[Immunologic deficiency diseases and immunoglobulin--selective immunoglobulin A deficiency].
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Biomedical subjects
Publications and source records attributed to T Hibi.
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The HLA antigens in 44 cases of ulcerative colitis and 271 control individuals in Japan were studied. The NIH tissue typing method was used according to the new leukocyte nomenclature adapted by the WHO Committee. In normal Japanese populations, the HLA antigens, which were of high frequency, were HLA A2(37.3%), A9(60.9%) and B5 (40.6%). On the contrary, the significantly high frequency of HLA B5 was demonstrated in ulcerative colitis, compared with that in control. Moreover, HLA B5 in cases with ulcerative colitis excluding those with proctitis only, was found with higher frequency than that in total cases. Although the most frequent haplotype was HLA A9-B5 in control, so frequent haplotype was not found in ulcerative colitis. A family study revealed no significant diathesis on the hapolytpe of HLA in ulcerative colitis. The relationship between MLC locus and ulcerative colitis was not yet clarified from the study of one family whose two members suffered from ulcerative colitis.
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Lymphangiectasia of the small intestine was demonstrated in 9 to 18 cases with protein losing gastroenteropathy and in 10 of 26 cases with Behçhet's disease. Protein losing gastroenteropathy was compared to Behçet's disease in view of immunological aspects. Immunoglobulin containing cells in the jejunal mucosa of protein losing gastroenteropathy were decreased, whereas Behçet's disease had normal or increased distribution. This suggested that suggested that immunoglobulin may be lost into the intestinal lumen or that production of those cells may be inhibited in protein losing gastroenteropathy. Decreased DNCB skin reaction and impaired blastoid transformation of peripheral lymphocytes in both of two diseases suggested that there should be immunological defect in those diseases. However, in Behçet's disease, investigation of the thymus disclosed hyperplasia and the presence of lymphoid follicle which does not appear in normal state. In conclusion, protein losing gastroenteropathy is in immunological deficiency state due to the congenital or acquired disorders of lymphatics which implies abnormal protein loss, decreased immunoglobulin containing cells in the jejunal mucosa and decreased sensitivity. On the contrary, in Behçet's disease hyperimmune state is present based on thymic hyperplasia.
Bipedal lymphography was performed in 5 cases of Behçet's disease. In 4 of 5 cases, histologic examination of intestinal biopsy specimens showed lymphatic dilatation of the small intestine which were considered to be a characteristic finding of intestinal lymphangiectasia, a protein-losing enteropathy, but no patient with Behçet's disease showed reduced concentration of serum total protein as well as abnormal value of 131I-PVP test. Lymphograms showed an increase in number of iliopelvic and lumbar lymphatic vessels as a major finding, but they failed to demonstrate a hypoplasia or aplasia of lymphatic system or obstruction of thoracic duct. It is conceivable that the lymphatic dilatation of the small intestine in Behçet's disease may be related to increased flow of lymph due to excessive vascular hyperpermeability and may not be related to a block of lymphatic system which has been considered to be a cause of enteric protein loss in intestinal lymphangiectasia. The authors wish to emphasize that the dilatation of lymphatic vessel of the small intestine is not a sufficient finding to indicate the presence of protein-losing enteropathy.
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A quantitative test of optokinetic nystagmus was proposed. Horizontal nystagmus was examined by a large rotating cylinder with vertical stripes. Nystagmus responding to the cylinder rotation with an acceleration of 2 degrees/sec2 for 90 seconds was recorded with an electronystagmograph. On the records, the number of beats, average eye-speed, and average amplitude per each 10 seconds were calculated. This method was suitable for testing the nature of optokinetic nystagmus which indicates the ability of the eyes to adapt to objects moving through the visual field. Moreover, in order to save trouble in hand-scoring of each parameter of nystagmus, computer processing of electronystagmographic data was introduced. The results were printed numerically on the teletypewriter, and displayed graphically on a cathode ray tube and X-Y recorder. By displaying measured values on the form already printed with the normal ranges, the evaluation of the results was performed readily and objectively.
