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Biomedical subjects

Y Sumida

Publications and source records attributed to Y Sumida.

At least 19 recordsLinked to original sources

Laminin-10/11 and fibronectin differentially regulate integrin-dependent Rho and Rac activation via p130(Cas)-CrkII-DOCK180 pathway.

The alpha(5) chain-containing laminin isoforms, laminins-10 and -11 (laminin-10/11), are the major components of the basement membrane, having potent cell-adhesive activity. We examined the cell-adhesive and integrin-mediated signaling activities of laminin-10/11 in comparison to fibronectin, the best characterized extracellular adhesive ligand. We found that laminin-10/11 are more active than fibronectin in promoting cell migration and preferentially activate Rac, not Rho, via the p130(Cas)-CrkII-DOCK180 pathway. Cells adhering to fibronectin develop stress fibers and focal contacts, whereas cells adhering to laminin-10/11 do not, consistent with the high cell migration-promoting activity of laminin-10/11. Pull-down assays of GTP-loaded Rac and Rho demonstrated the preferential activation of Rac on laminin-10/11, in contrast to the activation of Rho on fibronectin. Activation of Rac by laminin-10/11 was associated with the phosphorylation of p130(Cas) and an increased formation of a p130(Cas)-CrkII-DOCK180 complex. Cell migration on laminin-10/11 was suppressed by the expression of either a dominant-negative Rac or CrkII mutants defective in p130(Cas) or DOCK180 binding. This is the first report demonstrating a distinct activation of Rho family GTPases resulting from adhesion to different extracellular ligands.

Cell Movement↗

Differences in the efficacy of ursodeoxycholic acid and bile acid metabolism between viral liver diseases and primary biliary cirrhosis.

AIM AND METHODS: The effects of ursodeoxycholic acid (UDCA, 600 mg/day) on liver function test values, and serum and urinary bile acids levels in hepatitis C virus-related chronic hepatitis (CH, n = 39) and liver cirrhosis (LC, n = 25), and in primary biliary cirrhosis (PBC, n = 25) were compared. RESULTS: The percentages of improvement in alanine transaminase (ALT) and gamma-glutamyl transpeptidase (gamma-GTP) in CH were almost the same in LC. The rates of improvement in ALT in PBC were negatively correlated with histological stages in the liver. Total serum bile acid levels in LC rose to the same extent as in CH, but the increases in PBC were significantly smaller at stages 3-4 than stages 1-2. The urinary levels of hydroxylated metabolites of UDCA only slightly increased in LC, but they increased significantly at PBC stages 3-4. CONCLUSIONS: The efficacy of UDCA was preserved in LC, but diminished at PBC stages 3-4. The poor enrichment of UDCA in the bile acid pool and extensive biotransformation of UDCA may cause the limited efficacy of UDCA in the cirrhotic stage of PBC.

Adult↗

Plasma levels of agouti-related protein are increased in obese men.

To investigate the relationship between peripheral blood levels of agouti-related protein (AGRP) and various parameters of obesity, we measured the plasma level of AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured by computed tomography, fasting insulin levels, glucose infusion rate during an euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH. Obese men had significantly higher plasma concentrations of AGRP than nonobese men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are proportionally correlated with BMI, body fat weight, and sc fat area in obese men (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r = 0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r = 0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma levels of AGRP were significantly correlated with the visceral fat area (r = 0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556, P < 0.01). In all subjects, multiple regression analysis showed that the plasma levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated with the plasma levels of alpha-MSH, independently from the total fat area. However, the correlation between plasma levels of AGRP and serum levels of leptin was found to be dependent on the total fat area. In brief, these findings showed that the circulating levels of AGRP are increased in obese men and that they are correlated with various parameters of obesity. Although correlation does not prove causation, the results of this study suggest that peripheral AGRP may play a role in the pathogenesis of obesity.

Adult↗

Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes.

