Abnormalities in the biosynthesis of type III procollagen in cultured skin fibroblasts from two patients with multiple aneurysms.

We examined the synthesis of collagenous proteins by cultured skin fibroblasts taken from 14 patients with an abdominal aortic aneurysm and either an aneurysm at a second site (8 patients) or a first order relative with an abdominal aortic aneurysm (6 patients). Fibroblasts were labeled with [3H] proline and, following pepsin digestion of media proteins, the ratio of type I/III collagen was examined by denaturing polyacrylamide gel electrophoresis (SDS-PAGE). With the exception of two patients, the ratio of type I/III collagen in the media of fibroblasts from aneurysm patients was similar to control values (6 controls). In two of the patients, the type I/III collagen ratio was greater than 3 standard deviations from the mean of both control ratios and those of other aneurysm patients. mRNA levels coding for type III procollagen, however, were normal in both patients. Patient #1 (ME) showed reduced type III procollagen on SDS-PAGE analysis of intracellular proteins. Intracellular and media type III procollagen levels were normal in patient #2 (HR), but media type III collagen was reduced by over 50% after digestion with a combination of trypsin and alpha-chymotrypsin for 5 minutes at 36 degrees C. Control type III collagen was only reduced after digestion at 39 degrees C. These data suggest an altered thermal stability of the type III collagen trimer synthesized by this patient, probably due to a mutation in the amino acid sequence. The data presented in this paper suggest that some forms of common abdominal aortic aneurysms may be caused by mutations in the gene coding for type III procollagen.

Factors regulating the exchange of nutrients and drugs between lymph and blood in the small intestine.

An experimental design was developed to study the factors regulating the absorption of nutrients and drugs into the intestinal lymphatic system in normal and cirrhotic rats. Test compounds given via in situ jejunal luminal perfusion or systemic intravenous infusion were measured simultaneously in intestinal lymph, portal venous plasma and intestinal perfusate. Steady-state lymph plasma concentration ratios were used to compare the permeability characteristics of the intestinal mucosal-lymph and blood-lymph barriers. The absorption of compounds from the interstitial space into the intestinal lymphatic system is determined primarily by their permeability through the capillary of the portal circulation and by their lipid solubility; if a compound is too large to be absorbed into the portal circulation it is absorbed into the intestinal lymphatics.

Five year survival in patients with carcinoma of the rectum treated by electrocoagulation.

Sixty-eight patients with rectal cancer treated by electrocoagulation are reviewed. All were followed up for a minimum of 5 years. The survival rate in patients with small exophytic cancers is greater than 70 percent. However, the recurrence rate after electrocoagulation is 40 percent. Electrocoagulation offers an alternative for the primary treatment of rectal cancer, particularly in older patients with small lesions.

Localization and histochemical correlation of 73As by whole-body autoradiography in mice.

Whole-body sagittal sections of mice administered [73As] H3AsO4 intravenously were processed for autoradiography and histochemistry for glucose-6-phosphatase or alkaline phosphatase. The intense localization of 73As in bone, kidney cortex, intestinal mucosa, and hair follicles corresponded exactly with the histochemical activity of glucose-6-phosphatase and alkaline phosphatase in sections containing no arsenic. The activity of glucose-6-phosphatase was inhibited in all of these sites in sections containing arsenic.