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Biomedical subjects

A D Phillips

Publications and source records attributed to A D Phillips.

At least 91 records · Page 5Linked to original sources

Lactosylceramide in inflammatory bowel disease: a biochemical study.

A simple technique for isolating lipids from small pieces of tissue was applied to mucosal biopsies and samples of resected intestine from patients with inflammatory bowel disease. Scanning densitometry of two dimensional chromatograms showed increased concentrations of the membrane associated glycosphingolipid lactosylceramide in Crohn's disease, on comparison with ulcerative colitis (p less than 0.01), or controls (p less than 0.01). This indicates either that normal glycosphingolipid metabolism is altered, or that a novel source of lactosylceramide is present in the inflamed mucosa of patients with Crohn's disease.

Adolescent↗

Specific autoantibodies to gut epithelium in two infants with severe protracted diarrhoea.

Two male infants with severe protracted diarrhoea presenting at 4 months (patient 1) and 10 weeks (patient 2) of age are reported. In both patients jejunal biopsy showed subtotal villous atrophy. Both had specific complement-fixing autoantibodies reacting by immunofluorescence with human duodenal, jejunal, and colonic epithelium. Patient 1 also had hypothyroidism and type 1 diabetes mellitus with thyroid and islet cell autoantibodies. His gut antibodies were of IgG class, reached a titre of 1:512, and remained positive throughout his illness. He died at 16 months of age. Patient 2 had gut antibodies of IgM class, which reached a titre of 1:128 and disappeared at the time of spontaneous recovery of the diarrhoea. The findings suggest that an autoimmune process was the basis for the enteropathy in these patients. We recommend that autoantibody tests should be performed in infants with unexplained protracted diarrhoea.

Antibody Specificity↗

Biochemical abnormality in brush border membrane protein of a patient with congenital microvillus atrophy.

Brush border membrane proteins from a child with congenital microvillus atrophy were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and compared with brush border membrane proteins from normal and disease controls. A predominant band of MW 200K was present in all preparations with the exception of the membrane preparation from the child with congenital microvillus atrophy. Although the band was present in the latter case, it was grossly diminished. The diminished 200K MW band may result in the abnormality of brush border structure. This could account for the involution of the microvilli, the distinguishing feature of congenital microvillus atrophy, and could be the underlying defect in this disease.

Epithelium↗

Congenital microvillous atrophy: specific diagnostic features.

Proximal small intestinal and colonoscopic mucosal biopsies from two children with the intractable diarrhea of infancy syndrome were examined by electron microscopy. Microvillous involutions were found in the small and large bowel of both patients. We suggest that this is a specific diagnostic finding for congenital microvillous atrophy, a distinct disorder within the intractable diarrhoea syndrome which has an extremely poor prognosis.

Atrophy↗

Absent ileal uptake of IF-bound vitamin B12 in vivo in the Imerslund-Grasbeck syndrome (familial vitamin B12 malabsorption with proteinuria).

A Syrian family is described with three children who had inherited selective vitamin B12 malabsorption associated with proteinuria. (Imerslund-Grasbeck syndrome). Although inherited the defect was apparently not present at birth. A third child had less severe vitamin B12 malabsorption, was not vitamin B12 deficient and had no proteinuria. Studies on two of the affected children with subcellular fractionation of the uptake of radioactive vitamin B12 by ileal tissue in vivo indicate a defect in the ileal receptors for IF-bound vitamin B12. These findings are different from the single in vitro experiment on a patient with this condition that has been previously reported.

Adolescent↗

Cryptosporidiosis in immunocompetent children.

Cryptosporidial oocysts were identified by modified Ziehl-Neelsen stain in the stools of seven (3.2%) of 213 children with acute or chronic diarrhoea and one (0.9%) of 112 controls. All children with cryptosporidia were immunocompetent. Four of the index cases had a short illness (3-14 days) with watery diarrhoea, vomiting (2), and abdominal pain (2). Two index cases had chronic diarrhoea for over four months and failure to thrive. Both had a small intestinal enteropathy; one had cryptosporidial oocysts in stool specimens two months apart and the other had cryptosporidial schizonts attached to the jejunal mucosa. One index case had a colitis of indeterminate cause. Four of the index cases had recently travelled abroad. There had been an outbreak of gastroenteritis in the family of one of the index cases, and three affected sisters and an asymptomatic brother had oocysts in their stools. Cryptosporidial infestation seems to be associated with acute gastroenteritis and sometimes with chronic diarrhoea and small bowel damage in immunocompetent children.

