Selective depletion of Kupffer cells in mice by intact ricin.
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Animals↗
Biomedical subjects
M E Zenilman
Publications and source records attributed to M E Zenilman.
Use of ricin A-chain to selectively deplete Kupffer cells.
We used the A-chain of the toxin ricin (RTA) as a toxin specific to Kupffer cells in mice. RTA is specifically taken up by the mannose receptor present exclusively in macrophages. Kupffer cells were quantitated by shifts in beta-glucuronidase clearance and microscopic counts of cells which phagocytosed India ink. When compared to saline controls, 20 mg/kg of RTA intraperitoneally (divided over 4 days) or intraportally (single doses) significantly prolonged the t 1/2 half-life of beta-glucuronidase by 270 +/- 37 and 210 +/- 8%, respectively. Kupffer cell numbers were significantly decreased by 27 +/- 8 and 33 +/- 16%. This effect persisted for at least 3 days after toxin administration. Despite effects on Kupffer cell number, minimal histological damage to liver, spleen, lung, and heart was noted. Higher doses of RTA or doses potentiated by ureteral ligation to prevent renal clearance resulted in prohibitive mortalities and histologic liver damage. Doses of Hura crepitans inhibitor, a toxin similar to RTA but not mannose-receptor specific, did not affect Kupffer cell numbers. We conclude that RTA given both intraperitoneally and intraportally at low doses is toxic specifically to Kupffer cells. Kupffer cell numbers can be indirectly measured by beta-glucuronidase clearance.
Animals↗
Emergencies in inflammatory bowel disease.
A review of acute emergencies in inflammatory bowel disease is presented. Caveats include prompt surgical drainage of loculated abscesses and aggressive management of bleeding or perforation. Adequate nutritional and immunologic assessment of all patients prior to surgery is paramount and has resulted in the widespread use of total parenteral nutrition. Aggressive medical therapy, particularly steroids, may be useful in "cooling down" cases of acute inflammation prior to surgery. This is particularly useful in Crohn's disease, in which recurrences abound and surgery has a significant degree of complication and recurrence. When urgent operation is necessary for acute ulcerative colitis, abdominal colectomy with ileostomy and preservation of the rectum is generally indicated. This will allow subsequent mucosal proctectomy and ileoanal anastomosis. When urgent colectomy is indicated for Crohn's colitis without rectal involvement, ileorectal anastomosis can be considered either as a primary or secondary procedure. If toxic megacolon is present, an initial trial of medical therapy is warranted in order to allow a single-staged operation to be performed electively.
Colitis, Ulcerative↗
Graded effect of protein on regional myoelectric activity of the opossum sphincter of Oddi.
Although it is known that the sphincter of Oddi exhibits a myoelectric response to intraluminal nutrients, the effect of specific dietary components has not been well characterized. The aim of this study was to determine the effect of intragastric instillation of a protein meal on regional myoelectric activity of the opossum sphincter of Oddi. Seven adult opossums were chronically prepared with self-retaining bipolar electrodes secured to the proximal and distal parts of the sphincter. After a 2-week recovery period, and with the animals fasted and conscious, myoelectric activity was recorded for two cycles of the migrating myoelectric complex. The animals then received graded calories of protein through an orogastric tube and recordings were continued until return of the fasted cyclic activity. Doses of 60, 120, and 240 kcal of protein elicited increases in myoelectric spike activity of the proximal sphincter of 18.7%, 41.9%, and 66.6%, respectively. Similarly, the length of the fed state was prolonged by increasing caloric loads, with mean (plus or minus standard error of the mean) times of 266 +/- 25, 292 +/- 15, and 375 +/- 42 minutes for each dose. A similar relationship was noted in the distal part of the sphincter. Regression analysis between the proximal and distal parts of the sphincter during the fasted and fed states showed a strong and persistent correlation of gradient of spikeburst frequency. We conclude that myoelectric spike frequency of the opossum sphincter of Oddi exhibits a dose-related response to intragastric protein calories. Furthermore, the proximal and distal parts of the sphincter remain electrically coupled, with the proximal region pacing the distal region during the fasted state and after protein administration.
Ampulla of Vater↗
Previous abdominal colectomy affects functional results after ileal pouch-anal anastomosis.
We assessed the effect of previous abdominal colectomy on functional results after ileal "J" pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Twenty-five patients with colectomy prior to IPAA were compared with 22 patients who underwent noncolonic abdominal operations prior to IPAA. No differences were observed in pre- or postoperative resting anal sphincter pressure, squeeze pressure, or rectal inhibitory reflex. Previous colectomy was associated with a greater incidence of postoperative small bowel obstruction. Mean +/- SEM daily stool frequency at 1 and 12 months postoperatively, respectively, was 8.9 +/- 0.8 and 5.7 +/- 0.3 for patients who had undergone previous colectomy, and 8.2 +/- 0.7 and 6.0 +/- 0.5 for the no-previous colectomy group (p = not significant). At the same postoperative intervals, nocturnal stool frequency was 1.9 +/- 0.3 and 1.1 +/- 0.2 for the colectomy group and 1.5 +/- 0.3 and 0.6 +/- 0.1 for the no colectomy group (p = 0.05 at 1 year). More patients in the previous colectomy group had greater than or equal to 1 nocturnal stool after 1 year (71% versus 33%, p = 0.03). Although pouch capacity at 1 year was not different in the 2 groups, pouch capacity was directly related to stool frequency in the no colectomy group (r2 = 0.48, p = 0.01), but not in the previous colectomy group (r2 = 0.08, p = not significant). We conclude that previous abdominal colectomy may be associated with a higher overall incidence of small bowel obstruction. Moreover, previous colectomy is a determinant of postoperative nocturnal stool frequency after IPAA, most likely due to altered ileal pouch function.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Ectopic expression of reg protein: A marker of colorectal mucosa at risk for neoplasia.
Pancreatic regenerating gene (reg I) messenger RNA is overexpressed within the pancreas following injury and resection. Its level of expression corresponds to the level of cellular dedifferentiation. Human reg I has been localized to chromosome 2p12, and ectopic expression of its mRNA has been found within colorectal tumors. We postulated that colorectal production of reg I might either be a marker for the presence of cancer or define mucosa at risk for development of neoplasia. Using a monoclonal antibody to reg I, regenerating gene protein was histochemically mapped in 56 cases of documented colorectal adenocarcinoma. In sections of colon from normal control subjects no reg I protein was noted, whereas 58.9% of the specimens from cancer patients stained positive for reg I. Although a correlation was noted between reg I staining and Dukes' stage, there was no correlation with histologic grade or 5-year patient survival. In 39 of 55 cancer specimens the transition zone (interface) between the neoplasm and normal mucosa was visualized; 100% of the transition zones contained cells that stained strongly positive for reg I. We conclude that reg I protein is ectopically expressed in colorectal mucosa at the transition zone of colorectal cancer, and occasionally within the tumor itself. Although ectopic reg I expression in colorectal epithelia is not a marker for the presence of carcinoma, it may be a sensitive marker for mucosa at risk for development of neoplasia.
Adenocarcinoma↗