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Biomedical subjects

Hiroyuki Sakata

Publications and source records attributed to Hiroyuki Sakata.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

[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↗

[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↗

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↗

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↗

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↗

[Barrett's esophagus and Helicobacter pylori].

Lifestyles of Japanese, including eating habits, have been similar to those in Western countries, which might be related to an increase in gastroesophageal reflux disease (GERD) in Japan. Barrett's esophagus is generally accepted as a complication of chronic and severe GERD. Helicobacter pylori (H. pylori) is a pathogen that is associated with atrophic gastritis, peptic ulcer disease, gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and so on. The relationship between H. pylori and GERD+ Barrett's esophagus is controversial. H. pylori eradication therapy may increase the risk for the development of GERD, which may lead to increase a risk factor of Barrett's esophagus and esophageal adenocarcinoma. This review gives the outline regarding GERD and the relation between Barrett's esophagus and H. pylori infection.

Adenocarcinoma↗

Dietary corn oil promotes colon cancer by inhibiting mitochondria-dependent apoptosis in azoxymethane-treated rats.

How dietary corn oil is involved in colon carcinogenesis and cancer development is poorly understood. The aim of this study was to investigate whether long-term dietary corn oil promotes colon cancer by inhibiting the tumor suppressor gene p53-mediated mitochondria-dependent apoptosis in azoxymethane (AOM)-treated rats. Male Sprague-Dawley rats were injected with AOM or with saline and fed on a basal diet or basal diet supplemented with 10% corn oil for 48 weeks. Colonic aberrant crypt foci (ACF) and tumors, including adenomas and carcinomas, were examined. Colonic apoptosis and cell proliferation were evaluated. Wild type (wt) p53 was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. In addition, Bcl-2, Bcl-xL, Bax, and Bak localized in the mitochondria were detected. Long-term dietary corn oil increased ACF in AOM-treated rats at 12 weeks and promoted colon cancer invasion at 48 weeks. Cancer invasion was not observed in the AOM-treated rats without dietary corn oil, although colon adenomas and cancers were detected. Apoptosis was decreased and cell proliferation was increased in the AOM-treated rats with dietary corn oil, compared with the AOM-treated rats with dietary basal diet. In these rats, mitochondrial wt p53 was significantly inhibited through decreased mitochondrial localization of wt p53 and increased cytosolic p53, resulting in the upregulation of Bcl-2 and Bcl-xL and the downregulation of Bak in the mitochondria. Results suggest that long-term dietary corn oil promotes AOM-induced colon cancer development partly by inhibiting the tumor suppressor gene p53-mediated mitochondria-dependent apoptosis.

Animals↗

Analysis of mutation spectra in UVB-exposed mouse skin epidermis and dermis: frequent occurrence of C-->T transition at methylated CpG-associated dipyrimidine sites.

We recently reported the kinetics of mutation induction by UVB in the skin epidermis and dermis of transgenic Muta trade mark mice [Ikehata and Ono, Mutat Res 508:41-47, 2002]. In the present study we determined the complete DNA sequence of the lacZ transgene in 208 mutants isolated from the dermis and epidermis of UVB-irradiated and control mice. The resulting mutation patterns for the dermis and epidermis were similar, although two CC-->TT tandem substitutions, one of the signature mutations for UV insult, were detected only among the UVB-induced epidermal mutants. The spectra of the UVB-induced and control mutations were both dominated by C-->T transitions (83% and 62%); however, the C-->T transitions from irradiated mice occurred almost exclusively in dipyrimidine sites, while those from control mice preferred CpG sites. Thus, the mutation spectrum detected for the irradiated skin tissues was different from the background spectrum and UV-specific, confirming the utility of the transgenic system for UVB-induced mutation studies in vivo. An analysis of the bases adjacent to the mutated cytosines from irradiated mice revealed that the dipyrimidine sites preferred for UVB-induced mutation were 5'-TC-3' > 5'-CC-3' > 5'-CT-3'. Among mutants from irradiated mice, C-->T transitions were recovered frequently at dipyrimidine sites associated with CpG. We showed that CpG sites in the lacZ transgene of Muta trade mark mice were heavily methylated in both the epidermis and dermis. Thus, CpG methylation could contribute to the UVB-induced recurrent or hotspot mutations in the mammalian genome.

