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Morphology and functional cytology of the small intestinal mucosa in malabsorptive disorders and other diseases.

Small intestinal biopsies from 98 patients have been studied macroscopically, histologically, and histochemically, and the results correlated with laboratory and clinical observations. Neither a convoluted nor a flat mucosa can be considered diagnostic for any specific disease. A flat mucosa was found in one adult with intestinal Hodgkin's disease and in another following total gastrectomy. Histochemically all specimens from subjects with coeliac disease and idiopathic steatorrhoea showed a deficiency of succinic dehydrogenase in the epithelial cells, and the histochemical test for this enzyme, although not specific, may be a useful aid to diagnosis, since the degree of deficiency in these diseases was usually grosser than that in any other conditions. Other but variable enzyme deficiencies that may be present in these two diseases showed no correlation with the reduction of succinic dehydrogenase activity, nor was there any correlation between reduced enzyme activities and the severity or otherwise of the clinical features.A number of specimens from patients with conditions other than coeliac disease and idiopathic steatorrhoea that had a normal macroscopic appearance showed some reduction of intracellular enzyme activities histochemically. This was not so in the control group, and if these deficiencies can be confirmed biochemically, then histochemical tests may give an earlier indication of disordered function than macroscopical or routine histological examination. At present neither the macroscopic appearance nor any single histological or histochemical test on the biopsy specimen is diagnostic for a particular disease. These findings must be considered with the clinical details and results of other investigations in establishing a diagnosis.

Biopsy↗

Transforming growth factor alpha expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric carcinoma--an immunohistochemical study.

Using a monoclonal antibody (GF10) and a standard immunohistochemical technique, immuno-expression of transforming growth factor alpha (TGF-alpha) was found consistently within the differentiated compartment of normal adult human gastric mucosa. In 70% of mucosal samples exhibiting intestinal metaplasia there was more or less uniform TGF-alpha immunoreactivity throughout the intestinalized mucosa. Similarly, 60% of cases of dysplasia and 60% of gastric carcinomas showed strong immunoreactivity in most of the cells. However, whereas 93% of intestinal-type cancers showed strong immunoreactivity only 30% of the diffuse type were stained and then only weakly. Transforming growth factor alpha expression is thus a fairly regular feature of several types of differentiated gastric epithelia (normal, metaplastic, dysplastic and intestinal-type carcinoma), while its relative absence may be a factor in the histogenesis of the diffuse type of gastric carcinoma.

Gastric Mucosa↗

ATPase and alkaline phosphatase activities of chick and rat small intestinal mucosa.

The alkaline phosphatase and (Ca2+ +Mg2+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) of chick and rat small intestine have been investigated. The same pH optimum was found for membrane-bound and solubilized alkaline phosphatase, whereas those of the corresponding ATPases differed. The solubilised ATPases had inhibition and activation characteristics similar to those of alkaline phosphatase but markedly different from those of the membrane-bound ATPase. These results suggest that membrane-bound alkaline phosphatase and ATPase are not the same enzyme.

Adenosine Triphosphatases↗

Structural and immunochemical identification of Le(a), Le(b), H type 1, and related glycolipids in small intestinal mucosa of a group O Le(a-b-) nonsecretor.

Total nonacid glycosphingolipids were isolated from small intestine mucosal scrapings of a red cell blood group O Le(a-b-) nonsecretor cadaver. Glycolipids were extracted and fractionated into five fractions based on chromatographic and immunostaining properties. These glycolipid fractions were then analysed by thin-layer chromatography for Lewis activity with antibodies reactive to the type 1 precursor (Le(c)), H type 1 (Le(d)), Le(a) and Le(b) epitopes. Fractions were structurally characterized by mass spectrometry (EI-MS and EI-MS/MS-TOF) and proton NMR spectroscopy. EI-MS/MS-TOF allowed for the identification of trace substances in fractions containing several other glycolipid species. Consistent with the red cell phenotype, large amounts of lactotetraosylceramide (Le(c)-4) were detected. Inconsistent with the red cell phenotype, small quantities of Le(a)-5, H-5-1 and Le(b)-6 glycolipids were immunochemically and structurally identified in the small intestine of this individual. By EI-MS/MS-TOF several large glycolipids with 9 and 10 sugar residues were also identified. The extensive carbohydrate chain elongation seen in this individual with a Lewis negative nonsecretor phenotype supports the concept that Lewis and Secretor blood group fucosylation may be a mechanism to control type 1 glycoconjugate chain extension.

