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M N Marsh

Publications and source records attributed to M N Marsh.

At least 55 records · Page 3Linked to original sources
PubMed1990

Studies of intestinal lymphoid tissue. XIV--HLA status, mucosal morphology, permeability and epithelial lymphocyte populations in first degree relatives of patients with coeliac disease.

Fifty two first degree relatives of patients with coeliac disease were investigated for HLA status, small intestinal permeability, and mucosal morphology together with the size of the intraepithelial lymphocyte pool and indices of lymphocyte activation, in an attempt to identify genetically determined markers of the disease. Thirty eight per cent of these subjects had increased intraepithelial lymphocyte populations and a highly significant association with HLA-DR3 compared with controls. Their intestinal permeability to 51chromium-labelled ethylenediamine tetraacetate was invariably normal and there was no evidence of abnormal mucosal architecture, increased crypt cell mitotic activity or lymphocyte 'activation'. Although increased intraepithelial lymphocyte counts clearly do not cause alterations in intestinal structure or function, it is likely that this parameter together with the HLA-DR3 status identifies a genetically determined predisposition to the disease which may only become clinically evident with larger doses of ingested gluten.

Adolescent↗
PubMed1989

Studies of intestinal lymphoid tissue. XV. Histopathologic features suggestive of cell-mediated reactivity in jejunal mucosae of patients with dermatitis herpetiformis.

Peroral jejunal mucosae from 32 patients with untreated DH were quantitated by computerized image-analysis in terms of surface (villous) and crypt epithelial volumes and their corresponding lymphoid infiltrates, together with lamina propria volumes, neutrophils, mast cells and basophils. Three distinctive patterns of mucosal abnormality were identified: (a) the "infiltrative" lesion in which normal villus epithelium was infiltrated by small, non-mitotic lymphocytes: (b) the "hyperplastic" type, in which crypt hyperplasia and hypertrophy together with lymphoid infiltration of crypt epithelium was additional to the "infiltrative" lesion, and in which lamina propria was swollen and contained modest neutrophilic and basophilic infiltration: and (c) the "destructive" lesion, identical to the classic celiac sprue appearances with effacement of villi, crypt hypertrophy and more intensive polymorph infiltration of lamina propria. These progressive lesions parallel those seen in experimental graft-versus-host reactions, so that the entire spectrum of changes described here in DH appear consistent with a cell-mediated mucosal response to gluten. The extent of mucosal abnormality was unrelated to individual HLA status.

Adolescent↗
PubMed1989

Studies of intestinal lymphoid tissue. XII. Epithelial lymphocyte and mucosal responses to rectal gluten challenge in celiac sprue.

The immunopathologic, structural, and functional changes within rectal mucosa of known celiac sprue subjects were quantitated during local challenge with a peptic-tryptic digest of gluten. In the celiac sprue patients challenged with 2 g of digest, major effects occurred in lamina propria, submucosa, and local microvasculature. The lamina propria swelling was biphasic, starting 1-2 h after challenge with widespread extravascular deposition of fibrinogen, indicative of increased microvascular permeability, receding by 24 h postchallenge. A rapid fall in mast cells together with granule discharge suggested their involvement in this response. The late-phase swelling (48-72 h) was preceded by a rapid influx of neutrophils and basophils, the latter showing evidence of degranulation beyond 72 h. Reestablishment of vessel lumina, a rise in mast cells, and loss of neutrophils indicated tapering of the inflammatory cellular cascade by 96 h. Lymphocytes, first seen to enter the lamina by 2 h postchallenge, increased progressively, thereby resulting in substantial infiltration between 36 and 96 h. A marked rise in epithelial lymphocytes, maximal at 6-8 h, waned by 24 h. Volumes of surface and crypt epithelium remained constant throughout. In another challenge series with 4 g of gluten digest, electrical potential difference across rectal mucosa decreased significantly 12 h postchallenge, but the associated decreases in net sodium and chloride absorptive fluxes were insignificant. It is concluded that rectal mucosa is sensitized to gluten in celiac sprue disease and thus offers a promising and convenient in vivo substrate for investigative and diagnostic purposes.