OBJECTIVE: To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (approximately 1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization. RESULTS: Univariate regression analysis disclosed a significant correlation between log-transformed HOMA-IR and log-transformed clamp IR before (r = -0.613, P < 0.0001) and after ( = -0.734, P < 0.0001) treatment. Neither the slopes (-0.71 +/- 0.12 vs. -0.79 +/- 0.09, F = 0.25, P = 0.61) nor the intercepts (y-intercept = 1.67 vs. 1.70, x-intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log-transformed HOMA-IR and the increase in clamp IR during treatment (r = -0.617, P < 0.0001). CONCLUSIONS: HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes.

Adult↗

Effects of both the emotional behavior and feeding conditions on the circulating plasma volume and plasma glucose levels in cats.

Influence of hypothalamically induced emotional behavior on the circulating plasma volume, plasma levels of glucose, epinephrine (E), norepinephrine (NE), dopamine (DA) and cortisol were examined in awake cats under both fasted and fed conditions. Restlessness was evoked intermittently for 6 h by electrical stimulation of the anteromedial hypothalamus (AMH). Blood was sampled immediately before, 1 h after and 6 h after the start of stimulation. Changes in the plasma volume was calculated by changes of hemoglobin (Hb) and hematocrit (Ht). As the control group, another 7 cats with electrodes implanted but unstimulated were identically treated under both fasted and fed conditions. Both E and glucose levels in restlessness group once markedly increased after 1 h and then tended to decrease after 6 h, whereas NE levels in restlessness group increased after 1 h and further increased after 6 h, whether cats were fasted or fed. DA levels increased under the fasted condition of restlessness. The cortisol level markedly increased in both fasted and fed restlessness groups. The plasma volume in control group increased under the fed condition, while in restlessness group it decreased remarkably and tended to decrease more in a fasted state than in a fed state. These results indicated that AMH induced restlessness elicited marked sympatho-adrenal activation, hyperglycemia and hemoconcentration, whether cats were fasted or fed. Relationship among such responses, and the difference in responses between fasted and fed conditions were also discussed in the paper.

Animals↗

Increase in phospholipase C-delta1 protein levels in aluminum-treated rat brains.

The effect of administration of aluminum to rats on the level of three phospholipase C (PLC) isozymes (beta1, gamma1, and delta1) was assessed in a variety of brain tissues. After exposure to aluminum, a statistically significant increase in malondialdehyde, an index of lipid peroxidation, was observed. In addition, there was a significant reduction in the catalytic activity of low molecular weight phosphotyrosine phosphatase, which loses its activity during oxidative stress. This suggests that oxidative stress is induced in brain tissues exposed to aluminum. The protein level of PLC-delta1, but not that of PLC-beta1 or -gamma1, was significantly increased in brains where oxidative stress had been induced. The total PLC activity in aluminum-treated rat brains was significantly higher than that in control brains. These results suggest that PLC-delta1 protein levels in brain tissues are increased by the induction of oxidative stress, giving an explanation for its up-regulation in Alzheimer's disease.

Aluminum↗

Serum thioredoxin levels as an indicator of oxidative stress in patients with hepatitis C virus infection.

