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Biomedical subjects

Ryuichi Iwakiri

Publications and source records attributed to Ryuichi Iwakiri.

At least 19 recordsLinked to original sources
PubMed2007

Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro.

Obesity, a risk factor for colon cancer, is associated with elevated serum levels of leptin, a protein produced by adipocytes. The aim of the present study was to clarify the effects of adipose tissue on colon cancer proliferation by using cultured cell lines. To achieve this, colon cancer cells (CACO-2, T84, and HT29) were cocultured with adipose tissue, isolated mature adipocytes, and isolated preadipocytes in a three-dimensional collagen gel culture system. The adipocytes and preadipocytes used were isolated from C57BL/6J and leptin-deficient ob/ob mice. Proliferation of the cancer cells was evaluated by nuclear bromodeoxyuridine uptake. The adipose tissue, mature adipocytes, and preadipocytes isolated from C57BL/6J mice significantly increased the proliferation of the colon cancer cells. This trophic effect of mature adipocytes on the cancer cell lines was observed only for cells from lean littermates and not for those from ob/ob mice. In contrast, the trophic effect of preadipocytes was not abolished in ob/ob mice, and this finding was supported by the result that leptin had a trophic effect on cancer cells. In conclusion, adipocytes were able to enhance the proliferation of colon cancer cells in vitro, partly via leptin, suggesting that adipose tissues, including mature adipocytes and preadipocytes, may promote the growth of colorectal cancer.

Adipocytes, White↗
PubMed2006

Long-term feeding of various fat diets modulates azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling in rats.

The Wnt signaling pathway plays an essential role in carcinogenesis, and the amount of fat intake and composition of dietary fatty acids are crucial factors for colon carcinogenesis. We investigated whether various dietary fats affected the Wnt signaling pathway of colon tumorigenesis in azoxymethane (AOM)-treated rats. Male Sprague-Dawley rats were given intraperitoneal injections of AOM and supplemented with 10% corn, olive, beef, and fish oil for 44 wk. Aberrant crypt foci (ACF) and tumors were examined at 12 and 44 wk. Normal appearing colon mucosal proliferation and apoptosis were evaluated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and percentages of fragmented DNA, respectively. Expressions of beta-catenin, cyclin D(1), Wnt2, Wnt3, and Wnt5a of normal appearing colon mucosa were analyzed by Western blot analysis. Long-term dietary corn oil and beef tallow increased ACF, tumor incidence, and tumor numbers in AOM-treated rats. In contrast, both olive and fish oil inhibited them. Dietary corn oil and beef tallow increased BrdU incorporation and the expression of cytosolic beta-catenin and cyclin D(1) and decreased apoptosis in the colon mucosa. Expressions of Wnt2 and Wnt3 in rats fed with beef tallow and Wnt5a in rats fed with corn oil increased with or without AOM-treatment. BrdU-incorporated cells were often observed at the tops of crypts in rats fed with beef tallow, whereas this was not observed in rats fed with the other diet. Long-term high intake of corn oil and beef tallow enhanced cell proliferation through Wnt signaling and modulated the distribution of proliferating cells, which might contribute to promoting effects in colon tumorigenesis.

Animals↗
PubMed2006

A pilot randomized control study to evaluate endoscopic resection using a ligation device for rectal carcinoid tumors.

AIM: Rectal carcinoid tumors smaller than 10 mm can be resected with local excision using endoscopy. In order to remove rectal carcinoid tumors completely, we evaluated endoscopic mucosal resection with a ligation device in this pilot control randomized study. METHODS: Fifteen patients were diagnosed with rectal carcinoid tumor (less than 10 mm) in our hospital from 1993 to 2002. There were 9 males and 6 females, with a mean age 61.5 years (range, 34-77 years). The patients had no complaints of carcinoid syndrome symptoms. Fifteen patients were randomly divided into 2 groups: 7 carcinoid tumors were treated by conventional endoscopic resection, and 8 carcinoid tumors were treated by endoscopic resection using a ligation device. RESULTS: All rectal carcinoid tumors were located at the middle to distal rectum. The size of the tumors varied from 3 mm to 10 mm and background characteristics of the patients were not different in the two groups. The rate of complete removal of carcinoid tumors using a ligation device (100%, 8/8) was significantly higher than that of conventional endoscopic resection (57.1%, 4/7). The three patients had tumor involvement of deep margin, for which additional treatment was performed. No complications occurred during or after endoscopic resection using a ligation device. All patients in the both groups were alive during the 3-year observation period. CONCLUSION: Endoscopic resection using a ligation device is a useful and safe method for resection of small rectal carcinoid tumors.