Adult↗
PubMed1989

Studies of intestinal lymphoid tissue. XIII. Immunopathology of the evolving celiac sprue lesion.

Observations, by computerised image-analysis on the evolution of flat mucosae in two celiac sprue patients, are described. Initial immunopathologic features comprised infiltration of epithelium of normal villi by small, non-mitotic lymphocytes, accompanied by crypt hypertrophy and increased crypt cell mitotic activity. The subsequent development, several years later, of flat mucosae was accompanied by mitotic, "immunoblastoid" EL thus fulfilling the diagnostic criteria for celiac sprue. These sequential phases in the evolving flat celiac mucosa parallel experimental graft-versus-host reactions, suggesting that they are fundamentally cell-mediated in type. In becoming flat, it appears obligatory for the mucosa to pass through the early "proliferative-infiltrative" stage in which crypt hypertrophy is a prominent feature.

Adult↗
PubMed1988

Studies of intestinal lymphoid tissue. X-observations on granular epithelial lymphocytes (gEL) in normal and diseased human jejunum.

A proportion of epithelial lymphocytes in various mammalian species is characterised by cells containing cytoplasmic granules. We have studied the total number of granular lymphocytes within surface and crypt epithelium of jejunal mucosae (per 10(4) micron2 muscularis mucosae) from six groups of subjects, comprising (i) young healthy volunteers (ii) family relatives of known coeliac patients, patients with gastrointestinal disorders associated with either (iii) normal or (iv) "flat" mucosae, and groups of (v) untreated and (vi) treated patients with coeliac disease. There was no difference in the absolute number of gEL between the three control groups with normal mucosal architecture, the proportion of granular to total EL per unit of tissue varying between 30-40%. In untreated coeliac mucosae, there was a significantly increased population of gEL, compared with the same control groups (p less than 0.001): the ratio of granular to total EL approximated 65%, and did not differ from flat-control mucosae in which the proportion of gEL was 55%. On withdrawal of gluten, the absolute number of gEL fell significantly in comparison with the untreated coeliac group (p less than 0.05). To further evaluate the effect of gluten challenge, granular lymphocytes were monitored during a five-day period in groups of treated coeliac patients orally challenged with increasing doses (500-3000 mg) of a peptic-tryptic digest of gluten. A significant rise in the absolute number of granular lymphocytes occurred at 12 h, but without any deterioration in mucosal architecture.

Adolescent↗
PubMed1988

Studies of intestinal lymphoid tissue. XI--The immunopathology of cell-mediated reactions in gluten sensitivity and other enteropathies.

Computerised image-analysis was used to quantitate small intestinal mucosae from celiac sprue and dermatitis herpetiformis patients, Gambian children with tropical-sprue-like malabsorption, first-degree celiac sprue relatives, and treated celiac sprue patients during challenge with a peptic-tryptic digest of gluten. A wide range of mucosal appearances was observed. Typically, 'flat' lesions (Type 2) revealed a reduced number of epithelial lymphocytes that were large and mitotically active. At the other extreme, mucosal architecture was relatively well preserved (Type 1) but surface epithelium contained an expanded population of small, non-mitotic lymphocytes, with or without crypt hyperplasia. Similar changes were observed in one-third of celiac relatives and following small dose gluten challenge. Larger dose challenges revealed a transition from Type 1 to Type 2 lesions over a 5-day period. Studies in a few patients over 2-4 years showed a similar type of progression. A major feature of this sequence was early appearance of crypt hypertrophy while villi persisted, indicating a role for factors other than increased loss of enterocytes from surface epithelium. These changes parallel the T lymphocyte-mediated events in graft-versus-host reactions in animals. It is thus concluded that the spectrum of immunopathologic changes observed in gluten sensitivity is fundamentally a cell-mediated effect, the degree of change being controlled by host genetic factors. In becoming flat, it appears obligatory for the mucosa to evolve through the earlier Type 1 lesion in which crypt hypertrophy is a prominent response.

Adult↗
PubMed1987

Reassessment of faecal alpha-1-antitrypsin excretion for use as screening test for intestinal protein loss.

