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N Hiwatashi

Publications and source records attributed to N Hiwatashi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Crohn's disease is associated with novel polymorphisms in the 5'-flanking region of the tumor necrosis factor gene.

BACKGROUND & AIMS: Tumor necrosis factor (TNF) is considered to play an important role in the pathogenesis of Crohn's disease (CD). Recently, 3 polymorphisms in the 5'-flanking region of the TNF gene at positions -1031, -863, and -857, which are related to high transcriptional promoter activity, have been identified in the Japanese population. In an effort to understand potential genetic association with CD, we evaluated patients diagnosed with CD and ulcerative colitis (UC) in the presence of other novel polymorphisms. METHODS: Blood samples were obtained from 103 patients with CD and 76 patients with UC. Polymorphisms in the TNF gene at their respective positions were analyzed by direct sequencing, and the allele frequencies were compared with those determined previously in a healthy Japanese population. RESULTS: Allele frequencies of -1031C, -863A, and -857T in normal controls were 16.0%, 14.0%, and 17.7%, respectively. Polymorphic allele frequencies at positions -1031, -863, and -857 were 24.3%, 21.8%, and 27.2% in CD and 11.8%, 11.2%, and 11.8% in UC, respectively. The frequencies at all 3 positions were significantly higher in CD patients than in UC patients or healthy controls. Among the subgroups of CD, small bowel disease showed the highest frequencies. CONCLUSIONS: Although the findings need to be confirmed in other populations with larger numbers of patients, TNF gene polymorphisms -1031C, -863A, and -857T are positively associated with CD; they may influence not only the susceptibility to CD but also the disease location.

Adult↗
PubMed1999

11Beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor in human fetal development.

11Beta-Hydroxysteroid dehydrogenase type II (11betaHSD2) confers specificity on the mineralocorticoid receptor (MR) by converting biologically active glucocorticoids to inactive 11-keto metabolites. The biological significance of 11betaHSD2 activity during fetal development is currently being explored, but the temporal and spatial distributions of the enzyme and receptor have not been examined. We therefore examined their distributions during various stages of human fetal development using immunohistochemistry. Both 11betaHSD2 and MR immunoreactivity were detected in the distal convoluted and collecting tubules of the kidney from early in gestation. Fetal skin, intermediate layer of the epidermis, peridermal cells, and hair follicles were positive for both 11betaHSD2 and MR. Weak 11betaHSD2 and MR immunoreactivity was detected in the superficial ciliated epithelium of the esophagus, the deep layer of gastric epithelial cells, and the superficial epithelium of the small intestine. Columnar epithelium in the terminal bronchiolar budding component of fetal lung and tracheal and bronchial ciliated epithelium were also positive for MR and 11betaHSD2 from early gestation. Colonic epithelium and pancreatic exocrine duct cells, which demonstrated marked immunoreactivity of both MR and 11betaHSD2 in the adult, did not express MR and 11betaHSD2 until very late in gestation. These results imply that mineralocorticoid action in the upper fetal gastrointestinal tract, kidney, skin, and lung is facilitated by 11betaHSD2 and is involved in water and electrolyte transport between fetus and amniotic fluid as well as fetal urine production.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

[Inflammatory bowel disease and pregnancy: clinical study of mutual influence, clinical course and treatment].

We studied the clinical courses of 70 pregnancies in 47 women with ulcerative colitis (UC) and 18 pregnancies in 12 women with Crohn's disease (CD) retrospectively. We concluded as follows. 1. Pregnancy has less influence on the course of UC. 2. The patients with UC who kept remission for more than 1 year before conception have less risk of relapse and severity during pregnancy. 3. The patients with active UC at the time of conception tend to worsen during pregnancy. The patients whose onset of UC is during pregnancy tend to worsen. 4. UC has a little influence on the course of pregnancy except severe active disease. 5. It is not obtained that pregnancy becomes a relapsing factor of CD. 6. CD during pregnancy has little influences on the course of pregnancy, if it is remitted. 7. Salazosulfapyridine and corticosteroids therapy has less influence on the fetus and the course of pregnancy.

