In the past Don W. Powell has collaborated on articles with R.Balfour Sartor and Roy C. Orlando. One of their most recent publications is Granulomatous enterocolitis induced in rats by purified bacterial cell wall fragments*. Which was published in journal Gastroenterology.

More information about Don W. Powell research including statistics on their citations can be found on their Copernicus Academic profile page.

Don W. Powell's Articles: (8)

Granulomatous enterocolitis induced in rats by purified bacterial cell wall fragments*

AbstractThis study was designed to determine if poorly biodegradable bacterial cell wall components can produce chronic intestinal inflammation. A sterile aqueous suspension of sonically disrupted group A or group D streptococcal cell wall fragments was injected intramurally into the small intestine and cecum of 100 rats. Gross findings in rats killed at intervals of 1 day to 6 mo included intestinal thickening, adhesions, and mesenteric contraction. Acute histologic inflammation subsided by 2 wk, but chronic granulomatous inflammation persisted for 6 mo in the rats injected with group A streptococcal cell wall fragments and 3 mo in the rats injected with group D streptococcal cell wall fragments. Ninety-six control rats identically injected with human serum albumin or phosphate-buffered saline demonstrated mild acute inflammation that resolved, with only 1 rat having chronic intestinal inflammation. Granulomas in the intestine, mesentery, and mesenteric lymph nodes developed in 46% of the rats injected with group A fragments and 45% of the rats injected with group D streptococcal cell wall fragments, compared with 20% of the controls injected with albumin and 4% of the controls injected with phosphate-buffered saline. Group A streptococcal antigen was detected by immunofluorescence at the site of inflammation for 4 mo, and possible reactivation of acute inflammation was seen up to 6 mo after injection. We conclude that bacterial cell wall fragments are capable of producing chronic granulomatous inflammation in the intestinal wall if present in appropriate particle size and concentration. We speculate that cell walls from the enteric microflora may leak across a permeable mucosa in chronic inflammatory bowel disease to initiate and sustain local and systemic inflammation.

Mucosal protection by sucralfate and its components in acid-exposed rabbit esophagus

AbstractSucralfate has been reported to protect the esophageal epithelium of the rabbit and cat against acid injury. To determine the contribution of its components, aluminum hydroxide and sucrose octasulfate (SOS), rabbit esophageal epithelia were mounted in Ussing chambers to monitor changes in electrical resistance (R) upon exposure to HCl (pH 1.4–1.6). In untreated tissues, acidification of the luminal bath produced a progressive decline in R, indicating increased epithelial permeability. Sucralfate added to the luminal bath 45 min after acidification increased R to preexposure levels—an effect accompanied by increased luminal pH. Similar to sucralfate, aluminum hydroxide added to the acidified bath increased R and luminal pH. However, the effect of aluminum hydroxide could be abolished by titration with HCl to maintain pH similar to acid-treated control tissues. Tissues treated with sucralfate and whose luminal solutions were titrated with HCl to maintain pH similar to controls no longer exhibited an increase in R but, in contrast to aluminum hydroxide treatment, the acid-induced decline in R was prevented. This action of sucralfate was shown to be a property of its other component, SOS. Sucrose octasulfate, like acid-titrated sucralfate solutions, did not increase luminal bath pH, yet prevented the acid-induced decline in R. Confirmation of protection by SOS was shown by additional morphologic and flux studies. Thus 1 h after luminal bath acidification in the Ussing chamber, SOS-treated tissues demonstrated less damage (injury score 0.6 ± 0.4 vs. 1.6 ± 0.3, p < 0.05) and lower permeability to mannitol (0.003 ± 0.001 vs. 0.013 ± 0.005 μmol/h · cm2, p < 0.05) than untreated tissues. Similarly, 1 h of luminal perfusion with HCl in vivo produced less damage (injury score 1.3 ± 0.5 vs. 3.5 ± 0.4, p < 0.05) and less H+ efflux from the lumen in SOS-treated than untreated tissues. These results indicate that sucralfate can protect against acid injury in esophagus and that this protection is mediated by (a) intraluminal pH buffering through its content of aluminum hydroxide and (b) enhancing mucosal defense against H+ entry and injury through its content of SOS.

