CYP3A isoform? are responsible for the biotransformation of a wide variety of exogenous chemicals and endogenous steroids in human tissues. Two members of the CYP3A subfamily display developmentally regulated expression in the liver; CYP3A7 is expressed in the fetal liver, whereas CYP3A4 is the major cyrochrome P-450 isoform present in the adult liver. To gain insight into the descriptive ontogenesis of CYP3A isoforms during the neonatal period, we have developed several approaches to explore a neonatal liver bank. Although CYP3A4 and CYP3A7 are structurally closely related, they differ in their capacity to carry out monooxygenase reactions. We have cloned CYP3A4 and CYP3A7 and established stable transfectants in Ad293 cells to investigate their substrate specificities. The 16a hydroxylation of dehydroepiandrosterone is catalyzed by both proteins, but CYP3A7 has a higher affinity and maximal velocity than CYP3A4. Conversely, the conversion of testosterone into its 6p derivative is essentially supported by CYP3A4. We used these two probes to determine the ontogenic evolution at the protein level; CYP3A7 was very active in the fetal liver and its activity was maximal during the first week following birth before to progressively decline and reached a very low level in adult livers. Conversely, the activity of CYP3A4 was extremely weak in the fetus and began to raise after birth to reach 30-40% of the adult activity after one month.CYP3A4 RNA accumulation displays a similar pattern of evolution; when probed with an oligonucleotide, its concentration increased rapidly after birth to reach a plateau as soon as the first week of age.These data supports the assumption that CYP3A4 expression is transcriptionally activated during the first week after birth and is accompanied by a simultaneous decrease of CYP3A7 expression, in such a way that the overall CYP3A protein content and the level of pentoxyresorufin dealkylase catalyzed by the two proteins remain nearly constant.Keywords: ontogenesis ; human liver; CYP3A7, CYP3A4 ; dehydroepiandrosterone.The cytochrome P-450 (P-450) gene superfamily encodes a group of hemoproteins that mostly catalyze the oxidative metabolism of hydrophobic endogenous compounds such as steroids, fatty acids, prostaglandins and exogenous chemicals including drugs, carcinogens and environmental pollutants. These substrates can be converted in presence of NADPH and molecular oxygen either to inert polar metabolites, further eliminated in a water-soluble form, or to cytotoxic or carcinogenic derivatives. One feature of the P-450 system is its capacity to act on thousands of compounds and to carry out a multiplicity of reactions, generically termed monooxygenations. To cope with the large number of substrates and the wide diversity of their chemical structures, several isoforms of P-450 coexist [l, 21 and exhibit overlapping substrate specificities (for review, see [3]). In the human liver, one can consider that the major P-450 isoforms are members of the CYP2C and CYP3A subfamilies. They are constitu...
English-speaking children (N = 122) in French immersion classes participated in a 1-year longitudinal study of the relation between phonological awareness and reading achievement in both languages. Participants were administered measures of word decoding and of phonological awareness in French and in English as well as measures of cognitive ability, speeded naming, and pseudoword repetition in English only. The relation of phonological awareness in French to reading achievement in each of the languages were equivalent to that in English. These relations remained significant after partialing out the influences of speeded naming and pseudoword repetition. Phonological awareness in both languages was specifically associated with 1-year increments in decoding skill in French. These findings support the transfer of phonological awareness skills across alphabetic languages.Children in immersion programs learn to read in a language different from the one spoken at home. Little is known about the cognitive mechanisms involved in this learning. The purpose of the present study was to investigate the relations between phonological processing skills and word decoding ability (reading isolated words) in children in French immersion. More precisely, we explored the possibil-
Vascularization is one of the great challenges that tissue engineering faces in order to achieve sizeable tissue and organ substitutes that contain living cells. There are instances, such as skin replacement, in which a tissue-engineered substitute does not absolutely need a preexisting vascularization. However, tissue or organ substitutes in which any dimension, such as thickness, exceeds 400 μm need to be vascularized to ensure cellular survival. Consistent with the wide spectrum of approaches to tissue engineering itself, which vary from acellular synthetic biomaterials to purely biological living constructs, approaches to tissue-engineered vascularization cover numerous techniques. Those techniques range from micropatterns engineered in biomaterials to microvascular networks created by endothelial cells. In this review, we strive to provide a critical overview of the elements that must be considered in the pursuit of this goal and the major approaches that are investigated in hopes of achieving it.
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