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Biomedical subjects

A D Phillips

Publications and source records attributed to A D Phillips.

At least 55 records · Page 3Linked to original sources
PubMed1995

Serum interleukin-2 receptor in infants and young children.

Soluble interleukin-2 receptor (IL-2R) concentrations were measured in 110 serum samples from 102 children undergoing routine small bowel biopsy for a wide range of gastrointestinal symptoms. Young children in the control group who had no gastrointestinal disease and a normal intestinal mucosa were found to have high concentrations of IL-2R. There was a significant inverse relationship between IL-2R concentration and age in the control group. Children with a gastrointestinal diagnosis appeared to have increased IL-2R concentrations, although some of the diagnostic groups were too small in size for statistical analysis. Children with cow's milk sensitive enteropathy had IL-2R concentrations equivalent to those of age-matched controls. High concentrations of IL-2R in young healthy children implies that serum IL-2R is of no clinical use as an index of inflammation in this age group.

Adolescent↗
PubMed1995

Molecular characterization of a carboxy-terminal eukaryotic-cell-binding domain of intimin from enteropathogenic Escherichia coli.

A eukaryotic cell-binding domain from the intimin (Int) polypeptide of enteropathogenic Escherichia coli O127 (EPEC) was investigated. Derivatives of the carboxy-terminal 280-amino-acid domains of Int (Int-EPEC280) and the Int homolog invasin (Inv) from Yersinia pseudotuberculosis (InvYP280) were fused to the E. coli maltose-binding protein (MBP), expressed, and purified. The smallest MBP-IntEPEC fusion protein that efficiently mediated binding to HEp-2 cells, monitored by using purified fusion proteins in fluorescence activated cell sorter analysis or by using fluorescent Covaspheres coated with purified fusions, contained the carboxy-terminal 150 amino acids of Int. Replacement of Cys-937 with Ser (IntEPEC280CS) destroyed the cell-binding activity of IntEPEC280. Covaspheres coated with MBP-IntEPEC280 were associated with HEp-2 cell microvilli but failed to induce actin accumulation underneath bound particles or cell spreading on coated plastic surfaces. MBP-IntEPEC280, but not MBP, MBP-IntEPEC280CS, or MBP-InvYP280, inhibited EPEC entry into HEp-2 cells.

Adhesins, Bacterial↗
PubMed1995

Coeliac disease in children of West Indian origin.

Coeliac disease is uncommon in populations of non-European origin. Two English born West Indian children with coeliac disease are presented. The diagnosis should be considered in children of West Indian origin with chronic diarrhoea.

Celiac Disease↗
PubMed1995

Sequential changes in small intestinal structure and function during rotavirus infection in neonatal rats.

Rotavirus infection is the most common cause of acute diarrhoea in children worldwide. The structural and functional consequences of mammalian rotavirus infection in the small intestine have been incompletely studied and the mechanism of enterocyte damage poorly defined. This study used a neonatal rat model of group B rotavirus infection to study the natural history, clinical features, and the structural and functional consequences of infection in the small intestine. Group B rotavirus infection in eight day old neonatal rats produced diarrhoea by 24-36 hours, which was accompanied by weight loss during the early stages of infection. By seven days the diarrhoea had ceased and body weight was similar to noninfected controls. Rotavirus could be recovered in faeces from 24-72 hours. Light microscopy and morphometry confirmed reduction in villous height in both jejunum and ileum, with a reduction in total mucosal thickness indicating true flat mucosa. Increase in crypt depth followed villous shortening and continued as villous height progressively increased between 96-168 hours. Steady state perfusion of the entire small intestine with a plasma electrolyte solution confirmed the presence of a net secretory state for water between 12-48 hours, with a parallel reduction in sodium absorption. Group B rotavirus infection produces a self limiting acute diarrhoeal illness in neonatal rats similar to human rotavirus infection. Infection causes a reversible flat mucosa resulting from enterocyte loss associated with a net secretory state for water and impaired sodium absorption as a functional correlate. These findings may have relevance for the pathogenesis of human rotavirus infection.

Animals↗
PubMed1995

Novel insights into human intestinal epithelial cell proliferation in health and disease using confocal microscopy.