Adrenal Cortex Hormones↗
PubMed1999

[Salazosulfapyridine and 5-aminosalicylic acid agents for the treatment of ulcerative colitis].

Sulfasalazine and 5-aminosalicylic acid are very useful therapeutic agents for the treatment of the inflammatory bowel disease, such as ulcerative colitis or Crohn's disease. However, the mechanism of action of the aminosalicylates remains obscure. Recently, many studies about their mechanism have been performed. As a result, aminosalicylates have been identified to have several antiinflammatory pathways: (1) alterations in eicosanoid metabolism of arachidonic acid; particularly inhibition of leukotrien B4 production, (2)free radical scavengers; scavenging reactive oxygen metabolites or nitric oxide (3)immunologic suppression; inhibition of HLA-DR expression on the intestinal epithelial cells, inflammatory cytokine(IL-1 and IL-2) production, adhesion molecule expression, platelet-activating factor release, or histamine release from mast cell, and so on.

Animals↗
PubMed1998

Telomere shortening in the colonic mucosa of patients with ulcerative colitis.

Telomere length in human somatic cells gradually decreases with the number of cell divisions and is regarded as a marker of somatic cell turnover. Mucosal cells of the affected colon show rapid turnover in individuals with active ulcerative colitis (UC). Telomere length was determined by Southern blot analysis of terminal restriction fragments (TRFs) from the colonic mucosa of 17 patients with UC in remission, two of whom showed dysplasia, and 17 control subjects without colitis. For each individual, mean TRF length was compared between rectal mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was significantly less than that of cecal mucosa in UC patients (7.87 +/- 0.36kb versus 8.77 +/- 0.21 kb; P = 0.0015, Wilcoxon signed rank test), whereas no significant difference was detected in the control subjects. The extent of telomere shortening was 10.6 +/- 3.35% in UC patients, compared with 0.8 +/- 0.64% in noncolitis controls (P = 0.0024, Mann-Whitney U-test). Four UC patients, two of whom had dysplasia, showed telomere shortening of more than 20% in the rectal mucosa. These observations suggest that telomere shortening in the colonic mucosa of individuals with UC may represent the history of mucosal inflammation during disease of long duration, and that it may contribute to aneuploidy in UC.

Adolescent↗
PubMed1998

Leukocyte removal filter-passed lymphocytes produce large amounts of interleukin-4 in immunotherapy for inflammatory bowel disease: role of bystander suppression.

To determine immunosuppression by leukocytapheresis, we studied the immune profiles of filter-passed lymphocytes (FPLs) in patients with ulcerative colitis. These patients were treated with a leukocytapheresis (LCAP) filter of granulocyte apheresis (GCAP) column. Cytokine profiles or FPLs and peripheral blood mononuclear cells (PBMCs) were examined using interleukin (IL)-4 and interferon-gamma (IFN-gamma) immunoassay with lectin stimulation. The IL-4 production of LCAP FPLs was significantly higher than in prefilter PBMCs and GCAP column-passed lymphocytes (median: 540 pg/ml x 10(6) cells versus 4.7 and 2.9, respectively, p = 0.001). IL-4 production in PBMCs was increased after LCAP. IFN-gamma production was not increased in the FPLs. The IL-4 immune deviation was not shown in the patients treated with GCAP. LCAP FPLs showed increased CD4+DR- cells and decreases CD4+DR+ cells in comparison to PBMCs. LCAP FPLs could produce IL-4 and may lead to bystander suppression.

