Autofluorescence imaging colonoscopy for the diagnosis of dysplasia in ulcerative colitis.
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Aged, 80 and over↗
Biomedical subjects
Takayuki Matsumoto
Publications and source records attributed to Takayuki Matsumoto.
Impact of Phospholipase A2 group IIa gene polymorphism on phenotypic features of patients with familial adenomatous polyposis.
PURPOSE: Phospholipase A2 Group IIa has been suggested to be a possible disease modifier gene in familial adenomatous polyposis. This investigation was designed to elucidate possible association between phospholipase A2 Group IIa polymorphism and phenotypes of patients with familial adenomatous polyposis. METHODS: Phospholipase A2 Group IIa was examined by polymerase chain reaction-based single strand conformation polymorphism and direct sequencing in 55 patients from 45 families with familial adenomatous polyposis. The patients were examined by gastroduodenoscopy plus biopsy with respect to fundic gland polyposis and gastroduodenal adenomas. Helicobacter pylori status was determined by rapid urease test. Contributions of genetic alteration and Helicobacter pylori infection to intestinal and extraintestinal lesions were investigated. RESULTS: Four types of single nucleotide polymorphism were found in exon 3 of phospholipase A2 Group IIa, among which single nucleotide polymorphism in codon 32 was the most frequent. The prevalence of fundic gland polyposis was higher in patients positive for single nucleotide polymorphism of phospholipase A2 Group IIa than those negative for single nucleotide polymorphism (61 vs. 33 percent; P < 0.05). In contrast, positive rate of Helicobacter pylori infection was lower in the former than in the latter (22 vs. 52 percent; P < 0.05). The prevalence of the other phenotypes was not different significantly. Logistic regression analysis revealed a possibility toward single nucleotide polymorphism of phospholipase A2 Group IIa as an independent risk factor for fundic gland polyposis (95 percent confidence interval, 00.9-14.3; P = 0.06). CONCLUSIONS: Phospholipase A2 Group IIa may be a modifier gene for fundic gland polyposis in patients with familial adenomatous polyposis.
Adenomatous Polyposis Coli↗
Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: a clinicopathologic and molecular study with reference to antibiotic treatment.
BACKGROUND: The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphoma develops in Helicobacter pylori-associated chronic gastritis. Little is still known regarding the clinicopathologic features of gastric MALT lymphoma not associated with H. pylori infection. METHODS: One hundred thirty-seven patients with gastric MALT lymphoma, in whom H. pylori status was evaluated using at least both serology and histology, were enrolled. Clinical, histopathologic, and molecular findings were compared between H. pylori-negative group (n = 12; 9%) and H. pylori-positive group (n = 125; 91%). t(11;18)(q21;q21) was investigated by reverse-transcription polymerase chain reaction and interphase fluorescence in situ hybridization. RESULTS: In cases without diffuse large B-cell lymphoma (DLBCL) component, H. pylori-negative lymphomas located more frequently in the proximal stomach (70%), less frequently appeared as superficial type (40%), and frequently invaded the submucosa or beyond (70%). Histologically, lymphoepithelial lesions (57%), lymphoid follicles (43%), and background mucosal atrophy (50%) in the H. pylori-negative group were less frequent than in the H. pylori-positive group (91%, 93%, and 100%, respectively). The frequencies of t(11;18)(q21;q21) (100%) and BCL10 nuclear expression (100%) in the H. pylori-negative group were significantly higher than in the H. pylori-positive group (2% and 27%, respectively). Response to antibiotic treatment was observed not only in the H. pylori-positive group (75%), but also in the H. pylori-negative group (2 of 7 patients, 29%). In cases with a DLBCL component, such differences were not observed between the 2 groups. CONCLUSIONS: H. pylori-negative gastric MALT lymphoma is characterized by frequent t(11;18)(q21;q21). Antibiotic treatment should be considered also for this disease, although cases with t(11;18)(q21;q21) may need additional strategies.
Adolescent↗
Enalapril improves impairment of SERCA-derived relaxation and enhancement of tyrosine nitration in diabetic rat aorta.
