[Clinical features and management of 7 cases of toxic megacolon].
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Biomedical subjects
Publications and source records attributed to H Asakura.
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The fluorescence activated cell sorter (FACS) was used for detecting circulating antibodies to the surface antigens on isolated colon epithelial cells (anti-colon antibodies) by indirect immunofluorescence. Anti-colon antibodies were found in the serum of 30 of 41 (73%) patients with ulcerative colitis. This incidence is much higher than one established in earlier reports by application of indirect immunofluorescence to colon tissue using the fluorescence microscope. The results suggest that FACS analysis is very useful for detecting antibodies to colon specific antigen.
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A total of 191 gastric adenomas in 178 patients was studied macroscopically by endoscopy and histopathologically by endoscopic biopsy. Among the lesions, 85 in 74 patients were followed-up for six months to 12 years. Gastric adenomas were found to be more frequent in the aged, with a rate of 0.1% in the third decade but 3.7% in the ninth decade, on gastroscopic examination. Gastric cancers coexistent with the gastric adenomas were seen in 14 cases (8%), and were more frequent in male than in female patients (sex ratio, 12:2). Only eight of the 85 lesions (9%) revealed macroscopic changes. Four of these showed a reduction in size, while the other four lesions showed enlargement. In 21 of the 85 lesions (25%), histologic changes were observed. Four (5%) changed from moderate dysplasia (Group III) to nondysplastic or intestinal metaplasia (Group I), eight lesions (9%) revealed histologic changes (Group III to IV, or vice versa) without malignant transformation, and nine lesions (11%) showed malignant changes. Neither submucosal invasion nor lymph node metastasis was found. These lesions consisted of carcinoma in situ with small foci in the lesions exhibiting moderate dysplasia, and a gradual transition from severe dysplasia to cancer was seen in resected lesions obtained by endoscopic polypectomy or surgical resection. In addition, a gradual increase in dysplasia of tissue from moderate to severe was revealed by repeated gastroscopic biopsy. These findings suggest that the gastric adenomas underwent malignant changes with gradual transformation from moderate through severe dysplasia.
Intestinal fat absorption was examined in rats with CCl4-induced liver cirrhosis. Marked lymphangiectasia of the small intestine was observed in rats after CCl4 was given subcutaneously biweekly for 10--12 weeks. Intestinal epithelial uptake of linoleic acid administered in the loop was not impaired, but accumulation of lipid droplets in the intestinal epithelial cells and disturbed lymphatic transport of absorbed fat were observed in these rats. These data suggest that lymphostasis of the intestine may play an important role in fat malabsorption in liver cirrhosis.
Ultrastructural and immunohistochemical studies of the small intestine are described in a Japanese patient with alpha heavy chain disease who had a history of colonic ulcers. Endoscopic examinations revealed multiple gastric erosion, duodenal ulcer, and a thickened, cobblestone-like pattern composed of small nodules in the duodenum and jejunum, which was similar in appearance to Crohn's disease. An electron microscopic study showed that the numerous, infiltrated cells in the jejunal lamina propria were matured plasma cells with atypical structure of the organelles. These plasma cells had alpha heavy chain protein devoid of light chain. Although secretory component was demonstrated normally in the epithelial cells by immunofluorescent methods, no association of this component with alpha heavy chain protein could be observed in any of the plasma and epithelial cells of this case. These facts suggest the absence of secretory alpha chain or secretory IgA, and a deficiency of the mucosal secretory immune system in this patient.
It is conceivable that brush border enzyme activities of the intestinal mucosa will change when bacterial toxins are exposed to the intestinal microvillous membranes. The effect of cholera toxin on the activity of intestinal alkaline phosphatase in rats was therefore determined in the intestinal mucosa by the histochemical method as well as in intestinal lymph by using lymph fistulated-rats. Activity of intestinal alkaline phosphatase in the intestinal mucosa and lymphatics changed biphasically after the oral administration of cholera toxin to rats. For the first three hours after the administration of cholera toxin it was depressed; it then increased and at eight hours reached a maximum. These changes in the activity of intestinal alkaline phosphatase were prevented by the administration of chlorpromazine, a known inhibitor of adenylate cyclase activity.
