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Biomedical subjects

A Hautanen

Publications and source records attributed to A Hautanen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cigarette smoking is associated with elevated adrenal androgen response to adrenocorticotropin.

Cigarette smoking alters the pattern of endogenous steroid levels. We examined this phenomenon in two separate male groups. Group A consisted of 189 dyslipidemic men participating in the Helsinki Heart Study and group B of 100 men including patients with heart disease and healthy controls. The subjects in the latter group underwent ACTH-testing. In group A, smokers had significantly higher basal androstenedione and dehydroepiandrosterone sulfate (DHEAS) levels and androstenedione/cortisol ratios than nonsmokers. Mean concentrations of cortisol, dehydroepiandrosterone (DHEA), androstanediol glucuronide, testosterone, and sex-hormone binding globulin (SHBG) did not differ between smokers and nonsmokers. In group B, smokers had lower high density lipoprotein (HDL)-cholesterol and apolipoprotein AI and higher triglyceride levels than nonsmokers. Basal androstenedione and ACTH stimulated androstenedione and DHEA concentrations were higher in smokers. No significant differences were found in basal insulin, SHBG, estrone, estradiol, testosterone, free testosterone, and dihydrotestosterone concentrations between smokers and nonsmokers. These results suggest that smoking decreases the activity of either 21- or 11 beta-hydroxylase in the adrenal cortex, which results in increased secretion of adrenal androgens.

Adrenal Glands↗
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↗
PubMed1983

Affinity of myeloma IgG proteins for fibronectin.

The ability of purified human myeloma IgG proteins to interact with human plasma fibronectin was studied by enzyme immunoassays. Seven of eight different myeloma IgG proteins representing all four IgG subclasses bound to solid phase fibronectin in a dose-dependent manner. The binding of myeloma IgG to solid phase fibronectin could be inhibited by soluble fibronectin and gelatin, but not by heparin or bovine serum albumin. Evidence for an antigen-antibody type interaction was not observed by double diffusion analysis. Affinity chromatography of radiolabelled cell culture medium over IgG-Sepharose showed that only fibronectin bound to the IgG-conjugates. The affinity of IgG molecules for fibronectin may play a role in cryoimmunoglobulinaemia associated with certain pathological states.

Cells, Cultured↗
PubMed1982

C3c and C3d fragments of human C3 bind myeloma IgG1 and IgG3 proteins.

Eight human myeloma proteins, two of each IgG subclass, were studied for binding to solid-phase C3c and C3d by the ELISA technique. Myeloma IgG1 kappa, IgG1 lambda, IgG3 kappa and IgG3 lambda proteins bound to C3c and C3d, while two IgG2 kappa, and two IgG4 kappa proteins failed to show significant binding affinity. The results suggest that like C1q, the stable binding sites of C3, located on the C3c and C3d parts of the molecule, have affinity for IgG subclasses 1 and 3.

Animals↗
PubMed1981

Circulating immune complexes, immunoconglutinins, and rheumatoid factors in nephropathia epidemica.

Circulating immune complexes (CICs), immunoconglutinins, and antiglobulins were studied in nephropathia epidemica, an acute infectious hemorrhagic fever occurring in Finland and Scandinavia. Sixty-one serum specimens from 18 serologically confirmed patients were collected between day -5 and day 230 from the onset of fever. Five CIC tests, three immunoconglutinin tests, and various other tests were used to characterize the disease immunologically. CICs were found in all patients. The percentage detection of positive cases varied in the tests from 100% to 22%. A marked stimulation of levels of the IgM class of immunoglobulins were observed. Antiglobulin tests were positive for all of the patients. No correlation between the test results and the clinical severity of the disease could be found. Of special interest was the delay in the rise of CIC levels compared with the chromologic pattern of the clinical course. In some patients a prolonged appearance of CICs for eight months was observed.

Antibodies, Anti-Idiotypic↗