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Biomedical subjects

M Shiner

Publications and source records attributed to M Shiner.

At least 19 recordsLinked to original sources

Mosaic expression of brush-border enzymes in infants with chronic diarrhea and malnutrition.

The chronic diarrhea observed in young malnourished infants that is sensitive to dietary glucose and other carbohydrates is associated with variable degrees of patchy mucosal villous atrophy. To explore intrinsic mucosal function in the pathogenesis of this alimentary intolerance, we have conducted an immunohistologic investigation of brush-border enzyme proteins of clinically obtained, mucosal biopsy samples. We used a group of monoclonal antibodies against human brush-border aminopeptidase, sucrase/isomaltase (SI), maltase, and lactase enzyme proteins. SI was strongly and uniformly expressed in crypts and villi of 11 of the 14 subjects; in 3 subjects, however, SI was expressed in a mosaic pattern. Maltase and lactase were occasionally absent, but more commonly were expressed in a mosaic distribution. The mosaic expression of brush-border enzyme proteins has been reported in congenital enzyme deficiencies associated with normal intestinal histology. We report the mosaic expression of brush-border enzyme proteins as a functional alteration associated with a pathological lesion of the mucosa in infants with chronic diarrhea. Our observation challenges the existing concept of ontogenic regulation of brush-border enzyme activity.

Aminopeptidases

Pathogenesis of small-intestinal mucosal lesions in chronic diarrhea of infancy: I. A light microscopic study.

In an effort to increase our understanding of the pathogenesis of chronic protracted diarrhea in infants, we examined 44 jejunal mucosal specimens. Only 3 of the 44 specimens showed a normal mucosa (grade 1). Partial villous atrophy was seen in 17 mucosal specimens (grade 2) with marked patchiness in all of the specimens. Subtotal or total villous atrophy (grade 3) was found in the remaining 24 mucosal biopsies. Plasma cells and macrophages were variably increased and intraepithelial lymphocytes were moderately increased in grades 2 and 3. Eight of ten mucosal biopsy specimens embedded in plastic material and cut at 1-2-mm thickness, showed bacteria of unidentified nature, situated either above the microvillous layer or on the mucosal surface. Both adherent and nonadherent bacteria could be identified in the same specimen. We concluded that severe pathological mucosal changes are common in young infants with protracted diarrhea and that the presence of bacteria may be more common than has previously been documented.

Atrophy

Pathogenesis of small-intestinal mucosal lesions in chronic diarrhea of infancy: II. An electron microscopic study.

Our electron microscopic study of biopsies taken from 10 infants with protracted diarrhea was conducted in an effort to determine the pathogenesis of the disorder. In this article, the ultrastructure of the jejunal mucosa of the infants is described in relation to overlying or adherent bacteria of unidentified type. In addition to the known changes on the enterocyte surface caused by adherent bacteria (cupping and effacement), other cytopathic changes, not previously reported, are documented. Included are widespread loss of enterocytes, including intraepithelial lymphocytes, into the bowel lumen; cytopathological changes within the enterocytes; and marked thickening of the basal laminae of the enterocytes and the endothelium of lamina propria blood vessels. In addition, we noted deposition of collagen fibrils in the lamina propria below the basal laminae, active phagolysis within macrophages, and lack of cisternal material (immunoglobulin) in the plasma-cell cytoplasm. Although these changes are nonspecific, they may be related in part to the presence of the nonadhering and adhering bacteria, and their identification may further our understanding of the "sick mucosa" that occurs in chronic diarrhea of infancy.

Bacteria

Ia-like antigens in the small intestinal mucosa of normal and celiac children.

The small-intestinal mucosa of normal children and of celiac patients was studied using the Class II DP (SB) Ia-like monoclonal antibody ILR-1 and an immunoperoxidase technique. Positive staining of the Golgi region of the epithelial cells of villi and crypts, and of the brush border of villous epithelium, was seen in the histologically normal mucosa. In active celiac disease with "flat" mucosa, the surface epithelium showed poor staining, but the crypt epithelium stained strongly in the Golgi region. We suggest that the Ia-like antigens are a product of the epithelial cells themselves, arising most likely in the Golgi apparatus, and that this staining pattern is altered in active celiac disease.

Celiac Disease

Clinical, histological, and electron microscopic study of mast cell disease of the small bowel.

A patient with mast cell disease of the small bowel is described in whom clinical, histological, and ultrastructural studies served to delineate the characteristic features of the disease. Urticaria pigmentosa, steatorrhea, eosinophilia, absence of antireticulin antibodies, and submucosal nodularity seen on radiographic study of the duodenum were the clinical characteristics. The endoscopic appearance was that of severe exudative duodenitis. The histology of the small intestinal mucosa showed crypt cell destruction and villous atrophy. Marked infiltration of the lamina propria with mast cells, eosinophils, and neutrophils was also distinctive. The enterocytes retained their columnar epithelium, confirmed on electron microscopy. The fine structural abnormalities of the mast cells are demonstrated for the first time. Degranulated mast cells predominated within the lamina propria and none was seen among the epithelial layers. The mast cell nuclei were irregular, often binuclear, and showed loss of their normal heterochromatin pattern. In their cytoplasm only few granulated bodies were seen and even more rarely inclusions with whorls and scrolls. We conclude that the clinical, histopathological, and ultrastructural appearances in mast cell disease of the small bowel are distinctive and should be used as criteria for diagnosis. Care should be taken in the evaluation of the number of mast cells since the demonstration of these cells may be affected by various fixing and staining techniques.