Faecal alpha-1-antitrypsin and 51Cr-albumin losses in 42 patients with either gastrointestinal or hepatic disease were compared. The reference range was derived from measurements in 20 controls without gastrointestinal disease. Alpha-1-antitrypsin excretion was increased in patients with excessive 51Cr-albumin loss, and correlations were found between alpha-1-antitrypsin clearance and 51Cr-albumin excretion. Because of the considerable overlap of faecal alpha-1-antitrypsin excretion between controls and patients, sensitivity and specificity of the test were only 58% and 80%, respectively. This poor reliability could not be explained by sampling error or temporal variations in alpha-1-antitrypsin excretion. These results show that although faecal alpha-1-antitrypsin excretion correlates with 51Cr-albumin excretion when whole groups of patients are studied, its poor sensitivity makes it an unreliable measure of enteric protein loss.

Albumins↗
PubMed1986

Morphometric analysis of small intestinal mucosa. III. The quantitation of crypt epithelial volumes and lymphoid cell infiltrates, with reference to celiac sprue mucosae.

With the aid of computerised image-analysis, morphometric techniques were used to measure the volumes of crypt epithelium, with reference to a constant test area (10(4) microns2) of muscularis mucosae, in untreated and treated celiac sprue mucosae in comparison with four other groups of control jejunal specimens. Crypt epithelial lymphocyte populations were also analyzed in terms of absolute numbers (N), mean nuclear (DN) and cytoplasmic (DCYT) diameters, and mean nuclear (VN) and cell (VCELL) volumes. Untreated celiac sprue crypts, despite a 3-5 fold increase in volume over control mucosae, contained a markedly expanded population of lymphocytes which was localised predominantly to the upper crypt regions and comprised approximately 6% large lymphocytes (DN greater than 6 microns: DCYT greater than 9 micron). These changes were entirely reversed by dietary treatment and hence were considered to be gluten-driven. The infiltrate might reflect the expression of gluten receptors on maturing upper crypt enterocytes: but why these lymphocytes do not cause any apparent injury to crypt epithelium (unlike surface epithelium) or influence its well-known compensatory response, remains unclear.

Adult↗
PubMed1985

Inflammatory component of celiac sprue mucosa. I. Mast cells, basophils, and eosinophils.

To study mast cell, basophil, and eosinophil populations within celiac sprue mucosae in comparison with various disease-control specimens, toluidine blue-stained 1-micron plastic sections were analyzed morphometrically by light microscopy. Within lamina propria of celiac sprue mucosae each population of cells was markedly expanded and fell to control levels during gluten restriction. Changes within surface and crypt epithelium, however, were not significantly different from those in the severer, "flat" disease-control lesions, and were not affected by gluten restriction. Basophils were not identified within surface or crypt epithelium of any specimen analyzed. The influx of eosinophils and basophils into lamina propria occurred by emigration via pericryptal venules. Mature mast cells were not seen within the microvasculature, neither were these cells undergoing mitosis: thus their origin was from unidentified precursors. The gluten-dependent alterations in each of these cell populations in celiac sprue mucosae are consistent with secondary effector mechanisms, probably resulting from cell-mediated reactions that occur primarily within the lamina propria, rather than the epithelium.

Basophils↗
PubMed1985

Studies of intestinal lymphoid tissue. VIII. Use of epithelial lymphocyte mitotic indices in differentiating untreated celiac sprue mucosa from other childhood enteropathies.

The mitotic activity of epithelial lymphocytes (expressed as percentage mitotic figures/3,000 lymphocytes/mucosal biopsy) was determined in a random sample of jejunal biopsies performed on 44 children with malabsorption, diarrhoea, or failure to thrive. The mitotic index (MI) exceeded 0.2% in 19 biopsies obtained from children with untreated celiac sprue (CS); there were no false positives. The remaining 25 biopsies (MI of less than 0.2%) were considered to be "nonceliac" in origin, among which were several with a severe degree of villous flattening. Conditions in this latter category excluded by a low MI included cow's milk protein enteropathy, selective immunoglobulin A deficiency, combined variable immunodeficiency, Crohn's jejunitis, and intractable diarrhoea of infancy. A high MI (greater than 0.2%) prospectively distinguishes mucosal lesions due to untreated CS from other causes of malabsorption, particularly those associated with villous flattening, but in which the MI is less than 0.2%. This index is therefore proposed as a simple, reliable, and prospective histological marker of CS, and one that could: reduce the need to perform multiple biopsies during a gluten-free diet; and avoid the necessity for follow-up "diagnostic" gluten challenges, especially in very young children.

