Mining microarray data to identify transcription factors expressed in naïve resting but not activated T lymphocytes.

Transcriptional repressors controlling the expression of cytokine genes have been implicated in a variety of physiological and pathological phenomena. An unknown repressor that binds to the distal NFAT element of the interleukin-2 (IL-2) gene promoter in naive T-helper lymphocytes has been implicated in autoimmune phenomena and has emerged as a potentially important factor controlling the latency of HIV-1. The aim of this paper was the identification of this repressor. We resorted to public microarray databases looking for DNA-binding proteins that are present in naïve resting T cells but are downregulated when the cells are activated. A Bayesian data mining statistical analysis uncovered 25 candidate factors. Of the 25, NFAT4 and the oncogene ets-2 bind to the common motif AAGGAG found in the HIV-1 LTR and IL-2 probes. Ets-2 binding site contains the three G's that have been shown to be important for binding of the unknown factor; hence, we considered it the likeliest candidate. Electrophoretic mobility shift assays confirmed cross-reactivity between the unknown repressor and anti-ets-2 antibodies, and cotransfection experiments demonstrated the direct involvement of Ets-2 in silencing the IL-2 promoter. Designing experiments for transcription factor analysis using microarrays and Bayesian statistical methodologies provides a novel way toward elucidation of gene control networks.

Wives of patients with acute myocardial infarction are at an increased risk of developing coronary artery disease.

BACKGROUND: The present study was carried out to investigate risk factors for developing coronary artery disease in wives of patients with acute myocardial infarction. SUBJECTS AND METHODS: Risk factors for developing coronary artery disease were investigated in 50 wives of patients who developed an acute myocardial infarction (group A) and were compared with those of 50 wives of normal healthy men (group B). The average age was 50.20 +/- 1.56 years (mean +/- SD) and 50.20 +/- 1.53 years for group A and group B respectively. The parameters assessed were: plasma cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), systolic and diastolic blood pressure, smoking habits and body mass index (BMI). RESULTS: The levels of LDL-C in the wives of patients with myocardial infarction were higher than those of the wives of normal healthy men (167.8 +/- 5.84 mg/dl and 148.4 +/- 4.85 mg/dl, respectively, P < 0.01). Moreover, HDL-C concentrations were lower in the wives of the patients (51.34 +/- 0.92 mg/dl) than in the wives of the healthy men (58.14 +/- 1.39 mg/dl), (P < 0.001). Finally, TG levels were higher in the wives of the patients (132.2 +/- 7.9 mg/dl) than in the wives of the normal healthy men (96.9 +/- 5.94 mg/dl) (P < 0.01). CONCLUSIONS: Although plasma lipid levels themselves were not excessively high, the wives of patients with an acute myocardial infarction are at a higher risk of developing coronary artery disease than the wives of normal healthy men, in the long term, due to higher levels of LDL-C and TG as well as lower levels of HDL-C.

Changes in protein composition and hydrolytic enzyme activity of Escherichia coli and Hafnia alvei grown in human fluids.

Growing of Escherichia coli and Hafnia alvei cells in several cell-free human fluids, such as normal serum, serum from diabetic patients, pleural, ascitic and spinal fluid, revealed that various biochemical changes occurred. Protein profile on SDS-PAGE as well as acid and alkaline phosphohydrolytic enzymes on native gels of cell extracts were affected after culturing of bacteria in the above fluids. Gelatinolytic and hyaluronolytic activity was of interest because both of them are histolytic enzymes. Although there was a potential appearance of gelatinolytic bands on gelatin-SDS-PAGE in cells starved in seawater, none of these activities were expressed in cells grown in human fluids. A hyaluronolytic activity of approximately 45 KDa was present in cells cultured in Mueller Hinton broth. This enzyme was decreased either in cells starved in seawater or in cells grown in human fluids to an almost invisible band on hyaluronan-SDS-PAGE.

High serum cholesterol levels in persons with 'high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?