Adult↗
PubMed2006

Apoptotic pathway in the rat small intestinal mucosa is different between fasting and ischemia-reperfusion.

We have previously demonstrated that fasting and ischemia-reperfusion (I/R) induced apoptosis in rat intestinal mucosa. It is widely accepted that apoptosis is induced through two main pathways. This study aimed to compare apoptotic pathways following fasting and I/R. Rats were divided into two groups: the I/R group involved occlusion of the superior mesenteric artery for 60 min, followed by 60-min reperfusion, whereas the fasting group involved fasting for 24 or 48 h. Intestinal apoptosis was assessed as percentage of fragmented DNA, by electrophoresis and by a terminal deoxynucleotidyl transferase mediated dUDP-biotin nick- end labeling (TUNEL) assay. Apoptotic proteins including death ligands/receptors and caspases were evaluated by Western blot analysis. Small intestinal mucosal height and mitochondrial dehydrogenase function were assessed. Fasting and I/R significantly induced intestinal apoptosis. Mucosal height was significantly decreased in fasting rats, and mitochondrial dysfunction was induced only by I/R. Expressions of Fas, Fas ligand, and TNF-alpha type 1 receptor were enhanced in fasting and I/R rats. After I/R, expressions of cytochrome c and cleaved caspase-9 were significantly increased. In contrast, expressions of cleaved caspase-8 and cleaved caspase-3 increased in fasting rats. Fasting promoted mucosal apoptosis via a receptor-mediated type I apoptotic pathway in the rat small intestine, and I/R induced apoptosis via a mitochondria-mediated type II pathway.

Animals↗
PubMed2006

High serum leptin is an independent risk factor for non-response patients with low viremia to antiviral treatment in chronic hepatitis C.

AIM: To determine whether body weight and/or serum leptin were independent predictors of response to antiviral treatment in patients with chronic hepatitis C. METHODS: A retrospective evaluation was performed in 139 patients with chronic hepatitis C treated with interferon (IFN) from 1996 to 2000. Sustained response was defined as negative by hepatitis C virus (HCV) RNA analysis using PCR and normal transaminase at 24 wk after cessation of IFN therapy. Patients who remained positive for HCV RNA at the end of IFN treatment were defined as resistant to IFN therapy. Sex, age, body mass index (BMI) (> or =25 vs <25), complication of diabetes mellitus, serum leptin level (> or =8.0 microg/L vs < 8.0 microg/L), and the stage of liver fibrosis by needle biopsy (F1/F2 vs F3/F4) were examined. RESULTS: Sustained response was achieved in 33 patients (23.7%), while others failed to show a response to IFN therapy. Overall, the factors associated with sustained antiviral effects were HCV-RNA load, HCV genotype, serum leptin level, and stage of liver fibrosis evaluated by univariate analysis. BMI was not associated with any therapeutic effect of IFN. Multivariate analysis indicated that HCV-RNA load was a significant risk factor, but among the patients with low viremia (HCV-RNA <100 MU/L), leptin level was an independent risk factor for IFN resistance. Namely, a high level of serum leptin attenuated the effect of IFN on both male and female patients with low viremia. CONCLUSION: High serum leptin level is a negative predictor of response to antiviral treatment in chronic hepatitis C with low viremia.

Adult↗
PubMed2006

Role of Helicobacter pylori infection and nonsteroidal anti-inflammatory drug use in bleeding peptic ulcers in Japan.

