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Biomedical subjects

Kazuaki Chayama

Publications and source records attributed to Kazuaki Chayama.

At least 19 recordsLinked to original sources
PubMed2003

Expression of hypoxia-inducible factor-1alpha is associated with tumor vascularization in human colorectal carcinoma.

HIF-1 is reported to transactivate expression of VEGF, which is an important angiogenic factor. To determine whether HIF-1alpha plays a role in angiogenesis through its regulation of VEGF, we examined expression of HIF-1alpha and its relation to clinicopathologic features, VEGF expression and prognosis of patients with colorectal carcinoma. Expression of HIF-1alpha and VEGF was examined in 4 colorectal carcinoma cell lines (COLO320DM, COLO201, DLD-1, WiDr) and 149 colorectal carcinoma tissues (10 fresh specimens, 139 archival, paraffin-embedded specimens). HIF-1alpha protein levels were increased by hypoxia in 3 of 4 colorectal carcinoma cell lines (COLO201, DLD-1, WiDr), and VEGF mRNA levels were also increased by hypoxia in the same cell lines. In 8 of 10 patients with colorectal cancer, expression of HIF-1alpha and VEGF was increased in tumor tissues compared to corresponding normal mucosa. Of 139 archival specimens of colorectal carcinoma, 81 (58.3%) expressed HIF-1alpha protein at a high level. HIF-1alpha expression was correlated with tumor invasion, tumor stage, lymphatic invasion, venous invasion and liver metastasis. Moreover, HIF-1alpha expression was correlated significantly with VEGF expression and microvessel density. Although there was a tendency for poorer prognosis in patients with high HIF-1alpha-expressing tumors, this correlation was not statistically significant. These findings suggest that HIF-1alpha may play a role in angiogenesis and tumor progression via regulation of VEGF in human colorectal carcinoma.

Adenocarcinoma↗
PubMed2003

Inhibition of cholesterol crystallization under bilirubin deconjugation: partial characterization of mechanisms whereby infected bile accelerates pigment stone formation.

Pigment gallstones have been reported to be closely associated with biliary tract infection. We previously reported that addition of unconjugated bilirubin (UCB), which is deconjugated by beta-glucuronidase in infected bile, could enhance cholesterol crystal formation in supersaturated model bile (MB). The present study evaluated the effect of beta-glucuronidase on the processes of pigment gallstone formation and cholesterol crystallization. Supersaturated MB (taurocholate/lecithin/cholesterol at 71:18:11, a total lipid concentration of 10.0 g/dl and a cholesterol saturation index (CSI) of 2.0) and native rat bile were mixed at a ratio of 3:1. Then, mixed bile was incubated with or without beta-glucuronidase and changes of the following parameters were investigated over time: (1) the UCB/total bilirubin ratio; (2) cholesterol crystal formation; (3) the precipitate weight and the cholesterol concentration in the precipitate and supernatant; and (4) the lipid distribution of vesicles in the supernatant. Compared with beta-glucuronidase-free bile, (1) beta-glucuronidase-containing bile showed a significant increase of the UCB/total bilirubin ratio, (2) as well as a significantly longer nucleation time (96+/-17.0 vs. 114+/-20.0) and fewer cholesterol crystals. (3) The precipitate weight and the cholesterol concentration in the precipitate were significantly increased, while the cholesterol concentration in supernatant was decreased. (4) When mixed bile was incubated with beta-glucuronidase, the cholesterol concentration in the vesicles was lower than in bile without beta-glucuronidase. The precipitate weight and the cholesterol concentration in the precipitate was increased by incubation with beta-glucuronidase, while cholesterol concentration was decreased in the supernatant (especially in the vesicles). This means that bile vesicles were more stable and it was more difficult for cholesterol crystals to form. Thus, the presence of beta-glucuronidase may inhibit the formation of pure cholesterol stones even in the presence of cholesterol supersaturation.

Animals↗
PubMed2003

Comparison of forearm endothelial function between premenopausal and postmenopausal women with or without hypercholesterolemia.

