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Biomedical subjects

N Oshitani

Publications and source records attributed to N Oshitani.

At least 55 records · Page 3Linked to original sources

Corticosteroids for the management of ulcerative colitis.

Two studies were carried out. In the first, 24 patients with severe ulcerative colitis (UC) were prospectively studied by the Research Group of Inflammatory Bowel Disease, sponsored by the Ministry of Health and Welfare of Japan. Patients were randomly assigned to two groups; one group (n = 13) was given prednisolone, 1.0 mg/kg body weight, daily, the other group (n = 11) was given prednisolone, 1.5 mg/kg body weight, daily. The 13 patients given 1.0 mg/kg prednisolone consisted of 7 with left-sided colitis and 6 with total colitis; 11 patients given 1.5 mg/kg prednisolone consisted of 5 with left-sided and 6 with total colitis. There were no statistically significant differences in clinical, endoscopic, and overall improvement between the two groups; however, 1.5 mg/kg prednisolone was significantly more effective in the treatment of the patients exhibiting the first attack. In the second study, 6 patients with severe and 7 with moderately severe UC were given megadose pulsed steroid therapy. Five hundred or 1000 mg of either hydrocortisone-21-sodium succinate or methylprednisolone was given once a day intravenously. Ten patients achieved clinical remission, 1 patient improved, and 2 patients did not respond. Endoscopically, 5 patients achieved remission, 6 patients improved, and 2 did not respond. Adverse effects severe enough to stop the medication were not noted. Steroid withdrawal syndrome also was not noted.

Adult↗

Location of nitroblue tetrazolium-reducing activity in human colonic mucosa obtained by biopsy.

The location of nitroblue tetrazolium-reducing activity was studied in colonic biopsy specimens from 28 patients with ulcerative colitis and from 23 controls. Nitroblue tetrazolium was reduced by epithelial cells, vascular endothelium, and interstitial mononuclear cells of the colonic mucosa from both groups. Blue formazan, a reduced form of nitroblue tetrazolium, was seen faintly after 30 min of culture; the amount increased up to 2 hr tested. The vascular endothelium of the patients with ulcerative colitis reduced nitroblue tetrazolium significantly more than that of the controls. The reduction of nitroblue tetrazolium was graded from 0 to 3 and was 1.0 +/- 0.6 in the controls, 1.6 +/- 0.8 in ulcerative colitis patients (P < 0.05), 1.9 +/- 0.7 (P < 0.01) in patients with active ulcerative colitis, and 1.4 +/- 0.9 in patients with inactive ulcerative colitis (difference not significant). Aggregates of mononuclear cells that reduced nitroblue tetrazolium were found in 10 of 28 patients with ulcerative colitis but not in the controls.

Adult↗

Multifunctional effects of anticomplementary agent K-76 on carrageenan-induced colitis in the rabbit.

In this study the effect of K-76, a sesquiterpene compound with anticomplementary activity isolated from a fungus culture, on carrageenan-induced colitis was studied from biochemical, histological and immunohistopathological aspects. K-76 suppressed epithelial cell loss, crypt abscess formation, inflammatory cell infiltration, mucosal atrophy, and ulceration. Immunohistochemical examination of the colonic mucosa showed that the number of IgG- and IgM-positive plasma cells and the staining intensity for IgG and C3 were increased in carrageenan-induced colitis, but these changes were inhibited by K-76. Besides, serum mucoprotein concentrations and CH50 levels were lower in the animals treated with carrageenan alone. K-76 exerted multifunctional activity, although its mechanisms of action remain obscure.

Animals↗

Location of superoxide anion generation in human colonic mucosa obtained by biopsy.

To identify which cells generate superoxide, inflamed human mucosa was tested with nitro-blue tetrazolium as a probe, because it is reduced by strong reducing agents to form insoluble blue formazan, which then precipitates in tissues. Biopsy specimens from control subjects and patients with ulcerative colitis were studied. The specimens were organ cultured with bubbling air or nitrogen, and inhibition of the reduction by catalase (a hydrogen peroxide scavenger), para-benzoquinone (a tissue permeable superoxide scavenger), or superoxide dismutase (a superoxide scavenger) was assayed. The dye was reduced by epithelial cells, vascular endothelium, and infiltrating mononuclear cells of the mucosa. Its reduction by vascular endothelium and infiltrating mononuclear cells was greater in inflamed mucosa. The reduction by vascular endothelium and infiltrating mononuclear cells was inhibited in cultures with nitrogen saturation or with 1 mM para-benzoquinone. The vascular endothelium seems to produce superoxide in the inflamed mucosa, which would exacerbate tissue injury in ulcerative colitis.

