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Biomedical subjects

A Hautanen

Publications and source records attributed to A Hautanen.

At least 19 recordsLinked to original sources
PubMed1994

Association of stress and depression with regional fat distribution in healthy middle-aged men.

We examined whether the association of regional fat distribution with stress, defined in terms of vital exhaustion, and depression varies according to the total amount of body fat accumulation in healthy middle-aged men (n = 64). Regional fat distribution was measured using the waist-to-hip circumference ratio (WHR), and the total amount of body fat accumulation was measured using the body mass index (BMI). The results indicate that WHR in lean men was associated with characteristics contrary to those in moderately obese men. In lean men WHR tended to be associated with a high level of stress, while in moderately obese men an association was found with a low level of stress and a low level of depressive symptomatology. The present results support the suggestion that there is a difference between abdominal obesity at different degrees of generalized obesity, and they are likely to further our understanding about the differing risk for cardiovascular disorders posed by abdominal obesity in lean men compared to abdominal obesity in moderately obese men.

Abdominal Muscles↗
PubMed1994

Adrenal androgens and testosterone as coronary risk factors in the Helsinki Heart Study.

We investigated the role of adrenal androgens, cortisol, testosterone and sex-hormone binding globulin (SHBG) as coronary risk factors using a nested case-control design. The study population consisted of 62 cases with cardiac end-points and 97 controls on placebo during the last 4 years in the Helsinki Heart Study. Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, androstanediol glucuronide, cortisol, testosterone, and SHBG at the first annual visit of the 5-year study period were determined by radioimmunoassays. The only significant difference was found in DHEAS, with cases having higher levels than controls (P < 0.04). DHEAS levels were positively associated with smoking (P < 0.001), alcohol consumption (P < 0.04) and triglyceride levels (P < 0.002) and with systolic (P < 0.04) and diastolic (P < 0.006) blood pressures, and negatively associated with age (P < 0.01) and HDL-cholesterol (P < 0.03). The association between DHEAS and the CHD risk was studied using logistic regression analyses with the classical risk factors--age, smoking, blood pressure, and lipid levels--as covariates in the models. Studies of the joint effects of age and DHEAS disclosed that the risk associated with elevated DHEAS was confirmed to older men (odds ratio (OR) 7.3, 95%, CI 2.3-23.3). A similar analysis with smoking revealed that the DHEAS-related risk was mainly found in smokers (OR 3.4, 95% CI 1.5-8.2). One possible explanation for these results is that some form of mild steroid biosynthetic defect of the adrenals or functional adrenal hyperplasia associated with high DHEAS levels increases the CHD risk in this population.

Adrenal Glands↗
PubMed1994

The role of psychological coronary risk factors in insulin and glucose metabolism.

The association between psychological coronary risk factors and serum insulin, and C-peptide and blood glucose concentrations, [the latter measured while fasting and during the oral glucose tolerance test (OGTT)], was examined in healthy middle-aged men (n = 64). The results indicate that among the evaluated psychological risk factors, high levels of hostile paranoia and vital exhaustion were most consistently associated with an enhanced insulin/glucose ratio, and enhanced insulin, C-peptide and glucose responses during OGTT. The associations persisted after controlling for age, smoking, alcohol consumption and visceral fat distribution. Thus, in addition to age, life-style factors and obesity, psychological factors may have an effect on insulin and glucose metabolism.

Adult↗
PubMed1994

Gemfibrozil treatment is associated with elevated adrenal androgen, androstanediol glucuronide and cortisol levels in dyslipidemic men.