The purpose of this study is to examine whether intestinal alkaline phosphatase (IAP) plays a role in transporting lipoproteins to lymphatics during fat absorption. In control rats, the increased activity of IAP in intestinal lymph was observed parallel with the amount of absorbed linoleic acid. In colchicine-treated rats, lymphatic absorption of intraduodenally administered linoleic acid was decreased and administered lipid was transported slowly to lymphatics, mostly in the form of free fatty acid. However, the equal or slightly larger amount of output of IAP to lymphatics was observed in spite of the decrease in lipid absorption in colchicine-treated rats. Histochemically, prolonged activity of IAP in stroma and submucosal lymphatics was found in colchicine-treated rats fed with fat. These results suggest that microtubules are not involved in IAP transport into lymphatics, and these data do not necessarily rule out that IAP plays a role in lipoprotein transport.
This study was performed to clarify how disturbance of lipid metabolism occurred in patients with protein-losing enteropathy (PLE) as compared with that of control individuals and patients with malabsorption syndrome. Analysis of plasma lipids at fasting state showed a decreased proportion of essential fatty acid, especially linoleic and arachidonic acid fractions in patients with malabsorption syndrome as well as in patients with PLE group A, which was due to proven disorders of intestinal lymphatics. An increase in percentage of oleic acid fraction and a percentage increase in plasma triglyceride levels after an oral administration of olive oil was depressed in patients with malabsorption syndrome and PLE group A when compared with that of normal subjects. Patients with PLE group B, which was not due to major lymphatic disorders, were similar to normal in these parameters. These abnormalities were found to be marked when remarkable abnormalities of lymphatics were accompanied.
The frequency deviation of human lymphocyte-DR antigens as well as human lymphocyte A, B, and C antigens was assessed in 40 Japanese patients with ulcerative colitis and compared with 51 ethnically matched healthy Japanese. The antigen that was of significantly higher frequency in patients with ulcerative colitis was HLA-DR2. This antigen was found in 70% of the patients vs. 31% of controls [chi 2 = 13.4, p less than 0.001, corrected p less than 0.01, relative risk = 5.1). In addition, an increased frequency of HLA-B5-DR2, which is the most common haplotype in Japanese populations, was found in 55% of the patients with ulcerative colitis compared with 22% of the controls (chi 2 = 10.84, p less than 0.001).
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The presence of anti-colon antibody in the sera from patients with ulcerative colitis was demonstrated by antibody-dependent cell-mediated cytotoxicity (ADCC) assay. In addition, the high prevalence of lymphocytophilic antibody in the sera from patients with ulcerative colitis was obtained by fluorescence activated cell sorter (FACS) analysis. This lymphocytophilic antibody was absorbed by rat colon epithelial cells. Moreover the lymphocytes from ulcerative colitis showed lower binding capacity to this antibody, but acquired higher binding capacity after 20 hr incubation at 37 degrees C in vitro. These data suggest that ADCC may have some role in the pathogenesis of ulcerative colitis.
Jejunal endoscopy and histopathological study of biopsied specimens were performed to clarify states of jejunal mucosa and the mechanism of enteric protein loss in six patients with protein-losing enteropathy, including four patients with intestinal lymphangiectasia, one patient with constrictive pericarditis associated with dilated lymphatics of the intestine, and one patient with Budd-Chiari syndrome. Three cardinal endoscopic findings, scattered white spots, white villi, and chyle-like substances covering the mucosa, were demonstrated in protein-losing enteropathy. Scattered white spots indicated markedly dilated lymphatics in the stroma of the villi. White villi seemed to be due to fats including chylomicrons or fat droplets in the absorptive cells, interepithelial spaces, and/or stroma, even though the biopsies were obtained in the fasting state. Therefore, white villi suggest impaired transport of fats from intestinal epithelial cells to intestinal lymphatics. These three cardinal findings are thought to be characteristic for protein-losing enteropathy secondary to lymphatic disorders.
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Histopathologic and lymphographic studies were performed in 4 patients with protein-losing gastropathy to elucidate the degree of lymphatic disorders and their contribution to clinical features. Histologic examination of gastric mucosa showed various degrees of hyperplasia of the surface epithelium and cystic dilatation of glands, which were considered to be characteristic findings of protein losing gastropathy. Moreover, in 3 of 4 patients there were edematous change of the lamina propria or the submucosa, and marked lymphangiectasia was seen in the submucosa of 3 patients and in the lamina propria of the other. Performed lymphograms showed an increase in the number of lymphatic vessels and lymph nodes in the iliopelvic and lumbar regions of 2 of the patients. This high incidence of lymphatic abnormalities in patients with protein-losing gastropathy suggested that such systemic lymphatic disorders were an important etiologic factor. However, such abnormalities in lymphatic system were not demonstrated in all cases of protein-losing gastropathy. Therefore, lymphatic disorders were not considered to be the primary cause of gastric protein loss, but the important factor that modifies the variety of lost protein and its clinical features.
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