PubMed · 7322399
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F P Grilli. 1981-12-15. [Indications for joint prostheses].. https://pubmed.ncbi.nlm.nih.gov/7322399/
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Glucose constitutes a major fuel for the heart, and high glucose uptake during fetal development is coincident with the highest level of expression of the glucose transporter GLUT-1 during life. We have previously reported that GLUT-1 is repressed perinatally in rat heart, and GLUT-4, which shows a low level of expression in the fetal stage, becomes the main glucose transporter in the adult. Here, we show that the perinatal expression of GLUT-1 and GLUT-4 glucose transporters in heart is controlled directly at the level of gene transcription. Transient transfection assays show that the -99/-33 fragment of the GLUT-1 gene is sufficient to drive transcriptional activity in rat neonatal cardiomyocytes. Electrophoretic mobility shift assays demonstrate that the transcription factor Sp1, a trans-activator of GLUT-1 promoter, binds to the -102/-82 region of GLUT-1 promoter during the fetal state but not during adulthood. Mutation of the Sp1 site in this region demonstrates that Sp1 is essential for maintaining a high transcriptional activity in cardiac myocytes. Sp1 is markedly down-regulated both in heart and in skeletal muscle during neonatal life, suggesting an active role for Sp1 in the regulation of GLUT-1 transcription. In all, these results indicate that the expression of GLUT-1 and GLUT-4 in heart during perinatal development is largely controlled at a transcriptional level by mechanisms that might be related to hyperplasia and that are independent from the signals that trigger cell hypertrophy in the developing heart. Furthermore, our results provide the first functional insight into the mechanisms regulating muscle GLUT-1 gene expression in a live animal.
BACKGROUND: Interest in the reporting of risk-adjusted outcomes for patients with acute myocardial infarction is growing. A useful risk-adjustment model must balance parsimony and ease of data collection with predictive ability. METHODS AND RESULTS: From our analysis of 82 359 patients >/=65 years of age admitted with acute myocardial infarction to 2401 hospitals, we derived a parsimonious model that predicts 30-day mortality. The model was validated on a similar group of 78 699 patients from 2386 hospitals. Of the 73 candidate predictor variables examined, 7 variables describing patient characteristics on arrival were selected for inclusion in the final model: age, cardiac arrest, anterior or lateral location of myocardial infarction, systolic blood pressure, white blood cell count, serum creatinine, and congestive heart failure. The area under the receiver-operating characteristic curve for the final model was 0.77 in the derivation cohort and 0.77 in the validation cohort. The rankings of hospitals by performance (in deciles) with this model were most similar to a comprehensive 27-variable model based on medical chart review and least similar to models based on administrative billing codes. CONCLUSIONS: A simple 7-variable risk model performs as well as more complex models in comparing hospital outcomes for acute myocardial infarction. Although there is a continuing need to improve methods of risk adjustment, our results provide a basis for hospitals to develop a simple approach to compare outcomes.
Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the components of the extracellular matrix (ECM). The balance between MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] in the pericellular environment determines the most significant proteolytic events in tissue remodeling. In vitro evidence is accumulating that these molecules may be crucial in the maturation of neural cells. Here, we investigated the in vivo expression of MMPs 2, 3, and 9 and TIMPs 1, 2, and 3 in the developing and adult rat cerebellum using immunohistochemistry and in situ hybridization. During postnatal development, all Purkinje (PK) cell somata expressed all the MMPs and TIMPs studied, whereas their growing dendritic trees expressed only MMP 3 and TIMP 3. In the adult, MMP 3 was confined to PK cell bodies, whereas TIMP 3 was expressed in PK cell somata and processes. Irrespective of the developmental stage, Bergmann glial processes contained only MMP 9, but their somata contained both TIMP 1 and MMP 9. In granular cells, MMPs 3 and 9 and TIMPs 1, 2, and 3 were chiefly detected at a time when migration is known to be maximal; except for that of TIMP 1, their expression persisted in the internal granular layer in the adult. The functional relevance of MMP expression was verified by gelatin zymography. MMP 9 activity was maximal on postnatal day 10 (P10) and was detectable at a low level on P15 and in the adult, whereas MMP 2 activity remained similar throughout postnatal development. Regional and cell-specific expression of MMPs and TIMPs closely reflects the successive stages of cerebellar development, thereby suggesting a pivotal role for ECM proteolysis in brain development and plasticity.