BACKGROUND: Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known major causes of peptic ulcers. This study aimed to characterize the features of bleeding peptic ulcers in Japan. METHODS: This prospective study evaluated 116 patients revealed to have bleeding peptic ulcers from January 2000 to December 2002. RESULTS: Eighty-eight of the 116 patients (75.9%) had H. pylori infection. Seventy (60.3%) patients were positive for H. pylori with no history of NSAID use (group A), and 18 (15.5%) were positive for H. pylori with a history of NSAID use (group B). Among the H. pylori-negative patients, 15 (12.9%) were associated with NSAID use (group C). Thirteen (11.2%) patients had no H. pylori infection or history of NSAID use (group D). Among the 33 patients with a history of NSAID use, 11 were on-demand NSAID users and 14 took daily low-dose aspirin. The patients in groups B and C were significantly older that those in groups A and D, and they more frequently had coexisting diseases compared with group A. In group D, 11 patients had atrophic changes revealed by endoscopic examination, suggesting a past H. pylori infection, and these atrophic changes remained at the time of bleeding. Many of the patients in group D had serious comorbidity. Compared with healthy control subjects, the concentrations of both phosphatidylcholine and phosphatidylethanolamine were significantly decreased in the antral gastric mucosa in all patient groups. CONCLUSIONS: NSAID use contributed to bleeding ulcers in 28.4% of patients; thus, low-dose aspirin or on-demand NSAID use may cause bleeding ulcers. There were only two (1.7%) confirmed cases of H. pylori-negative, non-NSAID ulcers.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Visceral fat accumulation and insulin resistance are important factors in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver diseases are often associated with obesity, insulin resistance, and excessive visceral fat accumulation. The aims of this study were (1) to evaluate the relationship between the severity of fatty liver and visceral fat accumulation in nonalcoholic fatty liver diseases, and (2) to investigate the relationships of fatty liver with biochemical data and insulin resistance. METHODS: One hundred twenty-nine subjects (63 women) with fatty liver diagnosed by ultrasonography were enrolled. Subjects positive for hepatitis B virus, hepatitis C virus, or autoimmune antibodies and those whose alcohol intake was over 20 g/day were excluded. The visceral fat area at the umbilical level and the liver-spleen ratio were evaluated by computed tomography. RESULTS: The severity of fatty liver evaluated by ultrasonography showed a significant positive relationship with the visceral fat area and waist circumstance (fatty liver severity: mild, 92.0 +/- 30.9 cm(2); moderate, 122.1 +/- 32.6 cm(2); severe, 161.0 +/- 48.4 cm(2); P < 0.0001). The visceral fat area and liver-spleen ratio were negatively correlated (r = -0.605, P < 0.0001). The severity of fatty liver showed strong positive relationships with serum aspartate aminotransferase, alanine aminotransferase, fasting plasma glucose, fasting plasma insulin, and insulin resistance. The severity of fatty liver was positively related to the visceral fat area in 49 nonobese subjects (body mass index <25). CONCLUSIONS: The severity of fatty liver was positively correlated with visceral fat accumulation and insulin resistance in both obese and nonobese subjects, suggesting that hepatic fat infiltration in nonalcoholic fatty liver disease may be influenced by visceral fat accumulation regardless of body mass index.

Adipose Tissue↗
PubMed2006

Oral dimethyl sulfoxide for systemic amyloid A amyloidosis complication in chronic inflammatory disease: a retrospective patient chart review.