Measurement of intestinal epithelial cell proliferation has provided important information concerning tissue responses in neoplasia, enteropathy, and adaptation. This study reexamined current concepts regarding intestinal proliferation by using a novel confocal microscopical technique to map mitotic figures accurately within the intact three dimensional framework of the crypts of Lieberkühn. The ability of confocal microscopy to simultaneously measure crypt morphology and internal detail, without disrupting spatial cell arrangements, has provided important new data. These question the ability of existing methods to accurately measure and interpret proliferative changes in the gut. This work investigates intestinal proliferation in children with coeliac disease, a well defined hyperproliferative disorder, in comparison with the healthy intestine. These results show that crypt cell division occurs with an equal probability in health and disease. In addition, increased crypt cell production rates are largely caused by a change in crypt size rather than a change in cell cycle time or crypt growth fraction and, as such, alter our understanding of kinetic responses in gastrointestinal disease.

Celiac Disease↗
PubMed1994

Endomysial antibody screening in children.

It has been suggested that endomysial antibodies are specific markers for coeliac disease. In a 13-month study, we examined the usefulness of screening for these antibodies in the diagnosis of coeliac disease in children. Twenty-one of 223 (9.4%) serum samples [or 17 of 192 (9%) children undergoing investigation for GI disorders] were found to be positive for serum IgA class endomysial antibodies. These included eight strong positives, eight positives, and five weak positives. One-hundred-thirty-four children had small bowel biopsies performed. Endomysial antibodies were found in all children with severe villous atrophy on a gluten-containing diet who were diagnosed as having coeliac disease. Three children with positive and four with weak-positive results did not have coeliac disease. One had partial villous atrophy consistent with the diagnosis of cow-milk-sensitive enteropathy and the others had a normal small bowel mucosa. This study confirms a strong association between endomysial antibodies and coeliac disease; however, not all cases with positive antibodies had the disease. At the present time, small bowel biopsy remains essential for the diagnosis of coeliac disease.

Adolescent↗
PubMed1994

Impact of rotavirus infection on a paediatric hospital in the east end of London.

AIMS: To study the impact of confirmed rotavirus infection at a paediatric hospital; to use the data to obtain a minimum estimate of the cost of treating reported cases of rotavirus in England and Wales. METHODS: Data were obtained on all patients with rotavirus over a two year period. Information was collected on 386 patients with rotavirus infection who were treated at the 120 bed Queen Elizabeth Hospital for Children in East London. This included the virus serotype, the patient's age, whether they required intravenous infusion, duration of hospital stay, numbers of patients treated in the casualty department, and numbers who had to be admitted. Treatment costs were obtained from the Finance Department of the Hospitals for Sick Children. RESULTS: The minimum cost of treating patients, excluding the cost of medical staff at the hospital, was estimated to be 95,400 pounds a year. One hundred and forty eight (38%) patients were admitted to the wards and a further 49 patients developed symptoms while in hospital. Intravenous infusion was required by 18 patients. The mean duration of hospital stay was 5.5 days. One hundred and eighty nine (49%) patients were treated with oral rehydration solution in casualty, given advice, and sent home. Ninety four per cent of the patients were aged under 2 years. The findings were comparable with those obtained in a study at Texas Children's Hospital, USA. The G serotype (VP7) of rotavirus did not influence the severity of infection. CONCLUSION: Rotavirus infections accounted for a significant number of patients treated in casualty, admissions to hospital, and bed occupancy in a paediatric hospital. The estimated cost of treating reported cases of rotavirus in England and Wales is in excess of 6.3 pounds million a year.

Age Factors↗
PubMed1994

Enteroaggregative Escherichia coli: another cause of acute and chronic diarrhoea in England?

Enteroaggregative Escherichia coli (EAggEC) has been found to be associated with acute and persistent diarrhoea in children in developing countries. Its clinical significance in developed countries has not been examined in much detail. In a survey of faecal samples from children with diarrhoea presenting to a children's hospital in East London between August and December 1988, EAggEC strains were isolated in 8 of 297 (2.7%) consecutive stool samples collected from 289 children and in 5 of 34 typed E. coli isolates during 1988. Of the 13 children found to be excreting EAggEC, 8 had acute diarrhoea and 5 had chronic diarrhoea of more than 14 days' duration; 5 children had mixed infections. Compared to other organisms found during the same period, EAggEC were isolated as frequently as many other better-known pathogens such as enteropathogenic E. coli, Campylobacter, Salmonella, Shigella, Giardia lamblia, and Cryptosporidium. We conclude that EAggEC may be an important pathogen in developed countries.