Adult↗
PubMed1998

Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF) alpha and TNF-beta are soluble ligands binding to TNF receptors with similar activities; soluble TNF receptors neutralise TNF activity by acting as inhibitors. Little is known about the cytokine/soluble receptor role in inflammatory bowel disease (IBD). AIMS: To test the hypothesis that an imbalance in secretion between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD. METHODS: The secretion of TNF-alpha, TNF-beta, and soluble TNF receptors was compared in the culture supernatants of colonic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD. RESULTS: Spontaneous secretion of TNF-alpha in involved IBD mucosa was higher than in normal control and self limited colitis mucosa. Secretion of TNF-beta was higher in patients with Crohn's disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was increased in active inflammation; release from lamina propria cells was not increased. Mucosal TNF-alpha production correlated with severity of disease. CONCLUSIONS: Results showed enhanced secretion of TNF-alpha but failure to release enhanced amounts of soluble TNF receptor in lamina propria mononuclear cells of patients with IBD. An imbalance in secretion between TNF and TNF inhibitor may be implicated in the pathogenesis of IBD.

Adolescent↗
PubMed1997

Enteral nutrition for Crohn's disease in Japan.

UNLABELLED: Indication for and an evaluation of enteral nutrition in Crohn's disease differ between Japan and western countries. PURPOSE: Japanese results are reported and differences are discussed. RESULTS: Enteral nutrition with an elemental diet is first-line therapy for active Crohn's disease in Japan. The remission induction rate of elemental diet therapy is approximately 80 percent, which is superior to steroids. Furthermore, elemental diet therapy induces radiographic and endoscopic remission. On the other hand, meta-analysis from randomized, controlled trials showed steroids to be more effective than enteral nutrition in western countries. The differences are considered to be the result of such differences as therapeutic duration of enteral nutrition, the composition of enteral diets used, criteria for remission, the quality of life score of a long-term fast with a nasogastric tube, medical care, and health insurance system. The main mechanism of the therapeutic effect of elemental diet is speculated to be attributable to removal of food antigens and decreases of secretion and motility (bowel rest) by very low fat. To prevent relapse and rehospitalization, home enteral nutrition is now used widely in Japan. The therapeutic effect is observed in patients with ileal involvement, and more than 1,200 kcal/day is more effective than a lower amount. CONCLUSION: Most Japanese studies were open-labeled, uncontrolled trials. We should conduct randomized, controlled trials comparing enteral nutrition with steroids during the active stage of Crohn's disease and home enteral nutrition with drugs in maintaining remission and investigate the therapeutic effect, quality of life, and costs.

Crohn Disease↗
PubMed1997

Relationship between glucocorticoid receptor and response to glucocorticoid therapy in ulcerative colitis.

PURPOSE: To clarify the relationship between the glucocorticoid receptor and the effectiveness of glucocorticoid therapy in patients with ulcerative colitis, we investigated the number and apparent dissociation constant of glucocorticoid receptor in peripheral blood mononuclear leukocytes of patients with ulcerative colitis. MATERIALS AND METHODS: Eleven patients with ulcerative colitis (5 who responded to intravenous glucocorticoids and 6 who did not) and ten control subjects were studied. The number and apparent dissociation constant of glucocorticoid receptor were measured using a whole-cell binding assay. Results were expressed as a median (interquartile range). RESULTS: The number of glucocorticoid receptors from the six nonresponders, five responders, and ten healthy controls were 4922 (range, 4484-5643), 3413 (range, 3183-4450), and 3610 (range, 2594-3979) binding sites/cell, respectively. The apparent dissociation constant of the glucocorticoid receptors from the nonresponders, responders, and healthy controls were 7.03 (range, 5.66-10), 4.27 (range, 4-5.13), and 6.18 (range, 5.86-6.74) nM, respectively. Nonresponders had a significant increase both in the number of binding sites and in the apparent dissociation constant compared with responders (P = 0.045; P = 0.029). CONCLUSIONS: The increased number and apparent dissociation constant of glucocorticoid receptor are closely associated with the effectiveness of glucocorticoid therapy. The measurement of the number and apparent dissociation constant of glucocorticoid receptor may be useful in predicting response to glucocorticoids.

Adult↗
PubMed1997

Accessory cell function of a human colonic epithelial cell line HT-29 for bacterial superantigens.