BACKGROUND/AIM: It has recently been suggested that oxidative stress may be associated with hepatitis C virus (HCV) infection. Thioredoxin (TRX) is a stress-inducible thiol-containing protein. The aim of this study was to evaluate the clinical significance of serum TRX levels in patients with HCV-related chronic liver diseases. METHODS: Serum TRX levels were determined with a sandwich enzyme-linked immunosorbent assay kit in 174 serum HCV-RNA positive patients, including 6 asymptomatic carriers, 124 chronic hepatitis, 20 liver cirrhosis, and 24 hepatocellular carcinoma, and in 15 healthy volunteers. RESULTS: The serum TRX levels (medians and [ranges], ng/ml) were significantly elevated in the HCV-infected patients; 30.9 [20.7-37.7] in asymptomatic carriers, 34.5 [8.6-135.6]* in chronic hepatitis, 42.5 [21.4-97.2]* in liver cirrhosis, and 43.9 [11.7-180.3]** in hepatocellular carcinoma (*p<0.05, **p<0.001, vs. 24.9 [1.3-50.7] in healthy controls). Serum TRX levels were significantly correlated with the serum levels of ferritin and fibrogenesis markers, and with the histological stage of hepatic fibrosis. The serum TRX levels before interferon treatment of patients whose serum HCV-RNA was still positive on day 14 following interferon treatment (42.6 [20.1-90.0]) were significantly higher than those of patients whose serum HCV-RNA was negative on day 14 following interferon treatment (25.8 [7.4-59.8], p<0.05). CONCLUSIONS: The serum TRX levels of patients with HCV infection increased with their serum ferritin levels and the progression of liver fibrosis. Patients with higher serum TRX levels exhibited resistance to interferon therapy. Oxidative stress may therefore be responsible for the pathological mechanism of HCV-related liver diseases and be one of the impediments to eradication of HCV during interferon treatment.

Adult↗

Elevated plasma levels of alpha-melanocyte stimulating hormone (alpha-MSH) are correlated with insulin resistance in obese men.

OBJECTIVE: The role of alpha-melanocyte stimulating hormone (MSH) in obesity has been well-documented. However, circulating alpha-MSH concentrations in obese men and their relationship with clinical indicators of obesity and glucose metabolism have not as yet been evaluated. METHODS: We measured the plasma concentrations of alpha-MSH in 15 obese and 15 non-obese male subjects. The relationship of the plasma concentrations of alpha-MSH with body mass index (BMI), body fat mass (measured by bioelectric impedance), body fat distribution (measured by computed tomography), insulin levels, insulin resistance (assessed by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study) and with the serum concentrations of leptin and TNF-alpha were also evaluated. RESULTS: In obese men, the plasma alpha-MSH concentrations were significantly increased compared with those in non-obese men (P< 0.02). The plasma levels of alpha-MSH were positively correlated with BMI (r= 0.560, P< 0.05), fasting insulin levels (r=0.528, P< 0.05) and with visceral fat area (r=0.716, P<0.01), but negatively correlated with GIR (r= -0.625, P< 0.02) in obese male subjects. There were significant correlations between plasma concentrations of alpha-MSH and visceral fat area (r=0.631, P< 0.02), and GIR (r = -0.549, P< 0.05) in non-obese male subjects. Circulating concentrations of alpha-MSH were not significantly correlated with the serum concentrations of leptin and TNF-alpha in both obese and non-obese men. CONCLUSION: Circulating concentrations of alpha-MSH are significantly increased and correlated with insulin resistance in obese men.

Adult↗

Troglitazone reduces plasma levels of tumour necrosis factor-alpha in obese patients with type 2 diabetes.

We evaluated the effect of troglitazone (given orally 400 mg/day) on glucose intolerance and on the plasma levels of tumour necrosis factor-alpha (TNF-alpha) in 12 obese patients with type 2 diabetes for 12 weeks. Troglitazone significantly decreased fasting plasma glucose, serum C-peptide, serum insulin and HbA1c levels. Plasma levels of TNF-alpha were significantly reduced by troglitazone administered for 8 and 12 weeks. Troglitazone administration significantly improved insulin resistance, but did not affect pancreatic beta-cell function as evaluated by the homeostasis model assessment (HOMA). In the present study, we reported for the first time that troglitazone administration significantly reduces plasma levels of TNF-alpha in obese patients with type 2 diabetes.

Blood Glucose↗

Thioredoxin levels in the sera of untreated viral hepatitis patients and those treated with glycyrrhizin or ursodeoxycholic acid.