We have investigated the role of steroid hormones as coronary risk factors in the Helsinki Heart Study population of dyslipidemic middle-aged men. We compare here the effects of gemfibrozil and placebo on the serum levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), their metabolite androstanediol glucuronide (3 alpha-AdiolG), androstenedione, cortisol, testosterone, and sex-hormone binding globulin (SHBG) in non-smokers. We also examined the associations between steroid and lipoprotein levels in both treatment groups. Compared with placebo gemfibrozil treatment was associated with significant elevations of the mean levels of DHEA 10.2 vs 8.0 nmol/l; P < 0.005, of DHEAS 8.0 vs 5.8 mumol/l; P < 0.001, of 3 alpha AdiolG 18.3 vs 8.4 nmol/l; P < 0.001, of androstenedione 5.7 vs 5.1 nmol/l; P < 0.02, and of cortisol 426 vs 358 nmol/l; P < 0.001. The mean SHBG levels decreased from 46.4 to 41.7 nmol/l; P = 0.03 with gemfibrozil treatment. No difference was found in testosterone levels 17.7 vs 18.8 nmol/l; P = 0.11, or the ratio of testosterone/SHBG 0.45 vs 0.43; P = 0.23. Positive correlations were found between high density lipoprotein-cholesterol and DHEAS (r = 0.267; P < 0.01) and DHEA (r = 0.282; P < 0.01) levels and negative correlations between low density lipoprotein-cholesterol and 3 alpha-AdiolG (r = -0.400; P < 0.001) and cortisol (r = -0.281; P < 0.01) levels in the gemfibrozil group. Our results indicate that gemfibrozil treatment increases the production and turnover of adrenal androgens and cortisol, and suggest that activation of the adrenocortical function and increased metabolism of androgens are related to the improved lipoprotein pattern during gemfibrozil treatment.

Adrenal Cortex Hormones↗
PubMed1993

Hyperinsulinaemia, dyslipidaemia and exaggerated adrenal androgen response to adrenocorticotropin in male smokers.

Insulin resistance and dyslipidaemia associated with smoking may result from increased secretion of anti-insulin hormones. We compared the pituitary-adrenocortical function using oral glucose tolerance, dexamethasone suppression and ACTH stimulation tests in smoking (n = 22) and non-smoking (n = 22) healthy males matched for age, body mass index, and waist-to-hip ratio. Smokers had lower HDL-cholesterol (p < 0.02), and higher triglyceride (p < 0.001), basal cortisol (p < 0.05), insulin (p < 0.05), and C-peptide (p < 0.02) levels, and a higher response of insulin and C-peptide to oral glucose (p < 0.005) than non-smokers, while the ACTH, cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone, and androstenedione responses to oral glucose were similar in both groups. No differences were found in the response of cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone, and androstenedione to dexamethasone. In contrast, the response of 17-hydroxyprogesterone (p = 0.04), dehydroepiandrosterone (p = 0.007), and androstenedione (p = 0.001) to ACTH was higher in smokers than non-smokers, while the increase in cortisol was of marginal significance (p = 0.07). In multiple regression analyses the dehydroepiandrosterone response to ACTH was a significant determinant of insulin, C-peptide, and triglyceride levels independent of physical activity, waist-to-hip ratio and HDL-cholesterol. Thus, smoking inhibits the adrenal 21-hydroxylase resulting in an increase in the production of adrenal androgens, which might contribute to the insulin resistance and dyslipidaemia in smokers.

17-alpha-Hydroxyprogesterone↗
PubMed1993

Serum sex hormone-binding globulin, cardiovascular risk factors, and adrenal cortisol responses to dexamethasone and corticotropin.

Basal cortisol levels and cortisol responses to dexamethasone (DXM) and corticotropin were studied in relation to serum levels of sex hormone-binding globulin (SHBG), testosterone (T), free T, estradiol (E2), insulin-like growth factor I (IGF-I), high-density lipoprotein cholesterol (HDLC), triglycerides (TG), and insulin in 30 men. SHBG was positively correlated to age (P < .01), HDLC (P < .05), and total T (P < .05) and negatively correlated to TG (P < .02) and insulin (P < .001). SHBG was inversely related to corticosteroid-binding globulin (P < .05), but was not significantly associated with IGF-I. Free T was positively related to TG (P < .05), insulin (P < .01), total T (P < .001), and basal (P < .01) and free cortisol (P < .05). Corticotropin-stimulated cortisol responses were negatively associated with SHBG (P < .001) and positively associated with insulin (P < .01). Multiple linear regression analyses with SHBG as the dependent variable indicated that cortisol response alone explained 34.0% and together with age 46.2% of the variation of SHBG levels. Only insulin and age, but not cortisol response, remained significant predictors of SHBG concentrations when entered simultaneously into the mathematical model; this model explained 55.1% of the variation of SHBG levels. Thus, in addition to insulin and age, cortisol reserves and secretion seem to have significant associations with serum SHBG and free T concentrations.

Adrenal Cortex↗
PubMed1993

Altered adrenocorticotropin and cortisol secretion in abdominal obesity: implications for the insulin resistance syndrome.