Animals↗

Endoscopic injection sclerotherapy for esophageal varices in cirrhotic patients without hepatocellular carcinoma: a comparison of longterm survival between prophylactic therapy and emergency therapy.

BACKGROUND: This study aimed to determine whether prophylactic endoscopic injection sclerotherapy prolonged survival in patients with esophageal varices complicated by liver cirrhosis in the absence of hepatocellular carcinoma, compared with emergency sclerotherapy. METHODS: The subjects included 160 patients suffering from esophageal varices complicated by liver cirrhosis without hepatocellular carcinoma. Sixty-eight patients underwent emergency therapy for bleeding varices and the remaining 92 patients underwent prophylactic sclerotherapy. All subjects continued to receive therapy until the varices disappeared. RESULTS: Five-year survival was significantly better in the prophylactic group compared with the emergency group. During the 5-year observation period, 20 of the 68 patients in the emergency group experienced rebleeding and 5 patients died as a result of rebleeding. These rates were significantly higher than those in the prophylactic group (1 of 9 patients with bleeding died among the 92 prophylactic sclerotherapy patients). Multivariate analysis showed that prophylactic therapy and Child's C hepatic function were significant factors for 5-year survival. CONCLUSIONS: Prophylactic sclerotherapy for esophageal varices might be more effective in prolonging longterm survival of patients complicated by liver cirrhosis in the absence of hepatocellular carcinoma, compared with emergency sclerotherapy.

Adult↗

Endoscopic closure of perforations caused by EMR in the stomach by application of metallic clips.

BACKGROUND: The number of complications associated with use of EMR for early-stage gastric cancer, including perforation, has increased with the increasing use of this procedure. Endoscopic clip application was performed in patients who sustained a perforation as a result of EMR for gastric neoplasm. PATIENTS AND METHODS: Seven patients who underwent endoscopic application of metallic clips to close perforations were studied. The omental patch method was applied in one case with a large perforation. OBSERVATIONS: In all patients, endoscopic clip application successfully closed the perforation of the stomach, which occurred after EMR. No patient required laparotomy. CONCLUSIONS: The technique of endoscopic clip application might be useful for treatment of patients who sustain a perforation caused by EMR.

Aged↗

Clinical symptoms in endoscopic reflux esophagitis: evaluation in 8031 adult subjects.

This study aimed to evaluate the correlation between symptoms and endoscopic findings in reflux esophagitis. Subjects, 8031 persons without medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia, and acid regurgitation by associated medical staff before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) were classified as positive reflux esophagitis, and 2223 (27.7%) had heartburn, 1522 (19.0%) had dysphagia, 493 (6.1%) had odynophagia, and 1466 (18.3%) had acid regurgitation. Multivariate analysis indicated that the symptom most related to esophagitis was heartburn (odds ratio: 2.46), although approximately 40% of subjects with grade C or D did not complain of heartburn. Regarding the other symptoms, less than 30% subjects with severe esophagitis complained of the symptoms and the odds ratio was approximately 1. These results indicate that endoscopic esophagitis was not equivalent to any reflux symptoms from which subjects suffered in their daily lives.

Adult↗

Evaluation of endoscopic hemostasis with metallic hemoclips for bleeding gastric ulcer: comparison with endoscopic injection of absolute ethanol in a prospective, randomized study.