We sought to determine whether menopausal status or postmenopausal hypercholesterolemia affects forearm resistance artery endothelial function. We studied the forearm resistance artery endothelial function in 75 Japanese women: 25 premenopausal volunteers, 25 postmenopausal women with normal serum low-density lipoprotein (LDL) cholesterol concentrations, and 25 hypercholesterolemic postmenopausal women. Excluded from the study were patients with hypertriglyceridemia, hypertension, or diabetes, cigarette smokers. The forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. The serum concentrations of lipoprotein (a) [Lp(a)] were significantly higher in the hypercholesterolemic postmenopausal group than in the other two groups (P<0.01). These lipid parameters were similar between the premenopausal and postmenopausal women with normal cholesterol. The FBF responses to reactive hyperemia were significantly lower in the postmenopausal hypercholesterolemic women than in the other two groups (P<0.01). The reactive hyperemia also was impaired in the postmenopausal group with normal cholesterol as compared with the premenopausal group (P<0.01). Increases in FBF after NTG were similar between the three groups. By stepwise multivariate analysis, menopausal status and serum LDL cholesterol was the significant predictor of forearm endothelial function. These findings suggest that reactive hyperemia is impaired in forearm resistance arteries after menopause, especially in postmenopausal women with hypercholesterolemia.

Adult↗
PubMed2003

PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers.

Smoking is associated with endothelial dysfunction. The purpose of this study was to determine the effect of sildenafil, an inhibitor of phosphodiesterase type 5 (PDE5), on endothelial function in smokers. We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after oral sildenafil administration (100 mg) with a strain-gauge plethysmograph in 10 young healthy male smokers and 10 young healthy male nonsmokers. FBF response to ACh was lower in smokers than in nonsmokers. The vasodilatory effects of SNP were similar in both groups. Sildenafil increased the FBF response to ACh from 9.3+/-2.0 to 12.5+/-3.5 mL/min per 100 mL tissue in smokers and from 12.6+/-5.6 to 19.6+/-8.4 mL/min per 100 mL tissue in nonsmokers, and it increased the response to SNP from 13.3+/-3.9 to 15.1+/-4.3 mL/min per 100 mL tissue in smokers and from 14.8+/-5.2 to 18.4+/-6.0 mL/min/100 mL tissue in nonsmokers (P<0.05 for all). The ratio of maximal ACh-stimulated FBF expressed as a ratio of maximal SNP-stimulated FBF significantly increased after administration of sildenafil in both groups. Infusion of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished sildenafil-induced augmentation of the FBF response to ACh in both groups. The findings suggest that endothelial function is impaired in smokers compared with that in nonsmokers, that inhibition of PDE5 by sildenafil significantly increases nitric oxide-mediated vasodilation, and that the activities of PDE5 in smokers and nonsmokers may be similar.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Smoking activates rho-kinase in smooth muscle cells of forearm vasculature in humans.

Previous studies have shown that smoking is strongly associated with atherosclerosis and coronary vascular disease. Rho-kinase plays an important role in various cellular functions associated with atherosclerosis and hypertension. However, there is no information on the relationship between smoking and Rho-kinase activity in humans. The purpose of this study was to determine the Rho-kinase activity in forearm vascular smooth muscle cells (VSMCs) in healthy young male smokers. We evaluated the forearm blood flow (FBF) responses to fasudil (3, 10, and 30 microg/min for 5 minutes), a Rho-kinase inhibitor, or sodium nitroprusside (0.75, 1.5, and 3.0 microg/min for 5 minutes) in current smokers (n=8) and nonsmokers (n=8). FBF was measured with a strain-gauge plethysmograph. The vasodilatory effect of fasudil was significantly greater in smokers than in nonsmokers (14.9+/-3.5 versus 10.5+/-3.6 mL/min per 100 mL tissue; P<0.01). The FBF responses to sodium nitroprusside were similar in the 2 groups (34.7+/-10.4 versus 33.2+/-10.2 mL/min per 100 mL tissue; P=0.78). These findings suggest that smoking activates Rho-kinase in forearm VSMCs but does not alter the vasodilatory effect induced by exogenous nitric oxide in forearm VSMCs in healthy young men.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2003

Giant gastric folds: differential diagnosis at US.