OBJECTIVE: The association between established hypothyroidism and high cholesterol levels is well known. The aim of the present study was to investigate the effect of thyroxine (T4) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range ('high-normal' TSH compared with 'low-normal' TSH). DESIGN AND METHODS: We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia (serum cholesterol >7.5 mmol/l). Those with 'high-normal' TSH (2.0-4.0 microU/ml) as well as those with 'low-normal' TSH (0.40-1.99 microU/ml) were randomly assigned to receive either 25 or 50 microg T4 daily for two months. Thus, groups A and B (low-normal TSH) received 25 and 50 microg T4 respectively and groups C and D (high-normal TSH) received 25 and 50 microg T4 respectively. Serum T4, tri-iodothyronine (T3), TSH, free thyroxine index, resin T3 uptake and thyroid autoantibodies (ThAab) as well as total cholesterol, high and low density lipoprotein cholesterol (HDL, LDL), and triglycerides were determined before and at the end of the two-month treatment period. RESULTS: TSH levels were reduced in all groups. The most striking effect was observed in group D (TSH levels before: 2.77+/-0.55, after: 1.41+/-0.85 microU/ml, P < 0.01). Subjects in groups C and D had a higher probability of having positive ThAabs. A significant reduction in total cholesterol (P < 0.01) and LDL (P < 0.01) was observed after treatment only in group D. In those subjects in group D who were ThAab negative, there was no significant effect of thyroxine on cholesterol levels. CONCLUSIONS: Subjects with high-normal TSH levels combined with ThAabs may, in fact, have subclinical hypothyroidism presenting with elevated cholesterol levels. It is possible that these patients might benefit from thyroxine administration.

Cholesterol and unsaturated fat diets influence lipid and glucose concentrations in rats.

The present study investigated the effects of dietary cholesterol and monounsaturated and polyunsaturated fatty acids on plasma lipids and glucose concentrations. Four groups of ten male Wistar albino rats were fed diets of different fatty acid composition for 40 days. The control group consumed nonpurified diet (containing fat 3.7 g/100 g diet), and cholesterol, olive oil, and safflower oil groups consumed the nonpurified diet enriched with 14 g fat/100 g diet with egg yolk, olive oil, or safflower oil, respectively. Compared with the control, the diet enriched with cholesterol significantly increased fasting plasma cholesterol (P < 0.01), triacylglycerol (P < 0.01), total lipid (P < 0.01) and glucose (P < 0.05) concentrations; in the olive oil group, cholesterol and triacylglycerol levels were significantly increased compared with control group (P < 0.01 in both instances). In safflower oil group, triacylglycerol levels were also significantly increased (P < 0.05) compared with the controls. After comparing diets providing the same amount of fat (cholesterol, olive oil, and safflower oil groups), higher cholesterol, triacylglycerol and total lipid levels were observed in the cholesterol group than in the olive oil group (P < 0.01, P < 0.05 and P < 0.01, respectively), and safflower oil group (P < 0.01 in all instances). High-density lipoprotein-cholesterol concentrations were significantly lower in the cholesterol group than in the olive oil and safflower oil groups (P < 0.05 in both instances) and fasting plasma glucose levels were higher in the cholesterol than in the olive oil (P < 0.05) and safflower oil groups (P < 0.01). Finally, after comparing lipid and glucose levels in the unsaturated fatty acids-enriched diets, higher plasma cholesterol concentrations were observed in the olive oil than in the safflower oil group (P < 0.05). These data suggest that not only the amount but also the type of dietary fat can influence serum lipid levels.

Precursors of atherosclerosis in a random sample from a Hellenic population: the Athens Study.

BACKGROUND: Atheromatosis, the principal lesion in atherosclerotic cardiovascular disease, is associated with increased levels of blood pressure, serum cholesterol, cigarette smoking and other variables. As these lesions are thought to appear first in childhood, this study was designed to assess the levels of these atherosclerotic precursors in children living in Athens, Greece. METHODS: The following parameters were measured in a random sample of 4117 school children aged 6-18 years, living in the centre of Athens: body mass index, blood pressure, serum lipids, glucose, uric acid, calcium, phosphorus, creatinine, and haematocrit. RESULTS: Mean levels of blood pressure, total cholesterol, cigarette smoking and body mass index increased with age in both sexes, levels being similar to those of children in developed countries. Smoking started at elementary school, and by puberty had reached adult levels. High levels of systolic blood pressure ( > or = 130 mmHg) and total cholesterol ( > or = 5.68 mmol/l) were seen in 22% and 13% of children respectively. Triglyceride and glucose levels did not increase with age; high-density lipoprotein cholesterol decreased and uric acid increased from 14 to 18 years, but only in boys. Levels of body mass index, total cholesterol, triglycerides, high-density lipoprotein and uric acid above the mean population values were found in 25% of children, and glucose levels above the mean in 50%. Multiple linear regression analysis showed a positive correlation between systolic blood pressure and age, body mass index, uric acid, sex, glucose, triglycerides and high-density lipoprotein cholesterol (in that order), and between diastolic blood pressure and age, body mass index and triglycerides. CONCLUSIONS: These findings indicate that the levels and prevalence of precursors of atherosclerosis are higher than expected in a southern European population, and are similar to those found in developed countries. This would indicate a need for greater awareness among the Greek population of preventive measures against developing cardiovascular disease.