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Six nonradioactive cDNA probes were compared for their sensitivities for detecting potato spindle tuber viroid (PSTVd) by dot-blot hybridization assay. Three biotinylated PSTVd cDNA probes, labeled by photoactivation with photobiotin, by nick translation or by random priming with biotinylated deoxyribonucleotides, were all capable of detecting 20 pg of purified PSTVd by a colorimetric assay and 2-20 pg by a chemiluminescent assay. Digoxigenin-labeled probe was able to detect 200 pg of purified PSTVd. Two biotinylated probes prepared with polymerase chain reaction (PCR) incorporating biotinylated dUTP or dATP were the most sensitive: 0.2-2 pg of PSTVd was detectable by both assays. All six probes could detect PSTVd also in extracts of infected tomato leaves at a dilution of up to 1/250-1/1250. These nonradioactive probes are equal to radioactive probes in their sensitivity, and the biotinylated probes produced with PCR amplification are particularly suitable for practical diagnosis, as they are sensitive and rapidly prepared in large quantities.
The effect of deprivation of Peyer's patches (PP) on transport of lymphocytes through intestinal lymph and intestinal mucosal immune responses was investigated in rats. All visible PP in the rat small intestine were excised in order to examine the roles of PP in the intestinal lymphatic system and mucosal immune responses of the intestine. Two weeks after the experimental excision of PP, lymphocyte transport in intestinal lymph was significantly decreased in PP-excised rats without significant changes in lymphocyte subsets as compared with sham operated control rats. Lymphocyte subsets as determined morphometrically in the intestinal mucosa showed no significant alteration in PP-excised rats. There was a significant decrease in the number of immunoglobulin A (IgA) containing cells in the intestinal mucosa of PP-excised rats, while IgM and IgG containing cells showed no statistically significant changes in number. Conversely, the macrophages in the intestinal mucosa increased in number, suggesting the enhanced accessory functions of these macrophages. Antigen-specific immune response was further studied in PP-excised rats using intraduodenal priming and challenge with cholera toxin (CT). Both the determinations of cells producing antigen-specific antibody in the intestinal mucosa using anti-CT antibody and those of cells secreting anti-CT Ig in the intestinal lymph by enzyme-linked immunospot (ELISPOT) assay showed a significant reduction of CT-specific antibody production in PP-excised rats compared with controls. Peyer's patches appear to have an important role in lymphocyte transportation through intestinal lymph and also in mucosal immune responses.
The study was designed to examine the changes of thymus in sulfhydryl blocker-induced colitis. We used N-ethylmaleimide (NEM) as sulfhydryl blockers. Fasted male Sprague-Dawley rats were given 3% NEM in 1% methyl cellulose into the colon. N-ethylmaleimide treatment caused severe diarrhoea with bleeding for the first 7 days. At autopsy, adhesions, colon dilatation, and single or multiple erosions and ulcers were observed. Time-course studies revealed that the lesions were most extensive and severe 3 or 7 days after the administration of NEM. Histological examination of colon on the 3rd day after NEM treatment demonstrated mucosal erosion, oedema and extensive infiltration of neutrophils. The mucosal lesions extended into the submucosa and muscle on the 7th day after NEM treatment. Immunohistochemical studies showed that T cells and macrophages were markedly increased in the lamina propria of colonic mucosa. After 3 weeks, the infiltration of chronic inflammatory cells was observed and regeneration of the mucosa was noticed. The thymus gland was significantly decreased in weight and size on the 3rd day after NEM treatment, but the weight loss of thymus gland was regained in 3 weeks. Transient atrophy of thymus gland was noticed in this colitis model. The phenotypes of thymocytes were not influenced by NEM treatment. It is concluded that the thymus abnormalities in human ulcerative colitis are not induced in this animal model and that other chronic models are necessary for the elucidation of the immunological abnormalities, including thymus abnormalities.