We investigated the involvement of angiotensin II and vascular smooth muscle sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) function in the impaired NO-induced relaxation seen in established streptozotocin-induced diabetes. Plasma angiotensin II levels, which were elevated in untreated diabetic rats (vs age-matched controls), were improved by treatment with the angiotensin-converting enzyme inhibitor enalapril. Systolic blood pressure was significantly decreased in chronic enalapril-treated diabetics (vs the other two groups). Intact aortae from diabetic rats and chronic angiotensin II-infused control rats, but not those from diabetic rats treated with enalapril, showed impaired endothelium-dependent relaxations to acetylcholine (vs controls). The relaxation induced by Angeli's Salt (a NO donor) was significantly impaired in endothelium-denuded aortae from diabetic rats (vs controls) but it was normalised by enalapril treatment. After preincubation with the irreversible SERCA inhibitor, thapsigargin, the relaxation induced by Angeli's Salt was significantly impaired in endothelium-denuded aortae from the controls, but not from the diabetics, and there was no significant difference between the thapsigargin-treated groups. Nitrotyrosine, an indirect marker of peroxynitrite, was markedly increased in aortic smooth muscle from diabetic rats, while chronic enalapril administration reduced this increase. These results suggest that in streptozotocin-induced diabetic rats, excessive angiotensin II production may lead to the generation of peroxynitrite and that this may in turn trigger a dysfunction of vascular smooth muscle SERCA. Enalapril improved the diabetes-related impairments.
Acetylcholine↗
Intramucosal gastric adenocarcinoma of poorly differentiated type in the young is characterized by Helicobacter pylori infection and antral lymphoid hyperplasia.
The aim of this investigation was to clarify the histological characteristics of gastric cancer in the young. Twenty-three surgically resected specimens of young patients (under 30 years of age; young group) with intramucosal cancer of poorly differentiated type and 42 surgically resected specimens of elderly patients (more than 40 years of age; elderly group) with tumors of the identical depth and histological type were examined. The degree of gastritis and Helicobacter pylori (H. pylori) infection was evaluated according to the updated Sydney system. The incidence of H. pylori infection was significantly higher in the young group than in the elderly group (96 vs 36%, P<0.05). Within the background mucosa, antral chronic inflammatory infiltrates with lymphoid-follicle hyperplasia were more severe, and intestinal metaplasia was less frequent in the young group than in the elderly group. Glandular atrophy was not different between the two groups. Intramucosal gastric adenocarcinomas of poorly differentiated type in the young may be associated with H. pylori infection with antral chronic inflammation with lymphoid-follicle hyperplasia, regardless of the existence of intestinal metaplasia within the background gastric mucosa.
Adenocarcinoma↗
[Cytokine targetting therapy for inflammatory bowel diseases].
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Antibodies, Monoclonal↗
Late-onset life threatening hemorrhage of omeprazole-resistant duodenal ulcer managed by interventional radiology: report of a case.
A 67-year-old diabetic man was emergently hospitalized in our department because of a huge duodenal ulcer without visible vessels. Despite of intravenous administration of 40 mg omeprazole and fasting with intravenous nutritional support, endoscopically unmanageable massive bleeding occurred on the 8th hospital day. Emergent angiography showed extravasation of contrast media from a duodenal branch of the proper hepatic artery, and superselective arterial embolization was successfully achieved. The patient recovered from the hemorrhagic shock and underwent subsequent successful surgery. Analysis of CYP2C19 enzyme genotype indicated the patient was a homozygous extensive metabolizer, considered a poor responder for omeprazole treatment.
Aged↗
Endoscopic features of chronic nonspecific multiple ulcers of the small intestine: comparison with nonsteroidal anti-inflammatory drug-induced enteropathy.
Chronic nonspecific multiple ulcers of the small intestine (CNSU) and nonsteroidal anti-inflammatory drug-induced enteropathy (NSAID-enteropathy) share common clinicopathologic features characterized by histologically nonspecific ulcers and persistent blood loss. The aim was to compare enteroscopic findings between CNSU and NSAID-enteropathy. Four patients with CNSU and five patients with NSAID-enteropathy were examined by enteroscopies. The site of involvement was heterogeneous in NSAID-enteropathy, while the ileum was the predominant site in CNSU. Three patients with NSAID-enteropathy and all four patients with CNSU had concentric stenosis. Circular ulcers were found in all five patients with NSAID-enteropathy and in three patients with CNSU. Active ulcer was seen in only two patients with NSAID-enteropathy. In contrast, all four patients with CNSU had active ulcer. These findings suggest that in patients with persistent GI bleeding and enteroscopically active small intestinal ulcers, CNSU, as well as NSAID-enteropathy, should be considered.
Adolescent↗
Apocynin normalizes hyperreactivity to phenylephrine in mesenteric arteries from cholesterol-fed mice by improving endothelium-derived hyperpolarizing factor response.
