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BACKGROUND: In adults, epithelial cell proliferation and apoptosis of the gastric mucosa are induced by Helicobacter pylori infection and are associated with gastric atrophy or gastric carcinoma. In children, there are few studies about such epithelial changes. To elucidate the role of H. pylori infection in gastric mucosal inflammation, we immunohistochemically examined gastric mucosa of Japanese children. METHODS: Biopsy specimens obtained from the gastric antrum and corpus of H. pylori-infected (n = 13) and noninfected children (n = 15) were studied for immunolocalization of Ki-67, single-strand DNA, manganese superoxide dismutase (Mn-SOD), and CD68, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In 10 patients with successful eradication, pre- and posttreatment results were compared. RESULTS: In both gastric antrum and corpus, neutrophil and mononuclear cell infiltration, epithelial cell proliferation, and apoptosis significantly increased in H. pylori-infected patients, predominantly in the antrum. In the antrum of H. pylori-infected patients, there was positive correlation between the degrees of neutrophil infiltration and cell proliferation (P < 0.05) or apoptosis (P < 0.05). H. pylori eradication improved mucosal inflammation, cell proliferation (P < 0.001), and apoptosis (P < 0.01) in the antrum. Mn-SOD immunoreactivity and CD68-positive macrophages in the antrum, which significantly increased in H. pylori-infected patients, decreased after the eradication. CONCLUSIONS: H. pylori infection induced gastric mucosal inflammation and epithelial cell turnover in children. Moreover, gastric mucosal defense mechanism against H. pylori infection was activated. H. pylori eradication in childhood might prevent the accumulation of gastric epithelial cell damage. [ABSTRACT FROM AUTHOR]

Background: Although there is great deal of evidence suggesting that vasoactive intestinal peptide (VIP) has immunomodulating effects on human colonic lamina propria mononuclear cells (LPMC), it remains unclear which type of cell carries functional VIP receptors. In this study we investigated the presence of functional VIP receptors by measuring intracellular cyclic adenosine monophosphate (cAMP) in isolated epithelial cells, bulk LPMC, T cells, and macrophages in human colonic mucosa. Methods: Epithelial cells and LPMC were isolated from non-pathologic segment of colonic mucosa of surgical specimens from five patients with colonic cancer. Mucosal T cells and macrophages were further isolated from LPMC. Each cell population was cultured with various concentration of VIP for 60 min at most. Then, intracellular cAMP was extracted and measured by enzyme-linked immunoassay. Results: When isolated epithelial cells were examined, VIP increased intracellular cAMP in a dose-dependent fashion, as observed in HT-29 cells used as a positive control. In contrast, the concentration of cAMP was essentially stable in response to VIP when isolated LPMC were examined. This was the case even when separated T cells and macrophages were individually investigated. To evaluate the possible effects of enzyme digestion for LPMC isolation on the VIP response, HT-29 cells were precultured with collagenase and deoxyribonuclease (DNase I), resulting in less enhancement of cAMP by VIP. Conclusions: In this study we failed to show VIP-responsive enhancement of cAMP in mucosal immune cells, suggesting that epithelial cells may be major effecter cells of VIP in human colonic mucosa. [ABSTRACT FROM AUTHOR]

Type IIbeta-hydroxysteroid dehydrogenase endows specificity on the mineralocorticoid receptor by metabolizing cortisol and regulates sodium absorption in renal and colonic epithelium. Altered expression of this enzyme may be associated with impaired sodium absorption often seen in colonic mucosa of inflammatory bowel disease. The aim of this study was to investigate possible abnormality of 11beta-hydroxysteroid dehydrogenase protein and mRNA expression in inflammatory bowel disease. In Crohn's disease, the colonic epithelium showed comparable levels of immunoreactivity and mRNA expression to those of control, except for the decreased immunoreactivity in severe inflamed lesions with deep ulcer. In contrary, a lack or decrease of immunoreactivity was relevant in ulcerative colitis regardless of the histological degree of inflammation. The mRNA expression was also significantly decreased in ulcerative colitis. This study demonstrates that abnormality of epithelial cells in ulcerative colitis includes the enzyme that regulates water and sodium absorption, which are physiologically essential. [ABSTRACT FROM AUTHOR]

IgA synthesized in hepatobiliary tissues accounts for about one-half of the IgA present in human hepatic bile, but the location of the IgA synthesizing cells has been in doubt because few plasma cells are present in normal liver. Therefore, we immunocytochemically localized IgA. J chain and secretory component in bile duel tissues of six patients operated upon for biliary duct obstruction. Numerous plasma cells containing IgA and J chain were found surrounding the accessory glands of the major bile ducts and in the area just beneath the surface epithelium of the ducts. At the ultrastructural level, IgA and SC in the epithelial cells had the features characteristic of secretory component-mediated endocytic translocation of IgA. We conclude that plasma cells in biliary duct mucosa are the likely source of much of the locally synthesized IgA that is secreted into human hepatic bile. The IgA probably reaches the bile by direct transfer across biliary epithelium. [ABSTRACT FROM AUTHOR]