BACKGROUND: Amyloid A amyloidosis is an obstinate disease complication in chronic inflammatory disease, and there are few effective therapies. The objective of this study was to investigate the effect of oral dimethyl sulfoxide (DMSO) on amyloid A amyloidosis. METHODS: Fifteen secondary amyloid A amyloidosis patients (4 men, 11 women; age, 23-70 years) were treated with DMSO between 1995 and 2003. DMSO was administered orally in all patients at a dose of 3-20 g/day. The clinical symptoms together with the renal and gastrointestinal functions were evaluated before and after treatment. RESULTS: Among the 15 patients, amyloid A amyloidosis was a complication of rheumatoid arthritis (RA) in 10, of Crohn's disease in 4, and of Adult Still's disease in 1. Nine cases mainly involved the kidney, with renal dysfunction and proteinuria, five mainly involved the gastrointestinal tract, with protein-losing gastroenteropathy and intractable diarrhea, and one involved both gastrointestinal and renal amyloidosis. DMSO treatment was successful in 10 (66.7%) of the 15 patients (RA, 6/10; Crohn's disease, 4/4; Adult Still's disease, 0/1). Eight weeks of DMSO administration improved the renal function and proteinuria in five out of ten renal amyloidosis patients, but had no effect on those patients with severe and/or advanced renal dysfunction. With regard to gastrointestinal amyloidosis, gastrointestinal symptoms, including diarrhea and protein-losing gastroenteropathy, were improved in six patients. No serious side effects were encountered with the DMSO treatment. CONCLUSIONS: Oral administration of DMSO is an effective treatment for amyloid A amyloidosis, especially for gastrointestinal involvement and the early stage of renal dysfunction.

Administration, Oral↗
PubMed2006

Clinical outcomes of EMR for gastric tumors: historical pilot evaluation between endoscopic submucosal dissection and conventional mucosal resection.

BACKGROUND: EMR is currently a standard treatment for mucosal gastric tumors. Endoscopic submucosal dissection (ESD) has been developed for en bloc resection. OBJECTIVE: We evaluated the clinical outcomes of ESD compared with conventional EMR. DESIGN: Not applicable. SETTING: A historical control study was performed between EMR and ESD. PATIENTS: EMR of 245 gastric tumors was performed in 229 patients. Lesions were divided into two groups. Conventional EMR was performed in group A from February 1999 to June 2001, and ESD was performed in group B from July 2001 to March 2004. Group B was divided into subgroups: subgroup B-1 underwent ESD from July 2001 to March 2003 and subgroup B-2 from April 2003 to March 2004. INTERVENTIONS: All lesions were resected with conventional EMR or with ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection rate, rate in completeness of resection, required time, remnant ratio, and complications were evaluated. RESULTS: With regard to lesions >10 mm in size, the en bloc resection rate and the rate in completeness of resection of group B was significantly higher than that of group A (p < 0.01). Although the required time was longer in group B than A (p < 0.01), it was shorter in subgroup B-2 compared with B-1 (p < 0.05) with lesions < or =10 mm in size. The remnant ratio and perforation rate were not different between groups. LIMITATIONS: Not applicable. CONCLUSIONS: The en bloc resection rate was better with ESD than with conventional EMR. The required time was longer in ESD, but this disadvantage might be improved with experience.

Adenocarcinoma↗
PubMed2006

T cell deficiency leads to liver carcinogenesis in azoxymethane-treated rats.

There is an increasing amount of evidence suggesting that T cell deficiency contributes to tumor development. However, it is unclear whether T cell deficiency leads to liver and colon carcinogenesis. The aim of this study was to investigate the role of T cells on liver and colon carcinogenesis. Athymic F344/N Jcl-rnu/- (nu/nu) rats and euthymic F344/N Jcl-rnu/+(nu/+) rats were administered the carcinogen azoxymethane (AOM) at a dose of 15 mg/kg body wt once a week for 2 weeks. At 48 weeks after the second carcinogen treatment, the rats were sacrificed, and livers and colons were examined. Apoptosis and cell proliferation were evaluated by DNA fragmentation and proliferating cell nuclear antigen assays, respectively. Wild-type p53 and members of the Jun and Fos oncogene families were detected by Western blotting. AOM treatment induced 100% liver tumor and 63.6% colon tumor incidence in T cell-deficient nu/nu rats, compared with 0% and 38.5% incidence in nu/+ rats. T cell deficiency promoted the inhibitory action of AOM on apoptosis in both liver and colon at 48 weeks. In contrast, T cell deficiency increased cell proliferation after AOM treatment in both tissues. Wild-type p53 was reduced in both tissues of T cell-deficient rats. AOM treatment induced c-Jun and c-Fos expressions in the liver but increased only Fos B in the colon, whereas T cell deficiency enhanced c-Jun overexpression in the liver. These results suggest that T cell deficiency leads to liver carcinogenesis partly by a reduction in wild-type p53 and increasing c-Jun expression in AOM-treated rats.