Transdermal estradiol plus oral medroxyprogesterone acetate replacement therapy in primary amenorrheic adolescents. Clinical, hormonal and metabolic aspects.

Twelve primary amenorrheic adolescents were treated with transdermal estradiol 100 micrograms (Estraderm TTS-100 (R)) twice weekly for 3 weeks, plus MPA 10 mg per os daily (Provera) for the last 11 days, following an interval of 1 week. A basic examination and a re-examination at 6- and 12-month intervals were carried out for clinical evaluation, hormonal assays, lipid, carbohydrate and bone metabolism. No significant changes were recorded on the FSH, LH, 17 beta-estradiol and PRL serum levels. A significant decrease of TC values and atheromatic indices 1 (TC/HDL) and 2 (LDL/HDL) was seen (P < 0.05) at the end of treatment. On the other hand a significant increase in apolipoproteins A1 was found. A beneficial effect was also recorded on the bone mass. Finally, no significant side-effects were reported. It is concluded that this kind of hormone replacement therapy is efficient and safe for the treatment of amenorrheic adolescents due to gonadal dysgenesis.

Physical activity and relationship with coronary heart disease risk factors.

Physical activity was recorded as walking in kilometers per week during leisure time and at work in a random sample of 1205 Athenian adults and was correlated to the coronary heart disease (CHD) risk factors. In general, a low level of physical activity was found in daily life. In particular, 53% of the men and 73% of the women examined walked less than 7 km/week. No difference in walking distance was observed among the 10-year age groups, for both sexes. In men, the logarithm (log) of walking was significantly correlated with log triglycerides (r = -0.0971, p = 0.0185), total lipids (r = +0.0927, p = 0.0246), high density lipoprotein-cholesterol (HDL-C) concentration in mg/dl (r = +0.0842, p = 0.0409), very low density lipoprotein-cholesterol (VLDL-C) concentration in mg/dl (r = -0.1149, p = 0.0052), alpha-lipoproteins as percentage of total lipoproteins (r = +0.0809, p = 0.0497) and pre-beta-lipoproteins as percentage of total lipoproteins (r = -0.1024, p = 0.0129). In women, respectively, log walking was significantly correlated with age (r = -0.1318, p = 0.0011), body mass index (BMI) (r = -0.1459, p = 0.0003), maximal heart rate (r = +0.1181, p = 0.0281), diastolic blood pressure (r = -0.1153, p = 0.0043), cigarette smoking (r = -0.810, p = 0.0448), log triglycerides (r = -0.1468, p = 0.0003), total lipids (r = -0.1415, p = 0.0004), VLDL-cholesterol concentration in mg/dl (r = -0.1475, p = 0.0002), total/HDL cholesterol ratio (r = -0.0968, p = 0.0165), alpha-lipoproteins as percentage of total lipoproteins (r = +0.1141, p = 0.0047), pre-beta-lipoproteins as percentage of total lipoproteins (r = -0.1324, p = 0.0010), urea (r = -0.1035, p = 0.0107) (r = +0.01221, p = 0.0107) and uric acid (r = -0.1221, p = 0.0026). Using a stepwise multiple linear regression analysis model, it was found that log walking was significantly and independently associated with alpha-lipoproteins as percentage of total lipoproteins in men (positive association) and with BMI in women (negative association).

Increased mean serum thyrotropin in apparently euthyroid hypercholesterolemic patients: does it mean occult hypothyroidism?