PURPOSE: To evaluate ultrasonographic (US) features in the differential diagnosis of giant gastric folds. MATERIALS AND METHODS: One hundred sixty-five patients with giant gastric folds at transabdominal US examination (five with Ménétrier disease, 24 with anisakiasis, 61 with acute gastric mucosal lesion [AGML], 13 with gastric lymphoma, and 62 with scirrhous carcinoma) were examined. With 3-6-MHz curved and 5-11-MHz linear-array transducers, the authors evaluated gastric wall thickness, wall stratification, main thickened layer, echogenicity, and compressibility of the lesion in each case. The Fisher protected least-significant-difference method was used to compare statistically the thickness of the gastric wall among diseases. RESULTS: Wall thickness of AGML was significantly (P <.001) less than that of anisakiasis, gastric lymphoma, and scirrhous carcinoma. US findings revealed regular gastric wall thickening of the second or third layer, with preservation of wall stratification in all patients with benign conditions. The fourth layer was thickened only in patients with malignancy. The echogenicity of gastric lymphoma was markedly lower than that of any other condition. Compressibility of scirrhous carcinoma was absent, whereas it was well preserved in all benign conditions. CONCLUSION: Transabdominal US can depict gastric wall stratification and is a useful noninvasive modality for differential diagnosis of giant gastric folds.

Adenocarcinoma, Scirrhous↗
PubMed2003

Natural histories of hepatitis C virus infection in men and women simulated by the Markov model.

The Markov model was introduced to simulate natural histories of hepatitis C virus (HCV) infection in men and women. The data set was constructed on 942 HCV carriers who were examined at least once a year without receiving antiviral therapies. Based on 2,251 patient-year data, the probabilities of transition between any two of the four clinical states, i.e., asymptomatic carrier state, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in 1 year were calculated. Hepatocellular carcinoma was defined as the absorbing state from where no transitions occur. Probability matrices thus obtained on six each subsets of HCV infection (asymptomatic carrier state, chronic hepatitis and liver cirrhosis in men and women) in their forties, fifties, and sixties, were used to simulate long-term outcomes of HCV infection. Male asymptomatic carriers aged 40 years were expected to retain the asymptomatic carrier state in 2.6%, evolve into chronic hepatitis in 48.4%, liver cirrhosis in 14.6% and hepatocellular carcinoma in 34.4% after 30 years when they reached 70 years of age, in contrast to 1.9%, 45.3%, 32.8% and 20.0%, respectively, of female asymptomatic carriers. Likewise, male patients with chronic hepatitis aged 40 years were expected to remain with chronic hepatitis in 43.8%, evolve into liver cirrhosis in 15.0% and hepatocellular carcinoma in 41.1%, contrasting with 38.9%, 32.7% and 22.0%, respectively, of female patients during 30 years. The Markov model could simulate the outcomes of 153 HCV carriers identified among blood donors after 5 years. The Markov simulation would help in assessing the long-term outcome of HCV infection and making decisions in the management of HCV carriers toward prevention of hepatocellular carcinoma.

Adult↗
PubMed2003

Serum pepsinogen concentration as a marker of Helicobacter pyloriinfection and the histologic grade of gastritis; evaluation of gastric mucosa by serum pepsinogen levels.