ABO Blood-Group System↗

Mitochondrial hexokinase from small-intestinal mucosa and brain.

1. The submitochondrial localization of hexokinase activity in preparations of mitochondria from the small intestine of the guinea pig was studied by conventional methods. 2. Hexokinase activity in this tissue was predominantly associated with the outer mitochondrial membrane. 3. The inactivation of mitochondrial enzymes by trypsin in iso-osmotic and hypo-osmotic conditions was also used to determine the submitochondrial localization of hexokinase activity. 4. Hexokinase activity was found to be on the outside of the outer mitochondrial membrane. 5. It was shown that both type I and type II hexokinase activities are bound to the outside of the outer mitochondrial membrane. The types are present in the same ratio as that in which they occur in the cytosol of the cell. 6. Mitochondrial hexokinase from the small intestine did not show the latency phenomenon demonstrated by mitochondrial hexokinase from brain when subjected to a variety of treatments. However, hexokinase activity was solubilized from preparations of mitochondria from the small intestine by the same treatments as for mitochondrial hexokinase from brain. 7. The submitochondrial distribution of hexokinase activity in mitochondrial preparations from rat brain was determined by the trypsin inactivation method. 8. Hexokinase activity in preparations of mitochondria from rat brain was found on the outside of the outer membrane, between the mitochondrial membranes, and within the inner mitochondrial membrane. 9. Hexokinase from rat brain showed latency properties irrespective of its submitochondrial location.

Animals↗

Scanning electron microscopy of mouse intestinal mucosa after cobalt 60 and D-T neutron irradiation.

The stem-cell population of the intestinal crypt is an important model system in experimental radiobiology. Standardized techniques have been developed to allow quantitation of the response of crypt cells to radiation injury following doses of 0-2 krad of D-T neutrons or 60Co gamma rays. These techniques rely on the identification of regenerating crypt cells three-and-a-half days after irradiation. The results are expressed as the number of regenerating crypts per circumference of small intestine, as determined by conventional histological examination; the more profound the injury, the smaller the crypt count. The practical relevance of crypt-counting techniques to clinical radiotherapy is limited by their relative insensitivity; the dose levels commonly used in fractionated radiotherapy produce no detectable response. Scanning electron microscopy of the mucosal surface provides a more sensitive measure of radiation injury. The earliest detectable changes occur at the level of 300 rad of gamma radiation, well below the threshold of the crypt-counting technique. At around 1,000 rad, where the first drop in crypt counts occurs, there are well-marked morphological changes which become more severe with increasing dose levels. Some differences have been observed between the morphological effects of gamma and neutron irradiation at points of radiobiological equivalence in terms of crypt counts (using an RBE value of about 2). The changes observed may reflect more than the disruption of epithelial cell kinetics. Mucosal morphology is the total expression of many different biological parameters of which the regenerative ability of the crypt cells is only one. The surface microanatomy of the gut may be the most sensitive indicator of radiation injury which is conveniently available for study.

Animals↗

[The influence of chenodeoxycholic acid on the concentrations of nonsulfated bile acids in the small and large intestinal mucosa of rats (author's transl)].

In male Wistar rats nonsulfated bile acids of small and large intestinal wall and feces are analysed after 2, 5, 9 and 14 days of oral administration of 20 or 90 mg chenodeoxycholic acid (CDCA)/kg. Development of body, intestinal, and fecal weights is assessed. A transient reduction of daily body weight gain and small and large intestinal weights is compensated after 14 days. Fecal weights are above controls under 20 mg/kg, below controls under 90 mg/kg. Containing about 2 mg, i.e. nearly 4% of the bile acid pool, the intestinal wall holds four times more bile acids than the liver. Under CDCA administration bile acid concentrations in the small intestinal wall and feces rise, and remain almost unchanged in the colonic wall. Changes after CDCA administration suggest that bile acid absorption is accompanied by an increase in mucosal bile concentration. In the colonic wall the increase in bile acid concentration after CDCA administration correlates with the passive permeability coefficient.

Animals↗

Transferrin associated with the porcine intestinal mucosa is a receptor specific for K88ab fimbriae of Escherichia coli.