Adolescent↗

[Pulsed steroid therapy for active ulcerative colitis patients].

Six severe and 7 moderately severe ulcerative colitis patients were treated by pulsed steroid therapy. For one course of the therapy, either 0.5 or 1 gram of hydrocortisone-21 sodium succinate or methylprednisolone sodium succinate was given once a day intravenously for 3 consecutive days, following 4 days with no infusion. The patients were treated for 3 to 6 courses. Ten patients entered clinical remission, 1 patient improved, and therapy failed for 2 patients. Judged endoscopically, 5 patients achieved remission. Six patients improved and 2 patients did not improve. Severe side effect was not noted as to stop the medication. One patient had hyperglycemia for a few days after the start of the first course, this patient received total parenteral nutrition. Three patients showed moon face. Steroid withdrawal syndrome did not develop.

Adolescent↗

New treatment of ulcerative colitis with K-76.

The complement inhibitor K-76 (Otsuka Pharmaceutical Co., Osaka, Japan) was clinically evaluated as a new drug for treatment of active stage ulcerative colitis (UC). As monotherapy, K-76 proved effective in four of five cases. Furthermore, in patients with active stage UC that continued despite administration of corticosteroid hormone and salicylazosulphapyridine (so-called refractory UC), concomitant administration of K-76 was effective in seven of 21 cases. Thus, we believe that the multifunctional agent K-76 will provide clinicians with a new therapeutic approach to inflammatory bowel diseases, including UC and Crohn's disease.

Adolescent↗

Predictive factors for the response of ulcerative colitis patients during the acute-phase treatment.

Twenty-six consecutive admissions of 24 patients with severe ulcerative colitis (UC) hospitalized in our Department at some time between January 1983 and December 1988 were studied to identify factors useful in the prediction of response to medical treatment in the acute inflammatory phase of this disease. Results of laboratory tests (white blood cells, red blood cells, platelet count, hemoglobin, erythrocyte sedimentation rate, total protein, albumin, alpha 2-microglobulin, cholinesterase, total cholesterol, and triglycerides) and of endoscopic findings (extent of disease, progress of the lesions, sparing of the rectum, and presence of geographic ulcers, longitudinal ulcers, and polypoid mucosal tags) were analyzed for any relationship with the effect of medical treatment during the acute phase. The effect of treatment was evaluated in terms of days it took for a severe condition to improve to an intermediate one defined by Truelove and Witts' categories for UC severity. C-Reactive protein, nutritive condition (total protein, albumin, and cholinesterase), extent of the lesions, and existence of polypoid mucosal tags provide predictive factors useful in the management of UC during the acute phase.

Acute Disease↗

Clinical and prognostic features of rectal sparing in ulcerative colitis.

Thirty patients with ulcerative colitis who had been followed clinically for more than 5 years were studied. Patients with total or left-sided colitis were investigated to evaluate the significance of rectal sparing in the prognosis of the disease. Patients were divided into two groups, one with complete or relative sparing of the rectum and the other with homogeneous lesions ranging from the rectum to the proximal colon based on endoscopic findings. The administration of topical corticosteroids seemed to have little effect on rectal sparing. However, the relapse index was significantly higher in patients with rectal sparing. The intractability index, representing the ratio of the duration of the active stage to the investigation period, was also higher, though not significantly so, in this group. The results suggest that rectal sparing may give information about intractability or a tendency to relapse.

Administration, Topical↗

[Immunocytochemical characterization of the DNA-polymerase alpha-positive colonic mucosal epithelial cells in patients with ulcerative colitis].

Colonic mucosal epithelial cells (EpC) in patients with ulcerative colitis (UC) have been shown to express HLA-DR antigen. In the present study, we observed the characteristics of HLA-DR-positive EpC using immunoperoxidase technique. In the control group, colonic EpC expressed HLA-ABC, but not HLA-DR. Only the EpC at the base of glands revealed positive for DNA-polymerase alpha (DNA-P). On the other hand, in actively inflamed mucosa of UC, about 80% of glands strongly expressed HLA-DR. Furthermore, most of EpC in the HLA-DR-positive glands showed positive nuclear stainings for DNA-P. This indicates that these EpC are not in the resting stage. It is strongly suggested that there are close relationships between the regeneration or proliferation of the EpC and class II MHC (HLA-DR) expression on the EpC in UC.

Adolescent↗

Functional diversity of polypeptides in primary culture supernatant of thymus epithelial cells.

