A potential mechanism for fumonisin B(1)-mediated hepatocarcinogenesis: cyclin D1 stabilization associated with activation of Akt and inhibition of GSK-3beta activity.

Fumonisin B(1) (FB(1)) is a worldwide corn contaminant and has been epidemiologically linked to the high incidence of human esophageal cancer in South Africa and China. FB(1) is hepatocarcinogenic in rats by an unknown mechanism. Inhibition of ceramide synthase and disruption of membrane phospholipids have been shown to be mechanisms of toxicity. Here we show overexpression of cyclin D1 protein in both preneoplastic and neoplastic liver specimens obtained from a long-term feeding study of FB(1) in rats. In rats fed FB(1) short-term, cyclin D1 protein levels in liver were increased up to five-fold in a dose-responsive manner. Northern blot analysis demonstrated no increase in mRNA levels of cyclin D1. 2D electrophoresis of cyclin D1 protein in FB(1)-treated samples showed a distinct pattern of migration (presence of less negatively charged form of the protein) that differed from controls. Recently, it has been shown that phosphorylation of cyclin D1 by glycogen synthase kinase 3beta (GSK-3beta) on a single threonine residue (Thr-286) positively regulates proteosomal degradation of cyclin D1. In FB(1)-treated samples we detected GSK-3beta phosphorylated on serine 9; activated protein kinase B (Akt) appears to be responsible for this activity-inhibiting phosphorylation. These findings suggest that overexpression of cyclin D1 results from stabilization due to a lack of phosphorylation mediated by GSK-3beta. We also observed an increase in cyclin dependent kinase 4 (Cdk4) complexes with cyclin D1 in FB(1)-treated samples; additionally, elevated Cdk4 activity was shown by increased phosphorylation of the retinoblastoma protein. In summary, the activation of Akt leads to increased survival, inhibition of GSK-3beta activity and post-translational stabilization of cyclin D1, all events responsible for disruption of the cell cycle G(1)/S restriction point in hepatocytes. This is the first report suggesting the mechanism by which FB(1) acts as a carcinogen.

Association of heart rate and heart-rate variability with scores on the emotion profile index in patients with acute coronary heart disease.

We investigated the link between the eight basic emotions named by Plutchik and heart rate, heart-rate variability in the 114 patients, 86 men and 28 women (M = 53.8 yr., SD = 8.0) with acute coronary heart disease during the initial 24-hr. stay in the coronary care unit and again at hospital discharge. Variability in heart rate was significantly positively associated with scores on Trust (the emotional state acceptance) at hospital admission and discharge in the patients with unstable angina and non-Q-wave infarction, on Aggression in the patients with unstable angina at hospital discharge and at hospital admission in the patients with non-Q-wave infarction. There was inverse relation on Timid (the emotional state fear) and Gregarious (joy) at hospital admission and on Distrust (disgust or rejection), Depressed (sadness), and Dyscontrol (impulsiveness) at hospital discharge in the patient with non-Q-wave infarction. There was no significant association between heart-rate variability and the scores on the Emotion Profile Index in the patients with anterior and posterior myocardial infarction. There was no statistically significant association between heart rate and scores on the Emotion Profile Index in the patients with acute coronary disease at hospital admission and discharge. Our results suggest psychological interventions that enhance emotional states represented by the Trust and Aggression scales and minimize those represented by Depressed, Dyscontrol, Timid, and Distrust scales could have a beneficial effect on cardiovascular function in the patients with unstable angina and non-Q-wave infarction in a hospital setting.

Stimulation of the high-affinity IgE receptor results in the tyrosine phosphorylation of a 60 kD protein which is associated with the protein-tyrosine kinase, Csk.

