There were no data concerning the incidence of inflammatory bowel disease (IBD) in France.

Phosphatidylethanol, whose synthesis is catalyzed by a phospholipase D in a transphosphatidylation reaction, is a unique metabolite of ethanol. Phorbol 12-tetradecanoate 13-acetate, a tumor-promoting phorbol ester and stimulator of protein kinase C, activates this enzyme in peripheral blood lymphocytes. This system has been developed into an assay for measuring the potential of this pathway in human subjects. A pilot study of phosphatidylethanol synthesis in lymphocytes of adult males who have both an alcohol dependency and a family history ofalcoholism has revealed that the average potential for phosphatidylethanol synthesis in this population is significantly elevated over that of control subjects.In the course of investigating the effects of the tumorpromoting phorbol ester, phorbol 12-tetradecanoate 13-acetate (TPA) on the metabolism of [3H]arachidonic acid during the mitogenic activation of lymphocytes, Wrighton et al.(1) discovered that a class of unusual lipid metabolites were rapidly formed in response to TPA. These products were subsequently characterized to be glycerolphospholipids in which the typical head group (i.e., choline, ethanolamine, inositol, or serine) had been replaced by ethanol (2) (Fig. 1) Our finding that the pathway for phosphatidylethanol synthesis could be activated by TPA in human lymphocytes from peripheral blood has opened the way to exploring whether the ability of human subjects to synthesize this unique metabolite of ethanol correlates in any way with the individual's dependency on alcohol. To explore this question, an assay was developed for measuring the induced synthesis of phosphatidylethanol in short-term cultures of human peripheral blood lymphocytes. This test has been used to assess the ability of two groups of males to synthesize phosphatidylethanol: group 1 consisted of 24 nonalcoholic males with no family history of alcoholism in any first degree relatives; and group 2 consisted of 25 males who met the DSM-III (Disease Statistical Manual, version 3, American Psychiatric Association) criteria for alcohol dependence and who also reported an alcoholic parent who met the DSM-III criteria for abuse and/or dependence (7).The results of this pilot study show that adult males with both a personal history of alcohol dependence and a family history of alcoholism (DSM-III criteria) have a significantly greater average ability to synthesize phosphatidylethanol than do their control counterparts. These preliminary findings provide the first evidence that the synthesis of phosphatidylethanol and the regulation of this phospholipase Dcatalyzed pathway may play an important role in alcohol dependency-and may contribute as well to the development of alcohol-related pathology. A molecular and genetic exploration of the components in this pathway is expected to provide new approaches to the therapy and prophylaxis of alcoholism in humans. MATERIALS AND METHODS Assay of Potential for Phosphatidylethanol Synthesis byUsing Human Lymphocytes. Approximately 20 ml of venous blood was...

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