Prostanoids inhibit intestinal NaCl absorption in experimental porcine cryptosporidiosis

AbstractBackground: Recent studies of piglet cryptosporidiosis have shown that impaired Na+-coupled glucose absorption is associated with a loss of two thirds of the villous absorptive surface and an inflammatory infiltration of the lamina propria. Because inflammatory cells release eicosanoids that may alter electrolyte transport, the present study examined the role of prostanoids on NaCl transport. Methods: Ileal mucosa was stripped of its muscle layers and mounted in Ussing chambers in the presence or absence of indomethacin. Adjacent tissue was also frozen for subsequent extraction and radioimmunoassay of prostaglandin E2 (PGE2). Results: Results showed that net Na+ absorption is inhibited and net Cl− secretion is induced in infected piglets. Indomethacin restored net Na+ and Cl− absorption to control levels and exogenous PGE reversed this effect. Radioimmunoassay of tissue extracts showed that PGE2 increased from 56.7 ± 9.6 ng/cm2 in control to 134 ± 16.8 ng/cm2 in infected ileum (P < 0.01). Conclusions: These data indicate that in addition to the Na-glucose malabsorption arising from structural damage, part of the diarrhea of these infected animals must be attributed to local prostanoid production.

Prostaglandin synthesis by enterocyte microsomes of rabbit small intestine

AbstractWe studied the prostaglandin (PG) synthetic capacity of microsomes of a relatively pure population of rabbit enterocytes and determined ideal conditions for product synthesis. The epithelial cells were freed from the basement membrane by a combination of calcium chelation and mechanical vibration, and 100,000 x g microsomes were prepared. These microsomes were found to synthesize PG from exogenously added arachidonic acid. The ideal conditions for the reaction were a microsomal protein concentration of 1.0 mg/ml, an arachidonic acid concentration of 33 μM, a reaction mixture pH of 8.0 − 9.5 and with epinephrine 1.5 mM added as a cofactor. The product yields increased linearly with time up to 30 min, of incubation and were inhibited by 100 μM indomethacin. Under the above ideal conditions enterocyte microsomes yielded the following products expressed as pmole/mg protein/20 min, incubation: PGF2α 98±7, PGE2 48±9, PGD2 28±7, TxB2 40±5, 6 Keto PGF1α 15 ± 6.

Basic—Alimentary TractHuman Colonic Myofibroblasts Promote Expansion of CD4+ CD25high Foxp3+ Regulatory T Cells

Background & AimsRegulatory T (Treg) cells (CD4+ CD25high FoxP3+) regulate mucosal tolerance; their adoptive transfer prevents or reduces symptoms of colitis in mouse models of inflammatory bowel disease. Colonic CD90+ mesenchymal myofibroblasts and fibroblasts (CMFs) are abundant, nonprofessional antigen-presenting cells in the normal human colonic mucosa that suppress proliferation of activated CD4+ effector T cells. We studied CMF suppressive capacity and evaluated the ability of CMF to induce Treg cells.MethodsAllogeneic cocultures of CD4+ T cells and CMFs, derived from normal mucosa of patients undergoing colectomy for colon cancer or inflamed colonic tissues from patients with ulcerative colitis or Crohn's disease, were used to assess activation of the Treg cells.ResultsCoculture of normal CMF with resting or naïve CD4+ T cells led to development of cells with a Treg phenotype; it also induced proliferation of a CD25+ CD127− FoxP3+ T cells, which expressed CTLA-4, interleukin-10, and transforming growth factor–β and had suppressive activities. In contrast to dendritic cells, normal CMFs required exogenous interleukin-2 to induce proliferation of naturally occurring Treg cells. Induction of Treg cells by normal CMFs required major histocompatibility complex class II and prostaglandin E2. CMFs from patients with inflammatory bowel diseases had reduced capacity to induce active Treg cells and increased capacity to transiently generate CD4+CD25+/− CD127+ T cells that express low levels of FoxP3.ConclusionsCMFs suppress the immune response in normal colon tissue and might therefore help maintain colonic mucosal tolerance. Alterations in CMF-mediated induction of Treg cells might promote pathogenesis of inflammatory bowel diseases.

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