We studied the relationship among endothelial function, oxidative stress, and phenylephrine (PE; alpha(1)-adrenoceptor agonist)-induced contraction in mesenteric arteries from high-cholesterol (HC)-diet-fed mice. In HC mice (vs age-matched normal-diet-fed mice): (1) PE-induced contraction in endothelium-intact rings was enhanced (endothelial denudation increased contraction in "normal-diet" rings, but did not enhance it further in "HC" rings); (2) the enhanced PE-induced contraction was further enhanced in the presence of N(G)-nitro-L-arginine (L-NNA; nitric oxide synthase inhibitor) or L-NNA plus indomethacin (cyclooxygenase inhibitor) [to preserve endothelium-derived hyperpolarizing factor (EDHF)], but unchanged in the presence of charybdotoxin plus apamin (to block EDHF); (3) ACh-induced EDHF-type relaxation was reduced; and (4) oxidative stress [indicated by the plasma 8-isoprostane level (reliable systemic marker) and aortic superoxide production] was greater. In HC mice, PE-induced contraction was normalized by apocynin [NAD(P)H oxidase inhibitor] or tempol (superoxide dismutase mimetic), but enhanced by NADH [NAD(P)H oxidase substrate]. Oral dietary supplementation with apocynin (30 mg/kg/day for 4 weeks) corrected the above abnormalities. Hence: (1) PE-induced contraction is modulated by the endothelium, and the enhanced contractility in HC mice results from defective EDHF signaling and elevated oxidative stress, and (2) apocynin normalizes PE-induced contraction in HC mice by improving EDHF signaling.
Acetophenones↗
Vascular NAD(P)H oxidase mediates endothelial dysfunction in basilar arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
We examined the responses of basilar arteries taken from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model. Both the nitric oxide (NO)-mediated relaxation and the cyclic 3',5'-guanosine monophosphate (cGMP) production elicited by acetylcholine (ACh) were much weaker in OLETF rats than in age-matched control Long Evans Tokushima Otsuka (LETO) rats. The contraction induced by an NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine (L-NNA)] was weaker in the OLETF group. In that group, application of apocynin, an NAD(P)H oxidase inhibitor, normalized (i) ACh-induced relaxation, (ii) L-NNA-induced contraction, and (iii) ACh-induced cGMP production to the LETO levels. Superoxide anion production was greater in basilar arteries from OLETF rats than in those from LETO rats. The protein expression of gp91(phox), an NAD(P)H oxidase subunit, was upregulated in the OLETF arteries (versus LETO ones). These results suggest that the existence of endothelial dysfunction in basilar arteries in type 2 diabetes is related to increased oxidative stress mediated via NAD(P)H oxidase. Possibly, an impairment of NO-dependent relaxation responses and a basal impairment of NO signaling may be responsible for the increased risk of adverse cerebrovascular events in type 2 diabetes.
Acetophenones↗
A prospective study of dietary salt intake and gastric cancer incidence in a defined Japanese population: the Hisayama study.
The results of prospective studies of the association between dietary salt intake and gastric cancer occurrence remain controversial. To examine this issue in a cohort study of a general population, 2,476 subjects aged 40 years or older were stratified into 4 groups according to the amount of daily salt intake: namely, <10.0, 10.0-12.9, 13.0-15.9, and > or = 16.0 per day and were followed up prospectively for 14 years. During the follow-up period, 93 subjects developed gastric cancer. The age- and sex-adjusted incidence was significantly higher in the second to fourth groups than in the first group (age- and sex-adjusted hazard ratio [95% confidence interval], 2.42 [1.24-4.71] for the second group; 2.10 [1.03-4.30] for the third group; 2.98 [1.53-5.82] for the fourth group). This association remained substantially unchanged even after adjusting for other confounding factors such as age, sex, Helicobacter pylori infection, atrophic gastritis, medical history of peptic ulcer, family history of cancer, body mass index, diabetes, total cholesterol, physical activity, alcohol intake, smoking habit and other dietary factors. In the stratified analysis, a significant salt-cancer association was observed only in subjects who had both Helicobacter pylori infection and atrophic gastritis (age- and sex-adjusted hazard ratio, 2.87 [1.14-7.24]). Our findings suggest that high dietary salt intake is a significant risk factor for gastric cancer; moreover, this association was found to be strong in the presence of Helicobacter pylori infection with atrophic gastritis.
Adult↗
Specific impairment of endothelium-derived hyperpolarizing factor-type relaxation in mesenteric arteries from streptozotocin-induced diabetic mice.
