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Sökning: WFRF:(Hellstrand Monika 1955)

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1.
  • Baghaei, Fariba, 1964, et al. (författare)
  • The lean woman.
  • 2002
  • Ingår i: Obesity research. - 1071-7323. ; 10:2, s. 115-21
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: In the current obesity epidemic, the ability to remain lean is beginning to be uncommon. Therefore, it was considered of interest to characterize such subjects. RESEARCH METHODS AND PROCEDURES: From a population of premenopausal women (n = 270), all 40 years of age, those with a similar body mass index (BMI) as women at the age of 21 years, born the same year (BMI = 21.1 kg/m(2)) were selected among nonsmokers and compared with the remaining nonsmoking women. RESULTS: Lean women showed, as expected, low waist-to-hip circumference ratio and abdominal sagittal diameter as well as absence of other disease risk factors. Compared with the remaining women, 17 beta-estradiol was high and androgens were low, whereas insulin-like growth factor I and thyroid hormones showed no differences. Dihydroepiandrosterone sulfate was lower, whereas cortisol, measured in saliva repeatedly over a day, and adrenocorticotropin hormone were not different. Results from questionnaires indicated higher education and socioeconomic status, frequent sports activities, and better psychosocial adaptation and psychological health. A tetranucleotide repeat polymorphism in the fourth [corrected] intron of the aromatase P450 gene was longer among the lean (187 base pairs) than the rest of the women. Women with opposite phylogenetic characteristic have a short microsatellite (168 base pairs) in this gene locus. DISCUSSION: Lean, nonsmoking women enjoy an excellent health in not only anthropometric and metabolic factors, but also in neuroendocrine, endocrine, and psychological variables. The endocrine measurements suggest a well-functioning aromatase, which in turn might have a genetic background, contributing to health. The aromatase gene might be important for regulation of body fat mass.
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2.
  • Melke, Jonas, 1971, et al. (författare)
  • Serotonin transporter gene polymorphisms are associated with anxiety-related personality traits in women.
  • 2001
  • Ingår i: American journal of medical genetics. - 0148-7299. ; 105:5, s. 458-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have reported an association between anxiety-related personality traits and a promoter polymorphism in the human serotonin transporter (5-HTT) gene (5-HTT gene-linked polymorphic region, 5-HTTLPR). In the present study, a population of 251 subjects was assessed with the Karolinska Scales of Personality (KSP) and genotyped both for the 5-HTTLPR and for a variable number of tandem repeats polymorphism in the second intron of the same gene. The interpretation of previous studies has to some extent been confounded by the studied subjects differing with respect to ethnicity, sex, and age. To circumvent this problem, all included subjects were Caucasians, women, and born in the same year (1956). Associations were found between the 5-HTTLPR and four of the five anxiety-related KSP scales (psychic anxiety, muscular tension, psychasthenia, and lack of assertiveness), subjects being homozygous for the short allele displaying higher anxiety scores than those of the long/long or long/short genotype. In addition, an association was found between the intron 2 polymorphism and one anxiety-related personality trait (somatic anxiety).
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3.
  • Westberg, Lars, 1973, et al. (författare)
  • Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women.
  • 2001
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 86:6, s. 2562-8
  • Tidskriftsartikel (refereegranskat)abstract
    • To elucidate the possible role of genetic variation in androgen receptor (AR), estrogen receptor alpha (ER alpha), and ER beta on serum androgen levels in premenopausal women, the CAG repeat polymorphism of the AR gene, the TA repeat polymorphism of the ER alpha gene, and the CA repeat polymorphism of the ER beta gene were studied in a population-based cohort of 270 women. Total testosterone, free testosterone, dehydroepiandrosterone sulfate, androstenedione, 17-hydroxyprogesterone, 3 alpha-androstanediol glucuronide, 17 beta-estradiol, LH, FSH, and sex steroid hormone-binding globulin (SHBG) were measured in serum samples obtained in the follicular phase of the menstrual cycle. Women with relatively few CAG repeats in the AR gene, resulting in higher transcriptional activity of the receptor, displayed higher levels of serum androgens, but lower levels of LH, than women with longer CAG repeat sequences. The CA repeat of the ER beta gene also was associated with androgen and SHBG levels; women with relatively short repeat regions hence displayed higher hormone levels and lower SHBG levels than those with many CA repeats. In contrast, the TA repeat of the ER alpha gene was not associated with the levels of any of the hormones measured. Our results suggest that the serum levels of androgens in premenopausal women may be influenced by variants of the AR gene and the ER beta gene, respectively.
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4.
  • Yonker, Julie E, et al. (författare)
  • Verified hormone therapy improves episodic memory performance in healthy postmenopausal women.
