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71.
L. Allainmat A. Le BorgneG. Pina-Jomir C. Moreau-TribyF.-C. Djemoussi G. Le RouzicJ.-L. Baulieu C. Prunier-Aesch 《Médecine Nucléaire》2011,35(2):54-62
Objectives
Tomoscintigraphy of dopamine transporters with 123I-FP-CIT is nowadays essential to visualise impairment of nigro-striatal system for the diagnosis of parkinsonism and for the differential diagnosis of dementia. With the development of hybrid cameras (SPECT-CT), the CT contribution in nuclear neurology needs to be assessed in diagnostic and semi-quantification performances. The main purpose of our study is to compare attenuation correction using CT to attenuation correction using the linear algorithm of Chang. SPECT-CT with parallel collimation results were also weighed against fan beam collimation and the contribution of partial volume effect correction was studied in secondary objective.Materials and methods
We used a trilinear phantom to define spatial resolution and an anthropomorphic striatal phantom to quantify the activity in striatal cavities. We compared the impact of attenuation and scatter correction on spatial resolution and semi-quantification in striatum. We performed the partial volume effect correction on reconstructed images according to the method of Rousset.Results
Attenuation correction by CT did not improve significantly spatial resolution compared to the algorithm of Chang. The semi-quantification of 123I-FPCIT in striata was not significantly different according to the various CA, but was significantly improved with CT attenuation and scatter correction. Partial volume effect correction improved the quantification from 40 to 60% in the striatal structures, when the activity was superior in at least twice the background noise.Conclusion
SPECT-CT hybrid cameras increase spatial resolution and improve semi-quantification of 123I-FPCIT because of CT attenuation and scatter correction. Another use of CT is the possibility of calibrating anatomic segmentation of striata for partial volume effect correction. Partial volume effect correction improves quantification and is essential for early diagnosis of nigro-striatal disease. 相似文献72.
DNA binding properties of glucocorticosteroid receptors bound to the steroid antagonist RU-486.
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RU-486 is an anti-fertility steroid which also has anti-glucocorticosteroid effects. RU-486 is shown to be a strong antagonist of the glucocorticosteroid-induced cytolytic response of the murine thymoma lines W7TB and T1M1b , and of the induction of mouse mammary tumor virus (MMTV) mRNA in T1M1b cells. The glucocorticosteroid receptor of W7 cells has high affinity for RU-486 (Kd = 3 X 10(-9) M) but the complex formed has low nuclear transfer capacity. Binding of RU-486, as compared with the glucocorticosteroid agonist triamcinolone acetonide, to mouse receptor results in a decreased affinity for DNA in general and a reduced specific recognition of a site in the promoter region of MMTV proviral DNA. The RU-486 complex formed with rat liver receptor exhibits the same behavior; in addition, it is shown that only a fraction of these complexes are activated by temperature and these form highly salt-sensitive interactions with DNA. These results indicate that the binding of RU-486 to glucocorticosteroid receptors mimics pharmacologically the properties of a class of receptor variants (nt-) which are non-functional and have reduced nuclear transfer and altered DNA binding capacity. These results substantiate the importance of DNA binding in receptor function. 相似文献
73.
A highly charged sequence of chick hsp90: a good candidate for interaction with steroid receptors 总被引:1,自引:0,他引:1
N Binart B Chambraud J M Levin J Garnier E E Baulieu 《Journal of steroid biochemistry》1989,34(1-6):369-374
The sequence of the entire chick 90 kDa heat shock protein (hsp90), the non hormone binding component of the heterooligomeric form of steroid receptors, is reported. A comparison of the amino acid sequence of the chick hsp90 to that of the homologous hsp90 from yeast to man, reveals 64-96% identity respectively, and even with E. coli hsp90 an identity of 44% is observed. Analysis of the sequence and a secondary structure prediction of chick hsp90 suggest that two hydrophilic regions A and B, predicted in alpha-helix may play a role in the interaction of hsp90 with other proteins such as steroid hormone receptors. While there are regions of the sequences completely conserved in all hsps90, the most negatively charged hydrophilic region (A) is absent in the E. coli protein. 相似文献
74.