Thioredoxin (TRX), a thiol-containing protein, is induced by various oxidative stresses. Serum TRX levels were measured with a sandwich enzyme-linked immunosorbent assay kit in 210 hepatitis C virus (HCV)-infected patients, 39 hepatitis B virus (HBV)-infected patients, and 17 healthy volunteers. The effects of hepatoprotective drugs on TRX levels were also examined. The median TRX levels were significantly higher in HCV-infected patients than in controls (34.2 vs. 23.5 ng/ml, respectively; p < 0.005), but were not elevated in HBV-infected patients (26.7 ng/ml). The TRX levels were significantly correlated with serum lipid peroxide levels and indocyanine green exclusion test values, and were markedly decreased following treatment with Stronger Neo-Minophagen C or ursodeoxycholic acid. In conclusion serum TRX levels, a marker of oxidative stress, were higher in patients with HCV infection than those with HBV infection and healthy controls. The therapeutic efficacy of hepatoprotective drugs may be connected with the decrease in oxidative stress in hepatitis patients.

Adult↗

Changes in the leukocyte distribution and surface expression of adhesion molecules accompanied with hypothalamically induced restlessness in the cat.

One type of emotional behavior called restlessness occurs when the anteromedial hypothalamus is stimulated in cats. We examined the changes in the distribution and surface expression of adhesion molecules in leukocytes accompanied with restlessness. Mature female cats were used for this study. The cats were stimulated with 60 Hz sine wave train pulses (20-90 microA, 10 s in duration, at 5-min intervals) for 60 min. Samples of blood were collected from 30 min before stimulation up to several hours after the final stimulation. The number of granulocytes increased just after stimulation, while at the same time the expression of L-selectin decreased. On the other hand, the number of CD4+ and CD8+ T lymphocytes decreased at 1-2 h after the end of the stimulation, while the expression of L-selectin increased. In addition, the expression of LFA-1 and VLA-4 did not change. These data suggest that hypothalamically elicited restlessness is thus accompanied by a leukocyte distribution change, which might be mediated by changes in the expression of L-selectin on leukocytes. Plasma cortisol increased during stimulation in restlessness. However, during in vitro culture experiments, cortisol did not alter the expression of leukocyte L-selectin which thus indicated that cortisol does not directly affect the surface expression of L-selectin. These results thus suggest that hypothalamically induced restlessness is a useful stress model for psychoneuroimmunological studies.

Animals↗

A case of obesity, diabetes and hypertension treated with very low calorie diet (VLCD) followed by successful pregnancy with intrauterine insemination (IUI).

The patient was a 32-year-old obese woman with a history of type 2 diabetes and hypertension for 6 years. Although she was treated with antihypertensive agents and intensive insulin therapy, her hyperglycemia was difficult to control. She wanted to have a baby but pregnancy was not recommended because her diabetes was under poor control and the use of antihypertensive medication. To achieve good control of obesity, diabetes and hypertension, she was admitted to our clinical department for weight reduction using very low calorie diet (VLCD). During VLCD she had a 19.8 kg reduction in body weight and her blood glucose and blood pressure were in good control without the use of drugs. Five months later, she became pregnant after the fourth trial of intrauterine insemination (IUI) and gave birth to a female baby under insulin therapy. This is the first report that showed the usefulness of VLCD for prepregnant control of glucose metabolism and blood pressure in an obese hypertensive patient with type 2 diabetes mellitus.

Adult↗

[Colpocephaly].

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Cerebral Ventricles↗

Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants.

The therapeutic efficacy of ursodeoxycholic acid (UDCA) has been widely demonstrated in various liver diseases, suggesting that UDCA might protect hepatocytes against common mechanisms of liver damage. A candidate for such protection is oxidative injury induced by reactive oxygen species. This study was designed to assess the effects of UDCA on oxidative injury and antioxidative systems in cultured rat hepatocytes. The viability of the hepatocytes dose-dependently decreased after hydrogen peroxide or cadmium administration. Pretreatment with UDCA significantly prevented this decrease in viability. The amounts of glutathione (GSH) and protein thiol increased significantly, but the activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and catalase were unchanged in UDCA-treated hepatocytes. The mRNA levels of gamma-glutamylcysteine synthetase and metallothionein (MT) were significantly higher in UDCA-treated hepatocytes than in controls. In conclusion, UDCA increased hepatocyte levels of GSH and thiol-containing proteins such as MT, thereby protecting hepatocytes against oxidative injury. Our results provide a new perspective on the hepatoprotective effect of UDCA.

