A novel phosphorylation-dependent inhibitory protein (IP) of porcine aorta myosin light chain phosphatase (PA-MLCP) was purified to homogeneity from porcine aorta media. The molecular mass of IP was 20 kDa. IP phosphorylated by endogenous potentiating kinase (IP-K) inhibited not only PA-MLCP activity, but also that of the catalytic subunit of protein phosphatase-1. The amino acid sequence of a peptide derived from IP phosphorylated with IP-K, RHARVT*VK, shared one of the consensus sequences phosphorylatable by protein kinase C (PKC), where T* was phosphorylated. IP was phosphorylated by PKC and the phosphorylated product inhibited PA-MLCP as strongly as IP phosphorylated with IP-K.

Aldehyde dehydrogenase-2 (ALDH2) eliminates most of the acetaldehyde produced during alcohol metabolism. In some drinkers, a mutant ALDH2 allele contributes to diminished activity of the enzyme, dramatically increasing the risk for esophageal cancer. This study was designed to evaluate the ALDH2 gene polymorphism as a predictor of the development of cancers prevalent in Japanese alcoholics. We performed ALDH2 genotyping on lymphocyte DNA samples from Japanese alcoholic men (487 cancer-free; 237 with cancer, including 34 oropharyngolaryngeal, 87 esophageal, 58 stomach, 46 colon, 18 liver, 7 lung, 9 other sites, and 19 multiple primary cancers in two or three organs). The frequencies of the mutant ALDH2*2 allele were significantly higher in alcoholics with oropharyngolaryngeal (52.9%), esophageal (52.9%), stomach (22.4%), colon (21.7%) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (78.6%), than in cancer-free alcoholics (9.0%). After adjustment for age, daily alcohol consumption and amount of cigarette smoking, significantly increased risks (odds ratios) in the presence of the ALDH2 *2 allele were found for oropharyngolaryngeal (11.14), esophageal (12.50), stomach (3.49), colon (3.35), lung (8.20) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (54.20) but not for liver or other cancers. These results suggest a general role of acetaldehyde, a recognized animal carcinogen, in the development of human cancers.

Background. Epidemiologic studies have provided evidence that alcohol abuse is an important risk factor for esophageal carcinoma. However, no systematic screening program has been established yet in the early detection of esophageal cancer in high risk populations of heavy drinkers. Methods. A cohort of 629 male alcoholics (54 ± 8 years old) were consecutively and systematically screened by endoscopy combined with iodine staining and targeted biopsy at the National Institute on Alcoholism (Kanagawa, Japan). For mucosal carcinomas, endoscopic esophageal mucosal resection (EEMR) was used to serve confirmatory diagnostic and therapeutic purposes. Results. Iodine‐unstained lesions, distinctly demarcated, white, and 5 mm or larger in greatest dimension, were observed on the esophageal wall in 162 patients (25.8%). Thirty‐six such unstained lesions in 21 of 629 patients, with an unexpectedly high rate of 3.3%, turned out to be squamous cell carcinomas of the superficial type. According to some established criteria, EEMR was performed in 17 of these patients, 3 of whom were given additional irradiation. Esophagectomy was performed in two patients, chemotherapy combined with irradiation in one, whereas still another was followed endoscopically. The cancer invasion was confined within the epithelium in eight patients, to the proper mucosal layer in nine, and to the submucosa in four. Multiple logistic regression revealed that the risks for distinct iodine‐unstained lesions and superficial esophageal carcinoma increased independently for users of stronger alcoholic beverages, i.e., whiskey or shochu (odds ratio [OR] = 1.47 and 2.94, respectively) compared with lighter beverages, i.e., sake or beer and 30+ cigarettes/day (OR = 1.68 and 3.85, respectively). Conclusion. Routine application of this program for these high risk individuals yielded an unusually high rate of detection of esophageal carcinoma. Cancer 1995;76:928–34.

Four examples of an endoscopically detected oesophageal melanotic lesion were examined by light microscopy, light microscope histochemistry and transmission electron microscopy, and were compared with 13 control samples of normal oesophageal epithelium. By light microscopy, pigmented melanocytes lacking atypia and mitoses were observed amongst the keratinocytes in the basal layer of the oesophageal mucosa. Junctional activity was absent. The mechanism of pigmentation was studied and found to consist of: an increase in the number of melanocytes in the basal layer of the mucosa, an increase in the quantity of melanin in these melanocytes, transfer of melanin from melanocytes to keratinocytes and to macrophages and fibroblasts in the tunica propria. Since all the lesions demonstrated increased numbers of both melanocytes and melanosomes, the term oesophageal melanocytosis rather than melanosis is suggested, to emphasise the essential character of the lesion as a cellular proliferation. The value of sampling these pigmented lesions during endoscopy is emphasised as a means of obtaining well-preserved material for the evaluation of a lesion which some authorities have viewed as a possible precursor for oesophageal malignant melanoma.

BACKGROUND.Multiple intraesophageal primary cancer and upper aerodigestive tract (UADT) cancer associated uith esophageal cancer are common diseases, especially in heavy drinkers. Thev are often explained by the concept of field cancerization, which suggests a similar etiology. However, little is known about the nature of the hypothesized etiology. METHODS.Among 901 Japanese male alcoholics systeriiatically screened by upper gastrointestinal endoscopy (with esophageal iodine staining), 33 had squamous cell carcinoma of the esophagus. The multiplicity of their esophageal carcinoma and their concurrent UADT cancer was compared with their genotype for aldehyde dehydrogenase-2 (ALDH2), the major determinant of blood acetaldehyde concentration after drinking. RESULTS.Of 17 patients with inactive ALDH2, 13 (76.5%) had multiple primary carcinoma of the esophagus, whereas 5 of 16 (31.3%) with active ALDH2 had multiple carcinomas ( P < 0.01). The prevalence of concurrent UADT cancer was 29.4% in those patients with inactive ALDH2, compared with 6.3% in those patients with active ALDH2. CONCLUSIONS.Inactive ALDH2 is a risk factor for multiple Carcinoma of the esophagus in alcoholics. Acetaldehyde, a recognized animal carcinogen, appears to play a critical role in field cancerization.