As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significandy affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8-8 (0.6) nmol/min/mg protein; p<0-001 and 6-0 (1-3) v 9.5 (1.3) nmol/min/mg protein; p<0001). Over 50 years ofage this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2-2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence.The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism ofethanol associated with raised ethanol blood concentrations seen in these people. (Gut 1993; 34: 1433-1437 Recent studies in men '-3and

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Secretory phospholipase A(2) group IIA(sPLA(2) IIA) can be produced and secreted by various cell types either constitutionally or as an acute-phase reactant upon stimulation by proinflammatory cytokines. The enzyme prefers phosphatidylethanolamine and phosphatidylserine as substrates. One important biological function may be the hydrolytic destruction of bacterial membranes. It has been demonstrated, however, that sPLA(2) can also hydrolyse the phospholipid monolayers of high density lipoprotein (HDL) and low density lipoprotein (LDL) in vitro. Secretory phospholipase A(2)-modified LDL show increased affinity to glycosaminoglycans and proteoglycans, a tendency to aggregate, and an enhanced ability to deliver cholesterol to cells. Incubation of cultured macrophages with PLA(2)-treated LDL and HDL is associated with increased intracellular lipid accumulation, resulting in the formation of foam cells. Elevated sPLA(2)(IIA) activity in blood serum leads to an increased clearance of serum cholesterol. Secretory phospholipase A(2)(IIA) can also be detected in the intima, adventitia and media of the atherosclerotic wall not only in developed lesions but also in very early stages of atherosclerosis. The presence of DNA of Chlamydia pneumoniae, herpes simplex virus, and cytomegalovirus was found to be associated with sPLA(2)(IIA) expression and other signs of local inflammation. Thus, sPLA(2)(IIA) appears to be one important link between the lipid and the inflammation hypothesis of atherosclerosis.

Genotyping of mitochondrial aldehyde dehydrogenase (ALDH I) was performed in enzymatically amplified DNA of 20 Chinese, Japanese and South Korean families (85 individuals) and in 113 unrelated persons by employing allele-specific oligonucleotide probes and dot blot hybridization. Genotyping individuals with phenotypic deficiency of ALDH I activity always showed the presence of at least one mutant allele. The data are compatible with a model assuming dominant inheritance of the mutant allele, which we have previously suggested on the basis of a population study.

Abstract-Recent seroepidemiological and immunohistochemical studies have demonstrated an association between microbial infections and atherosclerosis. However, the mechanisms underlying this association are widely unknown. In the present study, arterial specimens obtained at autopsy after sudden death were analyzed concerning (1) the presence of Chlamydia pneumoniae, cytomegalovirus, herpes simplex virus, and Helicobacter pylori; (2) the expression of secretory group IIA phospholipase A 2 (sPLA 2 -IIA) and of proinflammatory cytokines; and (3) the stage of atherosclerosis. Genomic DNA of microbial pathogens was determined by the polymerase chain reaction technique. The expression of sPLA 2 -IIA was studied immunohistochemically by using monoclonal antibodies against human sPLA 2 -IIA. Transcripts specific for sPLA 2 -IIA, interleukin-1␤, tumor necrosis factor-␣, and interferon-␥ were identified by reverse transcription-polymerase chain reaction. In 18 of 102 analyzed specimens, DNA of microbial pathogens was found. Thirteen sections were positive for C pneumoniae, whereas 2 specimens were positive either for cytomegalovirus or for herpes simplex virus. One section contained genomic DNA of all 3 pathogens simultaneously. None of the analyzed tissues exhibited nucleic acids specific for H pylori. In addition to macrophage infiltrates, the presence of microbial DNA was closely associated with the occurrence of transcripts specific for proinflammatory cytokines and sPLA 2 -IIA. Pathogens as well as sPLA 2 -IIA and cytokines were found to be present not only in advanced but also in early stages of atherosclerosis. In tissues negative for sPLA 2 -IIA and cytokine expression, none of the pathogens could be identified. Because macrophages exposed to phospholipase A 2 -treated lipoproteins are transformed into foam cells in vitro, the results of this study suggest an alternative mechanism by which microbial infections may act in a proatherogenic fashion in vessel walls.