Acute Disease↗
PubMed1993

Enteric disease in early childhood inhibits microvillus expression by potential stem cells.

1. Enterocyte development of microvillus structure has been measured in intestinal biopsies obtained from children suffering from coeliac disease, cow's milk protein intolerance and microvillus atrophy, and the results compared with similar measurements carried out in control children. 2. All types of enteric disease caused a significant 30% reduction in the length of microvilli present on undifferentiated basal crypt enterocytes, here referred to as potential stem cells. 3. Microvillus growth measured in control enterocytes took place mainly over the basal third of the villus. There was then little further change in structure during subsequent enterocyte migration to the villus tip. 4. Microvillus length in diseased tissue remained more or less constant during enterocyte migration to the crypt-villus junction. Microvillus length then decreased slightly during subsequent enterocyte migration over stunted villi. 5. The present results are discussed in relation to the supposed properties of potential stem cells. Comparisons are also made between profiles of microvillus development measured in healthy children and mature adults.

Adult↗
PubMed1992

Neutrophil response to mucosal infection.

Total white cell counts were reviewed in paediatric in-patients with viral gastroenteritis, bacterial gastroenteritis, delayed recovery following acute gastroenteritis, viral lower respiratory tract infections and cow's milk protein intolerance. The prevalence of neutrophilia was not different in the five groups. Neutropenia was common in association with the presence of viruses in stool or sputum, and was significantly more common in these groups than in patients with bacterial gastroenteritis and cow's milk protein intolerance. Neutropenia has not been previously reported in viral gastroenteritis. It was transient in nature and not related to age, sex, weight or antibiotic treatment; no pancreatic disorders were noted.

Bacterial Infections↗
PubMed1992

Confocal analysis of fluorescent bead uptake by mouse Peyer's patch follicle-associated M cells.

Latex beads coated with secretory immunoglobulin (IgA) instilled into mouse intestinal loops are taken up by M cells present in Peyer's patch follicle-associated epithelial tissue. Bead adsorption and uptake is greater at the edge compared with the apex of follicle domes. Coating beads with bovine serum albumin (BSA) causes a fourfold reduction in adsorption and a twentyfold reduction in uptake. Results demonstrate selectivity between adsorption and uptake and between the ability of different proteins to facilitate uptake.

Adsorption↗
PubMed1992

The value of proximal small intestinal biopsy in the differential diagnosis of chronic diarrhoea.

The value of proximal intestinal mucosal biopsy was reviewed in 381 children presenting with chronic diarrhoea over an eight year period. An enteropathy was detected in 44% of cases and was more frequently seen in those aged less than 6 months. A diagnosis was established in 91% of cases. The most common diagnosis was the postenteritis syndrome where the presence of an enteropathy indicated those requiring treatment with a cows' milk free diet. Other conditions where a biopsy facilitated diagnosis or treatment included giardiasis, enteropathogenic Escheriichia coli, crytosporidiosis, autoimmune enteropathy, and microvillous atrophy. Coeliac disease was considered in 55% of children and established in 8%, clearly identifying those requiring a gluten free diet. This also emphasises the important role of the biopsy procedure in the exclusion of specific diseases. Proximal small intestinal mucosal biopsy is an essential investigation in children with chronic diarrhoea in whom an enteropathy is suspected.

Adolescent↗
PubMed1992

Activation of lamina propria T cells induces crypt epithelial proliferation and goblet cell depletion in cultured human fetal colon.

An organ culture model has been used to study the effects of T cell activation in the human colon. Lamina propria T cells in explant cultures of human fetal colon (11 to 23 weeks gestation) were activated in situ using pokeweed mitogen or an anti-CD3 monoclonal antibody, and compared with unstimulated controls. After three days of culture, there was a two to four-fold increase in crypt epithelial cell proliferation in T cell stimulated explants of more than 15 weeks gestation, associated with a fall in crypt goblet cell numbers of up to 20-fold. By three days, the surface epithelium of stimulated explants appeared thin with loss of goblet cells, and by day 7, severe and extensive mucosal damage was observed by light and electron microscopy. These changes did not occur in control cultures and explants deficient in T cells (less than 16 weeks gestation), and were inhibited by cyclosporin A. These experiments indicate that the increase in epithelial cell proliferation and accompanying goblet cell depletion observed in colorectal crypts in chronic inflammatory bowel disease may be mediated by activated T cells.

Cell Division↗