronary arteries to nitrate was not significantly correlated with 24-h PP. CONCLUSIONS: Increased 24-h PP is independently associated with endothelial vasomotor dysfunction in conduit and resistance coronary arteries irrespective of the presence of hypertension. Increased ambulatory PP may have an intimate relation to coronary endothelial vasomotor dysfunction.

Acetylcholine↗

Remnant lipoproteinemia is a risk factor for endothelial vasomotor dysfunction and coronary artery disease in metabolic syndrome.

This study aimed to determine whether elevated levels of remnant lipoprotein, an atherogenic triglyceride-rich lipoprotein, might be associated with coronary artery disease (CAD) and endothelial vasomotor dysfunction in metabolic syndrome. The fasting serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol; RLP-C) were measured by an immunoseparation method in 210 patients with metabolic syndrome meeting ATP III criteria. Flow-mediated endothelium-dependent dilatation (FMD) in the brachial artery during reactive hyperemia was examined by high-resolution ultrasound technique. This study found that elevated RLP-C levels were a significant and independent risk factor for impaired FMD and angiographically proven coronary artery disease (CAD). Treatment with bezafibrate (n = 20) or atorvastatin (n = 20) for 4 weeks significantly reduced RLP-C levels, with a concomitant improvement in FMD. The % reduction in RLP-C levels from baseline after the treatment was independently correlated with the magnitude of improvement in FMD after adjustment for the % changes in levels of triglyceride, hsCRP, and IL-6, and HOMA index. Thus, elevated levels of RLP-C are a risk factor for CAD and endothelial vasomotor dysfunction, a predictor of coronary events, in metabolic syndrome. Measurement of RLP-C is useful for assessment of CAD risk and therapeutic effects in metabolic syndrome.

Aged↗

Early open thoracotomy and mediastinopleural irrigation for severe descending necrotizing mediastinitis.

OBJECTIVE: Descending necrotizing mediastinitis (DNM) is a severe infection spreading from the cervical region to the mediastinal connective tissue. The mortality rate was reported as 40% until the 1980s. Since DNM is uncommon, few reports of large series of patients with DNM (i.e. more than 10 cases) have been published. The present aim was to evaluate our treatment strategy for DNM by retrospective chart review. METHODS: Retrospective chart review was performed in 10 patients with DNM between 1991 and 2003. The mean age was 53.8+/-23.3 years (median 58, range 16-82). The causes of DNM were primary peritonsillar or parapharyngeal abscess in 5 patients, post-extraction odontogenic abscess in 3, cervical abscess of post-tracheostomy in 1, and unknown in 1 patient. In nine cases, the abscess extended from the cervical region to the lower mediastinum. Immediately after the diagnosis of DNM, broad-spectrum antibiotics were administered empirically, and surgical treatments consisting of cervical drainage, thoracotomy with radical surgical debridement of the mediastinum and excision of necrotic tissue, decortication, and irrigation were performed in all cases. Post-operatively, mediastinopleural irrigation with saline was performed once or twice a day until a culture of pleural effusion became negative. RESULTS: The mean duration of chest tube retention was 26.7+/-17.0 days, and the mean hospital stay was 62.3+/-33.9 days. Five patients suffered from severe complications including septic shock, acute respiratory distress syndrome, disseminated intravascular coagulation, and pan-peritonitis due to duodenal perforation. The outcome was favorable in 8 patients. Of those with severe complications, two patients, who were older than 75 and had diabetes, died of multiple organ failure due to septic shock. Therefore, the mortality rate was 20%. CONCLUSION: Our treatment strategy for severe DNM was efficacious for early treatment and reduced the mortality rate. Early detection of DNM, and immediate thoracotomy and irrigation of the mediastinum and thoracic cavity, are recommended.

Abscess↗

Lipopolysaccharide induces CD25-positive, IL-10-producing lymphocytes without secretion of proinflammatory cytokines in the human colon: low MD-2 mRNA expression in colonic macrophages.

Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.

Aged↗

[Foods with complaints of fungal contamination and physical problems caused by their ingestion].

A survey concerning foods for which complaints of fungal contamination had been made was carried out by distributing and retrieving a questionnaire. The subject of the survey was foods that were examined for fungi by institutes and laboratories belonging to regulatory agencies following consumers' complaints or upon request from food companies to solve problems. We analyzed 1,096 cases recovered from 40 organizations located in 30 prefectures. Most foods with fungal contamination were "cake and snacks", "beverages" and "bakery products", and processed and cooked foods and beverages accounted for more than 90% of the complaints. The numbers of cases were greater in the summer and less in the winter. The major fungal genus detected in the suspect foods were Penicillium, Aspergillus and Cladosporium. Aspergillus niger was the dominant species contaminating bakery products. Complainers reported physical symptoms including diarrhea, stomach ache, nausea and vomiting in 18% of the cases in which they had eaten or drunk fungus-contaminated foods or beverages. There was no clear difference in the fungi detected between foods and beverages that caused symptoms and those that did not. The proportion of beverages was greater in the foods that induced symptoms than in the whole of the foods for which complaints were made. This was presumed to be because consumers drank fungus-contaminated beverages more often than they ate fungus-contaminated foods.

Aspergillus↗

Multiresidue determination of pesticides in agricultural products by gas chromatography/mass spectrometry with large volume injection.

A method is described for the rapid determination of pesticide residues in agricultural products. Pesticides were extracted from samples with acetonitrile. To remove pigments and fatty acids, an aliquot of the extract was cleaned up by a minicolumn that was packed both with graphitized carbon black and primary secondary amine. Analysis was performed by gas chromatography/ mass spectrometry with programmable temperature vaporizer-based large volume injection using a liner packed with phenylmethylsilicone chemically bonded silica. The method was evaluated for 114 pesticides by spiking into tomato, spinach, Japanese pear, grape, and brown rice at various concentrations of each pesticide (0.02-0.4 microg/g). The method, which gave good recovery (>60%) for 108 pesticides, is characterized by high cleanup efficiency and short cleanup time, and is useful as a rapid screening analysis.

Buffers↗