The protein tyrosine kinase Csk downregulates the activity of the Src family of kinases and has a negative effect on signal transduction through several Src kinase-associated receptors. Because the Src-family kinase Lyn plays a pivotal role in FcepsilonRI-mediated cellular activation, we examined whether Csk is involved in FcepsilonRI signaling events. Using anti-Csk antibodies and recombinant fusion proteins we detected a single tyrosine-phosphorylated protein of 60 kD (herein referred to as 'p60') that associates with the SH2 domain of Csk after stimulation of the FcepsilonRI. p60 phosphorylation reached a maximum within one minute and remained constant while the receptors were aggregated; disaggregation of the receptors resulted in rapid dephosphorylation of p60. The phosphorylation of p60 was only detected after activation by IgE and antigen and not by stimulation with PMA and/or ionomycin. Phosphorylated p60 was associated entirely with the membrane fraction of the cells. A considerable fraction of Csk was associated with the membrane in both unstimulated and stimulated cells, this fraction did not change upon activation. p60 coprecipitated with Csk from both unstimulated and FcepsilonRI stimulated cells and was phosphorylated by the immunocomplex. Total kinase activity of Csk immunoprecipitates increased upon FcepsilonRI stimulation. p60 did not react with antibodies to a number of known signaling molecules, including the recently cloned, GAP-associated protein, p62dok. Our data demonstrate that Csk associates with a membrane-anchored protein complex that is directly involved in FcepsilonRI signal transduction.

Peptide binding to MHC class I is determined by individual pockets in the binding groove.

H-2Kb and HLA-A2 are MHC4 class I molecules with a similar overall structure. Important differences between these two class I molecules reside in the structure of the individual pockets in the antigenic-peptide-binding groove. H-2Kb, which has a deep C pocket, binds specifically peptides with a tyrosine or a phenylalanine at position 5. In contrast, HLA-A2 has a shallow C pocket, which cannot accommodate large side chains at position 5. Site-directed mutagenesis was used to generate a chimera between the murine H-2Kb and the human HLA-A2 [H-2Kb/HLA-A2(C')]. The structure of this chimera is similar to H-2Kb except for the region around the deep C pocket, where residues at positions 9, 97 and 99 were substituted with those bulkier residues from HLA-A2. Peptide binding between this chimera and H-2Kb-binding peptides [VSV (52-59), OVA (257-264), and MCMV pp89 (168-176)], revealed that the deep C pocket of H-2Kb was crucial for high-affinity binding. While a peptide, VSV (52-59), was found to bind with severalfold lower 'affinity' to H-2Kb/HLA-A2(C') than to the wild-type H-2Kb, a VSV analogue with the tyrosine in position 5 (Tyr5) substituted with an alanine was found to bind with a similar 'affinity' to both MHC class I molecules. Computer-aided modelling of the H-2Kb/HLA-A2(C') complex indicates that the VSV (52-59) peptide probably binds to the chimeric MHC molecule with the peptide side chain of anchor residue Tyr5 pointing away from the groove. These results confirm a role of the individual pockets in determining peptide-binding affinity and specificity and suggest that this may be accomplished by changes in side-chain orientation.

Heart rate and heart-rate variability in patients with acute coronary heart disease classified on Bortner's scale as type A and type B.

We investigated heart rate and heart-rate variability in 82 patients, 60 men and 22 women (M = 54 yr., SD = 9) with acute coronary heart disease and scores on Bortner's scale at hospital admission and discharge. 48 patients were classified by their scores on Bortner's scale as Type A and 34 as Type B. Patients with acute coronary heart disease classified as Type A had a significantly lower mean heart rate than patients with acute coronary heart disease classified as Type B during the day at hospital admission and discharge and during the night at hospital discharge. Mean heart-rate variability was also significantly higher in the patients with acute coronary heart disease classified as Type A than in the patients with acute coronary heart disease classified as Type B during the day at hospital admission and discharge. The differences between two groups on the average heart rate and heart-rate variability were not significant during the night at hospital admission. In our study the patients with acute coronary heart disease classified by scores on Bortner's scale as Type A had higher vagal tone and more favorable sympathovagal balance than patients classified as Type B. This finding may have implications for the treatment of patients with acute coronary heart disease and may suggest some explanation about the protective effect of Type A behavior also.

Interleukin-4 (IL-4) induces phosphatidylinositol 3-kinase (p85) dephosphorylation. Implications for the role of SHP-1 in the IL-4-induced signals in human B cells.

