Faculty Bibliography

We have examined alterations in six oncogenes--H-ras, K-ras, N-ras, myc, fos, and N-myc--in nine primary human colon tumors. Tumors were obtained within an hour of resection; as a control for each tumor, adjacent normal colon tissue was also obtained. Deoxyribonucleic acid extracted from each tissue sample was assayed by digesting with appropriate restriction endonucleases and, after gel electrophoresis and transfer to nitrocellulose, hybridizing with radiolabeled oncogene probes. Amplification of the myc locus, relative to adjacent normal colon tissue, was observed in two of these tumors; by dot-blotting, it was estimated that myc was amplified twofold to fivefold in each tumor. No rearrangements of myc, however, were observed in any of these tumors. Examination of the H-ras alleles of these nine tumors revealed that eight possess only 'common' alleles of this gene, and that each was identical to its control. Normal colon DNA of the ninth patient, however, was found to possess both a 'common' and a 'rare' allele, and the 'common' allele of H-ras appeared to be deleted in the tumor DNA of this patient. A restriction polymorphism indicative of a mutation in the 12th codon of K-ras was not found in any of these tumors, and we observed no evidence of rearrangement of amplification of the N-ras, K-ras, fos, or N-myc genes

Identifying the source of lower gastrointestinal hemorrhage in patients with chronic liver disease and portal hypertension can be challenging. We present 2 cases of hemorrhage from rectal varices and a discussion on the differences between simple hemorrhoids and rectal varices. Evaluation of rectal bleeding in patients with portal hypertension is discussed and possible therapeutic options are described

Gastrointestinal complications are an important aspect of the acquired immune deficiency syndrome. In this report we describe two male homosexuals with the acquired immune deficiency syndrome whose gastrointestinal symptoms culminated in the complication of intestinal perforation. Cytomegalovirus inclusions are seen prominently in the areas of perforation. The pathogenic role of cytomegalovirus in these cases is discussed. We propose that cytomegalovirus-induced enteritis may lead to bowel perforation in patients with the acquired immune deficiency syndrome.

Patient populations with a propensity to develop colon cancer have increased amounts of fecal cholesterol (and/or cholesterol metabolites). In this study, we report the effect of increased colonic concentrations of cholesterol and its metabolites on colon tumor promotion. The chemical carcinogen N-methyl-N-nitrosourea was instilled intrarectally into rats to initiate colon tumor formation. Following initiation, a cholesterol-supplemented diet was given. Despite a 2-fold elevation of fecal cholesterol, the number of colon tumors found was significantly reduced. These studies suggest that under certain conditions cholesterol may inhibit colon carcinogenesis

The effect of dietary supplementation with beta-sitosterol (0.2% of diet) was followed in Fischer rats after both acute and chronic feeding. Compared to controls after 3 and 7 days, the number of epithelial cells per crypt column in both plant sterol fed groups was shifted to lower values; moreover, fewer cells above cell position 12 were engaged in DNA synthesis. Continued feeding of beta-sitosterol for 28 weeks revealed the number and position of 3HTdR-labeled cells per crypt column after 1 pulse labeling to be similar to that seen in the acute phase. However, differences were more marked after 24 h showing the maximum number of labeled cells per column to be at least 25% less than the untreated group and the leading edge of labeled cells moving more slowly up the crypt wall. Rats treated with N-methyl-N-nitrosourea (MNU) intrarectally (8 mg/animal) while simultaneously consuming beta-sitosterol demonstrated a reduction in the size of the proliferative compartment as well as the number of labeled cells per crypt column as compared to rodents receiving just the carcinogen (3.3 and 5.4 mean labeled cells per column, respectively). At this time, MNU-treated rats fed beta-sitosterol had a significantly decreased colonic tumor incidence (Raicht et al. 1980). This plant sterol which passes through the digestive tract relatively unabsorbed appears to slow colonic epithelial cell proliferation resulting in a reduced expression of neoplastic transformation