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Biomedical subjects

P M Sherman

Publications and source records attributed to P M Sherman.

At least 19 recordsLinked to original sources
PubMed2000

cagE is a virulence factor associated with Helicobacter pylori-induced duodenal ulceration in children.

This study was undertaken to determine whether infection with Helicobacter pylori strains that contain the cagE gene was associated with duodenal ulceration in children. The presence of flaA, cagA, and cagE genes was determined by polymerase chain reaction in H. pylori previously cultured from 29 children. Twelve (92%) of 13 children with duodenal ulcers were infected with cagE-positive isolates, compared with only 5 (31%) of 16 with gastritis alone (P<.01). Infection of gastric cells in tissue culture by cagE-positive H. pylori resulted in greater increments in interleukin-8 levels compared with cagE-negative strains (2.3+/-0.1 vs. 1.3+/-0.2 ng/mL in AGS cells [P<.005]; 1.5+/-0.3 vs. 0.5+/-0.2 ng/mL in KATO-III cells [P<.05]). H. pylori-containing cagE was associated with the presence of duodenal ulceration in children. Enhanced chemokine production after infection with cagE-positive H. pylori could affect disease outcome.

Adolescent↗
PubMed2000

Escherichia coli Shiga toxins induce apoptosis in epithelial cells that is regulated by the Bcl-2 family.

Human intestinal cells lack globotriaosylceramide (Gb(3)), the receptor for Shiga toxin-1 (Stx1) and Shiga toxin-2 (Stx2). Therefore, the role of these toxins in mediating intestinal disease during infection with Shiga toxin-producing Escherichia coli is unclear. The aims of this study were to determine whether Stx1 and Stx2 induce apoptosis in epithelial cells expressing (HEp-2, Caco-2) or lacking (T84) Gb(3) and to characterize the role of the Bcl-2 family. Stx1 (12.5 ng/ml) induced apoptosis in both HEp-2 (21.9 +/- 7.9% vs. 0.8 +/- 0.3%, P = 0.01) and Caco-2 (10.1 +/- 1.2% vs. 3.1 +/- 0.4%, P = 0.006) cells but not in Gb(3)-deficient T84 cells. Toxin-mediated apoptosis of HEp-2 cells was associated with enhanced expression of the proapoptotic protein Bax. Inhibition of caspase activation prevented toxin-stimulated apoptosis. In addition, overexpression of Bcl-2 by transient transfection blocked Stx1-stimulated cell death. These findings indicate that Shiga toxins produced by E. coli signal Gb(3)-expressing epithelial cells to undergo apoptosis in association with enhanced Bax expression, thereby resulting in activation of the caspase cascade.

Apoptosis↗
PubMed2000

Implications of antibiotic resistance in the management of Helicobacter pylori infection: Canadian Helicobacter Study Group.

Eradication of Helicobacter pylori from the gastric and duodenal mucosa is an important clinical goal in the treatment of infected patients with peptic ulcer disease and other H pylori-associated conditions. Although several oral drug combination regimens are associated with eradication rates of approximately 85% in controlled trials, the success rate in patients infected with a resistant strain of H pylori is closer to 75%. Resistance to metronidazole and clarithromycin, which are common components of combination treatment regimens, is of greatest concern. Reported rates of H pylori resistance to various antibiotics vary considerably. In Canada, the data documenting H pylori susceptibility are limited but suggest that resistance to these antibiotics varies geographically and within specific treatment groups. Although susceptibility testing is not a prerequisite for initial treatment of individual patients infected with H pylori, formal efforts to identify and monitor both the causes and prevalence of antibiotic resistance across Canada are a much needed step in the ongoing management of this important infection. Recommended treatment regimens may be useful, even for treating apparently resistant H pylori strains. However, it is important to understand the mechanisms of the development of resistant strains to manage patients with treatment failure better.

Anti-Bacterial Agents↗
PubMed1999

Phosphatidylethanolamine recognition promotes enteropathogenic E. coli and enterohemorrhagic E. coli host cell attachment.