OBJECTIVES: To investigate the relationship between the pituitary-adrenocortical function, abdominal obesity, and insulin resistance syndrome. DESIGN: A prospective study. SETTING: Helsinki University Hospital, Finland. SUBJECTS: Sixty-six healthy males aged 30-55 years. MAIN OUTCOME MEASURES: Insulin, C-peptide, cortisol and ACTH responses during the oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone suppression and intravenous adrenocorticotrophic hormone (ACTH) stimulation. RESULTS: The subjects in the highest tertile of the waist-to-hip ratio (WHR) had lower high-density lipoprotein cholesterol (HDLC) (P < 0.05), but higher triglyceride (TG), insulin, and C-peptide levels, ACTH response to glucose at 2 h, and cortisol response to ACTH (P < 0.01) than those in the lowest tertile. The cortisol response to ACTH correlated positively, but cortisol levels during the OGTT correlated negatively with WHR. The ratio of these cortisol determinations correlated positively with the body-mass index (BMI) (r = 0.554; P < 0.001), WHR (r = 0.536; P < 0.001), TG (r = 0.397; P = 0.001), fasting insulin (r = 0.534; P < 0.001) and C-peptide (r = 0.458; P < 0.001), and negatively with HDLC (r = 0.353; P = 0.004). In multiple regression analyses, BMI and the 2-h ACTH response to glucose were significant predictors of WHR and, in addition, the cortisol ratio, WHR, and BMI of insulin. CONCLUSIONS: Abdominal obesity may be associated with subtle central adrenal insufficiency, which might also affect insulin and lipoprotein metabolism.

Abdomen↗
PubMed1992

Effects of gemfibrozil treatment on serum levels of androstanediol glucuronide and adrenal androgens.

We have prospectively investigated the role of adrenal cortical androgens as a risk factor for coronary heart disease in the Helsinki Heart Study population. Simultaneously we studied the effects of gemfibrozil treatment on the serum levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and their metabolite androstanediol glucuronide (3 alpha AdiolG) with those of placebo. Gemfibrozil (n = 133) vs placebo (n = 159) treatment was associated with significant elevation of mean (SD) DHEAS (mumol/l) 8.35 (5.31) vs 6.98 (3.85); P less than 0.02, and of 3 alpha AdiolG (nmol/l) 17.45 (7.57) vs 8.62 (3.56); P less than 0.001), and of almost significant elevation of DHEA (nmol/l) 10.12 (6.64) vs 8.78 (5.86); P less than 0.07). These new observations suggest that gemfibrozil treatment increases the production and turnover of DHEA and DHEAS and may in addition stimulate the 5 alpha-reduction of androgens.

Androgens↗
PubMed1991

Enhancement of vitronectin expression in human HepG2 hepatoma cells by transforming growth factor-beta 1.

Liver cells are considered the principal source of plasma vitronectin. The human hepatoma cell line HepG2 produces vitronectin into its culture medium. In the current work we have analyzed the regulation of vitronectin by transforming growth factor-beta 1 (TGF beta 1) in this hepatoma cell line by Northern hybridization, polypeptide and immunoprecipitation analyses and compared the response to another TGF beta-regulated gene, plasminogen activator inhibitor (PAI-1). Rabbit antibodies raised against human plasma-derived vitronectin were used in immunodetection. Polypeptide and immunoprecipitation analyses of the medium and cells, as well as immunoblotting analysis of the cells and their extracellular matrices, indicated enhanced TGF beta 1-induced production and extracellular deposition of vitronectin. Accordingly, TGF beta 1 enhanced the expression of vitronectin mRNA at picomolar concentrations (2-20 ng/ml) as shown by Northern hybridization analysis. Comparison of the temporal TGF beta induction profiles of vitronectin and PAI-1 mRNAs showed that vitronectin was induced more slowly but the vitronectin mRNAs persisted longer. In addition, platelet-derived and epidermal growth factors had an effect on vitronectin expression, but it was of lower magnitude. TGF beta 1 enhanced the expression of PAI-1 but, unlike previous reports, epidermal growth factor did not have any notable effect on PAI-1 in these cells. The results indicate that TGF beta 1 is an efficient regulator of the production of vitronectin by HepG2 cells and that PAI-1 and vitronectin are not coordinately regulated. In addition, with affinity purified antibodies to vitronectin receptor, we observed strong enhancement of the alpha subunit of the receptor in response to TGF beta 1. These effects of TGF beta are probably involved in various processes of the liver where matrix induction and controlled pericellular proteolysis is needed, as in tissue repair.

