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11.
Kose Segawa M.D. Saburo Nakazawa M.D. Yoshihisa Tsukamoto M.D. Hidemi Goto M.D. Kenji Yamao M.D. Satoshi Hase M.D. Toshimasa Osada M.D. Tomiyasu Arisawa M.D. 《The American journal of gastroenterology》1988,83(4):373-379
We performed morphological and physiological studies in 43 male patients with alcohol dependence (ALC) who had no other apparent lesions in the upper gastrointestinal tract except atrophic and erosive gastritis. A gastric secretory study in which tetragastrin was used as the stimulant revealed that acid and pepsin secretion was less in ALC patients than in hospital controls (p less than 0.001). Endoscopic biopsy specimens of gastric mucosa from ALC patients revealed that atrophy of the gastric mucosa advanced with age. A strong negative correlation was also found between the secretory capacity of the stomach and the degree of atrophy. Possibly, the interval between recurrent episodes of acute mucosal damage was too short to allow complete healing of mucosal lesions. Failure to regenerate denuded epithelium would result in a decrease in the gastric secretory area. Thus, chronic alcohol abuse seems to be an etiological factor in atrophic gastritis. 相似文献
12.
Yoshihisa Tsukamoto M.D. Hidemi Goto Satoshi Hase Tomiyasu Arisawa 《Journal of gastroenterology》1991,26(4):424-429
To clarify the role of mucosal blood flow in the pathogenesis of ulcer formation, the authors investigated dulcerozine-induced
duodenal ulcers in rats. Administration of dulcerozine, 500 mg/kg by intragastric route or 250 mg/kg given intraperitoneally,
induced acute ulcers in the duodenum, but not the stomach, in all rats. Using the pyloric ligation method, it was determined
that although dulcerozine significantly increased gastric acid secretion, no duodenal ulcers were observed in these animals.
The administration of 1 ml of 0.1 N HC1 every hour for 6 hours did not induce duodenal ulceration. The mucus glycoprotein
content of the corpus, antrum and proximal duodenum did not differ following dulcerozine administration. Duodenal mucosal
blood flow, which was measured by an electrolytically generated hydrogen gas clearance technique, decreased significantly
following dulcerozine administration even in pylorus-ligated rats. In contrast, there was an increase in the gastric mucosal
blood flow following administration of the drug. Therefore, not only an increase in gastric acid secretion but also a decrease
in duodenal mucosal blood flow are suggested to be responsible for dulcerozine-induced duodenal ulceration. 相似文献
13.
John Ford Matt Lawson David Fowler Nobuko Maruyama Seiji Mito Koichi Tomiyasu Shuji Kinoshita Chisa Suzuki Atsuhiro Kawaguchi Patrick Round Malcolm Boyce Steve Warrington Werner Weber Sander van Deventer John J P Kastelein 《British journal of clinical pharmacology》2014,78(3):498-508
Aims
Two double-blind, randomized studies were conducted to assess the tolerability, pharmacokinetics and pharmacodynamics of oral TA-8995, a new cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.Methods
Study 1: Subjects received single doses of TA-8995 or placebo (fasted). Doses were 5, 10, 25, 50 (fed/fasted), 100 and 150 mg (Caucasian males, 18–55 years), 25 mg (Caucasian males, > 65 years and Caucasian females, 18–55 years), 25, 50, 100 and 150 mg (Japanese males, 18–55 years). Study 2: Caucasian males (18–55 years) received 1, 2.5, 10 or 25 mg once daily TA-8995 or placebo for 21–28 days. Blood and urine for pharmacokinetics and/or pharmacodynamics were collected. Tolerability was assessed by adverse events, vital signs, electrocardiograms and laboratory safety tests.Results
Peak TA-8995 concentrations occurred approximately 4 h post-dose. Mean half-lives ranged from 81 to 166 h, without an obvious dose relationship. Exposure increased less than proportionally to dose. TA-8995 was not excreted in urine. Following 2.5 to 25 mg once daily dosing, TA-8995 demonstrated nearly complete inhibition of CETP activity (92–99%), increased high density lipoprotein-cholesterol (HDL-C) by 96 to 140% and decreased low density liporotein-cholesterol (LDL-C) by 40% to 53%. There were dose-related increases in apolipoproteins A-1 and E, HDL2-C and HDL3-C, and decreases in apolipoprotein B and lipoprotein A. There was no evidence of significant effects of age, gender, ethnicity or food on pharmacokinetics or pharmacodynamics. All doses were well tolerated.Conclusions
TA-8995 is a potent CETP inhibitor and warrants further investigation. 相似文献14.
Kuwahara K Tomiyasu S Fujimura S Nomura K Xing Y Nishiyama N Ogawa M Imajoh-Ohmi S Izuta S Sakaguchi N 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(18):10279-10283
Antigen stimulation induces a rapid proliferation of B cells for expansion of specific B cell clones and their further differentiation into antibody-producing cells in germinal centers of T-dependent antigen-immunized mice. Previously, we identified a 210-kDa germinal center-associated nuclear protein (GANP) that is up-regulated selectively in germinal centers and carries an MCM-binding domain in the carboxyl-terminal side. In addition, here, we found a region (from 414 to 550 aa) in GANP molecule that is slightly similar to the known DNA-primase component p49. The recombinant GANP fragment covering this region synthesizes RNA primers for extension by DNA polymerase I with single-stranded DNA templates in vitro. GANP DNA-primase activity is controlled by phosphorylation at Ser(502) that is induced by CD40-mediated signaling in vitro and in the germinal center B cells stimulated with antigen in vivo. Overexpression of ganp cDNA in Daudi B cells caused the increased DNA synthesis more than the levels of the mock-transfectants. These evidences suggested that the novel DNA-primase GANP is involved in regulation of cell proliferation of antigen-driven B cells in germinal centers. 相似文献
15.