Putative receptors of Escherichia coli K88 fimbriae are either tightly membrane bound or an integral part of membranes. Thus, proteins associated with piglet small intestinal mucosae were solubilized by a detergent (deoxycholate). A 74-kDa glycoprotein (GP74) purified from enterocyte and brush border membrane preparations was specifically detected in vitro by K88ab fimbriae. GP74 was recognized only in the mucosae of phenotypically adhesive animals. Metaperiodate treatment abolished the recognition, indicating that K88ab fimbriae-GP74 binding required the carbohydrate moiety. This glycoprotein belongs to the transferrin family and differed from the serum transferrin of the same adhesive-phenotype piglets. Unlike intestinal transferrin, serum transferrin was recognized independently of the adhesion phenotype. The glycan moieties of intestinal and serum transferrins differed in their molar compositions. Transferrin GP74 contained one monosialylated and monofucosylated glycan chain of the N-acetyllactosamine type. Intestinal holotransferrin exhibited pI values of 5.2, 5.3, 5.5, and 5.6, whereas serum holotransferrin pI values ranged between 5.4 and 6.2. Since mucosal transferrin was found intimately entrapped on membranes, we hypothesize that a K88ab fimbriae-transferrin-cell transferrin receptor complex might allow the bacteria to adhere to specific sites of the mucosa.

Amino Acid Sequence↗

Enzymatic synthesis of purine 2'-deoxyriboside and its properties as an inhibitor of adenosine deaminases from calf intestinal mucosa and Bacillus cereus.

Enzymatic synthesis of purine 2'-deoxyriboside was obtained by reacting purine with excess 2-deoxy-alpha-D-ribose-1-phosphate in the presence of commercial bovine nucleoside phosphorylase; the product was isolated by semipreparative reverse phase HPLC with an overall 62% yield. Purine 2'-deoxyriboside was shown to behave as a competitive inhibitor of adenosine deaminase from calf intestinal mucosa and Bacillus cereus, with apparent Ki values of 4.5 and 8.5 microM, respectively.

Adenosine Deaminase Inhibitors↗

[Ultrastructural changes in the intestinal mucosa of children with chronic diarrhea].

Observations were made on biopsied small bowel mucosa by scanning and transmission electron microscopy in 21 infants and children, with chronic diarrhea, their age ranging from 3 months to 24 months, 85.7% of the patients showed various degrees of malnutrition. Ultrastructural changes in the small intestinal mucosa occurred in all of the cases analyzed. The major findings were: (1) villous atrophy; (2) damage to enterocytes, presenting increased extrusion of cytoplasm and enterocytes, with damage of the microvillar surface and degenerative changes of cytoplasm; (3) presence of microorganisms on the mucosal surface; and (4) excessive mucus on the mucosal surface. These results suggest that prolonged mucosal injury, extensive colonization of the mucosal surface by microorganisms, and malnutrition, may be the main causes of chronic diarrhea in children.

Biopsy↗

T-cell activation in human intestinal mucosa: the role of superantigens.

BACKGROUND: Superantigens are a class of potent T-cell mitogens that activate T cells using specific antigen receptor V regions. Superantigens have been implicated in the pathogenesis of several autoimmune diseases, including inflammatory bowel disease. The present study examines the role of superantigens in the human gastrointestinal immune response. METHODS: Human intestinal epithelial cells and T lymphocytes were obtained from surgical specimens and cultured in the presence or absence of exogenous superantigens. Activation of T cells and V region usage were measured by thymidine incorporation and by cell staining using a panel of monoclonal antibodies. RESULTS: Neither epithelial cells from normal nor diseased intestinal mucosa expressed virally encoded, endogenous superantigens. However, 50% of epithelial cell preparations could present exogenous bacterial superantigens to T cells. In the other 50%, a defect in this function was observed, which did not represent production of suppressive factors or absence of accessory cytokines. Mucosal T lymphocytes proliferated in response to superantigens in vitro, expressing increased transferrin receptor, interleukin-2 receptor, and HLA-DR. CONCLUSIONS: A superantigen-driven mucosal immune response may occur in health and in chronic inflammatory states. The intestinal epithelial cell may mediate this response, through presentation of superantigens to mucosal T lymphocytes.

Antigen-Presenting Cells↗

[Innervation of the small intestinal mucosa of laboratory animals. II. Ultrastructure of neuro-cellular connections].

In addition to our light microscopic contribution (Stach, Hung 1978) giving an insight into the density, architecture, histochemical variety and relations between plexus mucosus and Lieberkühn's glands the herewith presented electron microscopic results reveal mainly neuro-cellular relations from the lamina propria. This means that the plexus mucosus has mainly the function to innervate blood vessels and lymphatics as well as smooth muscle cells and connective tissue cells (mast cells, histiocytes, plasma cells) of the small intestine mucosa.

Animals↗