BACKGROUND: Helicobacter pylori infection and associated gastritis are well-known significant factors in many gastrointestinal diseases, and evaluation of these conditions is important for health evaluation. We investigated the utility of serum pepsinogen (PG) concentrations for the diagnosis of H. pylori infection and evaluation of the grade of histologic gastritis. METHODS: The subjects consisted of 283 individuals (147 men and 136 women; mean age, 44.0 years). Biopsy specimens were obtained from the gastric antrum and body to assess grade of inflammation and atrophy and histologic evidence of H. pylori infection. H. pylori infection was judged by Giemsa staining and serum IgG antibodies against H. pylori. PG concentrations were determined by radioimmunoassay. RESULTS: In subjects with H. pylori infection, serum PGII concentrations were increased, and the PGI/PGII ratio (I/II ratio) was decreased. In patients with marked atrophy or intestinal metaplasia, both serum PGI and the I/II ratio were decreased. When PGII concentrations of 12 ng/ml or more, or a I/II ratio of 4.0 or less were used as the cutoff points for the diagnosis of H. pylori infection, the sensitivity and specificity of diagnosis were 90.0% and 93.5%, respectively. All subjects with serum PGI concentrations of 85 or more ng/ml, or serum PGII concentrations of 15 or more ng/ml were H. pylori-positive and all subjects with a I/II ratio of more than 6.5 were H. pylori-negative. CONCLUSIONS: These results suggest that H. pylori infection, gastritis, and glandular atrophy of the stomach can be evaluated via serum PG concentrations, allowing the evaluation of gastric mucosal integrity.

Adolescent↗
PubMed2003

Isolated granulomatous gastritis successfully treated by Helicobacter pylori eradication: a possible association between granulomatous gastritis and Helicobacter pylori.

We report two cases of granulomatous gastritis that resolved completely with Helicobacter pylori eradication. Two Japanese women, one 61 years old and one 58 years old, presented to our hospital with epigastralgia. Endoscopy revealed multiple shallow ulcerative lesions in the gastric corpus of both patients. Biopsy specimens demonstrated acute and chronic inflammation with multiple small, noncaseating granulomas at the level of the foveolar isthmi-the junction between the pits and the glands. Both specimens were positive for Helicobacter pylori. No other causes of organic granulomatous disease could be found. Both patients were diagnosed as having isolated granulomatous gastritis and were given triple therapy for Helicobacter pylorieradication, with their fully informed consent. The granulomatous gastritis resolved after successful Helicobacter pylorieradication therapy. This report describes a possible association between isolated granulomatous gastritis and Helicobacter pyloriinfection. To our knowledge, this is the first report describing isolated granulomatous gastritis successfully treated by triple therapy ( Helicobacter pylorieradication therapy).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Hydrophilic bile salts have a cytoprotective effect against cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity.

Cyclosporine A (CsA) reduces liver canalicular membrane (CM) fluidity to cause a disproportionate reduction of biliary lipid secretion (the uncoupling phenomenon) without affecting adenosine triphosphate-dependent (ABC) transporters except for Mdr1. This study investigated whether hydrophilic bile salts inhibit CsA-induced cholestasis, focusing on CM fluidity and ABC transporter expression. Male Sprague-Dawley rats were infused with taurocholate (TC) (200 nmol/min/100 g body weight) for 2 h, flowed by infusion with tauroursodeoxycholate (TUDC), tauroalphamuricholate, or taurobetamuricholate (100 nmol/min/100 g body weight plus TC at 100 nmol/min/100 g body weight). Thereafter, CsA (20 mg/kg body weight) was injected as a bolus and bile was collected for 2 h. Canalicular membrane vesicles were prepared for analysis of cholesterol (CH), phospholipid (PL), CM fluidity, and expression of ABC transporters (Mdr1, Bsep, Mdr2, and Mrp2). CsA administration reduced biliary lipid secretion along with a disproportionately smaller decline of bile salt secretion. Hydrophilic bile salts significantly inhibited cholestasis after CsA injection by increasing CM fluidity and by increasing the expression of Mrp2 and Bsep, whereas Mdr1 and Mdr2 were unaltered. (1) Hydrophilic bile salts inhibit CsA-induced cholestasis, presumably by increasing CM fluidity, and this action was greatest with TUDC. (2) The fact that ABC transporters, except for Mdr1 and Mdr2, were overexpressed in the CM after infusion of these bile salts suggests that cytoprotective bile salts functions may increase transporter mass as well as enhancing transporter activity.

Journal Article↗
PubMed2003

Choleretic action of diosgenin is based upon the increases in canalicular membrane fluidity and transporter activity mediating bile acid independent bile flow.