Chick heat-shock protein of Mr = 90,000, free or released from progesterone receptor, is in a dimeric form 总被引:4,自引:0,他引:4
C Radanyi J M Renoir M Sabbah E E Baulieu 《The Journal of biological chemistry》1989,264(5):2568-2573
A monoclonal antibody (BF4) has been used to characterize and purify the heat-shock protein of Mr approximately 90,000 (hsp 90) present in the chick oviduct. In low salt cytosol, the sedimentation coefficient of hsp 90 is approximately 6.8 S, the Stokes radius approximately 7.1 nm, and the calculated Mr approximately 204,000, thus suggesting a dimeric structure. In 0.4 M KCl cytosol, only slightly smaller values were determined (approximately 6.5 S, approximately 6.8 nm, and approximately 187,000). Following purification by ion exchange and immunoaffinity chromatography, hsp 90 migrated as a single silver-stained band at Mr approximately 90,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while the sedimentation coefficient 6.2 S, the Stokes radius approximately 6.8 nm, and the Mr approximately 178,000 confirmed the dimeric structure. However, in both antigen or antibody excess conditions, only one molecule of monoclonal antibody could be bound to the hsp 90 dimer. Whether steric hindrance in a homodimer or the presence of two different 90-kDa proteins in a heterodimer explains this result cannot yet be decided. The dimer is not dissociated by high salt (1 M KCl) or the chaotropic agent (0.5 M NaSCN), but is disrupted by 4 M urea, suggesting a stabilization of the structure by hydrogen bonds. The molybdate-stabilized progesterone receptor hetero-oligomer form of approximately 8 S sedimentation coefficient was purified, and its hsp 90 component was then released by salt treatment. It was found to sediment at approximately 5.8 S and have a Stokes radius approximately 7.1 nm, giving Mr approximately 174,000. This observation is consistent with a previous report suggesting from specific activity determination, scanning of polyacrylamide gels, and cross-linking experiments that each purified nontransformed progesterone receptor molecule includes one progesterone binding unit per two 90-kDa protein molecules (Renoir, J. M., Buchou, T., Mester, J., Radanyi, C., and Baulieu, E. E. (1984) Biochemistry 23, 6016-6023). This work brings direct evidence that both free hsp 90 and the non-hormone binding hsp 90 component released from the nontransformed steroid receptor in the cytosol are in a dimeric form. 相似文献
75.
Mineralocorticosteroid receptor of the chick intestine. Oligomeric structure and transformation 总被引:6,自引:0,他引:6
M E Rafestin-Oblin B Couette C Radanyi M Lombes E E Baulieu 《The Journal of biological chemistry》1989,264(16):9304-9309
The binding of [3H]aldosterone in the chick intestine cytosol was analyzed in terms of affinity and specificity. In this tissue, aldosterone binds to the mineralocorticosteroid receptor, with a high affinity (Kd approximately 0.3 nM) and low capacity (approximately 50 fmol/mg protein), and to the glucocorticosteroid receptor. The selective labeling of the mineralocorticosteroid receptor was achieved by incubating the cytosol with [3H]aldosterone in the presence of RU 486. This synthetic steroid completely inhibited the binding of [3H]aldosterone to the glucocorticosteroid receptor and did not bind to the mineralocorticosteroid receptor. The oligomeric structure of the mineralocorticosteroid receptor was studied by using BF4, a monoclonal antibody which reacts with the 90-kDa heat shock protein (hsp 90), a nonhormone-binding component of nontransformed steroid receptors. The mineralocorticosteroid receptor sedimented at 8.5 +/- 0.4 S (n = 8) in a 15-40% glycerol gradient. This peak was shifted to 11.2 +/- 0.6 S (n = 5) after incubation with BF4, indicating that, in the cytosol, hsp 90 was associated with the mineralocorticosteroid receptor. Dissociation of the complex was observed on gradients containing 0.4 M KCl, as judged by the absence of displacement by BF4 of the 4.3 +/- 0.4 S (n = 10) peak. The effect of molybdate and tungstate