Polypeptide fractions A-C (M.W., 7 kd, 4.7 kd, and 3 kd) were obtained from the primary culture supernatant of thymus epithelial cells from Wistar rats by high-pressure liquid chromatography with a gel-filtration column. Changes in the mitogen responses of rat thymocytes and their subpopulations with addition of a fraction were studied. One subpopulation was rich in non-rosette-forming cells (non-RFCs), and the other was cortisone resistant thymocytes (CRTs). These subpopulations were incubated with a fraction for 24 hrs. before mitogen stimulation. Fractions A and C increased the response of the non-RFCs to concanavalin A (Con A) and that of total thymocytes and CRTs to phytohemagglutinin (PHA). Fraction B inhibited Con A and PHA response of total thymocytes and CRTs. Fraction B was cytotoxic toward total thymocytes and CRTs when viability was evaluated by [3H]uridine prelabelling. This cytotoxicity was suppressed by treatment with trypsin. Subfractions B3 and B4 obtained by reversed-phase column chromatography were cytotoxic toward CRTs. The effects of the fractions on thymocyte maturation were different, showing their functional diversity.

Animals↗

Possible role of vascular endothelial cells in immune responses in colonic mucosa examined immunocytochemically in subjects with and without ulcerative colitis.

Phenotypic characteristics of vascular endothelial cells of the colonic mucosa in patients with ulcerative colitis and healthy controls were studied with immunoperoxidase staining by light and electron microscopy. The cells could be classified into two groups according to their phenotypes; one was positive for von Willebrand factor and the other had an antigen detected by a monoclonal antibody, OKM5. The endothelial cells positive for von Willebrand factor were usually in relatively large blood vessels, and OKM5-positive cells were mostly located in small capillaries along the glandular epithelium. OKM5-positive endothelial cells also expressed HLA-DR and interleukin-1 (IL-1). In patients with ulcerative colitis, OKM5-positive endothelial cells and spindle-shaped cells that might be precursors of endothelial cells were more numerous in the lamina propria than in the other subjects. Thus, OKM5-positive endothelial cells may be important as antigen-presenting cells and immunoregulatory cells in the intramucosal immune system. Furthermore, colonic epithelial cells in patients with ulcerative colitis synthesized HLA-DR and IL-1, and may have a close relation to immune responses, such as antigen processing and presentation to immunocompetent cells. It was suggested that these cells have a close relation to the pathogenesis of the impaired immune responses in situ in ulcerative colitis.

Colitis, Ulcerative↗

Immunoglobulin-containing cells in the colonic mucosa of rabbits with carrageenan-induced colitis.

Immunohistochemical analysis of immunocompetent cells in the colonic mucosa was performed with carrageenan-induced experimental colitis in rabbits. Colitis was induced by seven months of oral administration of lambda-degraded carrageenan following immunization with the same substances containing Freund's complete adjuvant. In the colonic mucosa with colitis, IgG- and IgM-containing cells were significantly increased in number (IgG: 540 +/- 94/mm2 in experimental group, vs. 120 +/- 54/mm2 in control, P less than .05, IgM: 55.0 +/- 19.7/mm2 in experimental group, vs. 6.7 +/- 2.4/mm2 in control, P less than .05). There was no significant increase of IgA-containing cells either in number or in proportion to the total mononuclear cells. These changes, induced by carrageenan in rabbits, had resembled those in human ulcerative colitis well. These observations suggested an impairment of the IgA-regulated local immune system and an abnormality in the differentiation process of immunoglobulin-secreting cells.

Animals↗

Dissociation between the functional activity and immunoreactive concentration of C1 esterase inhibitor in active and quiescent Crohn's disease.

The plasma immunoreactive concentration and the functional activity of C1 esterase inhibitor (C1INH) were measured in 17 samples from 15 patients with Crohn's disease (CD) and 10 samples from healthy volunteers. C1INH activity was measured by the chromogen substrate method and the immunoreactive concentration by the single radial immunodiffusion method. The functional activity was 95.7 +/- 4.6% in the controls. In CD it was 60.8 +/- 7.5% in the active stage (CDAI greater than 100) and 113.4 +/- 4.9% in the quiescent stage (CDAI less than or equal to 100). There were significant differences between the controls and both the active and quiescent stages (p less than 0.05). The activity was significantly lower in the active than in the quiescent stages (p less than 0.01). However, the difference in the immunoreactive concentration of C1INH in the active and quiescent stages was not significant; it was 27.8 +/- 3.5 mg/dl in the active stage and 33.7 +/- 2.0 mg/dl in the quiescent stage. This difference in the pattern of change between the immunoreactive concentration and the functional activity of C1INH might arise from the mode of C1INH action, with stoichiometric binding to substrates, giving rise to irreversible complexes. These results showed the functional consumption of C1INH in active CD, which may be an aggravating factor in the pathogenesis of the inflammatory process in the patient.

Adult↗