Animals↗
PubMed2006

[A case of Crohn's disease successfully treated with infliximab without steroid].

A 39-year-old man diagnosed as Crohn's disease suffered steroid induced psycosis during treatment for Crohn's disease on July 2001. He was admitted on May 2002, because of progressing high fever, abdominal pain and diarrhea. He was treated with infriximab (5mg/kg) together with mesalazine without steroid. The treatment induced rapid improvement of systematic symptoms together with laboratory data and colonoscopic findings. He kept remission for more than 10 months after a single administration of infliximab (5mg/kg). The case is suggestive of wider indication of infliximab for Crohn' s disease.

Adult↗
PubMed2006

[A case of relapsed ischemic colitis with colon cast-like stripped mucosa].

An 82-year-old woman who had 5 relapses of ischemic colitis was admitted with sudden lower abdominal pain. Colonoscopic examination performed on the 2nd day revealed colon cast-like stripped colonic mucosa in the lower portion of the descending colon. She was treated conservatively. After 2 weeks, ischemic colitis healed, with slight residual stenosis. Most reports of colon cast indicated that colon cast was caused by abdominal aneurysm, operation, or external wound. The only predisposing conditions in this case were arteriosclerosis of abdominal aorta and chronic constipation. Arteriosclerosis and chronic constipation might be the important risk factors of ischemic colitis with colon cast and relapsing of ischemic colitis.

Aged, 80 and over↗
PubMed2005

Decreased apoptosis and increased ornithine decarboxylase activity in the intestinal mucosa of rats with bilateral ventromedial hypothalamus lesions.

BACKGROUND: It has not been clearly demonstrated whether the ventromedial hypothalamus regulates intestinal cell growth. Ornithine decarboxylase is a key enzyme in polyamine synthesis, which plays an important role in intestinal mucosal growth. The aim of this study was to investigate whether bilateral ventromedial hypothalamus lesions affect mucosal cell growth. This was done by evaluating ornithine decarboxylase activity and apoptosis in rat small intestines. METHODS: Bilateral ventromedial hypothalamus lesions were produced by thermocoagulation, done with rats under halothane anesthesia 7 days before the experiments. Rats with lesions were pair-fed with sham-operated rats. Total (truncal) vagotomy was performed before the development of ventromedial hypothalamus lesions. Ornithine decarboxylase activity and apoptosis were evaluated in the jejunal mucosa. RESULTS: Ornithine decarboxylase activity in the jejunal mucosa increased significantly 1 week after the development of the bilateral ventromedial lesions, and was attenuated by truncal vagotomy. Apoptosis in the jejunal mucosa was suppressed in rats with ventromedial hypothalamus lesions. In contrast to the effect on ornithine decarboxylase activity, the truncal vagotomies had no effect on apoptosis in rats with lesions. Apoptosis increased in the sham-operated rats after 24-h and 48-h fasting. Apoptosis in the jejunal mucosa of rats with ventromedial hypothalamus lesions did not increase after 24-h fasting. After 48-h fasting, jejunal apoptosis increased in rats with lesions, but not markedly. CONCLUSIONS: The ventromedial hypothalamus may regulate cell growth in the intestinal mucosa partly through the vagal nerve; however, the vagal nerve was not related to intestinal apoptosis controlled by the ventromedial hypothalamus.

Animals↗
PubMed2005

Dysphagia associated with gastroesophageal reflux disease is improved by proton pump inhibitor.

