| 1. |
- Collingwood, T N, et al.
(författare)
-
A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.
- 1997
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 94:1, s. 248-53
-
Tidskriftsartikel (refereegranskat)abstract
- The syndrome of resistance to thyroid hormone is characterized by elevated serum free thyroid hormones, failure to suppress pituitary thyrotropin secretion, and variable peripheral refractoriness to hormone action. Here we describe a novel leucine to valine mutation in codon 454 (L454V) of the thyroid hormone beta receptor (TR beta) in this disorder, resulting in a mutant receptor with unusual functional properties. Although the mutant protein binds ligand comparably to wild-type receptor and forms homo- and heterodimers on direct repeat, everted repeat, or palindromic thyroid response elements, its ability to activate transcription via these elements is markedly impaired. The hydrophobic leucine residue lies within an amphipathic alpha-helix at the carboxyl terminus of TR beta and the position of the homologous residue in the crystal structure of TR alpha indicates that its side chain is solvent-exposed and might interact with other proteins. We find that two putative transcriptional mediators (RIP140 and SRC-1) exhibit hormone-dependent association with wild-type TR. In comparison, the interaction of this natural mutant (L454V) and artificial mutants (L454A, E457A) with RIP140 and SRC-1 is markedly reduced. Furthermore, coexpression of SRC-1 is able to restore the transcriptional activity of the L454V mutant receptor, indicating that the interaction of this residue with accessory proteins is critical for transcriptional activation. Finally, the occurrence of the L454V mutation in resistance to thyroid hormone, together with impaired negative regulation of the thyroid-stimulating hormone alpha promoter by this mutant, suggests that the amphipathic alpha-helix also mediates hormone-dependent transcriptional inhibition, perhaps via interaction with these or other accessory factors.
|
|
| 2. |
|
|
| 3. |
- Lönn, Lars, 1956, et al.
(författare)
-
Body weight and body composition changes after treatment of hyperthyroidism.
- 1998
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X. ; 83:12, s. 4269-73
-
Tidskriftsartikel (refereegranskat)abstract
- Body composition changes in nine adults with hyperthyroidism were determined with dual energy x-ray absorptiometry and computed tomography at diagnosis and after 3 and 12 months of euthyroidism achieved by surgery, antithyroid drugs, or treatment with radioiodine. Mean body weight was 67.6 kg at diagnosis and increased 2.7 kg (P=0.06) and 8.7 kg (P < 0.001) after 3 and 12 months of euthyroidism, respectively. Basal metabolic rate decreased from 2087 Cal/24 h at diagnosis to 1601 Cal/24 h at 12 months (P=0.001), whereas reported energy intake dropped from 3244 to 2436 Cal/24 h (P=0.01). According to dual energy x-ray absorptiometry, body fat was unchanged at 3 months, but increased by 5.3 kg (P < 0.0001) at 12 months. Fat-free mass increased 2.7 kg (P=0.003) at 3 months and 3.5 kg (P < 0.0001) at 12 months. Changes in bone mineral content and density did not reach significance. According to computed tomography, skeletal muscle plus skin areas increased by 11% (trunk) and 18% (thigh) at 3 months and by 17% (trunk) and 25% (thigh) at 12 months. There was no increase in sc adipose tissue (AT) at 3 months, but at 12 months this AT depot increased by 15% (thigh) and 33% (trunk). Intraperitoneal AT showed a borderline significant increase by 28% (P=0.08) at 3 months and by 40% (P=0.015) at 12 months. Areas of visceral organs and bone tissue of femur did not change significantly during the study. It is concluded that during early recovery from hyperthyroidism, priority is given to the replenishment of skeletal muscles and ip AT, whereas sc AT is increased at a later stage.
|
|
| 4. |
- Nilsson, T, et al.
(författare)
-
The relations of microalbuminuria to ambulatory blood pressure and myocardial wall thickness in a population.
- 1998
-
Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 244:1, s. 55-9
-
Tidskriftsartikel (refereegranskat)abstract
- To examine the relationship between microalbuminuria (20-200 microg min(-1)) and 24 h ambulatory blood pressure and heart wall thickness, in a representative population sample of men and women aged 56-65 years.Every second individual aged 56-65 years (n=488) in the district, was invited for a health examination, which included determination of urinary albumin and creatinine (overnight sample). The highest and lowest decentile of urinary albumin/creatinine ratio were compared.The district of the Primary Health Care and Research Centre of Mölnlycke, Sweden.After excluding 2 individuals with a urinary albumin excretion exceeding 200 microg min(-1). 26 subjects (group 1) could be compared with 27 subjects in the lowest decentile (group 2).Comparison between the determinations of the ambulatory blood pressure and echocardiographic variables in the two groups.Group 1 had significantly higher 24 h ambulatory blood pressure, and heart septum and posterior wall thickness as well as significantly higher fasting blood glucose and serum triglyceride concentrations. The differences in blood pressure (P < 0.05) but not heart wall thickness remained significant (P<0.05) after excluding subjects with hypertension, angina pectoris, treated diabetes mellitus, and/or history of heart or cerebrovascular disease. When excluding individuals with both treated and untreated diabetes mellitus, fasting blood glucose concentration was higher in group 1. The waist-hip ratio, weight and body mass index did not differ between the groups.The findings indicate that microalbuminuria is related to signs of cardiovascular and metabolic influence and therefore could be a valuable tool for grading the risk of later cardiovascular morbidity.
|
|