Interleukin 4 (IL-4) is a potent cytokine produced by T cells and to a lesser extent by tumor-associated natural killer cells, basophils, and mast cells. IL-4 treatment of T cells and macrophages leads to augmentation of their cytotoxic activity. In human B cells, IL-4 is a potent stimulator of Ig class switching from IgM to IgE. The diverse biological responses induced by IL-4 are mediated through a high affinity receptor complex (IL-4R). Although a wealth of information has accumulated regarding IL-4R, the exact mechanisms of IL-4R-mediated signaling pathways in human B cells are not well defined. In an attempt to characterize the IL-4-induced signals in human B cells, we have found that IL-4 treatment induced rapid dephosphorylation of the 85-kDa regulatory subunit of phosphatidylinositol 3-kinase. To identify the protein-tyrosine phosphatase involved in the IL-4-mediated dephosphorylation, we performed Western blot analysis using monoclonal antibodies specific to protein-tyrosine phosphatases. Upon IL-4 treatment, SHP-1 was specifically translocated to the cellular membrane fraction. Furthermore, immunoprecipitation studies revealed that SHP-1 could be specifically coimmunoprecipitated with the IL-4R as well as with phosphatidylinositol 3-kinase (p85). Collectively, our observations suggest that in addition to protein phosphorylation, protein tyrosine dephosphorylation may play a role in the IL-4-induced signaling pathways.

Bortner type A scores and eight basic emotions for survivors of ventricular fibrillation and left ventricular failure during acute myocardial infarction.

We examined Bortner scores for behavioral patterns and eight basic emotional dimensions named by Plutchik for patients with acute myocardial infarction who survived ventricular fibrillation and left ventricular failure. There were 70 patients, 48 men and 22 women ages 26 to 69 yr. (M = 54, SD = 8), admitted to the coronary care unit within 24 hours of the onset of a long-lasting chest pain. Six patients survived an episode of ventricular fibrillation that occurred within 24 to 48 hours after their admission. 15 patients developed left ventricular failure and were in Killip Classes II and III. Patients with acute myocardial infarction and left ventricular failure had mean Bortner scores significantly lower than others with acute myocardial infarction and were classed as Type B behavior. There was no difference in Bortner scores between patients with ventricular fibrillation and others with acute myocardial infarction. Patients with acute myocardial infarction and left ventricular failure scored significantly higher on Timid than others with acute myocardial infarction. Patients with acute myocardial infarction and ventricular fibrillation scored significantly lower on Depressed and higher on Distrust than other patients with acute myocardial infarction. Our findings suggest that patients with ventricular fibrillation and low scores on Depressed have good hospital prognosis. They are more critical and tend to reject people and ideas more than patients with acute myocardial infarction. This study suggests that the way in which patients with acute myocardial infarction react to their infarction, in terms of eight basic emotions and test patterns, is dependent on the complications of myocardial infarction.

CSK associates with the TCR zeta and epsilon chains via its SH2 domain; a mechanism for turning off TCR signaling.

Recent biochemical and genetic studies implicate Csk (carboxy-terminal Src kinase) as the one of the main downregulators of the activity of members of the Src family of kinases. Csk is probably involved in the downregulation of TCR signaling by C-terminal tyrosine phosphorylation of Lck and Fyn, but the mechanism whereby Csk targets these Src family members is not known. Here we report the association of Csk with the TCR complex, an interaction mediated by the binding of the Csk-SH2 domain to phosphorylated zeta and epsilon chains of the TCR complex. The interaction with TCR brings Csk into close contact with Lck and Fyn which are known to be associated with TCR, either functionally and/or physically. This finding suggests a novel mechanism whereby TCR signaling is turned off.

Csk is constitutively associated with a 60-kDa tyrosine-phosphorylated protein in human T cells.

The protein-tyrosine kinase Csk is one of the main down-regulators of the Src family of kinases. Csk may be involved in the down-regulation of T cell receptor (TCR) signaling by C-terminal tyrosine phosphorylation of Lck and Fyn; however, it is not known how Csk activity is regulated or how it targets these Src family members. We used Jurkat T cells and normal human T cells to examine proteins that bind to the SH2 domain of Csk. In both Jurkat and normal T cells, the Src homology 2 (SH2) domain of Csk bound constitutively to a tyrosine-phosphorylated protein of 60 kDa (p60). The 60-kDa protein was detected in Csk immunoprecipitates from both unstimulated and CD3-stimulated cells. In addition to p60, a protein of 190 kDa coprecipitated with Csk, and both proteins were phosphorylated on tyrosine residues by the immunocomplex. Small amounts of GTPase-activating protein (GAP) were detected in anti-Csk immunoprecipitates, suggesting that p60 may be a GAP-associated protein. Our data demonstrate that the SH2 domain of Csk specifically associates with at least two tyrosine-phosphorylated proteins in normal human T cells, that this association is independent of TCR/CD3 activation, and that Csk may be a part of a multiprotein complex containing GAP.