Blood Proteins↗
PubMed1989

Effects of modifications of the RGD sequence and its context on recognition by the fibronectin receptor.

The receptor for fibronectin is a member of the integrin superfamily of cell surface adhesion receptors, many of which recognize the sequence RGD in their ligands. We have developed sensitive enzyme-linked and radioreceptor assays to examine the ligand specificity of the fibronectin receptor. The fibronectin receptor bound only to fibronectin of the various Arg-Gly-Asp (RGD)-containing proteins tested. The smallest amount of receptor detectable in the assay was about 10 ng. Mn2+ enhanced the binding of the receptor to fibronectin 3-10-fold as compared to Ca2+ and Mg2+. Scatchard analysis of the saturation plot from the radioreceptor assay gave a dissociation constant (Kd) of 3 x 10(-8) M for the binding of fibronectin receptor to fibronectin in the presence of Mn2+. Inhibition experiments showed that the affinities of the ligands for the receptor decreased in the order of fibronectin approximately 110-kDa fibronectin fragment greater than GRGDSP peptide greater than 11.5-kDa fragment. Peptides not containing an RGD were several hundred to several thousand-fold less inhibitory than GRGDSP. These included the closely related peptides GRADSP and GRGESP, as well as three peptides containing the reverse sequence DGR. A peptide from the fibrinogen gamma-chain, KQAGDV, which had about 0.5% of the inhibitory activity of the standard GRGDSP peptide, was the most active peptide not containing an RGD. These results document the exquisite specificity of the fibronectin receptor for the RGD sequence.

Calcium↗
PubMed1989

Desmin antibodies in acute infectious myopericarditis.

The role of autoantibodies against cardiac tissue in the pathogenesis of acute myopericarditis is poorly understood--partly because the specificity of the antibodies is unknown. We assayed antibodies against desmin, a cytoskeletal muscle protein, in 18 patients with acute infectious myopericarditis (AIM), in 24 patients with acute uncomplicated infections, in ten patients with acute myocardial infarction, and in 68 blood donors by an immunoenzymatic assay using purified desmin from Purkinje fibers of cow heart. In addition, anti-heart antibodies were assayed by indirect immunofluorescence. Anti-heart antibodies were detected in all groups by indirect immunofluorescence. On the other hand, anti-desmin antibody levels exceeding the mean + 2 SD of the blood donors could demonstrated in seven (39%) AIM patients but in only one patient in the other groups. The analysis of serial samples indicated that the antibody level was highest in the acute phase of AIM and declined during the recovery.

Acute Disease↗
PubMed1988

Nephropathia epidemica encephalitis.

A case of serologically proven Nephropathia epidemica (NE) with encephalitis is described. Follow up of serum and CSF antibody titres demonstrated NE virus antibody production in the CNS concomitantly with clinical encephalitis. Decrease of initially high CSF antibody titres was followed by a simultaneous increase of serum antibody titres corresponding to the clinical picture shifting from encephalitis to nephritis. This suggests that the first replication of NE virus may undertake in the CNS.

Adult↗
PubMed1986

Elevated serum immune complex levels in Pogosta disease, an acute alphavirus infection with rash and arthritis.

Circulating immune complexes (CIC) were studied in Pogosta disease, an acute alphavirus infection with fever, rash and arthritis. The disease is caused by a virus antigenically closely related to Sindbis virus. 75 serum specimens from 25 patients with serologically verified infection were obtained from 1-87 days after the onset. Six different CIC detection methods were used and CICs were observed in all patients at least with one test. Tests based on CIC binding onto human platelets followed the natural course of the disease and maximal values were observed between 10-15 days after onset. Slightly elevated levels were observed 2-3 months after onset. The mean conglutinin binding test values were slightly elevated during the whole follow-up period. The severity of arthritis did not directly correlate to CIC levels. C3c and C1q-binding test were positive only in a few cases. Latex and enzyme immunoassay tests for rheumatoid factors gave low positive values in some of the sera. Agarose gel electrophoresis of serum proteins revealed non-specific changes in alpha 1-alpha 2 interzone characteristic of an acute infectious disease. The presence of CIC in the sera of patients with Pogosta disease may indicate body's natural clearange mechanisms of viral antigens. CIC may have a pathogenic role in the prolonged arthritis, even though no direct correlation with CIC levels and severity of arthritis was observed.