We hypothesized that the contribution made by endothelium-derived hyperpolarizing factor (EDHF) to acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) might be altered in mesenteric arteries from streptozotocin (STZ)-induced diabetic mice. In endothelium-intact preparations, the ACh-induced EDR (but not the sodium nitroprusside-induced relaxation) was weaker in the STZ group than in age-matched controls. Indomethacin (10 muM) had no significant effect on EDR in either group, indicating that cyclooxygenase products, including prostacyclin, are not involved. This indomethacin-resistant EDR was weaker in the STZ group than in the controls. To isolate the EDHF-resistant component of EDR, charybdotoxin (100 nM) and apamin (100 nM) were present in the bath solution throughout the next experiment. This EDHF-resistant relaxation did not differ significantly between the two groups. On the other hand, the EDHF-mediated relaxation was significantly weaker in the STZ group than in the controls, and it was completely blocked by lysophosphatidylcholine (LPC, 10 microM) in each group. The eNOS protein expression was similar between the two groups. These results suggest that (a) the endothelial dysfunction present in mesenteric arteries from type 1 diabetic mice is largely attributable to reduced EDHF signaling, and (b) LPC may be involved in this attenuation of EDHF-mediated relaxation.
Acetylcholine↗
Mechanisms underlying the impaired EDHF-type relaxation response in mesenteric arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
We previously reported that in mesenteric arteries from streptozotocin-induced diabetic rats, the endothelium-derived hyperpolarizing factor (EDHF)-type relaxation is impaired, possibly due to a reduced action of cAMP. Here, we observed an impairment of acetylcholine-induced EDHF-type relaxation in mesenteric arteries from a type 2 diabetic model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats [vs. age-matched control Long-Evans Tokushima Otsuka (LETO) rats], and we investigated the mechanism underlying this impairment. In the LETO group, this EDHF-type relaxation was attenuated by 18alpha-glycyrrhetinic acid (a gap-junction inhibitor) and by a protein kinase A (PKA) inhibitor. In both groups (OLETF and LETO), it was enhanced by 3-isobutyl-1-methylxanthine, a cAMP-phosphodiesterase (PDE) inhibitor, but following these enhancements it was still weaker in OLETF rats than in LETO rats. The relaxations induced by cilostamide (a selective PDE3 inhibitor) and 8-bromo-cAMP (a cell-permeant cAMP analog) were reduced in OLETF rats, as was PKA activity. The relaxations induced by two activators of Ca(2+)-activated K(+) channels (K(Ca)) [1-ethyl-2-benzimidazolinone (1-EBIO), intermediate-conductance K(Ca) channel (IK(Ca)) activator, and riluzole, small-conductance K(Ca) channel (SK(Ca)) activator] were also impaired in OLETF rats. We conclude that the impairment of EDHF-type relaxation seen in OLETF rats may be attributable not only to a reduction in cAMP/PKA signaling, but also to reduced endothelial K(Ca) channel activities.
Acetylcholine↗
ANG II enhances contractile responses via PI3-kinase p110 delta pathway in aortas from diabetic rats with systemic hyperinsulinemia.
We investigated the involvement of ANG II and phosphatidylinositol 3-kinase (PI3-K) in the enhanced aortic contractile responses induced by hyperinsulinemia in chronic insulin-treated Type 1 diabetic rats. Plasma ANG II levels were elevated in untreated compared with control diabetic rats and further increased in insulin-treated diabetic rats. Aortic contractile responses and systolic blood pressure were significantly enhanced in chronic insulin-treated diabetic rats compared with the other groups. These insulin-induced increases were largely prevented by cotreatment with losartan (an ANG II type 1 receptor antagonist) or enalapril (an angiotensin-converting enzyme inhibitor). LY-294002 (a PI3-K inhibitor) diminished the increases in contractile responses in ANG II-incubated aortas and aortas from chronic insulin-treated diabetic rats. The norepinephrine (NE)-stimulated levels of p110 delta-associated PI3-K activity and p110 delta protein expression were increased in aortas from insulin-treated diabetic compared with control and untreated diabetic rats, and chronic administration of losartan blunted these increases. Contractions were significantly larger in aortas from diabetic rats incubated with a low concentration (inducing approximately 10% of the maximum contraction) of ANG II or with NE or isotonic K+ than in aortas from nonincubated diabetic rats. NE-stimulated p110 PI3-K activity was elevated in aortas from diabetic rats coincubated with a noncontractile dose of ANG II. These results suggest that, in insulin-treated Type 1 diabetic rats with hyperinsulinemia, chronic ANG II type 1 receptor blockade blunts the increases in vascular contractility and blood pressure via a decrease in p110 delta-associated PI3-K activity.