Arterial hypertension in workers: prevalence, awareness, treatment, control and heart changes.

Hypertension prevalence, awareness of high blood pressure, its treatment and control were estimated in 1100 workers, between the ages 35 and 59. Hypertension was defined as blood pressure > or = 160/95 mm Hg. The incidence of hypertensive heart disease was also investigated. All hypertensive persons were taken M-mode and 2-dimensional echocardiograms, electrocardiogram and chest X-ray. The criteria for both sexes were Casale's ECG for left ventricular hypertrophy and echocardiographic left ventricular mass index of 120 g/m or greater. The prevalence of hypertension was 14%. The percentage of persons who were aware of hypertension but did not receive treatment was 66%; 28% were treated but were not adequately controlled for high blood pressure. Only 6% of hypertensive workers received treatment and had high blood pressure under control. The prevalence of heart changes among the hypertensive workers as determined by echocardiographic standards was 67%, by electrocardiographic standards 19% and chest X-ray standards 29%. Systolic blood pressure was significantly related to ventricular mass (r = 0.34; 0.26) and voltage of R in a VL + S in V3 (r = 0.28; 0.24) in all hypertensive subjects, irrespective of treatment. Our study showed a high prevalence of hypertensive heart disease, 100% awareness of disorder and a low rate of treatment and control.

Relationship of eight basic emotions with age, sex, education, satisfaction of life needs, and religion.

Personality scores of Croatian men and women by age, occupation, education, satisfaction of life needs, and religion were examined. 842 men and 242 women whose mean age was 42 yr. (SD, 8) represented manual labor, clerical work, and management. Employees were administered the Emotions Profile Index and a test of Life Needs Satisfaction. The Croatian women scored lower on Distrustful and Dyscontrol than the Croatian men and higher on Depression and Gregarious. Scores on Aggression, Depression, and Gregarious varied across age groups. The Reproduction scores of sociable and affectionate were significantly higher for managers and persons with university education. The religious employees scored higher on Depression than nonreligious persons. The Reproduction scores were significantly positively associated with all needs satisfaction scores. The Destruction scores (Aggression, Depression) were significantly negatively associated with most life needs satisfactions. The present analysis suggests men and women from Croatian groups have different personality profiles. Correlations of emotional scores with ages, occupations, education, life needs satisfaction, and religion could help in modification toward positive emotional dimensions.

Association of scores for Type A behavior with age, sex, occupation, education, life needs satisfaction, smoking, and religion in 1084 employees.

The associations of Type A or B behavior with age, sex, occupation, education, life needs satisfaction, smoking, and religion were studied. 242 women and 842 men, ages 21 to 64 years, (M age 42 +/- 8 yr.), completed the Bortner scale and rated on a 5-point scale their life needs satisfaction. Information on age, occupation, education, cigarette smoking, and religion were obtained from each subject. Scores for Type A and Type B behavior patterns in different age groups were very similar. Scores on Type A behavior were significantly more common in women than men. Type A behavior scores were identified in a larger proportion of managers, clerks, and in persons with university education than in manual workers and persons with only primary and secondary education. There was no difference between smokers and non-smokers and religious and nonreligious scorers. There was no difference in ratings for life needs satisfaction between persons identified as having scores on Type A and Type B behavior. The present analyses enhance our understanding of Type A behavior as related to age, sex, occupation, education, and life needs satisfaction in a Croatian sample.

Type A/B behavior and eight basic emotions in 1084 employees.

We examined the prevalence of Type A/B behavior and Emotion Profiles in 1084 employees. This report focused on the relationship between Type A behavior and eight basic emotion dimensions. Of the 1084 subjects 710 (65%) scored as Type A and 374 (34.5%) as Type B. The mean Bortner scores for all subjects were 182.8 (SD = 33.7), scores on emotional dimensions for Incorporation and Reproduction were high, and intensities for Ejection and Destruction were low; mean scores on other emotions were normal. Significant differences between Type A and Type B scores were found on six emotional dimensions. Subjects classified as Type A had ratings lower on trustful, controlled, and timid and higher on aggressive, distrustful, and uncontrolled than did persons classified as Type B. There were no differences between Type A and Type B scores on the emotion dimensions of Reproduction and Deprivation. Our data suggest multiple emotional components may comprise the Type A behavior pattern. This is important for behavioral counseling programs and early preventive efforts which could be aimed at reducing the intensity of Type A behaviors.