It is known that diosgenin alters the lipid composition of hepatic plasma membranes as well as bile lipids. We recently reported that changes in the lipid composition of the canalicular membrane bilayer were associated with alterations of membrane fluidity. Therefore, the present study was performed to determine the effect of diosgenin on bile secretion, focusing on canalicular membrane composition, membrane fluidity, transporter expression, and transporter activity. METHODS: SD rats were fed a diet with or without diosgenin. Bile duct cannulation was done and the bile acid pool was depleted, followed by infusion of sodium taurocholate for 120 min to collect bile samples. Bile flow and the biliary output of cholesterol (Ch), phospholipids, bile salt, and total glutathione (GSH+GSSG) were estimated. Liver canalicular membrane vesicles (CMV) were prepared for the assessment of lipid composition, ATP-dependent transporters, and membrane fluidity. RESULTS: Bile flow, especially bile acid-independent fraction, was increased significantly by diosgenin. Biliary output of Ch and total glutathione were significantly increased by diosgenin. CMV fluidity and Mrp2 expression were increased by diosgenin. CONCLUSION: The fact that diosgenin increased bile flow and biliary cholesterol and glutathione output indicates a choleretic action along with enhancement of solute secretion. The increase of CMV fluidity and Mrp2 suggests that the choleretic action of diosgenin was based upon both the direct stimulation of transporter expression and indirect transporter activation by an increase of membrane fluidity.

Journal Article↗
PubMed2003

Unique reciprocal changes of hepatocellular membrane transporter expression and fluidity in rats with selective biliary obstruction.

BACKGROUND AND AIMS: The localized occlusion of bile ducts by intrahepaticlithiasis and intrahepatic neoplasms dose not cause severe jaundice, although the reason is unclear. The aim of this study was to clarify the molecular change of the liver in partial cholestasis, especially with respect to transporter expression (Mrp2, Mrp3, Bsep, P-gps) and membrane fluidity. METHODS AND RESULTS: After 3 days of selective bile duct ligation in Sprague-Dawley rats, the obstructed lobe (OL) and non-OL were analyzed. Canalicular and sinusoidal membrane fluidity were decreased in the OL compared with the non-OL. Mrp2 protein expression was significantly lower in the OL (by 62.9+/-6.9%) when compared with the non-OL. Mdr1b and Mdr2 mRNA were up-regulated in the OL when compared with the non-OL. Interestingly, Mrp3 protein and mRNA were induced in both the non-OL and OL of rats without hyperbilirubinemia. CONCLUSIONS: It seems that the reduction of membrane fluidity in the OL is a local response to localized cholestasis, while the induction of Mrp3 observed in both the OL and non-OL may be a response of the whole liver to localized impairment of bile secretion, although the regulatory mechanism is yet to be established.

Journal Article↗
PubMed2003

Significance of an exaggerated meal-stimulated gastrin response in pathogenesis of Helicobacter pylori-negative duodenal ulcer.

The aim of this study was to clarify the pathogenesis of Helicobacter pylori-negative duodenal ulcer (DU) by investigating the meal-stimulated serum gastrin (SG) response. The subjects were 9 patients with H. pylori-negative DU, 28 H. pylori-positive DU, 11 H. pylori-positive volunteers, and 30 H. pylori-negative volunteers. Blood samples were taken before and after consumption of a test meal. The integrated 1-hr gastrin response (IGR) was taken to be the area under the SG time curve, calculated by the trapezoid method. H. pylori infection status was determined by histology, serology, and the [13C] urea breath test. The mean basal SG concentration was lower in the H. pylori-negative DU patients than in the H. pylori-positive DU patients, but an exaggerated IGR was observed in three patients (33.3%) with H. pylori-negative DU. In conclusion, our findings indicate that an exaggerated meal-stimulated gastrin response may contribute to the pathogenesis of H. pylori-negative DU.

Adolescent↗
PubMed2003

Nodular gastritis in adults is caused by Helicobacter pylori infection.