OBJECTIVE: Although metallic hemoclips have been used for hemostasis of bleeding ulcer, there have been few prospective trials to evaluate their efficacy. In this study, a prospective, randomized trial was performed to evaluate endoscopic hemoclipping for bleeding gastric ulcer in comparison with endoscopic injection of absolute ethanol. METHODS: During the period 1995-1998, 126 gastric ulcer patients with bleeding or nonbleeding visible vessel were considered for entry. They were randomly assigned to one of three groups: endoscopic hemostasis performed with injection of absolute ethanol (group I, n = 42), hemoclipping (group II, n = 42), and a combination of the two methods (group III, n = 42). RESULTS: The permanent hemostatic rate was 85.7% in group I, 90.5% in group II, and 92.9% in group III. The mean volume of blood transfusion was 313 +/- 77 ml in group I, 274 +/- 54 ml in group II, and 163 +/- 42 ml in group III, which was significantly less than in groups I or II (p < 0.05). No patients required emergency surgery. Five patients died within a month after initial hemostasis as a result of unrelated conditions. CONCLUSIONS: Endoscopic hemostasis with hemoclips for bleeding gastric ulcer was as effective and safe as that with injection of absolute ethanol, and a combination of ethanol injection and hemoclips did not result in a great advantage over the two individual procedures.

Equipment Design↗

Intracerebroventricular administration of leptin-induced apoptosis in the rat small intestinal mucosa.

The localization of leptin and leptin receptors in the stomach and small intestine has been reported. Their function is still unknown, although leptin is a hormone that regulates appetite and fat-related metabolism. The small intestine is one of the important organs for regulating metabolism. The purpose of the present study was to investigate whether leptin regulates apoptosis in the small intestinal mucosa. Intestinal apoptosis was evaluated by percent fragmented DNA, electrophoresis, TUNEL staining, and western blotting analysis of caspase-3. Mucosal apoptosis in the rat jejunum and ileum was evaluated at 0, 3, 6, 12, and 24 hrs after injection. Rats were tested after ad libitum feeding and 24-hr fasting to exclude the anorectic effect of leptin. Leptin was injected intraperitoneally (ip) at a dose of 200 microg/rat and infused into the rat third cerebroventricle (icv) at a dose of 8 microg/rat. Leptin at a dose of 8 microg/rat significantly induced intestinal apoptosis in the small intestine at 3 and 6 hrs after icv administration in both ad libitum feeding and 24-hr fasted rats. This increase in apoptosis was not attenuated by vagotomy. Intestinal apoptosis increased 12 and 24 hrs after ip injection of leptin at a dose of 200 microg/rat. The peak of the increase in apoptosis in icv rats appeared earlier than that in ip rats. Leptin induced jejunal and ileal mucosal apoptosis in the rat, indicating that leptin might control intestinal function through the regulation of intestinal apoptosis.

Animals↗

Characteristics of gastroesophageal reflux disease in Japan: increased prevalence in elderly women.

The aim of this study was to examine the characteristics of gastroesophageal reflux disease in Japan. We evaluated the correlation between clinical symptoms and endoscopic findings in an age- and sex-specific manner. This study included 6010 Japanese subjects who had not received medication or undergone laparotomy for gastrointestinal disease. All subjects were questioned in regard to clinical symptoms by paramedical personnel before endoscopic examination. Esophageal mucosal breaks were evaluated according to the Los Angeles Classification of Esophagitis. The ratio of subjects with each complaint to all subjects is as follows: heartburn, 27.0%; dysphagia, 16.9%; odynophagia, 19.2%; acid regurgitation, 7.1%. The proportion of each grade was grade A, 9.6%; grade B, 4.6%; and grade C + D, 2.0%. The most common related symptom for endoscopic esophagitis among these four symptoms was heartburn (odds ration, 2.5), although about 40% of subjects with severe esophagitis of grade C or D did not complain of heartburn. Regarding odynophagia, acid regurgitation, and dysphagia, odds ratios were about 1.0. The age-related ratio of esophagitis and severe disease with grades C and D increased in women over 60 years of age. An age-related slouched position was related to the increased esophagitis in these elderly women. Male subjects whose body mass index was more than 25 tended to show a greater prevalence in the age group 30-50 years. The prevalence of hiatal herniation increased in an age-related manner. These data indicate the characteristics of esophagitis in Japan are as follows: (1) the prevalence of reflux esophagitis is about 15% and most of these cases are grade A or B; and (2) the prevalence of severe esophagitis increases in older women, who do not always complain of clinical symptoms.

Adult↗