Serum thyroid hormones and antithyroid autoantibodies (AAB) were assayed in 87 randomly selected hypercholesterolemic persons compared to 80 controls with normal serum total cholesterol (TC). Of the 87 hypercholesterolemic persons 22 (25%) had positive AAB compared to 5 (6%) controls. Furthermore, 8 of the hypercholesterolemic patients had a serum TSH level above 5 mU/l, i.e. the had subclinical hypothyroidism, not diagnosed before, whereas thyroid function was normal in all normocholesterolemic persons. The new and unexpected finding was that the hypercholesterolemic persons had on average a significantly higher serum TSH than the controls, and this was true even when persons with positive AAB were excluded. There was a significant correlation between TC and serum TSH. It is concluded that hypothyroidism may not be an all-or-none phenomenon, and that many hypercholesterolemic persons with thyroid tests within the conventional normal range may have a slight impairment of their thyroid function.

Blood pressure and other risk factors of cardiovascular disease in two communities with different socio-economic statuses: the Athens study.

Blood pressure and other risk factors of cardiovascular diseases were studied in two rural communities of 631 adults (greater than or equal to 18 years old) with different socio-economic statuses, populations A and B. Population A (n = 381) lived in a tourist village on an island, and population B (n = 250) in a remote mountain village. The socio-economic status of population A had improved considerably over the last decade but the physical environment, habits, culture and way of life had been disrupted. Blood pressure, prevalence of hypertension and other risk factors were higher than in population B where socio-economic status was lower but where there had been no disruption of the environment, traditional habits, culture or way of life. These findings might be due to the lack of preventive medicine services in the community.

Serum calcium and blood pressure in Greek girls.

In a random sample of 492 girls 12-15-years-old total serum calcium appeared to be correlated with blood pressure. Adolescents with total serum calcium equal to a greater than the cohort mean (2.5 mmol/l) had higher systolic blood pressures than those with a value below the cohort mean. This was present at all ages.

Table salt and blood pressure in Greek children.

The habit of adding table salt was studied in a random sample of 2209 children 6-18 years old. Of these 10% routinely added table salt to prepared food before tasting it (group A), 29% after tasting it (group B) and 61% ate their food as it was prepared, without additional use of table salt (group C). Group A had higher blood pressure (BP), prevalence of systolic BP greater than or equal to 130 mmHG and body mass index (BMI) than groups B and C (P less than 0.0001). These differences were also observed in group B versus C (P less than 0.0001).

Coronary heart disease risk factors in a random sample of Athenian adults. The Athens Study.

Risk factors for cardiovascular diseases not previously investigated in Greece were studied in a random sample of 4,097 Athenian adults. Mean systolic and diastolic blood pressures increased with age in both sexes. Similar findings were observed for mean serum total cholesterol up to age 50 years, but no significant changes were observed in older persons. Smoking was more common for men than for women and less common in those aged more than 50 years. Mean values of body mass index were higher for men than for women in those less than 45 years, but the opposite was observed for the older age groups. The age-adjusted prevalence rate of borderline hypertension was 10.1% for men and 9.1% for women and of stable hypertension (greater than 160/95 mmHg), 8.1% and 8.6%, respectively; the age-adjusted prevalence rate of obesity was 23.5% for men and 23.2% for women and of hypercholesterolemia (total cholesterol greater than or equal to 260 mg/100 ml), 20.1% for men and 17.3% for women. The associations of age and systolic blood pressure and of age and diastolic blood pressure persisted even after controlling for body mass index, total cholesterol, and smoking. In the examined representative sample, the prevalence rates of risk factors for cardiovascular diseases are the same or greater than those in industrialized countries.

Intra-aortic ballon pump for relief of aortic regurgitation. Experimental study.

Backflow from the aorta to the left ventricle during diastole in aortic regurgitation can be reduced by expanding, during diastole, a small air balloon positioned in the ascending aorta downstream to the regurgitant valve. A spherical catheter-mounted balloon, acting as a prosthetic aortic valve for the correction of acute aortic regurgitation, was tested in 12 dogs. This "valve" was actively inflated and deflated by means of a common intra-aortic balloon pumping system (Datascope). A significant increase of end-diastolic pressure in the descending aorta, from 51.72 +/- 1.72 to 70.35 +/- 1.92 mm Hg (mean +/- standard error, p less than 0.001), was obtained, without a significant pressure gradient across the "valve". The "valve" prevented the backward flow of the descending aorta by up to 100%, so that there was a mean increase in t-e effective forward flow of 12.61 +/- 5.27% (mean +/- standard error, p less than 0.05). Coronary arterial flow changes varied during the application of the "valve." They depended directly on the changes of the diastolic component of the flow velocity wave, and this relationship was significant (x2 = 33.04, p less than 0.0001). Contractility indices were not significantly affected during the function of the "valve." It is suggested that the spherical "valve" mounted on a catheter may easily be inserted without thoracotomy for a temporary satisfactory correction of the aortic regurgitation.