A close relationship exists between nodular gastritis and Helicobacter pylori infection in children. The pathogenesis and optimal management of nodular gastritis in adults, however, are unclear. This study describes the clinicopathologic features of nodular gastritis in adults and correlates treatment with outcome. Of 97,262 adult patients who underwent endoscopy, 187 (0.19%) were diagnosed with nodular gastritis, 151 (81%) of whom had dyspepsia. Nodular gastritis predominantly affects young women (49 men and 138 women, mean age, 32.6 years). All 134 patients tested for Helicobacter pylori infection were infected, and 65/66 (98%) had inflammation of both the antrum and the corpus. Twenty-five (13%) had associated lesions (peptic ulcers or cancer). Dyspepsia improved after eradication of Helicobacter pylori infection, but did not improve spontaneously. Nodular gastritis in adults is caused by Helicobacter pylori infection and shows a predilection for females and young adults. Helicobacter pylori eradication decreases symptoms and reduces the risk of peptic ulcers and possibly gastric cancer.

Adolescent↗
PubMed2003

Impaired gallbladder mucosal function in aged gallstone patients suppresses gallstone recurrence after successful extracorporeal shockwave lithotripsy.

BACKGROUND: Absorption of water, as well as emptying of bile, are important functions of the gallbladder. We studied the changes of gallbladder function with age in gallstone patients and their influence on the outcome of extracorporeal shockwave lithotripsy (ESWL). METHODS: (i) A total of 123 consecutive patients with complete stone clearance by ESWL were examined. Gallbladder emptying was assessed before treatment using intravenous cholecystography. After stone clearance, the recurrence of gallstones was monitored by using ultrasonography. Cox regression analysis was used to determine the risk factors associated with stone recurrence. (ii) Gallbladder bile was sampled from 59 gallstone patients during surgery. Biliary cholesterol, phospholipids, and total bile acids were simultaneously quantified by using gas-liquid chromatography. RESULTS: Impaired gallbladder function, but not gallstone recurrence, was more frequently observed in older patients (>/=65 years old) than in younger patients (<65 years old). Cox regression analysis revealed that poor gallbladder emptying was an independent predictor of stone recurrence after ESWL in the total study population, but not in the older patients (>/=65 years old). Analysis of bile from surgically treated patients with cholesterol stones showed a significantly higher total lipid concentration and a shorter nucleation time in the younger group (<65 years old), but the cholesterol saturation index did not differ between the younger and older groups. CONCLUSIONS: Our data suggest that the reduced concentrating function of the gallbladder in elderly gallstone patients helps to counteract stone recurrence despite their abnormal gallbladder motility. Therefore, aged gallstone patients may be preferentially treated by a non-surgical strategy.

Age Factors↗
PubMed2003

Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival.

INTRODUCTION: It has been reported that angiogenic factors play an important role in proliferation and metastasis in various cancers.AIMTo investigate the expression of angiogenic factors and microvessel density (MVD) in pancreatic ductal carcinoma and to examine the correlations among expression of angiogenic factors, clinicopathologic parameters, and clinical prognosis. METHODOLOGY: Paraffin-embedded specimens from 55 patients with pancreatic ductal carcinoma were immunostained for vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), platelet-derived endothelial cell growth factor (PD-ECGF), and CD34. The correlations among the expression of individual angiogenic factors and MVD, the clinicopathologic features, and the clinical prognoses were analyzed statistically. RESULTS: Immunostaining demonstrated that 70.8% of pancreatic ductal carcinomas were positive for VEGF, 60.9% for FGF-2, and 57.2% for PD-ECGF. A significant correlation was observed between VEGF expression and MVD (p < 0.05) but not between FGF-2 or PD-ECGF and MVD. Although the expression of each angiogenic factor had no correlation with clinicopathologic features, the patients with tumors that showed high expression of VEGF and FGF-2 had significantly shorter survival times than those with low or no such expression (p < 0.05). CONCLUSIONS: These observations suggest that the expression of VEGF closely correlates with MVD and with a poor prognosis in pancreatic ductal carcinoma.

Angiogenesis Inducing Agents↗