The expression and up-regulation of cell adhesion molecules on a human colonic epithelial cell line HT-29, and the peripheral blood T lymphocyte proliferation responses to bacterial superantigens presented by this cell line were investigated, compared with peripheral blood monocytes. In HT-29 cells, there was constitutive expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3) at a low level, but no constitutive expression of HLA-DR, LFA-1, B7-1 and B7-2 molecules. After stimulation with the supernatants of staphylococcal enterotoxin B (SEB)-stimulated peripheral blood mononuclear cells for 48 h, there was significant up-regulation of HLA-DR and ICAM-1 molecules (both > 90% positive). However, this stimulation had no effect on the expression of LFA-1, B7-1, B7-2 and LFA-3 molecules. In the presence of all tested superantigens SEB, toxic shock syndrome toxin-1, and streptococcal pyogenic exotoxin A, stimulated HT-29 cells caused significant T cell proliferation. When monocytes were used as antigen-presenting cells (APC), the MoAbs against HLA-DR, B7-2 and LFA-3 showed a significant inhibition of SEB-induced T cell proliferation. Anti-ICAM-1 MoAb had no effect on this response. On the other hand, when stimulated HT-29 cells were used as APC, the MoAbs against HLA-DR and ICAM-1 significantly inhibited SEB-induced T cell proliferation. In contrast to monocytes, anti-B7-2 and anti-LFA-3 had no effect on this response. SEB could not induce HT-29 cells to produce IL-8 directly; however, SEB significantly induced the stimulated HT-29 cells to produce IL-8 in the presence of T cells. Thus these data demonstrate that the products of superantigen-stimulated T cell activation can increase the expression of HLA-DR and ICAM-1 molecules on HT-29 cells significantly. Stimulated HT-29 cells can serve as APC to bacterial superantigens. This response is an HLA-DR- and ICAM-1-dependent, but B7-2- and LFA-3-independent process, which was different from professional APC monocytes.

Antigen-Presenting Cells↗
PubMed1997

Colocalization of 11 beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human epithelia.

The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2) has been shown to confer specificity on mineralocorticoid receptors (MR) by inactivating glucocorticoids. In the present study we examined the colocalization of 11 beta HSD2 and MR in various exocrine and secretory glands by immunostaining of serial mirror tissue sections with subsequent computerized image analysis. Both 11 beta HSD2 and MR proteins were expressed in the same cells in the distal convoluted tubules, Henle's loop, and collecting tubules of the kidney and the absorptive epithelia of duodenum, jejunum, ileum, colon, and excretory ducts of anal and esophageal glands. Significantly, 11 beta HSD2 and MR immunoreactivity also colocalized in the respiratory tract, in collecting ducts of the tracheal and bronchial glands, ciliated bronchial epithelial cells, and type II alveolar epithelial cells, suggesting important and unexpected roles for mineralocorticoids in the lung. In the skin, 11 beta HSD2 and MR were present only in excretory ducts of eccrine sweat glands, but not in sebaceous or apocrine glands. In eccrine glands, MR immunoreactivity was present in the basal cells of excretory ducts, while 11 beta HSD2 immunoreactivity was localized in the luminal cells. Neither 11 beta HSD2 nor MR proteins were expressed in the lacrimal gland, prostate, bile ducts, gall bladder, urinary bladder, urethra, or ureter. These results indicate that 11 beta HSD2 protein colocalizes with MR protein in the great majority of sodium-transporting epithelia involved in serous secretion and supports the proposal that 11 beta HSD2 is a pivotal determinant of mineralocorticoid receptor occupancy in man. Furthermore, our demonstration of colocalization in discrete areas of the lung suggests that mineralocorticoid agonists or antagonists, and/or inhibitors of 11 beta HSD2, may have unexpected applications in respiratory disease.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Increased expression of costimulatory molecules on peripheral blood monocytes in patients with Crohn's disease.

