Stem cell antigen 2: a new gene involved in the self-renewal of erythroid progenitors.

OBJECTIVES: Stem cell antigen 2 (SCA2), also known as TSA1 and LY6E, is a glycosylphosphatidylinositol-anchored molecule that belongs to the Ly-6 family and whose function remains largely unknown. We have previously shown that SCA2 is overexpressed in self-renewing avian erythroid progenitors (T2ECs) as opposed to differentiating T2ECs. The aim of this study was to define the role of SCA2 in the switch between self-renewal and differentiation of erythroid progenitors. MATERIALS AND METHODS: We have investigated the cellular processes controlled by SCA2 in T2ECs by RNA interference and overexpression approaches. Moreover, we have used a SAGE Querying and analysis tools developed in our laboratory, to investigate the expression level of SCA2 gene in different human cell types. RESULTS: We demonstrate the regulation of SCA2 expression by TGF-beta, a growth factor essential for self-renewal of T2ECs. We establish that SCA2 knockdown by RNA interference reduced the proliferation and promoted the differentiation of T2ECs. In contrast, SCA2 overexpression inhibited differentiation of T2ECs only. Furthermore, by using a bioinformatic approach, we found that SCA2 is highly expressed in a variety of human cancer cells. We confirmed this result by quantitative PCR on human colon and kidney tissues. CONCLUSIONS: Altogether, these findings imply that SCA2 may function in a dose-dependent manner to support the self-renewal state and that its deregulation might contribute to the development of some human cancers.

Involvement of the TGF-beta and mTOR/p70S6Kinase pathways in the transformation process induced by v-ErbA.

v-ErbA is the oncogenic form of TRalpha/c-ErbA which transforms chicken erythrocytic progenitors by blocking differentiation. The oncogenic property of v-ErbA has been correlated with its ability to antagonize ligand-dependent gene activation by TRalpha/c-ErbA and retinoic acid receptors. Nevertheless, its cytoplasmic retention suggests that v-ErbA could interfere with intracellular signaling pathways. We demonstrate that only the transforming form of v-ErbA confers to chicken erythroid progenitors a TGF-beta independency and induces an activation of the mTOR/p70S6K pathway. In these cells, TGF-beta and mTOR/p70S6K pathways regulate the expression of a known target gene of v-ErbA, band3. This is the first demonstration that v-ErbA is able to modulate specifically some signaling pathways leading to changes in the expression level of a gene involved in transformation.

[Primary prevention of hypertension in the general population. The Lyon Action for the Prevention of Hypertension and Atherosclerosis]. / Prévention primaire de l'hypertension artérielle dans la population. L'action lyonnaise de prévention de l'hypertension et de l'athérosclérose.

UNLABELLED: The aim of ALPHA (1976-1982) was to realize an action of cardiovascular prevention in a professional population, by combining a) an education of the general population and b) an individual managing of the high risk people. The "Study" (S) population originated from Lyon; the "Reference" (R) population originated from two smaller cities. There was no randomization. The plan of the study included: A baseline cross study, dealing respectively with 9,598 and 9,558 subjects in S and R; The educational intervention, aiming chiefly at reducing caloric and sodium intakes, and at increasing the potassium intake; The evaluation was done after five years, by re-examining the subjects seen at the baseline study and still present in the enterprises. Mainly because of the economic crisis, the re-examination rates were only about 45%. RESULTS: at the baseline, BP's were not significantly different: 137/77 S vs 132/75 R for men, and 129/74 S vs 126/73 R for women. The final comparisons about primary prevention of hypertension were computed after adjustment for age and sex, after exclusion of the subjects who were hypertensive at baseline. The knowledges about hygiene were significantly but moderately better in S. The urinary Na/K and Na/Creatinine ratios did not differ significantly. The alcohol intake was lower in S (p less than 0.001). The incidence of HT was greater in S (p less than 0.001). The means of the individual variations of systolic and diastolic BP were computed: the adjusted differences S-R were respectively + 1.53 and 2.19 mmHg for systolic and diastolic (p less than 0.001 for both). CONCLUSION: the feasibility of the intervention was moderate. The failure to demonstrate any prevention of HT might indicate that the hypothesis was wrong, and/or that the methodology was inadequate.

[Cardiogenic shock caused by 5-fluorouracil]. / Choc cardiogénique dû au 5-fluorouracile.

The authors report the observation of one patient in whom the first administration of chemotherapy with fluoro-5 uracil has induced a severe but reversible cardiogenic shock. The latter was preceded by a prolonged, constrictive thoracic pain without myocardial infarction constitution. The cardiac toxicity of fluoro-5 uracil has been well described in the form of anginal pains receding with the discontinuation of the treatment. However, the possible occurrence of arrhythmias, of collapse and even sudden deaths leads the authors to suggest the daily clinical and electrical observation of the patients treated with fluoro-5 uractil.