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Biomedical subjects

M Shiner

Publications and source records attributed to M Shiner.

At least 19 recordsLinked to original sources
PubMed2000

Contribution of villous atrophy to reduced intestinal maltase in infants with malnutrition.

BACKGROUND: It has been known for many years that small intestinal maltase activities are reduced in malnourished infants and in other patients with villous atrophy. The recent availability of human maltase-glucoamylase cDNA provides the opportunity to test the hypothesis that villous atrophy accounts for the reduced maltase enzyme activity in malnourished infants. METHODS: Mucosal biopsy specimens obtained for clinical evaluation of malnourished infants with poor responses to refeeding were examined by quantitative methods for enzyme activity and mRNA levels. RESULTS: Maltase activity and maltase-glucoamylase mRNA were reduced (approximately 45% of normal). When maltase-glucoamylase message was normalized to villin message, a structural protein expressed only in enterocytes, a preservation of maltase messages in surviving enterocytes was documented. The luminal glucose transporter-villin message was also preserved. CONCLUSIONS: The loss of maltase-glucoamylase message paralleled the reduction in villin message and degree of villous atrophy. The reduced maltase-glucoamylase message also paralleled sucrase-isomaltase message, previously found to be decreased in proportion to villous atrophy of malnourished infants. The data directly demonstrate, for the first time, that the terminal steps of starch 1-4 starch digestion and sucrase-isomaltase 1-6 starch digestion are decreased in malnourished infants, secondary to villous atrophy. These data in prior and present reports suggest that mechanisms underlying the chronic villous atrophy of malnutrition should be a priority for investigations in malnourished infants with slower than expected weight gain during refeeding.

Actins↗
PubMed1999

Defining peer education.

Although popular, peer education is surrounded by considerable ambiguity. To encourage greater clarity an operational framework for defining and interpreting peer interventions is presented in this article. The author recommends that consideration should be given to what it is that constitutes "peerness", the aims and methods of an intervention and the way in which peer educators are involved. Reflecting a gap in the existing literature, particular attention is paid to the nature of peer involvement. A key distinction is posited between "peer development" and "peer delivery" and it is suggested that there is a "fit" between location, approach and client group.

Adolescent↗
PubMed1998

Histologic evaluation of endoscopic versus suction biopsies of small intestinal mucosae in children with and without celiac disease.

BACKGROUND: Concern over the adequacy of histologic diagnosis of endoscopic duodenal biopsies in children prompted this comparative study on the histologic quality of endoscopic versus capsule biopsies. We found this problem addressed in only six previous reports. METHODS: Blind examinations of the histologic sections of 48 duodenal biopsies obtained by gastrointestinal endoscopy in children aged 2-18 years were compared to 52 biopsies obtained by the small bowel suction method (from children aged 1-16 years). RESULTS: Although 87.5% of endoscopic biopsies and 94.2% of capsule biopsies were adequate for histologic diagnosis, fragmentation or squashing was seen in 83.3% of endoscopic biopsies and only in 25% of capsule biopsies. CONCLUSIONS: Biopsies obtained by suction are of better quality than those obtained by endoscopy. If endoscopy is preferred for technical reasons, the following conditions should be observed: the patients should be aged over 2 years, and a minimum of four biopsies should be obtained with forceps of a diameter greater than 2 mm. Adequate histologic criteria for diagnosis should include at least one full-thickness mucosal specimen more than 3 mm in length, vertically oriented, and not fragmented. In children under age 2, duodenal or jejunal capsule biopsies are preferred, since the specimens are usually larger and less fragmented. Endoscopy is technically more difficult in the very young patient.

Adolescent↗
PubMed1998

Are intraepithelial lymphocytes in celiac mucosa responsible for inducing programmed cell death (apoptosis) in enterocytes? Histochemical demonstration of perforins in cytoplasmic granules of intraepithelial lymphocytes.

BACKGROUND: Programmed cell death refers to the genetically determined processes by which cells die in response to physiologic extracellular and intracellular signals, morphologically described as apoptosis. In physiologic and pathologic circumstances this process may involve effector and target cells. METHODS: To identify serine esterase granules in intraepithelial lymphocytes, fresh-frozen human small intestine mucosal sections from normal and celiac-affected mucosa were incubated with substrate-specific N-alpha-benzyloxy-carbonyl-L-lysine thiobenzyl (BLT) and a chromogen (4 Benzoylamino-2,5-diethoxybenzene-dazonium chloride hemi [zinc chloride] salt as capture agent and were examined by light microscopy. RESULTS: Normal mucosa showed an occasional intraepithelial lymphocyte with BLT-positive intracytoplasmic granules. Some large mononuclear cells of the lamina propria were similarly stained. Many more intraepithelial lymphocytes were BLT-positive among the surface enterocytes of untreated celiac mucosa. Lamina propria mononuclear cells close to the basal layer of crypt cells also appeared to be increased. CONCLUSIONS: The histochemical identification of BLT-positive esters within intraepithelial lymphocytes suggests their involvement in enterocyte death under physiologic conditions. The increased BLT-positive intraepithelial lymphocytes found in the celiac mucosa may be related to the known increase in cytotoxic intraepithelial lymphocytes in untreated celiac disease.