Relationship of eight basic emotions, life needs satisfaction and Type A behavior with body mass index and some biochemical characteristics in healthy blue-collar workers.

Studies of the relationship of eight basic emotion dimensions according to Plutchik, life needs satisfaction and Type A behavior with plasma cholesterol, triglyceride and glucose concentrations, and body mass index (BMI) were performed in 137 healthy blue-collar workers. Plasma cholesterol correlated positively with emotion dimensions of destruction and deprivation (r = +0.18, +0.21; p < 0.05) and negatively with the components of love in EPI (reproduction and incorporation; r = -0.24, -0.25; p < 0.01) and life needs satisfaction (family relationships, relationship with friends; r = -0.20, -0.17; p < 0.05). Triglycerides correlated negatively with satisfaction of life needs concerning health, family and friend relationships (r = -0.20, -0.20, 0.25; p < 0.05). Plasma glucose correlated positively with emotions of destruction and orientation (r = +0.22, +0.20; p < 0.05), and negatively with incorporation and reproduction (r = -0.22, -0.24; p < 0.01). BMI correlated positively with plasma cholesterol, triglyceride and glucose concentrations (r = +0.37, +0.40, +0.24; p < 0.01), and emotion of deprivation (r = +0.21; p < 0.01). Results of the study suggested the successful approach to the prevention of coronary heart disease to be related with certain basic emotions, life needs satisfaction and BMI.

Analysis of the structure of empty and peptide-loaded major histocompatibility complex molecules at the cell surface.

We compared the conformation of empty and peptide-loaded class I major histocompatibility complex (MHC) molecules at the cell surface. Molecular conformations were analyzed by fluorescence resonance energy transfer (FRET) between fluorescent-labeled Fab fragments bound to the alpha 2 domain of the MHC heavy chain and fluorescent-labeled Fab fragments bound to beta 2-microglobulin. No FRET was found between Fab fragments bound to empty H-2Kb, but FRET was detected when empty H-2Kb molecules were loaded with peptide. The magnitude of FRET depended on the sequence of the peptide used. The results imply that empty H-2Kb molecules are in a relatively extended conformation, and that this conformation becomes more compact when peptide is bound. These changes, which are reflected in peptide-dependent binding of monoclonal antibodies, affect the surfaces of MHC molecules available for contact with T cell receptors and hence may influence T cell-receptor recognition of MHC molecules.

A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations.

Genetically engineered or chemically purified soluble monovalent major histocompatibility complex (MHC) molecules, which have previously been used to study T cells, have not blocked cytotoxic T-cell responses. Here we describe a genetically engineered divalent class I MHC molecule which inhibits lysis of target cells by alloreactive cytotoxic T cells. This protein, H-2Kb/IgG, was generated as a fusion protein between the extracellular domains of a murine class I polypeptide, H-2Kb, and an immunoglobulin heavy chain polypeptide. The chimeric protein has serological and biochemical characteristics of both the MHC and IgG polypeptides. Nanomolar concentrations of H-2Kb/IgG inhibited lysis of H-2Kb-expressing target cells not only by alloreactive H-2Kb-specific T-cell clones but also by alloreactive H-2Kb-specific primary T-cell cultures. A direct binding assay showed high-affinity binding between the H-2Kb/IgG molecule and an H-2Kb-specific alloreactive T-cell clone. Unlabeled H-2Kb/IgG displaced 125I-labeled H-2Kb/IgG from T cells with an IC50 of 1.2 nM.

Efficient amidation of C-peptide deleted NPY precursors by non-endocrine cells is affected by the presence of Lys-Arg at the C-terminus.

