Cytosolic aldehyde dehydrogenase (ALDH1) variants found in alcohol flushers

Although mitochondrial aldehyde dehydrogenase (ALDH2) has been thought to play a major role in acetaldehyde detoxification, and the high incidence of 'alcohol flushing' among Orientals is attributed to the inherited deficiency of ALDH2, the role of cytosolic aldehyde dehydrogenase (ALDH1) cannot be ignored. On the premise that alcohol flushing in Caucasians could be related to ALDH1 abnormalities, we examined the enzyme properties and electrophoretic mobilities of ALDH1 partially purified from red blood cells of nine unrelated alcohol flushers. One exhibited very low activity (10–20% of control level), and another exhibited moderately low activity (60%) and altered kinetic properties. The electrophoretic mobilities of these two samples were also distinguishable from the control samples. Immunological quantitation indicated that the amounts of ALDH1 protein in these two samples were not reduced in parallel with their enzyme deficiency. In the first case, the two characteristics, i.e. very low enzyme activity and alcohol flushing, were inherited by her daughter.     

Rapid screening of organosulfur agents for potential chemopreventive activity using the murine NA assay

The chemopreventive efficacy of 11 organosulfur compounds was assessed using the murine nuclear aberration (NA) assay in C57BL/6J mice. The sulfur compounds were introduced by stomach gavage. Benzo[a]pyrene (BP), which is a carcinogen known to a) undergo biotransformation by pathways mediated by P-450 and b) induce NA in the intestine, was used as the challenge. All animals were killed 48 hours after BP injection, and NA per crypt were scored. The results indicated that several agents were active in inhibiting BP nucleotoxicity to the colon, most notably, allyl mercaptan, benzyl mercaptan, and phenylethyl mercaptan. The NA assay was useful in effectively prescreening certain compounds for potential interactions with chemical carcinogens, thus serving as one indicator of chemopreventive activity.     

Prognostic value of ultrastructural characteristics of dysplastic changes in the esophagus

Dysplasia foci in the esophageal squamous epithelium against the background of various reactions of proliferation were studied by electron microscopy. Slightly altered tissue showed diverse cellularity, with dark cambial elements invariably present. With dysplasia advancing, the cell composition became uniform, with a high nuclear-cytoplasmic index. The dark cell pattern with numerous ribosomes was seen more often than that of keratinized clear cells. Small-cell focal proliferations are highly suggestive of precancer. Electron microscopy may be instrumental in eliciting more information on the risk of esophageal squamous epithelium precancer progressing to cancer since it provides data on cell composition, degree of cell differentiation and polysome formation as well as early signs of keratinization.     

Comparison of right colon, left colon, and rectal carcinoma

Three hundred fifteen cases of adenocarcinoma were analyzed for differences between lesions in the right colon, left colon, and rectum for the period 1978 to 1983. The right colon cancers accounted for 1/3 of the cases and were associated with a higher incidence of anemia. The incidence of obstruction was the same between the right and left colon but lower for the rectal lesions. Left colon and rectal cancers had a higher incidence of gross bleeding than right colon cancers, but all had a high rate of occult blood in the stool. The Duke stage of the lesions, which was similar throughout the colon and rectum, is a reliable prognostic indicator.     

Treatment of the anemia of rheumatoid arthritis with recombinant human erythropoietin: clinical and in vitro studies

Two anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (EPO) for 5 months. Both patients showed significant increases in hematocrit, red cell volumes, and marrow erythroid and megakaryocyte progenitor cells. No significant toxic effects from EPO were observed. These data indicate that EPO may be effective in overcoming the pathogenetic factors that limit erythropoiesis in rheumatoid arthritis.