Apoptosis↗
PubMed1997

Effects of malnutrition on expression and activity of lactase in children.

BACKGROUND & AIMS: Many malnourished infants have reduced lactase specific activity in the small intestine. The aim of this study was to test the hypothesis that the hypolactasia of malnourished infants results from transcriptional suppression of lactase expression. METHODS: Biopsy specimens were studied from two groups of infants: 29 with malnutrition and 10 normally nourished controls with normal morphology and lactase activity. RESULTS: In malnourished infants, lactase messenger RNA (mRNA) was reduced to 32% and sucrase to 61% of normal. Lactase and sucrase enzyme proteins and activities were lower in malnourished infants, and partial villus atrophy was present. The genotype of adult hypolactasia was not present. CONCLUSIONS: Because the hypolactasia of malnourished children was associated with much lower lactase than sucrase mRNA abundance and because the epigenetic suppression, which accounted for the reduction of sucrase mRNA, was inadequate to explain the greater reduction of lactase mRNA, this study concludes that malnutrition suppresses lactase gene transcription or mRNA stability in infants. The reductions of lactase mRNA, distinct from those found in adults with genetic hypolactasia, explain the low lactase activities commonly found in malnourished infants.

Female↗
PubMed1992

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1983

Antibody production to milk proteins in the jejunal mucosa of children with Cow's milk protein intolerance.

A direct immunofluorescent technique with fluorescein-labeled antigens was used to examine the jejunal mucosa for specific antibody reduction in 23 children aged 2--25 months referred for diagnostic biopsy. Plasma cells containing antibodies to beta-lactoglobulin (beta LG) or bovine serum albumin (BSA) were present in 11 of 16 biopsies from patients with cow's milk protein intolerance (CMPI) but only one of eight controls, all on a diet containing cow's milk. Antibody-containing cells (ACC) constituted approximately 0.5--5% of the total (IgA + IgM) plasma cell population. Their presence did not correlate with either histologic abnormality or IgA plasma cell count. Double immunofluorescence with rhodamine-labeled antigens and fluorescein-labeled class-specific anti-human immunoglobulin sera showed the ACC to be approximately 70% IgA cells and 30% IgE cells.

Animals↗
PubMed1981

Eczema and atopy in early childhood: low IgA plasma cell counts in the jejunal mucosa.

Twenty-one children aged between 2 and 54 months, 14 with eczema and 7 with allergies in first-degree relatives, were referred for diagnostic jejunal mucosal biopsy for a variety of symptoms. A partial villous atrophy was found in 19 of the 21 biopsies obtained; the other 2 were normal. We report a highly significant (P less than 0.0001) lower IgA cell count in biopsies with partial villous atrophy compared with the results of our previous study of IgA and IgM plasma cells in the mucosal biopsies in children without eczema or a history of atopy matched for age and histological appearances. The IgM cell count was also lower.

Atrophy↗
PubMed1981

Coeliac disease with severe hypogammaglobulinaemia.

A patient with severe late onset primary hypogammaglobulinaemia developed coeliac disease. The case illustrates that coeliac disease can occur in the virtual absence of local antibody production by plasma cells in the mucosa of the small bowel. Furthermore, our inability to demonstrate specific cellular immunity to a subfraction of gluten raises doubts about the relevance of immunological reactions in the pathogenesis of coeliac disease.

Agammaglobulinemia↗
PubMed1981

Jejunal mucosal morphometry in children with and without gut symptoms and in normal adults.

Nineteen diagnostic peroral biopsy specimens from 18 children without diarrhoea, vomiting, or abdominal pain ('control' children) were compared with those taken from 23 children with diarrhoea of varying aetiology to establish the morphometric characteristics of jejunal mucosa in childhood. Comparison was also made with normal jejunal mucosa from adults. Statistical analysis of each characteristic individually showed no significant difference between the 'control' children and those with diarrhoea, but there were significant differences between the mucosae of 'control' children and those of adults; the villi tended to be shorter and the crypts longer in children. Thirty-seven per cent of specimens from the 'control' children showed a partial villous atrophy, that is, they were abnormal by adult criteria. Discriminant analysis of the features measured showed effective separation of the following groups: normal histology from partial villous atrophy in children, healthy adults from 'control' children, and normal histology in adults from normal histology in children.

Adult↗