  • 2006
  • Ingår i: Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition. - Hove : Psychology Press. - 1382-5585 .- 1744-4128. ; 13:3-4, s. 291-307
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of hormone therapy (HT) and cognition have yielded conflicting results. The aim of this observational study was to examine the effect of estradiol, via serum verified HT (estradiol, estriol, progesterone) and endogenous estradiol, on 108 healthy postmenopausal women's cognitive performance. The results demonstrated that the 43 HT-users performed at a significantly higher level than non-users on episodic memory tasks and on a verbal fluency task, whereas HT-users and non-users did not differ on tasks assessing semantic memory and spatial visualization. In addition, there was a positive relationship between serum estradiol level and episodic memory performance, indicating that postmenopausal HT is associated with enhanced episodic memory and verbal fluency, independent of age and education. These observational results suggest that HT use may be sufficient to exert small, yet positive effects on female sensitive cognitive tasks. Hormone therapy compliance and formulation is discussed as confounding factors in previous research.
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5.
  • Baghaei, Fariba, 1964, et al. (författare)
  • Phenotypic and genotypic characteristics of women in relation to personality traits.
  • 2003
  • Ingår i: International journal of behavioral medicine. - 1070-5503. ; 10:4, s. 365-78
  • Tidskriftsartikel (refereegranskat)abstract
    • The associations were examined in women between personality traits and steroid hormones, particularly androgens, as well as polymorphisms in genes regulating androgen concentration and effects. Women, all 42 years of age and premenopausal (n = 270), were recruited randomly. Conventional "masculine" and "feminine" personality traits were examined by questionnaire and set in relation to psychosocial and socioeconomic conditions, behavior in childhood, hormones, risk factors for disease, and polymorphisms in microsatellites in the CYP aromatase and the androgen receptor gene. The proportions of personality traits considered as being dominated by "masculinity" (M) or "femininity" (F) were 44.9%, respectively 15.0%, the rest consisting of a combination of M and F (33.2%) or "undifferentiated" (6.9%). M characteristics were positively associated with education, sporting, self-confidence, and good adaptation to work situation. M scores correlated with reports of "tomboyism" as girls. There was essentially no difference in hormones or disease risk factors between M and F women. The number of (CAG) repeats in the microsatellite of the transactivating domain of the androgen receptor was 19 (2.3; M and SD). M characteristics were more pronounced in the presence of longer repeat stretches (n > 20). No associations were found with F scores. There were no significant associations to the number of tetranucleotide repeats (TTTA) in the fourth introne of the aromatase gene. It was concluded that a majority of women showed M type of personality traits, associated with normal hormones, somatic health, and a long microsatellite in the transactivating domain of the AR gene.
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6.
  • Baghaei, Fariba, 1964, et al. (författare)
  • The CYP19 gene and associations with androgens and abdominal obesity in premenopausal women.
  • 2003
  • Ingår i: Obesity research. - 1071-7323. ; 11:4, s. 578-85
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Elevated androgens in women are associated with type 2 diabetes and are dependent on the conversion to estrogens by aromatase cytochrome P450. Polymorphisms of a tetranucleotide repeat [TTTA](n) in the fourth intron of the CYP19 gene are associated with endocrine-dependent diseases and were examined in relation to hormone levels and disease risk factors in premenopausal women. RESEARCH METHODS AND PROCEDURES: A population sample of women born in 1956 (n = 270) were genotyped for this polymorphism and the results set in relation to steroid hormones, including saliva cortisol, anthropometric variables, estimates of insulin, glucose and lipid metabolism, and blood pressure. RESULTS: Seven tetranucleotide repeat [TTTA](n) alleles were detected with allelic sizes of 168 to 195 bp, with a TCT deletion/insertion (168/171 bp) upstream of this microsatellite. Smoking was associated with elevated androgens (p = 0.005 to 0.019). Using the median (average stretch, 177.5 bp) as a dividing line, nonsmoking women with the shorter microsatellite had higher free testosterone (p = 0.018) and lower sex hormone binding globulin (p = 0.033). These differences were pronounced with the 168-bp allele. Such women were also characterized by a less-substantial decrease of morning cortisols ("unwinding"; p = 0.035) and central obesity (abdominal sagittal diameter, p = 0.049) and had waist/hip circumference ratios of borderline significance (p = 0.064). DISCUSSION: The results indicate that, in premenopausal women, a short microsatellite in the fourth intron of the CYP19 gene, caused by a TCT deletion upstream the [TTTA](n) tract, is associated with elevated androgens, perturbed regulation of the hypothalamic-pituitary-adrenal axis, and abdominal obesity.
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7.
  • Hellstrand, Monika, 1955, et al. (författare)
  • Dopamine D(2) receptor-induced COX-2-mediated production of prostaglandin E(2) in D(2)-transfected Chinese hamster ovary cells without simultaneous administration of a Ca(2+)-mobilizing agent.
