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.

[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.

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.

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.

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.

The leading cord method of colonofiberscopy.

Although the colonofiberscope has undergone various modifications and improvements, the insertion principle remains unchanged; that is, pushing and rotation and the elasticity of the scope itself are inevitable. It often is difficult to maintain proper balance among these dynamic factors; imbalance prevents deep insertion. Over-elongation of the scope leads to insertion failure, particularly if there are adhesions of the sigmoid colon, overextension of the colon, or transverse colon ptosis. Our "leading cord" method is an excellent aid to colonofiberscopy. It can be inserted from the clamp hole of a conventional fiberscope and hardened to straighten the scope, thereby permitting deep insertion. With this technique the region from the rectum to the descending colon, as well as a ptosed transverse colon, can be straightened. Our clinical experience indicates that the rate of successful insertions in colonofiberscopy will be increased considerably with this complementary device.

Epithelial dysplasia of the rabbit colon induced by degraded carrageenan.

Colonic mucosal lesions, characterized by crypt abscesses and mononuclear cell infiltration, which resemble human ulcerative colitis can be induced in rabbits by short-term (7 to 8 weeks) administration of carrageenan according to our method. In this study experimental epithelial dysplasia of the colon was induced by the p.o. administration of lambda-degraded carrageenan for a much longer period of time. Fifteen rabbits, sensitized i.m. with the same substance 1 week before, were subjected to 12 or 28 months of treatment with 1% carrageenan solution in drinking water. Histological examination disclosed chiefly mild inflammatory changes of the colonic mucosa in all animals and a focal but high-grade dysplasia (nonpolypoid) involving the mucosal epithelium in three of the five animals treated for 28 months. The present observations suggested that epithelial dysplasia of the colon may be caused in association with inflammation and that the pathological condition produced by us can be a useful model of carcinoma in situ possibly resulting from inflammation.