Animals↗

High serum concentrations of sialyl Tn antigen in carcinomas of the biliary tract and pancreas.

Sialyl-Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. In the present study, we compared the serum level of STn antigen in 14 patients with benign diseases of the biliary tract and pancreas, 15 patients with bile duct cancers, and 9 patients with cancer of the pancreas. High levels of serum STn (>45 U/ml) were frequently detected in patients with carcinoma of the biliary tract (53.3%) or pancreas (55.6%), compared with the detection of high levels in those with benign diseases (14.3%; P < 0.05). Serum levels of STn did not correlate with the presence of jaundice, cholangitis, or pancreatitis, or with the level of carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9. In cancer tissues, the expression of STn antigen detected by immunostaining correlated significantly with serum STn (P < 0.05). Our results indicate that measurement of serum STn level may be potentially useful for the diagnosis of carcinomas of the biliary tract and pancreas, particularly when combined with other tumor markers such as CEA or CA19-9.

Adult↗

Expression of multidrug resistance protein in metastatic colorectal carcinomas.

To clarify the relationship between multidrug resistance protein (MRP) and clinicopathologic features, the influence of adjuvant chemotherapy, and prognosis of patients who underwent resection of metastatic liver carcinomas originating from colorectal carcinomas, we examined the expression of MRP in tumor tissues by immunostaining. Specimens of 38 primary colorectal tumors and 44 metastatic liver tumors of colorectal origin were examined (metastatic group). We also examined 28 nonmetastatic colorectal carcinomas. The percentages of nonmetastatic tumors and of primary and metastatic tumors of the metastasis group that expressed MRP were similar. MRP expression in primary and metastatic tumors did not correlate with any clinicopathologic features. The use of adjuvant chemotherapy after operation for primary colorectal carcinomas was associated with increased MRP expression among metastatic liver tumors. Expression of MRP in the tumor did not influence the prognosis or survival rate after resection of primary or metastatic tumors. Our data suggest that MRP expression in metachronous liver metastases from colorectal carcinomas may be induced by administration of anticancer drugs but is not associated with clinicopathologic features of the tumor, liver metastasis, or prognosis.

ATP-Binding Cassette Transporters↗

Codon 54 polymorphism of the fatty acid binding protein gene and insulin resistance in the Japanese population.

AIM: To determine the relationship of the polymorphism at codon 54 of the intestinal fatty acid binding protein gene (FABP2) with insulin resistance and susceptibility to Type 2 diabetes mellitus (DM) in the Japanese population. METHODS: We evaluated the polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 150 Type 2 DM patients and 147 healthy control subjects. The frequency of alleles encoding threonine (Thr54) and alanine (Ala54) at codon 54 of FABP2 in Type 2 DM patients was compared with that of healthy controls. Insulin sensitivity was assessed by the hyperinsulinaemic euglycaemic clamp in Type 2 DM patients with Ala54 homozygotes, Ala54/Thr54 heterozygotes and Thr54 homozygotes and by homeostasis model assessment (HOMA) in the nondiabetic group. RESULTS: The frequency of alleles encoding Ala54 and Thr54 was 0.59 and 0.41 in Type 2 DM patients, respectively, similar to that observed in nondiabetic controls (0.64 for Ala54 and 0.36 for Thr54). Insulin sensitivity was not significantly different between subjects with and without Thr54 allele either within the DM group or healthy controls. CONCLUSIONS: The allele encoding threonine in the FABP2 does not predispose to Type 2 DM or insulin resistance in the Japanese population.

Carrier Proteins↗