Using both solid phase and liposome aggregation assays, we screened a variety of glycolipids and phospholipids and found that EHEC and EPEC bind specifically and in a dose-dependent manner to PE. This binding was consistently observed whether the lipid was immobilized on a thin layer chromatography plate, in a microtitre well or incorporated into a unilamellar vesicle suspended in aqueous solution. There was no evidence of binding to other phospholipids such as phosphatidylcholine (PC) or phosphatidylserine (PS). Bacterial binding to two epithelial cell lines also correlated with the level of outer leaflet PE and was reduced following preincubation with anti-PE. The PE-binding phenotype of EPEC appeared to correlate with the bundle-forming pilus (bfp) genotype of a number of clinical isolates. These results provide evidence of a receptor role for PE in the adhesion of EHEC and EPEC to host cells.

Bacterial Adhesion↗
PubMed1999

Assessing activity of pediatric Crohn's disease: which index to use?

BACKGROUND & AIMS: The Pediatric Crohn's Disease Activity Index (PCDAI) is a multi-item measure that, in contrast to the adult-derived CDAI, includes linear growth and places less emphasis on subjectively reported symptoms but more on laboratory parameters of intestinal inflammation. This study compared the feasibility, validity, and responsiveness of PCDAI vs. CDAI in the assessment of Crohn's disease activity among pediatric patients. METHODS: Eighty-one children and adolescents with Crohn's disease were studied. A gastroenterologist provided a categorical global assessment of disease activity as quiescent, mild, moderate, or severe after interview and physical examination. CDAI and PCDAI scores were calculated by an independent appraiser. RESULTS: Mean values within each category for CDAI and PCDAI differed significantly between strata. PCDAI values were quiescent, 6.8 +/- 6. 6; mild, 18.7 +/- 7.3; moderate, 38.5 +/- 12.9; and severe, 54.2 +/- 14.0. CDAI values were quiescent, 23.5 +/- 53.6; mild, 96.0 +/- 60. 7; moderate, 184.5 +/- 97.0; and severe, 284.4 +/- 85.8. Individual scores showed less overlap between strata for PCDAI than for CDAI. PCDAI showed better correlation with serum orosomucoid and platelet count, laboratory parameters of inflammation not included in either index. CONCLUSIONS: Both PCDAI and CDAI reflect disease activity in pediatric Crohn's disease. PCDAI is better at discriminating between levels of disease activity.

Adolescent↗
PubMed1999

Development of a quality-of-life index for pediatric inflammatory bowel disease: dealing with differences related to age and IBD type.

BACKGROUND: A child- and adolescent-generated IBD quality-of-life index was designed to be descriptive (to be used to assess the overall impact of IBD on individual patients), and evaluative (to be used as an outcome measure in clinical trials). METHODS: Item-generation and item-reduction interviews with 82 patients with IBD aged 8 to 17 years (61 with Crohn's disease, 21 with ulcerative colitis; 36 girls, 45 boys) generated a list of ways in which their lives were affected by IBD. These issues were incorporated into an item-reduction questionnaire, which was administered to 117 patients (87 Crohn's disease, 30 ulcerative colitis). Patients indicated on a visual analog scale how important an item was to them and how often it bothered them. Mean and median importance-plus-frequency scores for each issue were calculated for the entire group and among patients in subgroups according to age and IBD type. RESULTS: Ulcerative colitis and Crohn's disease affect the lives of children and adolescents differently. Bowel symptoms are more troubling and disabling to patients with ulcerative colitis, whereas systemic symptoms and body image concerns are greater for patients with Crohn's disease. The impact of Crohn's disease on ability to function in school and leisure activities is greater. Worries about future health problems and about the effects of IBD on the family are shared. Crohn's disease and ulcerative colitis trigger emotional responses of unfairness and frustration, but anger and embarrassment are more prevalent in ulcerative colitis. Disparities between age groups are fewer and less marked than those between types of IBD. CONCLUSION: In selection of items to be retained in a pediatric IBD quality-of-life measure, the variation in concerns with disease type must be considered. A single index to assess IBD-related quality of life must include items of major importance to one subgroup of patients, even if not important to all. Alternately, a core of common concerns could be supplemented by disease-specific modules, thereby increasing the content validity of the tool for all patients.

Adolescent↗