ions, and of dimethyl pimelimidate, an irreversible cross-linking agent, on the stability of the hsp 90-receptor complex was investigated. Complexes recovered in the presence of 20 mM molybdate ions dissociated on gradients containing 0.4 M KCl (5.2 +/- 0.6 S (n = 4), whereas complexes prepared in the presence of 20 mM tungstate ions sedimented at 8.5 +/- 0.4 S (n = 7). Similarly, complexes prepared in the presence of molybdate ions dissociated during high pressure liquid chromatography (HPLC) gel filtration analysis performed in 0.4 M KCl (RS (Stokes radius) = 3.9 +/- 0.5 nm (n = 3) versus 7.3 +/- 0.2 nm (n = 3) in the presence of 20 mM molybdate ions), whereas complexes prepared in the presence of tungstate ions did not dissociate (RS = 6.9 +/- 0.2 nm (n = 3]. As observed for the tungstate-stabilized receptor, the cross-linked receptor dissociated neither on gradient containing 0.4 M KCl (9.5 +/- 0.1 S (n = 3] nor during HPLC performed in 0.4 M KCl (RS = 6.5 +/- 0.3 (n = 4]. Furthermore, the cross-linked receptor was more resistant to the inactivating effect of urea on aldosterone binding than the noncross-linked receptor prepared in the presence of either molybdate or tungstate ions. 相似文献
76.
Compared intracellular localization of the glucocorticosteroid and progesterone receptors: an immunocytochemical study 总被引:5,自引:0,他引:5
The intracellular distribution of the glucocorticosteroid and progesterone receptors (GR and PR, respectively) was studied immunohistochemically. In control adrenalectomized (Adx) rat liver, immunostaining of paraffin sections revealed GR in cell nuclei, with a wide range of intensity between individuals. Following dexamethasone (Dex) treatment, the nuclear staining was uniformly high in all animals; the cytoplasmic staining was always weak and remained unchanged after Dex treatment. In frozen sections, the GR immunoreactivity in cell nuclei was weak in the absence and very strong in the presence of Dex, while no GR-specific cytoplasmic staining was observed. In frozen sections fixed in vapor of formaldehyde to avoid any artifactual redistribution of the receptor, some GR immunostaining was observed in the cytoplasm and the nucleus. In contrast, in paraffin as well as in frozen sections of chick oviduct, fixed by immersion or in vapor, PR was exclusively nuclear, including in the absence of progesterone, and the intensity of immunostaining was not modified by progesterone treatment. In order to verify if loss of nuclear receptors during tissue preparation could explain the differences in nuclear immunostaining observed between hormone-free and hormone-occupied GR, and between GR and PR, frozen sections of Adx rat liver and chick oviduct were preincubated at 4 degrees C in buffer solutions before the fixation procedure. It was found that hormone-free GR diffused out of the nucleus faster than hormone-occupied GR nuclei, and that nuclear GR diffused faster than nuclear PR. Based on these results, we propose that, during the fixation procedure, the fraction of nuclear GR which diffuses out of the nucleus is much smaller in the presence than in the absence of Dex. This lesser loss of nuclear GR after Dex treatment results in an increase of immunostaining after hormonal administration, which might have been erroneously interpreted as a sign of translocation from cytoplasm to nucleus. That the nuclear PR detection is not modified by progesterone treatment may be explained by its reduced diffusibility as compared to nuclear GR. This hypothesis does not rule out the existence of some cytoplasmic GR, whose significance remains unclear, but it offers a unified mechanism of action for all steroid hormone receptors. In the case of glucocorticosteroids, as already proposed for estradiol and progesterone, no step of cytoplasm to nucleus translocation would be required for hormone action, and transformation-activation would occur in the nucleus, resulting in tighter binding of the hormone receptor complexes.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
77.