BACKGROUND: Activation of T lymphocytes and monocytes/macrophages has been implicated in the pathogenesis of Crohn's disease (CD). Costimulatory molecules play important roles in optimal T-cell activation. METHODS: With flow cytometric analysis we have investigated the expression of the costimulatory molecules B7-1 (CD80), B7-2 (CD86), and CD18 and the intercellular adhesion molecule-1 (ICAM-1) on peripheral blood monocytes and the expression of the activation markers HLA-DR and IL-2R (CD25) on peripheral blood T lymphocytes from 31 CD patients, 17 ulcerative colitis (UC) patients, and 10 healthy controls. RESULTS: In CD patients the percentage of activated T cells (CD3+ HLA-DR+ and CD3+ IL-2R+) was significantly increased compared with those of controls and UC patients (P < 0.05). Most monocytes from all three groups expressed B7-2, CD18, and ICAM-1 molecules (all > 79%), but only a few positive cells expressed B7-1 molecules (< 5%). No significant differences were detected in the percentage positivity of all costimulatory molecules tested among CD, UC, and controls. The mean fluorescence intensity (MFI) of B7-1 in all three groups was very weak and not significantly different. However, in CD patients there was a significantly increased MFI of B7-2, CD18, and ICAM-1 molecules compared with UC and controls (P < 0.05). On the other hand, both the percentage positivity and MFI of HLA-DR molecules on monocytes of UC patients were significantly lower than those of CD patients and controls (P < 0.05). CONCLUSIONS: Expression of the costimulatory molecules B7-2, CD18, and ICAM-1 on peripheral blood monocytes of CD patients is increased. In CD patients activation of peripheral T lymphocytes may correlate with increased expression of these costimulatory molecules on peripheral blood monocytes.

Adolescent↗
PubMed1997

[Effects of NSAIDs and PGE1 analogue on the permeability of human small intestine].

We studied permeability of human small intestine to clarify the following questions. 1) Does indomethacin increase intestinal permeability (IP)? 2) Does ornoprostil (PGE1 analogue) prevent the increased IP due to indomethacin? 3) Does acemetacin (pro-drug) increase IP? Eleven healthy volunteers were studied before and after ingestion of indomethacin, acemetacin, ornoprostil. After an overnight fast, they drank an isotonic solution containing 1.5 g rhamnose and 10.5 g lactulose. IP was estimated with lactulose/rhamnose percentage excretion in urine for 5 hours. An administration of indomethacin (75 mg) for one day increased IP significantly, and the coadministration of indomethacin and ornoprostil showed no significant change in IP compared with those of controls. Pro-drug administration did not increase IP. It is suggested that simultaneous administration of ornoprostil prevent the mucosal damage caused by indomethacin clinically, and that the mechanism of this increase IP is due to lack of mucosal prostaglandins on the small intestine.

Adult↗
PubMed1996

Relaxation of imprinting of the insulin-like growth factor II gene in colorectal cancer.

The insulin-like growth factor II gene (IGF2) is imprinted in normal human tissues, and relaxation of imprinting (ROI) of IGF2 is thought to play an important role in human childhood tumors. Taking advantage of an Apa I polymorphism in this gene, allelic expression of IGF2 has now been examined in colorectal cancer. Thirteen of 33 patients studied were informative. Colorectal cancer tissue from 5 of the 13 informative patients exhibited ROI of IGF2; furthermore, normal mucosa from 3 of these 5 patients also showed weak biallelic expression of IGF2. ROI of IGF2 may thus also play a role in colorectal cancer.

Alleles↗
PubMed1996

Psoas abscess complicating Crohn's disease: report of two cases.

We report herein the cases of two patients with Crohn's disease complicated by a psoas abscess. The first patient was a 29-year-old man who underwent definitive surgery after acute inflammation had been controlled by nutritional therapy. In the second patient, a 37-year-old man, the abscess required drainage under local anesthesia prior to surgery. Both patients have been free from recurrence of any abdominal symptoms for about 2 years since undergoing surgery. Although psoas abscess is still regarded as a rare complication, with the increasing prevalence of Crohn's disease in Japan it has become one of the most important complications requiring surgical intervention.

Adult↗