Localization of IgA, secretory component (SC) and J chain was investigated immunocytochemically in minor salivary glands of the lip and palate to define the mechanism involved in the transport of immunoglobulin A (sigA) into the saliva from the minor salivary glands. SC synthesis was detected in mucous acinar cells and ductal epithelial cells. Free SC is secreted into the saliva through secretory granules in the mucous acinar cells. Dimeric IgA containing J chain is translocated through these cells as sIgA by a SC-mediated transport mechanism involving cytoplasmic vesicles. [ABSTRACT FROM AUTHOR]

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-I (IL-1). In patients with ulcerative colitis. OKM5-posltive 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. [ABSTRACT FROM AUTHOR]

Rat liver arginase was isolated from extracts of liver in a pure form. Monospecitic antisera raised against the arginase reacted with arginase of liver but not with arginase of kidney, spleen, heart, lung, testis and brain. The antisera were, however, reactive with liver arginase of a variety of animals. including human, mouse. sheep. horse and cow as well as rabbit, a homologous animal used for immunization. The rabbit autoantibodies showed direct cytotoxic activity as well as antibody-dependent cell-mediated cytotoxicity to homologous rabbit hepatocytes. Immunocytochemical electron microscopic examination showed that the arginase was localized on the surfaces of rat hepatocytes and on intracellular organelles. These results suggest that liver arginase could be an important antigen of the liver with implications for the pathogenesis of autoimmune liver diseases. [ABSTRACT FROM AUTHOR]

Because human bile contains a lot of secretory IgA, it has been suspected that the human liver, like rat liver, transfers polymeric IgA from plasma to bile. Hence, a rich source of polymeric IgA might enter the general circulation of man. We examined human thoracic duct lymph, portal vein blood and aortic blood for content and molecular size of IgA. None of the fluids was found to have either a higher total concentration of IgA or a higher proportion of polymeric IgA than that found in peripheral venous blood. It is possible that hepatic clearance of plasma IgA does not occur in man to the extent that it does in the rat, and a relatively larger proportion of human biliary IgA might originate from synthesis in hepatobiliary tissues. [ABSTRACT FROM AUTHOR]

The ultrastructural sites of secretory component (SC) in the intestinal epithelium of severely immunoglobulin-deficient and immunologically intact persons were compared. SC was found in the same sites in the immunoglohulin-deficient and normal epithelium: perinuclear spaces, rough endoplasmic reticulum. Golgi complexes, external surfaces and endocytic invaginations of the basolateral plasmalemma, and in membranous, vesicles throughout the cytoplasm. These observations suggest that the synthesis, external expression and transcellular migration of SC occur in dependent of the presence of immunoglobulins. The migration of SC from the basolateral cell surfaces to apical surfaces may be an inherent property of epithelial cells and the primary event in the translocation of polymeric immunoglobulins across the cells to external body fluids. [ABSTRACT FROM AUTHOR]

In order to characterize immunohistochemically the possible in-situ effects of gonadal steroid hormones in the human ovary during the menstrual cycle, we immunolocalized progesterone (PR), androgen (AR) and oestrogen (ER) receptors in 50 normal cycling human ovaries, and examined the relationship between these findings and the cellular localization of steroidogenic enzymes including cytochrome P-450 cholesterol side-chain cleavage (P-450scc) enzyme, 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), cytochrome P-450 17 alpha-hydroxylase (P-450c17) and cytochrome P-450 aromatase (P-450arom). A large number of stromal cells were positive for AR, regardless of the distance from a follicle. No steroidogenic enzymes were observed in the stromal cells. In the pre-antral follicle, AR was observed in the theca cells. P-450scc, 3 beta HSD and P-450c17 were sporadically expressed in the theca cells in relatively large-sized pre-antral follicles. ER was positive in the granulosa cells only in the P-450arom-positive antral or pre-ovulatory follicle, which is likely to be a selected follicle. In the corpus luteum, in the period from ovulation to the mid-secretory phase, PR immunoreactivity was observed in a large number of both the luteinized granulosa and the theca cells. All steroidogenic enzymes were observed in all corpora lutea, but ER was negative in any corpus luteum. In the atretic follicle, AR was present in the theca interna cells. P-450scc, 3 beta HSD and P-450c17 were observed in the theca interna cells in some atretic follicles.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

The localization and distribution of gamma delta T cell receptor (TCR)-positive cells (gamma delta T cells) in hepatocellular carcinoma capsules was investigated immunohistochemically at both light and electron microscopic levels. Most of the mononuclear cells infiltrating the tumor capsules were CD3-positive. Together with gamma delta T cells, they were significantly increased in the tumor capsules compared to amounts in the fibrous septa in non-cancerous cirrhotic areas of the same liver, and compared to amounts in the liver of patients with cirrhosis. Phenotypic characterization by the two-color double-staining technique showed that CD8/gamma delta cells were significantly increased in the tumor capsule, and that more than one-third of gamma delta TCR-positive cells also expressed the CD56 antigen. Morphological observation revealed that large gamma delta T cells were increased in number in the tumor capsule and that the cytoplasm of these cells contained multivesicular bodies and dense granules. These morphological features were similar to those of large granular lymphocytes, and most of the gamma delta T cells were also positive for BB3. This suggests that extrathymic maturation of gamma delta T cells occurs in the tumor capsule, and that these gamma delta T cells may have a cytolytic effect on tumor cells, as shown in large granular lymphocytes; further, the results suggest that these cells may play a role in the defense against tumor expansion. [ABSTRACT FROM AUTHOR]