Adult

Lactase degradation by human enteric bacteria.

Twelve non-pathogenic bacteria and two yeast strains isolated from the duodenal aspirate or mucosa of five children with diarrhoea were tested for their ability to degrade non-human lactase in vitro. Both yeast strains and eleven of the bacterial strains significantly reduced lactase activity. A similar action on human lactase could be a cause of lactose intolerance.

Bacteria

Jejunal mucosa in marasmic children. Clinical, pathological, and fine structural evaluation of the effect of protein-energy malnutrition and environmental contamination.

Seven children suffering from marasmus were investigated clinically, biochemically and morphologically. The fine structure of the jejunal mucosa obtained by peroral biopsy was evaluated. The mucosal changes noted agree with the only other ultrastructural study reported by Brunser et al. (8) and add information on three additional features: an increase in theliolymphocytes, excessive epithelial cell extrusion and abnormalities in the appearances of the mucosal plasma cells, suggesting possible local deficiency in immune function.

Animals

Histopathologic changes and the immune response within the jejunal mucosa in infants and children.

Jejunal biopsies obtained from 45 children referred for a variety of clinical conditions were examined histologically and by standard immunofluorescence methods. The number of plasma cells was recorded per "mucosal tissue unit". The results showed that most of the immunoglobulin A (IgA) counts in infants under 3 yr with normal mucosa were low and that there was a rise in the number of IgA plasma cells starting after this age. Despite this, under pathologic conditions (partial villous atrophy with increased inflammatory cell infiltration--PVA) a significant rise in IgA plasma cells occurred in all age groups. Patients with coeliac disease tended to show the highest IgA as well as IgM plasma cell counts. In all other patients, IgM counts did not change significantly with age or histologic abnormalities.

Adolescent

Small-intestinal mucosal antibodies against antigens of non-pathogenic luminal or mucosal bacteria in young children with and without diarrhoea.

Duodenal mucosal antibody against non-pathogenic bacteria, grown either from the luminal juices or the mucosa itself, was demonstrated for the first time in 7 of 8 children with diarrhoea and only 2 of 7 without diarrhoea. Neither group showed significant histological abnormalities on duodenal biopsy. An aetiological relation between the antibody and the persistence of postenteritis diarrhoea is possible.

Antibodies, Bacterial

Nodular lymphoid hyperplasia of the bowel in primary hypogammaglobulinaemia: study of in vivo and in vitro lymphocyte function.

In vitro and in vivo lymphocyte function was studied in six patients with primary hypogammaglobulinaemia and nodular lymphoid hyperplasia (NLH) of the bowel. Lymphocyte transformation, numbers of circulating T and B lymphocytes, and delayed hypersensitivity skin tests did not significantly differ when compared with hypogammaglobulinaemic patients without NLH. However, patients with NLH had higher jejunal juice IgM concentrations and a tendency to higher serum IgM concentrations than those without NLH. The morphological features of NLH are similar to the germinal centres of lymph nodes but more closely resemble the follicle zone of Peyer's patches. These findings suggest that NLH represents a local immune response to antigens originating in the gut lumen.

Adolescent

Small-bowel abnormalities in multiple sclerosis.

Jejunal biopsies were performed in 12 randomly chosen patients with multiple sclerosis. The jejunal mucosa was examined histologically, ultrastructurally, and by tissue immune techniques. Histology showed a normal mucosa in 7 patients, increased inflammatory-cell infiltration in 3, a partial villous atrophy in 1, and a subtotal villous atrophy in the remaining patient. Fine structural abnormalities were seen in 6 of 8 patients studied. These included microvillous changes, increase in theliolymphocytes and epithelial lysosomes, thickening of the connective tissue with or without collagen fibres, and numerous macrophages containing large amounts of membrane-bound electron-dense material. The latter was seen in 5 of the 8 mucosae examined.

Adult

Intestinal biopsy in the diagnosis of cow's milk protein intolerance without acute symptoms.

4 infants, suspected of cow's milk protein intolerance, were placed on an elimination diet and then challenged with cow's milk. None reacted clinically, yet in 2 of the 4 patients jejunal biopsy revealed clear histological, ultrastructural, and immunological changes. It is suggested that these changes are the objective criteria on which the diagnosis of cow's milk intolerance should be based, and that the clinical evidence derived from milk challenge after an elimination diet may be unreliable.

Biopsy

The small-intestinal mucosa in cow's milk allergy.

Two infants investigated for allergy to cow's milk proteins exhibited a local reaginic reaction in the small intestine after ingesting cow's milk, as shown by increased mucosal IgE plasma-cells and degranulation of mast cells. IgM plasma-cells and the staining of connective tissue and basement membranes with antisera to IgG and C3 complement were also increased, indicating several simultaneous immune reactions in the intestinal mucosa. These findings may provide a sound basis for diagnosis of such an allergy and for the treatment of similar patients with disodium cromoglycate.

Biopsy