Animals↗

Intestinal sugar permeability: relationship to diarrhoeal disease and small bowel morphology.

The permeability of the intestine was studied in 39 children (1 month to 3 years of age) with diarrhoea and in 28 children (6 months to 15 years of age) undergoing duodenal biopsy. Permeability was measured by differential absorption from an isotonic oral load containing 3.5 g lactulose, 0.5 g L-rhamnose, 0.5 g D-xylose, and 5 g lactose. Urinary sugar excretion was determined by quantitative thin-layer chromatography. Children with acute gastroenteritis had a greatly increased permeability, with a mean lactulose/L-rhamnose excretion ratio of 0.43 +/- 0.31 (normal less than 0.07). Children retested 3-16 weeks after complete recovery of their gastroenteritis had normal permeability (0.045 +/- 0.018). Children with chronic diarrhoea also had an increased permeability (0.12 +/- 0.074), but significantly less than the acute gastroenteritis group (p less than 0.01). Abnormal proximal small bowel morphology was associated with increased permeability, and a strong correlation between crypt depth and permeability was observed (r = 0.66, p less than 0.001). Abnormal intestinal permeability was associated with diarrhoeal disease and with mucosal damage. It appears to be a reliable and useful index of mucosal integrity.

Adolescent↗

Microvilli- and desmosome-associated bodies in Crohn's disease and other disorders in childhood: an ultrastructural abnormality of the small and large intestine.

Ultrastructural studies of the small and large intestine from children revealed five cases showing abnormal small electron-dense bodies within enterocytes and goblet cells. The characteristic features of the bodies were: (a) they occurred within microvilli and within the apical part of the cell cytoplasm; (b) they showed an association with the most apically located desmosomes of the epithelial cells; (c) in the microvilli they were present within protrusions of the membrane, suggesting that they may bud out of the cell; and (d) they were not membrane-bound within the cell but were found outside the cell as luminal, membrane-bound particles. These bodies occurred in two children with Crohn's disease and in three children having other gastrointestinal disorders. Similar electron-dense bodies which did not have all of the characteristics listed above were found in a sixth child who had Crohn's disease. These electron-dense bodies do not resemble any known inclusion of intestinal epithelium, nor do they resemble any previously described microorganism, although their apparent release from the cell by a process of budding is suggestive of a microbial identity. The occurrence of these bodies in childhood Crohn's disease suggests that they may be disease-related, but their precise nature and relevance to this or other gastrointestinal disorders remain unknown.

Adolescent↗

Quantitative analysis of small intestinal mucosa in cow's milk-sensitive enteropathy.

The appearance of the small intestinal mucosa in cow's milk protein intolerance (CMPI) was studied using quantitative morphometry. The parameters under study were the numbers of eosinophil cells in the lamina propria and epithelium, villous height, crypt zone depth, villous height/crypt zone depth ratio, and total mucosal thickness. Tracings of whole sections were analysed using a suitably programmed minicomputer linked to a digitising table. Small bowel biopsy specimens from children with untreated CMPI, from children before and after clinical relapse on cow's milk challenges, and from children with resolved CMPI were compared to each other, to those from control infants, and to those from children with coeliac disease. No change of diagnostic significance could be found in the number of lamina propria eosinophil cells, but levels of intraepithelial eosinophils were significantly increased following cow's milk challenge. Quantification of mucosal dimensions confirmed the presence of a cow's milk-sensitive enteropathy and established the finding of a thin mucosa in CMPI regardless of clinical disease activity. Mucosal thickness was not different from control values following resolution of the disease. In coeliac disease mucosal thickness was significantly greater than in CMPI (apart from young children with untreated coeliac disease whose mucosa was not thicker than that of children with untreated CMPI) but not different from control values. It is suggested that in CMPI there is a limitation in the capacity of crypt cells to compensate for the loss of villous epithelium.

