| 1. |
- Collingwood, T N, et al.
(författare)
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A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.
- 1997
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 94:1, s. 248-53
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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.
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| 5. |
- Ahlman, Håkan, 1947, et al.
(författare)
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En "ny" tumörmarkör.
- 1996
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Ingår i: Klinisk Kemi i Norden, 8.. - Göteborg. ; , s. 45-52
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Amiri-Mosavi, A, et al.
(författare)
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Expression of cholecystokinin-B/gastrin receptors in medullary thyroid cancer.
- 1999
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Ingår i: The European journal of surgery = Acta chirurgica. - : Oxford University Press (OUP). - 1102-4151. ; 165:7, s. 628-31
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Tidskriftsartikel (refereegranskat)abstract
- To characterise the cholecystokinin (CCK) receptor subtypes in medullary thyroid cancer by measuring the expression of CCK-A and CCK-B/gastrin receptor mRNA.
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| 7. |
- Fjälling, M, et al.
(författare)
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Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.
- 1996
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:9, s. 1519-21
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Tidskriftsartikel (refereegranskat)abstract
- A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.
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| 9. |
- Oscarsson, J, et al.
(författare)
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Diurnal variation in serum insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations during daily subcutaneous injections of recombinant human growth hormone in GH-deficient adults.
- 1997
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Ingår i: Clinical endocrinology. - 0300-0664. ; 46:1, s. 63-8
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Tidskriftsartikel (refereegranskat)abstract
- Whereas there seems to be little, if any, circadian variation in circulating concentrations of IGF-I and IGFBP-3 in healthy subjects, there are conflicting reports on this issue in GH-deficient patients treated with GH as a daily subcutaneous injection. We have therefore investigated the 24-hour serum profiles of IGF-I and IGFBP-3 concentrations after one week and more than one year of GH treatment.Eleven subjects, with adult onset GH deficiency mainly caused by pituitary adenomas were included in the study.In an open study, six subjects (three women and three men; age (+/-SEM) 41.2 +/- 3.9 years) were investigated after one week of GH therapy and five subjects (three women and two men; age (+/-SEM) 61.4 +/- 3.3 years) were investigated after 13-40 months of GH therapy. The GH injections were given at 2000 h. The subjects were hospitalized for 24-hour blood sampling at 1-hour intervals and serum concentrations of GH, IGF-I and IGFBP-3 were determined.There was a significant diurnal variation in serum IGF-I and IGFBP-3 concentrations both in the subjects who had received GH for one week and in those who had received GH treatment for more than one year. The serum concentrations of IGF-I and IGFBP-3 were highest in the morning and lowest during night-time and early morning. The molar IGF-I/IGFBP-3 ratio varied significantly with time in both groups of patients in a similar way as IGF-I and IGFBP-3 indicating a more pronounced variation in IGF-I compared with IGFBP-3 in response to the GH therapy.Significant diurnal variations in serum IGF-I and IGFBP-3 concentrations occur after one week and more than one year of GH treatment with daily subcutaneous injections. The results indicate that the free fraction of IGF-I may exhibit a diurnal variation.
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