  • 2002
  • Ingår i: Biochemical pharmacology. - 0006-2952. ; 63:12, s. 2151-8
  • Tidskriftsartikel (refereegranskat)abstract
    • We have earlier demonstrated that dopamine stimulates the liberation of the prostaglandin E(2) (PGE(2)) precursor, arachidonic acid, in Chinese hamster ovary cells transfected with the rat dopamine D(2) receptor (long isoform), also without concomitant administration of a Ca(2+)-releasing agent [Nilsson et al., Br J Pharmacol 1998;124:1651-8]. In the present report, we show that dopamine, under the same conditions, also induces a concentration-dependent increase in the production of PGE(2), with a maximal effect of 235% at approximately 100 microM, and with an EC(50) of 794 nM. The effect was counteracted by the D(2) antagonist eticlopride, pertussis toxin, the inhibitor of intracellular Ca(2+) release TMB-8, incubation in Ca(2+)-free experimental medium, and PKC desensitization obtained by chronic pretreatment with the phorbol ester TPA. It was also antagonized by the non-specific cyclooxygenase (COX) inhibitor, indomethacin, and by the selective COX-2 inhibitor, NS-398, but not by the specific COX-1 inhibitor, valeryl salicylate. Both the non-specific phospholipase A(2) inhibitor, quinacrine, and an inhibitor of cPLA(2) and iPLA(2), AACOF3, counteracted the effect; in contrast, a selective iPLA(2) inhibitor, BEL, and a selective sPLA(2) inhibitor, TAPC, were ineffective. No effects of dopamine were obtained in control cells mock-transfected with the p3C vector only. The results reinforce previous assumptions that dopamine may interact with eicosanoid metabolism by means of D(2) receptor activation, and implicate an involvement of cPLA(2) and COX-2 in this effect. It is suggested that measurement of dopamine-induced PGE(2) production may serve as a convenient way to study D(2) receptor function in vitro.
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8.
  • Hellstrand, Monika, 1955 (författare)
  • Dopamine D2 and D3 receptors. Studies on transduction mechanisms and on the role of a D3 gene polymorphism
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The neurotransmitter dopamine has been implicated in the pathophysiology of, e.g., Parkinson s disease and schizophrenia, and dopamine receptor-active compounds are commonly employed therapeutically in these and other disorders. An overall aim of this thesis was to illuminate how the signal transduction system involving arachidonic acid (AA) and its metabolite, prostaglandin E2 (PGE2), is influenced by D2 and D3 dopamine receptors, respectively, and to what extent assessment of the effects of ligands with affinity for these receptors on the AA pathway may serve to study phenomena such as partial and inverse agonism. In addition, the possible functional importance of a polymorphism in the gene encoding the D3 receptor was assessed both in vitro, using cAMP and PGE2 as markers of receptor activation, and in vivo, by means of an association study.The results presented in paper I suggest that dopamine potently increases AA formation in D2 receptor-transfected Chinese hamster ovary (CHO) cells. Challenging previous reports, this effect was observed also in the absence of the concomitant administration of a Ca2+-mobilizer. Paper I also outlined the respective roles of G-proteins, Ca2+, and phospholipases for this effect to occur. Whereas ( )-3-PPP, in line with previous studies, displayed the properties of a partial D2 receptor agonist, the alleged dopamine receptor antagonist haloperidol displayed the profile of an inverse agonist. Paper II extends the findings of paper I by showing that the D2-induced induction of AA leads to the formation of PGE2 as the result of the catalytic action of cyclooxygenase 2 (COX-2). In this paper, we also present data supporting the notion that the D2-induced AA mobilization is catalyzed by the cPLA2 phospholipase subtype. Paper III shows that dopamine at low, but not high, concentrations inhibits AA formation in CHO cells transfected with the rat D3 receptor, i.e. an effect opposite to that observed in cells expressing D2 receptors. The dopamine receptor ligand PNU-99194A, which previously has been regarded as a D3 receptor antagonist, displayed agonist-like properties.Paper IV was an attempt to clarify the functional role of a polymorphism in the dopamine D3 receptor gene, the ser9gly polymorphism, using CHO cells transfected with either the ser9 or the gly9 variant of this receptor. The ser9gly polymorphism was found to alter the effect of dopamine on cellular transduction from inhibition of cyclic AMP (ser9) to inhibition of PGE2 (gly9). Haloperidol displayed antagonist properties at ser9-type receptors, and agonist-like properties at gly9 receptors. Finally, paper V aimed at further exploring the notion that the ser9gly polymorphism is functionally important by assessing its possible association with personality traits in healthy humans. The results suggest that the ser9gly polymorphism may be weakly linked to neuroticism in males and females, and to non-conformity traits in women.The main conclusions are (i) that the AA/PGE2 pathway is a useful marker for assessment of D2 and D3 receptor activity in vitro, (ii) that compounds previously assumed to act as neutral antagonists at D2 or D3 receptors may display agonism or inverse agonism vis-à-vis these receptors, hence illustrating the difficulties associated with the characterization of a receptor ligand in terms of intrinsic activity, and (iii) that the ser9gly polymorphism may influence D3 receptor function by means of a hitherto unknown mechanism, i.e. by shifting cellular transduction from one second messenger system (cAMP) to another (PGE2).
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