Angiotensin II↗
The serum pepsinogen test as a predictor of gastric cancer: the Hisayama study.
The authors examined whether a serum pepsinogen test (SPT) based on the combination of the serum pepsinogen I level and pepsinogen I/II ratio is a good predictor of gastric cancer occurrence in a general Japanese population. A total of 2,446 subjects aged > or =40 years were classified into negative, positive, and strong-positive SPT groups and were followed prospectively for 14 years (1988-2002). Compared with that for the negative SPT group (26 men, 10 women), gastric cancer incidence increased significantly for both men (n = 17; age-adjusted hazard ratio = 4.56, 95% confidence interval: 2.42, 8.60) and women (n = 6; age-adjusted hazard ratio = 5.84, 95% confidence interval: 2.00, 17.11) in the strong-positive SPT group. It was also significantly higher in the positive SPT group for men (n = 23; age-adjusted hazard ratio = 3.91, 95% confidence interval: 2.23, 6.86). These associations did not attenuate even after adjustment for other comprehensive risk factors. Stratified analysis revealed significant associations between the SPT and development of intestinal-type gastric cancer as well as of cancer in both Helicobacter pylori-negative and -positive subjects. These findings suggest that the SPT can serve as a predictor of intestinal-type gastric cancer, irrespective of H. pylori infection.
Adult↗
Infiltration of CD19+ plasma cells with frequent labeling of Ki-67 in corticosteroid-resistant active ulcerative colitis.
Abnormalities in humoral immunity are implicated in the pathogenesis of ulcerative colitis. However, the detailed mechanisms of B-cell activation in the locale remain unaccounted for. We analyzed ulcerative colitis from the standpoint of lymphocytic expansion in the loco. Intestinal specimens obtained at surgery from 30 patients with ulcerative colitis treated with corticosteroids and 15 with Crohn's disease were analyzed by immunohistochemistry and flow cytometry. Ulcerative colitis was characterized by a diffuse distribution of Ki-67(+) small round cells particularly in the ulcer base (that were CD19(+) and CD20(-)), with a significant number of them also CD138(+). Immunoelectron microscopy for CD19 revealed an abundance of rough endoplasmic reticulum in the cytoplasm. These indicated that they are of immature plasma lineage cells. By contrast, plasma cells in Crohn's disease were negative for CD19, and the labeling for Ki-67 was infrequent, showing mature phenotype. Flow cytometry revealed an occurrence of CD19(+) and CD20(-) cells in ulcerative colitis but not in Crohn's disease. The labeling index of Ki-67 among CD19(+) plasma cells was positively correlated with the clinical activity of ulcerative colitis. High labeling of Ki-67 in CD19(+) plasma cells is specific for active ulcerative colitis that was resistant to medical treatment by corticosteroids.
Adolescent↗
Platelets in inflammatory bowel disease.
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Blood Platelets↗
Activated platelets as a possible early marker to predict clinical efficacy of leukocytapheresis in severe ulcerative colitis patients.
BACKGROUND: Leukocytapheresis (LCAP) is an effective adjunct for patients with active ulcerative colitis (UC). Because LCAP may have the potential to remove and modulate not only leukocytes but also platelets, we evaluated the correlation between activated platelets and the therapeutic response to LCAP. METHODS: Fourteen patients with severe UC received weekly LCAP for 5 consecutive weeks. Their average clinical activity index (CAI) and endoscopic index (EI) were 9.6 +/- 3.4 and 10.9 +/- 1.0, respectively. Their peripheral blood was sampled before and after every LCAP and stained with fluorescent antibodies to the activation-dependent surface antigens of platelets (CD63, CD62-P) prior to flow cytometry. Endoscopic evaluations were performed after the last LCAP. RESULTS: Clinical remission (CAI < 4) was induced in 50% of the patients (7/14) after 5 weeks, and there were no significant differences observed in clinical background between the responder group (RG) and the nonresponder group (NG). In the RG, the populations of CD63(+) (P < 0.03) and CD62-P(+) (P < 0.05) platelets were significantly decreased after the first LCAP, and their reduction ratio decreased gradually with repeated LCAP. A significant improvement of the EI score, especially mucosal damage, was achieved in RG (P < 0.04) but not in NG. CONCLUSIONS: These results indicate that the therapeutic responses to LCAP were reflected in modulations of population and/or platelet functions, especially after the first session. The decrease of such activated platelets immediately after the first LCAP may be an early marker for predicting the response in patients with severe UC.
Adolescent↗