Acute Disease↗
PubMed1985

Detection of rotavirus in faecal specimens by enzyme immunoassay, latex agglutination and electron microscopy.

Faecal specimens from 570 patients with gastroenteritis were studied for rotaviruses by enzyme immunoassay (EIA), electron microscopy (EM) and latex agglutination test (LX). Specimens from 127 patients were positive and 379 were negative with all 3 methods. 64 (11%) specimens gave contradictory results in the tests. EIA gave significantly more positive results than EM (168 vs 145). 30 EM-negative and EIA-positive specimens were positive in a confirmatory test. LX was positive in 161 specimens and no significant differences to EM or EIA were observed. There were 16 (2.8%) LX-positive samples that were negative both in EM and EIA. The positivity of these samples could not be confirmed and 15 of them were only slightly positive. Our results can be concluded: (1) Enzyme immunoassay may be more sensitive than electron microscopy but requires a confirmatory test and is tedious when only a few specimens per day are to be examined; (2) LX seems to be suitable for primary screening of faecal specimens for rotavirus; for definitely positive results the test is reliable.

Feces↗
PubMed1984

Transformation of cultured epithelial cells by ethylnitrosourea. Altered expression of type I procollagen chains.

Cultured epithelial rodent cells were transformed in vitro using ethylnitrosourea as a carcinogen either alone or in combination with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The frequency of transformation in the absence of TPA was 5 X 10(-4) at 10 micrograms/ml ethylnitrosourea. Growth of ethylnitrosourea-treated cells in TPA-substituted medium increased the transformation frequency 8-fold. Colonies of transformed cells were isolated from soft agar and analyzed for the production of pericellular matrix glycoproteins. The ethylnitrosourea-transformed cells retained pericellular matrix structures, typical of the nontransformed control cells. Parent cells produced into their culture media fibronectin and procollagen types I and III as their major pericellular glycoproteins. The ethylnitrosourea-transformed cells synthesized and secreted altered procollagen polypeptides. The procollagen of ethylnitrosourea-transformed cells apparently consisted mainly of homotrimeric pro alpha 1 molecules, with smaller amounts of basement membrane procollagen-like chains. Fibronectin synthesis or secretion was not affected by ethylnitrosourea-induced transformation, but the production of fibronectin was enhanced in the transformed cultures treated with TPA. Also, the deposition of procollagen and fibronectin into the pericellular matrix was not affected by ethylnitrosourea-transformation. Very similar changes had previously been observed in murine sarcoma virus-transformed cells. The change of procollagen type I thus appears to be a correlate of malignant transformation of cultured epithelial cells. The results indicate that ethylnitrosourea can induce malignant transformation of epithelial cells in culture and modify production and deposition of pericullular glycoproteins.

Animals↗
PubMed1983

Interaction of fibronectin with complement component C3.

The activation of the complement component C3 generates C3a and C3b fragments, and the physiological cleavage of C3b further yields C3c and C3d fragments. We studied here by enzyme immunoassay the ability of human plasma fibronectin to interact with native C3 of human sera and with isolated C3c and C3d fragments of C3. C3 from sera of all six individuals tested bound to solid-phase fibronectin. Soluble fibronectin bound to solid-phase C3c and C3d, and fluid-phase C3c and C3d also bound to solid-phase fibronectin. The binding of fibronectin to solid-phase C3c and C3d could be inhibited by fluid-phase C3c and C3d. The results suggest the possibility that soluble fibronectin may attach to C3-coated particles or that C3-coated particles may adhere to fibronectin-containing structures.

Complement Activation↗
PubMed1983

Interaction of viral envelope glycoproteins with fibronectin.

An interaction between fibronectin and viral envelope glycoprotein micelles isolated from influenza A, parainfluenza 1, and mumps viruses was found by enzyme immunoassay. All three different glycoprotein micelles bound efficiently to solid-phase fibronectin. When fibronectin was permitted to bind to solid-phase viral glycoproteins, dose-dependent binding was observed. Soluble glycoprotein micelles inhibited the binding of fibronectin to immobilized glycoprotein preparations. The binding was not observed when fibronectin was pretreated with neuraminidase, suggesting that the sugar moieties of fibronectin are responsible for the affinity. This affinity may play a role in virus-cell interactions or in the opsonization of certain viruses during infection.

Fibronectins↗