Epidemiology of coronary artery disease among Hansen's patients.

The prevalence of coronary heart disease (CHD) and its risk factors were studied in 475 Hansen's patients (HP's) by a special questionnaire, physical examination, electrocardiogram at rest and after exercise, and biochemical and hematologic investigations. It was found that the prevalence of CHD (Minnesota codes 1-1 to 1-3 and 4-1) was 10.92%, which is higher than that found in epidemiologic studies of nonHansen's populations. The only CHD risk factors detected were age, obesity, and hypertension. There was no statistically significant difference in the prevalence of CHD between HP's living confined in the institution and those living in their homes. Factors enhancing the development of CHD in this group may include hypertension and obesity as well as psychological factors, which particularly common in these patients, and of course old age.

Action of Nitroglycerin and amyl nitrite in labile and essential hypertension: hemodynamic differences.

Seventeen patients with labile hypertension received nitroglycerin and 18 received amyl nitrite. Twelve patients with established essential hypertension received nitroglycerin and 12 received amyl nitrite. Nitroglycerin reduced the systolic and mean arterial pressures and cardiac output in both groups, but had no effect on diastolic pressure and total peripheral resistance. Amyl nitrite decreased systolic, diastolic, and mean arterial pressures and peripheral vascular resistance and increased heart rate and cardiac output in labile hypertensives. In established hypertensive patients, amyl nitrite decreased systolic, diastolic, and mean arterial pressures and cardiac output, and had little effect on peripheral vascular resistance. Nitroglycerin reduced arterial pressure in labile and established hypertensives through venodilation and peripheral venous pooling. Amyl nitrite and effects similar to nitroglycerin in established hypertensives; in labile hypertensives it reduced arterial pressure through arterial dilation and a decrease in peripheral vascular resistance.

Systemic and renal hemodynamic effects of bupicomide: a new vasodilator.

The systemic and renal hemodyanmic effects of bupicomide were studied in 10 male patients with uncomplicated essential hypertension of moderate severity. Bupicomide significantly reduced systolic, diastolic, and mean arterial pressure and peripheral vascular resistance and this hypotensive effect was associated with a reflexive increase in heart rate, left ventricular ejection rate, and cardiac index; it had no effect upon other reflexive sympathetic adjustments induced by upright tilt and the Valsalva maneuver. Bupicomide also increased renal blood flow and decreased renal vascular resistance, but it had no effect upon the glomerular filtration rate. The hypotensive mechanism of bupicomide therefore is mediated by peripheral arteriolar dilation, through vascular smooth muscle relaxation. The more immediate clinical side effects of bupicomide are related to its strong vasodialting action and include headaches, cutaneous flushing, and tachycardia.

Systolic hypertension: nonhomogeneous diseases.

Prospective studies have shown that systolic hypertension is associated with increased cardiovascular risk, but few physiologic studies have characterized the problem. Therefore, two groups of men (older and younger than 35 years) with systolic hypertension (systolic pressure 150 mm Hg or greater and diastolic pressure 95 mm Hg or less) were studied hemodynamically. The 13 younger patients demonstrated a hyperkinetic circulation manifested by a significantly increased heart rate, elevated left ventricular ejection rate and cardiac indexes and normal vascular resistance. The 13 older patients had a normal heart rate, significantly reduced cardiac and left ventricular ejection rate indexes, and increased vascular resistance with respect to the younger men with systolic hypertension and normotensive control subjects. Plasma volume was reduced only in the older patients (P less than 0.05). These data demonstrate that systolic hypertension should not be considered a homogeneous disease entity clinically or physiologically. The physiologic differences between the younger and older patients suggest that different mechanisms may be operative.