Post-translational processing of peptide precursors producing amidated, biologically active peptides generally occurs in specially differentiated endocrine or neural cells. However, we have previously shown that a C-peptide-deleted precursor of neuropeptide Y (NPY1-39) in which the precursor terminates in the sequence Gly-Lys-Arg was partially amidated by the non-endocrine cell line, CHO. In the present study we show that two other non-endocrine cell lines, NIH 3T3 and BHK, also possess amidating activities and that the NPY1-39 precursor was completely converted to NPY1-36 amide by the NIH 3T3 cell line. The role of the two basic residues (Lys-Arg) in the C-terminus was studied by transfection of a construct encoding a NPY precursor terminating with glycine alone. Both the CHO and NIH 3T3 cell lines, transfected with this construct, secreted a significantly smaller fraction of NPY reactive material as amidated NPY compared to the fraction of amidated NPY secreted by the cells transfected with the NPY1-39 precursor. It is concluded that the capacity to perform C-terminal amidation appears to be a universal feature of eukaryotic cells and that the carboxypeptidase E-like enzyme influences the amidation process, beyond its known ability to remove the C-terminal basic residues.

Ventricular arrhythmias during exercise testing and daily activities in patients with stable angina pectoris before and during Aldisem and penbutolol treatment.

The authors investigated the prevalence of ventricular ectopic activity (VEA) during exercise testing and 24-hour ambulatory Holter monitoring and its relation with ischemic episodes during daily activities before and during therapy with diltiazem and penbutolol in 41 patients with stable and typical angina pectoris. Seven (17%) of the 41 patients had exercise-induced ventricular ectopic activity (EIVA). Premature ventricular complexes (PVC) Lown grade I disappeared in 6 patients on therapy and appeared in another 6 new patients. PVC Lown grade IV A in one patient before therapy changed to Lown grade IV B upon therapy. There was no difference between patients with and without EIVA in the ages, average number of angina onset per day, percentage patients with exercise angina, average functional class, percentage of patients with exercise ST depression, average maximal ST depression, heart rate and systolic blood pressure at peak exercise and duration of exercise. The workload before therapy was similar in the 2 groups, but was significantly greater during therapy in patients without EIVA. During 984 hours of recording, 185 ischemic episodes were detected in 25 patients before therapy, and 111 ischemic episodes in 20 patients during therapy. PVC was observed in 12 (48%) of the 25 patients and in 81 (27%) of the 295 ischemic episodes. VEA during ischemic episodes was observed in patients with and without baseline PVC. The ventricular arrhythmias found were more complex types during ischemic episodes than baseline. Thus, the incidence of VEA in patients with stable and typical angina pectoris was 17% during exercise and 52% during daily activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Emotion profile and behaviour pattern of patients with active duodenal ulcer compared with acute coronary patients.

The authors examined personality profiles and type A/B behaviour in 100 patients with active duodenal ulcer, and a mean age of 39 years, using the Bortner scale and the Plutchnik Emotional Profile Index (EPI). The authors compared them with acute coronary patients and healthy controls. The mean EPI percentages for the duodenal ulcer patients, compared with acute coronary patients and healthy controls, display the trustful dimension (84.1 +/- 27.4--69.1 +/- 20.4--69.3 +/- 20.0), the aggressive dimension (56.7 +/- 9.3--41.3 +/- 19.2--37.6 +/- 17.3), the depressed dimension (84.5 +/- 12.3--52.8 +/- 19.1--51.4 +/- 23.1) and the dyscontrol dimension (73.5 +/- 32.2--48.4 +/- 27.7--50.2 +/- 17.5) to be significantly higher (P < 0.005). The mean percent scores of the gregarious dimension (44.2 +/- 13.2--72.7 +/- 22.7--68.0 +/- 22.0), control dimension (25.2 +/- 91.--39.1 +/- 31.9--44.3 +/- 15.5) and timid dimension (26.2 23.3--56.0 +/- 19.9--59.8 +/- 29.5), are significantly lower in duodenal ulcer patients than in acute coronary patients and controls (P < 0.005). Behaviour type A was found in 95 (95%) duodenal ulcer patients, in 76 (73.7%) acute coronary patients and in 58 (68%) healthy controls (P < 0.001). The Bortner scale was significantly higher in duodenal ulcer patients than in coronary and control subjects (P < 0.005). The EPI of duodenal ulcer patients in comparison to acute coronary patients and healthy controls, are sadder, more impulsive, do more risky things and are more disorganized and dependent. Type A behaviour was more often in duodenal ulcer patients than in the coronary and control groups.