This study aimed to determine whether dysphagia associated with gastroesophageal reflux disease was effectively treated with rabeprazole, a proton pump inhibitor. Sixty-eight outpatients with gastroesophageal reflux-associated dysphagia were enrolled in this study. Endoscopic esophagitis was confirmed in 52 of 68 subjects. The proton pump inhibitor rabeprazole was administered at 20 mg daily for 8 weeks. Rabeprazole was administered for a further 6 months to 16 subjects whose dysphagia was improved (10 mg/day) and 5 of these underwent 24-hr esophageal pH monitoring before and after treatment. Dysphagia was completely resolved in 40 of 68 subjects, which were categorized in Group I. Dysphagia improved partially in 20 subjects and was unchanged in 8 subjects. These 28 subjects were categorized into Group II. Comparison was made between Group I and Group II and multivariate analysis demonstrated that the only factor that correlated with the effect of rabeprazole on dysphagia was "improvement in heartburn symptoms." There were no relapses of symptoms during the 6-month follow-up period, and pH monitoring showed sustained suppression of acid secretion. The results indicate that rabeprazole is effective in the treatment of dysphagia associated with gastroesophageal reflux disease. We were, however, unable to elicit any factors that could predict the therapeutic effect of rabeprazole before commencing treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Apoptosis in rat jejunal mucosa is regulated partly through the central nervous system, which controls feeding behavior.

AIM: The aim of this study was to investigate whether central nervous system-related feeding behavior regulates mucosal apoptosis in rat small intestines. METHODS: The test solutions used in this study were an H(1) receptor antagonist (chlorpheniramine maleate), 2-deoxy-D-glucose, leptin, and 1-deoxy-D-glucosamine (2-amino-1,5-anhydro-2-deoxy-D-glucitol). Test solutions were injected into the third cerebroventricles of rats. Feeding behavior and jejunal apoptosis were evaluated both with and without truncal vagotomy. Intestinal apoptosis was evaluated by percentage fragmented DNA, electrophoresis, and TUNEL staining. RESULTS: Chlorpheniramine and 2-deoxy-D-glucose elicited feeding, whereas leptin and 1-deoxy-D-glucosamine suppressed feeding. The test solutions, which elicited feeding (0.24 and 24 micromol/rat of chlorpheniramine and 2-deoxy-D-glucose, respectively), suppressed mucosal apoptosis in the rat jejunum 1 h after cerebroventricular infusion. In contrast, the test solutions, which suppressed feeding (8 and 24 micromol/rat of leptin and 1-deoxy-D-glucosamine, respectively), induced jejunal mucosal apoptosis 3 h after infusion. The effects of the test solutions on feeding behavior and changes in apoptosis were not affected by truncal vagotomy. CONCLUSION: The central nervous system, which regulates feeding behavior, might control intestinal function through the regulation of intestinal apoptosis.

Animals↗
PubMed2005

[B cells as key contributors in determining the level of immune responses -B-cell-targeted therapy in patients with autoimmune diseases].

The levels and types of immune responses are determined dependent on the extent of pathogen invasion, reactions to antigens mediated by macrophage-dendritic cells, T cells and antibodies. Recently, accumulating evidence suggests that B cells also play an important role in the regulation of immune responses. Here we have made a review to present a role of B cells in determining the level of immune responses and discussed about the clinical significance of B cell-targeted therapy in patients with autoimmune diseases. Type 1 diabetes is a T cell-mediated autoimmune disease characterized by the destruction of insulin-producing pancreatic beta cells. We and other groups have elucidated that B cells play a critical role in the development of insulitis and diabetes, as B-cell-deficient NOD mice are protected from developing type 1 diabetes. B cells are essential for the T cell receptor clonotype spreading of islet-infiltrating T cells, indicating that B cells may play a role in determining the level of immune responses by antigen presentation to antigen specific T cells. There are now numerous case reports and small series of clinical trials regarding rituximab therapy in autoimmune diseases, such as refractory autoimmune hemolytic anemia, IgM antibody-associated polyneuropathy, systemic lupus erythematosus and rheumatoid arthritis. Rituximab is a genetically engineered chimeric anti-CD 20 monoclonal antibody that is approved for the treatment of lymphoma. CD20 is a B-cell surface antigen that is expressed only on pre- B and mature B cells. Thus, rituximab causes a selective transient depletion of the CD20+ B -cell subpopulation. Rationale and strategy for targeting B cells in the treatment of autoimmune diseases consist of the inhibition of antigen-presentation and co-stimulation that induces T cell expansion and activation. Further careful mechanistic studies are required to develop therapies in patients with autoimmune diseases.

Animals↗