Adolescent↗
PubMed1985

Intestinal permeability in patients with coeliac disease and dermatitis herpetiformis.

Intestinal permeability was investigated in patients with coeliac disease and dermatitis herpetiformis by a 51Chromium-labelled ethylenediaminetetraacetate (51Cr-EDTA) absorption test and the results correlated with histomorphometric analysis and intraepithelial lymphocyte counts of jejunal biopsies. The mean (+/- SD) 24 hour urine excretion of 51Cr-EDTA in 34 healthy volunteers was 1.9 +/- 0.5% of the orally administered test dose. Patients with untreated coeliac disease (19) or untreated dermatitis herpetiformis (five) excreted significantly more 51Cr-EDTA than controls (5.9 +/- 2.7% and 4.6 +/- 2.1%, respectively, p less than 0.001) and all were outside the normal range of 1.0-2.6%. Patients with coeliac disease (42) treated for 6 months-23 years (mean 5 years) and patients with dermatitis herpetiformis (11) treated for 6 months-8 years (mean 3 years) excreted significantly more 51Cr-EDTA than controls, 4.2 +/- 2.4% p less than 0.0001 and 3.0 +/- 0.9% p less than 0.003 respectively. Eleven of 14 (79%) treated patients with coeliac disease with an entirely normal jejunal mucosae demonstrated abnormal intestinal permeability. Intestinal permeability did not correlate significantly with either the mucosal height/crypt depth ratio or intraepithelial lymphocyte counts in jejunal biopsies from patients with untreated or treated coeliac disease. The demonstration of a persistent increase in intestinal permeability in patients with both coeliac disease and dermatitis herpetiformis may suggest a common pathogenetic mechanism in both disorders. It is postulated that altered permeability may facilitate the entry of gluten or a fraction thereof into the lamina propria where it causes a cascade of immunological events.

Adolescent↗
PubMed1985

Chylous ascites, intestinal lymphangiectasia and the 'yellow-nail' syndrome.

In 1964 Samman and White described 13 patients with lymphoedema of the lower extremities associated with an unusual dystrophy of the finger and toe nails: this they termed the 'yellow-nail' syndrome. Affected nails were thickened, excessively curved along both axes, very slow growing and of yellowish-grey hue; cuticle and lunula were usually absent and onycholysis was frequently evident. Lower limb lymphangiography in most individuals revealed hypoplasia, or aplasia of the lymphatics, similar to that occurring in primary lymphoedema: other patients also developed pleural effusions of high protein content or ascites suggestive of a more generalised disorder of the lymphatic system. Here we describe a patient in whom the classical 'yellow-nail' syndrome was associated with intestinal and chylous ascites.

Chylous Ascites↗
PubMed1985

Studies of intestinal lymphoid tissue. IX. Dose-dependent, gluten-induced lymphoid infiltration of coeliac jejunal epithelium.

Jejunal biopsy specimens from coeliac patients who had received small, oral doses (100-1500 mg) of a peptic-tryptic gluten digest were analysed by morphometric methods. An increase in the total number of surface epithelial lymphocytes, maximal at 12 h after challenge, was dose-dependent, the mean percentage rise at this time being 53% (p less than 0.005), 44% (p = 0.01), and 25% (p greater than 0.05) with 1500, 1000, and 500 mg of gluten digest, respectively. This effect was not accompanied by any increased mitotic activity or blast transformation among the infiltrating lymphocytes, nor was there any demonstrable alteration in mucosal structure-that is, reduction in surface or increase in crypt epithelial volumes. The results of this controlled morphometric analysis indicate that oral gluten challenge causes an increase in the lymphocyte population of surface epithelium in coeliac disease but that this effect does not necessarily result in mucosal damage.

Celiac Disease↗