Tahara T Arisawa T Shibata T Nakamura M Okubo M Yoshioka D Wang F Nakano H Hirata I 《Journal of gastroenterology》2008,43(3):208-215
Background The relationship between endoscopic appearances such as endoscopic gastritis and duodenitis and dyspeptic symptoms has not
been clearly demonstrated. We aimed to clarify the association of endoscopic appearances with Helicobacter pylori infection, histological severity of gastritis, and dyspeptic symptoms in a Japanese population.
Methods We enrolled 87 dyspeptic and 93 nondyspeptic subjects in this study. All subjects underwent gastroscopy, and patients with
active peptic ulcer disease, reflex esophagitis with erosion, polyps >1 cm, or cancer were excluded. Endoscopic appearances
in patients with dyspeptic symptoms and in those without were assessed retrospectively on the basis of endoscopic images.
The degree of atrophy by the Kimura-Takemoto classification system was also assessed. Helicobacter pylori infection status was examined by histology or antibody against H. pylori. Histological severity of inflammation and glandular atrophy in the antrum were assessed according to the updated Sydney
System. The odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression using the variables age,
sex, H. pylori infection status, and all endoscopic appearances.
Results The degree of atrophy tended to be lower among dyspeptic patients (P = 0.06). Among all endoscopic appearances, the liner redness (friability) in the antrum (OR = 3.90, 95% CI = 1.20−12.64)
and duodenal ulcer (DU) scarring (OR = 3.41, 95% CI = 1.08−10.79) were independently associated with dyspepsia. Histological
severity of inflammation and glandular atrophy were not associated with dyspeptic symptoms. Also, no correlation was found
between endoscopic appearances and any of the different subgroups of dyspeptic symptoms. Patients with friability in the antrum
and DU scar, which correlated with dyspeptic symptom showed some of communal symptoms such as epigastric pain, epigastric
discomfort, hypochondriac pain, early satiation/postprandial fullness, and belching, but they differed considerably with respect
to H. pylori positivity and the histological severity of gastritis.
Conclusions Some endoscopic appearances such as friability in the antrum and DU scarring may be associated with dyspeptic symptoms, and
endoscopic appearances may be useful markers to perform clinical implementation reflecting an individual’s pathophysiology
of dyspeptic symptoms. 相似文献
16.
Hiroshi Okada Michiaki Fukui Muhei Tanaka Shinobu Matsumoto Kanae Kobayashi Hiroya Iwase Kiichiro Tomiyasu Koji Nakano Goji Hasegawa Naoto Nakamura 《Metabolism: clinical and experimental》2014
Objective
Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes.Materials and Methods
We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2 ± 0.9 years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria.Results
During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93).Conclusions
Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes. 相似文献17.
18.
19.
Arisawa T Tahara T Shibata T Nagasaka M Nakamura M Kamiya Y Fujita H Nakamura M Yoshioka D Arima Y Okubo M Hirata I Nakano H 《International journal of molecular medicine》2007,20(4):539-544
Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator, which plays a pivotal role in inflammatory and immune diseases. We attempted to clarify associations of the functional polymorphisms of the MIF gene promoter with the development of chronic gastritis. The study was performed with 290 stocked DNAs from subjects with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. Both the 7/7-CATT repeat at position -794 and the -173 C/C genotypes were significantly associated with a risk of developing severe gastric mucosal atrophy (OR, 9.69; 95% CI, 1.29-72.5; and OR, 4.60; 95% CI, 1.05-20.2, respectively). In subjects younger than 60 years old, the number of 7-CATT alleles was significantly correlated with both the activity and inflammation scores (p=0.0079 and 0.0080, respectively). Our results suggested that functional promoter polymorphisms of the MIF gene might be associated with the severity of gastric mucosal inflammation in younger subjects and with the subsequent development of mucosal atrophy. 相似文献
20.
Okuma T Ozaki T Abe S Yamamura K Shigaki H Sawayama H Tanaka H Mizumoto T Yamaguchi Y Matsumoto T Tomiyasu S Hongoh H Kamio T Mita S Kanemitsu K 《Surgery today》2011,41(4):568-571
We report a case of adenocarcinoma of the minor duodenal papilla, a rare type of duodenal neoplasm. A 76-year-old man with a history of surgery for rectal cancer and gastric cancer was referred to us after a follow-up upper gastrointestinal endoscopy revealed an abnormal elevation in the minor duodenal papilla. The pathological diagnosis of a biopsy specimen was adenocarcinoma. Preoperative examination of other organs revealed a tumor in the ascending colon, which was also identified as adenocarcinoma. We performed synchronous pancreatoduodenectomy and ileocecal resection with lymph node dissection. Histopathological examination of the resected specimen revealed that the papilla tumor arose from the duodenal mucosa and infiltrated the submucosa of the duodenal wall, but not the pancreatic parenchyma. Based on these findings, we diagnosed primary adenocarcinoma of the minor duodenal papilla. To our knowledge, this is only the sixth such case reported in the English-language literature, and we review all six cases after this case report. 相似文献