TSH Isoforms: About a Case of Hypothyroidism in a Down's Syndrome Young Adult

Background. For unknown reasons, the prevalence of thyroid autoimmune disorders is higher in patients with Down's syndrome than in the general population. The present case strongly supports a recent evaluation of propagating screening for thyroid disease in this group of patients to assure early diagnosis of hypothyroidism. Methods. In a 25-year-old man diagnosed with Down's syndrome, clinical manifestations of hypothyroidism were lacking, but profound biochemical abnormalities were found with particularly high levels of thyroid stimulating hormone (TSH). Antigenic properties of TSH were characterized using a panel of anti-TSH antibodies. Results. Technical problems not infrequently associated with TSH measurements are convincingly ruled out. Antigenic characterization of the patient's circulating TSH revealed circulating forms of TSH different from pituitary TSH which closely resembled TSH recombinant human hormone. Conclusions. It appears counterintuitive that the bioactivity of TSH decreases in the hypothyroid state as higher bioactivity of TSH is anticipated in hypothyroidism promoted by an increased hypothalamic TRH drive. In contrast, diminished negative thyroid hormone feedback will enhance posttranslational glycosylation of TSH subunits and increase sialylation of the carbohydrate side chains. Both exert a negative effect on TSH bioactivity, only compensated by the very high levels of the hormone as in the present case

Use of Human Cancer Cell Lines Mitochondria to Explore the Mechanisms of BH3 Peptides and ABT-737-Induced Mitochondrial Membrane Permeabilization

Current limitations of chemotherapy include toxicity on healthy tissues and multidrug resistance of malignant cells. A number of recent anti-cancer strategies aim at targeting the mitochondrial apoptotic machinery to induce tumor cell death. In this study, we set up protocols to purify functional mitochondria from various human cell lines to analyze the effect of peptidic and xenobiotic compounds described to harbour either Bcl-2 inhibition properties or toxic effects related to mitochondria. Mitochondrial inner and outer membrane permeabilization were systematically investigated in cancer cell mitochondria versus non-cancerous mitochondria. The truncated (t-) Bid protein, synthetic BH3 peptides from Bim and Bak, and the small molecule ABT-737 induced a tumor-specific and OMP-restricted mitochondrio-toxicity, while compounds like HA-14.1, YC-137, Chelerythrine, Gossypol, TW-37 or EM20-25 did not. We found that ABT-737 can induce the Bax-dependent release of apoptotic proteins (cytochrome c, Smac/Diablo and Omi/HtrA2 but not AIF) from various but not all cancer cell mitochondria. Furthermore, ABT-737 addition to isolated cancer cell mitochondria induced oligomerization of Bax and/or Bak monomers already inserted in the mitochondrial membrane. Finally immunoprecipatations indicated that ABT-737 induces Bax, Bak and Bim desequestration from Bcl-2 and Bcl-xL but not from Mcl-1L. This study investigates for the first time the mechanism of action of ABT-737 as a single agent on isolated cancer cell mitochondria. Hence, this method based on MOMP (mitochondrial outer membrane permeabilization) is an interesting screening tool, tailored for identifying Bcl-2 antagonists with selective toxicity profile against cancer cell mitochondria but devoid of toxicity against healthy mitochondria

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Background. For unknown reasons, the prevalence of thyroid autoimmune disorders is higher in patients with Down's syndrome than in the general population. The present case strongly supports a recent evaluation of propagating screening for thyroid disease in this group of patients to assure early diagnosis of hypothyroidism. Methods. In a 25-year-old man diagnosed with Down's syndrome, clinical manifestations of hypothyroidism were lacking, but profound biochemical abnormalities were found with particularly high levels of thyroid stimulating hormone (TSH). Antigenic properties of TSH were characterized using a panel of anti-TSH antibodies. Results. Technical problems not infrequently associated with TSH measurements are convincingly ruled out. Antigenic characterization of the patient's circulating TSH revealed circulating forms of TSH different from pituitary TSH which closely resembled TSH recombinant human hormone. Conclusions. It appears counterintuitive that the bioactivity of TSH decreases in the hypothyroid state as higher bioactivity of TSH is anticipated in hypothyroidism promoted by an increased hypothalamic TRH drive. In contrast, diminished negative thyroid hormone feedback will enhance posttranslational glycosylation of TSH subunits and increase sialylation of the carbohydrate side chains. Both exert a negative effect on TSH bioactivity, only compensated by the very high levels of the hormone as in the present case

Viêtnam : renouveau et transitions

La désintégration du Comecom et la fin de l'aide soviétique obligent le Vietnam en 1986 à opérer un changement radical de son orientation politique. Abandonnant l'économie planifiée, il s'ouvre à l'économie de marché. Ces dix dernières années correspondent aussi au passage d'une société agricole à une société plus diversifiée et désireuse d'accéder à de nouvelles technologies et à de nouvelles richesses. Ce mouvement s'est accompagné d’une ouverture sur le monde tous azimuts dont le point d'orgue a été l'entrée dans l'Asean en juillet 1995. La politique de rénovation et les importants besoins de recherche ont conduit les autorités scientifiques vietnamiennes à développer des relations avec de nombreux instituts étrangers, dont l’Orstom. Les collaborations de l'Orstom au Vietnam s'organisent autour des thèmes de recherches suivants : les changements économiques et sociaux, la santé publique et la nutrition, sujets traités en première partie de ce dossier ; la filière halieutique, l'écologie des mangroves et les systèmes de production aquacole, abordés en seconde partie

ABT-737 induces relatively large MOMP in cancer cell mitochondria.

<p>Isolated mitochondria from mouse liver, PC-3 and Jurkat cells were untreated (NT) or incubated either with alamethicin (Ala; 20 µg/ml; positive control), Bak BH3 peptide (10 µM), ABT-737 (1 µM) or recombinant t-Bid (1 nM) for 45 min. Mitochondrial supernatants were subjected to immunodetection of cytochrome c, Smac/DIABLO, Omi/Htra2 and AIF (Western blots are representative of 3 independent experiments). Note that cytochrome c (15 kDa), Smac/DIABLO (23 kDa), and Omi/Htra2 (37 kDa) but not AIF (56 kDa) are released from cancer cell mitochondria.</p

ABT-737 induces Bax and Bak liberation from Bcl-2 and Bcl-xL.

<p>Mitochondria isolated from PC-3 (<b>A</b>), HT-29 (<b>B</b>) and Jurkat (<b>C</b>) cells were untreated (NT) or treated with t-Bid (Bid; 2 nM) or ABT-737 (ABT; 1 µM) before to be immunoprecipitated by the antibodies directed against the Bcl-2, Bcl-xL and Mcl-1 anti-apoptotic proteins. Mitochondrial total extracts (TE; positive control of immunoblot; 25 µg) were used as control while a mitochondrial lysate was subjected to immunoprecipitation process without antibody (C; negative control of immunoprecipitation). Thus Western blot analysis was performed to determine bindings between anti-apoptotic proteins and pro-apoptotic Bax and Bak proteins (representative Western Blots of 3 independent experiments).</p

Pro- and anti-apoptotic protein pattern of isolated mitochondria.

<p>Total cell extracts (TE) and mitochondrial extracts (M) from PC-3, HT-29, Jurkat and HCT-116 cancer cell lines or from healthy HME-1 cell line and mouse liver were analyzed by Western blot for detection of the anti-apoptotic (<b>A</b>) Bcl-2, Bcl-xL, Bcl-w, Mcl-1L and A1 proteins and the pro-apoptotic (<b>B</b>) Bak, Bax, Bim, Bad and Mcl-1S proteins.</p