Biopsy↗

The microvillus in adult jejunal mucosa--an electron microscopic study.

The increase in surface area contributed by microvilli per square unit mucosal surface area in the jejunal villus, i.e. amplification factor, has been studied in four normal adults and three adults with treated coeliac disease. Villi were split into three regions, photomicrographs of microvilli were taken from each region and the microvillus amplification factor calculated. The mid-villus region contributed a significantly greater microvillus amplification factor than either the low or upper regions in all patients studied. In addition surface cell heights were greatest in the low- and mid-villus regions. This suggests that the enterocytes in the mid-villus region are best adapted for absorption, and that the enterocytes in the upper-villus regions are undergoing an ageing process.

Adolescent↗

The spectrum of gastrointestinal allergies to food.

Gastrointestinal food allergies may be defined as clinical syndromes which are characterised by the onset of gastrointestinal symptoms following food ingestion where the underlying mechanism is an immunologically mediated reaction within the gastrointestinal tract. These gastrointestinal symptoms, principally vomiting and diarrhoea, sometimes abdominal colic, may be accompanied by other symptoms outside the alimentary tract. The clinical spectrum of these disorders ranges from acute anaphylaxis (rarely leading to death in infancy) to relatively minor symptoms which are difficult to distinguish from other disorders such as toddler's diarrhoea or psychologic disorders. The same food, e.g. cow's milk, may produce a wide range of clinical manifestations. In the one individual, clinical features may change with age. The incidence of gastrointestinal food allergic disease is greatest in the first year of life and decreases with age. There are, broadly speaking, two categories of clinical syndromes which are related to speed of onset of symptoms: immediate and delayed. Those syndromes which manifest immediately after food ingestion are usually easy to diagnose and specific IgE tests and skin prick tests are frequently positive. Those which have a delayed onset of up to several days are difficult to diagnose, and currently available investigations may be unsatisfactory for routine use. In current clinical practice, gastrointestinal syndromes which can be manifestations of food allergy, may be grouped as follows: 1) immediate syndromes, including anaphylaxis and b) acute vomiting +/- diarrhoea in association with cutaneous and respiratory manifestations; and 2) delayed syndromes, including a) food-sensitive small intestinal enteropathies, b) food-sensitive colitis, c) multiple food allergy +/- enteropathy, and d) infantile colic.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Macromolecular absorption by histologically normal and abnormal small intestinal mucosa in childhood: an in vitro study using organ culture.

Knowledge of the mechanism of macromolecular absorption in the small intestine is based largely on animal studies. We have attempted to assess qualitatively and quantitatively the amount and the mechanism of uptake of horseradish peroxidase (HRP), a model macromolecule, in human small intestine, employing biopsy material from children undergoing gastrointestinal investigations. The biopsy material was incubated in culture medium containing HRP, and a comparison was made between histologically normal and histologically abnormal biopsies. In the normal specimens HRP was detected in pinocytotic vesicles along the villous epithelium. It was also seen in multivesicular bodies and in the interepithelial cell spaces at the base and tip of the villus. These latter areas corresponded to regions where damaged and extruding enterocytes, diffusely penetrated by HRP, were seen. This demonstrates that intact macromolecules can be taken up by normal small intestine in vitro in childhood and indicates two possible routes of antigen entry: (a) by active absorption through intact enterocytes and (b) through damaged or extruding cells. In the abnormal specimens the distribution of HRP was more varied. Most specimens showed an increased presence of HRP in the interepithelial cell spaces and an increased number of enterocytes diffusely penetrated by HRP, but a decrease in pinocytosis in the most severely abnormal enterocytes. An increase in HRP was also observed in the basement membrane and, in one instance, within capillaries of the lamina propria. It was concluded that when an enteropathy is present, an increase in mucosal permeability to macromolecules may result. This is most likely due to an increase in the passive diffusion of macromolecules into the mucosa.

Adolescent↗