Oestrogen and progesterone receptors in chick oviduct chromatin after administration of oestradiol, progesterone or anti-oestrogen. 总被引:2,自引:0,他引:2
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Oestrogen-primed and withdrawn chicks were injected with oestradiol benzoate, progesterone, and/or the anti-oestrogens tamoxifen and 4-hydroxytamoxifen. Oestrogen receptors were studied in oviduct chromatin solubilized by mild digestion of purified nuclei with micrococcal nuclease. After a single injection of oestradiol benzoate, ultracentrifugation on sucrose gradients of chromatin extracts labelled with [3H]-oestradiol showed two peaks of oestradiol binding sites, sedimenting at 13--14 S and 7--8 S. After repeated injections of oestradiol benzoate, the 13--14 S peak increased more than the 7--8 S peak. After injection of anti-oestrogen alone or together with oestradiol benzoate, no [3H]oestradiol-binding or 4-hydroxy[3H]tamoxifen-binding peaks were detected in the chromatin. Injection of progesterone also produced an increase of the 13--14 S and 7--8 S chromatin oestradiol receptor. Progesterone receptor could only by detected in chromatin early after progesterone administration, and it sedimented in density gradients with the 12 S mononucleosome fraction. Tamoxifen injected together with progesterone gave higher levels of 13--14 S oestrogen binding sites than did progesterone alone. The presence of a 13--14 S peak of oestrogen binding sites in hormonal situations which promote a biological response in the chick oviduct, and the absence of this peak after administration of anti-oestrogens, suggest that this subfraction of chromatin contains elements involved in gene regulation. 相似文献
78.
M Best-Belpomme J Mester H Weintraub E E Baulieu 《European journal of biochemistry》1975,57(2):537-547
Macromolecular components with properties of oestrogen receptors have been identified in the 0.5 M KCl nuclear soluble, the nuclear insoluble and the cytosol fractions of laying hen and immature (2--4 weeks, untreated by hormone) chicken oviduct. 7n the 0.5 M KCl extract of laying hen oviduct nuclei, a receptor, of protein nature according to the effects of enzymic treatments, has been identified. It exhibits high affinity for oestradiol with an apparent equilibrium association constant KA = 4 - 109 M-1 at 4 degrees C. The binding of [3H] oestradiol is abolished by 1 muM oestriol, oestrone and diethylstilboestrol, but not by the same concentration of progesterone, testosterone, and cortisol. Sucrose gradient ultracentrifugation studies in the presence of 0.5 M KCl indicate a sedimentation coefficient of 4.3 S, and there is partial aggregation in low-ionic-strength medium. The estimated number of binding sites per nucleus is about 5000, as calculated from DNA content of chick diploid genome. Most of the binding sites were found to be occupied by endogenous oestrogen(s). Oestradiol dissociates from the receptor according to an apparent two-step mechanism. The half-life time for the faster dissociation step is 18 h at 0 degrees C, 25 min at 20 degrees C and 10 min at 30 degrees C, and for the slower one is 180 h, 115 min and 60 min, respectively. In the 0.5 M KCl extract of immature chicken oviduct nuclei, there are approximately 500 receptor sites per nucleus; their affinity for oestradiol is the same as in the case of laying hen soluble nuclear receptor. After repeated extractions of nuclei with 0.5 M KCl medium, a substantial quantity of oestrogen binding sites remains in the residual fraction. Binding characteristics of this insoluble nuclear receptor resemble those of the soluble nuclear receptor: high affinity for oestradiol (KA = 7 - 10(8) M-1 at 37 degrees C) and specificity for oestrogens. The estimated number of binding sites are approximately 2000/cell for laying hen, and approximately 1000/cell for immature chicken. In the high-speed supernatant fraction of laying hen oviduct homogenates, an oestrogen receptor is also present, but its concentration is low (less than or equal to 100 sites/cell) and at the limits of sensitivity of the methods used. In the cytosol of immature chicken oviduct, there are approximately 2500 oestradiol receptor sites per cell. 相似文献
79.