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Biomedical subjects

P Tremblay

Publications and source records attributed to P Tremblay.

51 records · Page 3Linked to original sources

Pax: genes for mice and men.

The murine Pax family consists of nine genes containing a highly conserved sequence, the paired box. The expression of these genes is temporally and spatially restricted during development. Evidence gathered indicates that Pax genes are involved in the regionalization of the nervous system and in important inductive events leading to the formation of various organs. The demonstration that mutations in Pax-1, Pax-3 and Pax-6 are linked with various murine mutants (undulated, splotch and small eye) and human diseases (Waardenburg syndrome and aniridia) confirms the importance of these genes as essential morphoregulators. Recent observations also indicate that inappropriate expression of these genes can lead to the appearance of cancer.

Animals↗

Pax-3 is required for the development of limb muscles: a possible role for the migration of dermomyotomal muscle progenitor cells.

Limb muscles in vertebrates originate from dermomyotomal cells, which during early development migrate from the ventrolateral region of somites into the limb buds. These progenitor cells do not express any muscle-specific marker genes or myogenic transcription factors until they reach their destination in the limbs. Here, we demonstrate by in situ hybridization that myogenic cells in somites and a population of presumably migratory muscle precursor cells in somatopleural tissue as well as myoblasts in the developing limbs express Pax-3. Significantly, in homozygous splotch mutant mice, which synthesize altered Pax-3 mRNA but make no normal protein, no cells positive for Pax-3 transcripts can be detected in the region of migrating limb muscle precursors or in the limb itself. In contrast, myotomal precursor cells and axial skeletal muscles contain Pax-3 transcripts also in the mutant. Interestingly, these animals fail to develop limb musculature as demonstrated by the lack of hybridization with various probes for myogenic transcription factors (Myf-5, myogenin, MyoD) but make apparently normal axial muscles. These observations suggest that Pax-3 is necessary for the formation of limb muscles, affecting either the generation of myogenic precursors in the somitic dermomyotome or the migration of these cells into the limb field.

Animals↗

Pax: gene regulators in the developing nervous system.

In recent years, the discovery of Pax genes in mouse has played an invaluable role in furthering our understanding in mouse developmental processes and disorders. To date, eight murine paired box-containing genes have been cloned. Seven of these exhibit a distinct spatiotemporal expression pattern in the developing nervous system implying a role in the regional specification of the developing spinal cord and brain. The Pax genes encode for sequence-specific DNA binding transcription factors that play a key role in embryonic development. Three of these developmental control genes are altered in mutant mice and two are associated with human diseases. Disruption of these Pax genes leads to abnormalities in neural crest derivatives, neuroectoderm, sclerotome or myotome-derived tissues. Disruption of the Pax-3 gene causes the Splotch phenotype in mice and Waardenburg syndrome in humans. Pax-6 mutations result in Small eye mice and the human genetic disorder aniridia. The Pax-1 gene is mutated in undulated mice. Pax proteins can transform cells in culture which then form tumours following injection in nude mice. Consistent with this activity, PAX3 has been recently implicated in the generation of the tumour alveolar rhabdomyosarcoma.

Animals↗

The Vin-1 gene, identified by provirus insertional mutagenesis, is the cyclin D2.

The Vin-1 gene was initially identified as a gene whose expression is altered by the integration of proviruses in the Vin-1 common site of integration in retrovirus-induced rodent T-cell leukemias. We have now isolated the Vin-1 cDNA. Sequencing of the Vin-1 cDNA and Vin-1 exons revealed that the proviruses are integrated at the 5' end of the Vin-1 gene in an inverse transcriptional orientation. The sequence of the Vin-1 gene is identical to that of the recently identified G1-phase cyclin D2 gene. The human homolog of the Vin-1/cyclin D2 gene (CCND2) was mapped to chromosome 12, band p13.3, by in situ hybridization, confirming previous mapping data. Our results strongly support a role of the cyclin D2 gene in oncogenesis and thereby implicate altered cell cycle regulation in transformation.

Amino Acid Sequence↗

Pax genes, mutants and molecular function.

The paired domain is a conserved DNA binding motif which was first found in Drosophila segmentation gene products. This paired domain is encoded by a well conserved, paired box DNA sequence, also detected in the genomes of other species. The mouse paired box-containing genes are referred to as Pax genes and are expressed in a distinct spatiotemporal pattern during embryogenesis. Pax proteins are able to bind to specific DNA sequences and modulate transcriptional activity. Interestingly, three different Pax genes have already been shown to correspond to some mouse and human mutants, emphasizing their role as developmental control genes.

Animals↗

Modulation of CD4 expression on lymphoma cells transplanted to mice fed (n - 3) polyunsaturated fatty acids.

Groups of adult AKR mice were fed well defined fats controlled diet regimens. These consisted of either saturated (beef tallow: 'BT') or (n - 3) polyunsaturated (fish oil: 'FO') fatty acids supplementation to basal mix mouse food. In other groups, the basal mix was given without any fat supplement ('NF'). Six weeks or more after the initiation of these diet regimens, mice received intraperitoneal injection of histocompatible RDM-4 lymphoma cells. Ascites RDM-4 tumors were harvested approximately two weeks later, and some of their physicochemical properties were studied. It was repeatedly found that: (1) the tumor grew considerably faster in the FO-fed donor than in the BT- or NF-fed donors; (2) cell membrane fluidity, content of C20(n - 3) and of C22(n - 3) fatty acids were significantly higher in the FO groups than in both BT and NF groups, while the content of C20(n - 6) and 22:4(n - 6) fatty acids was concomitantly decreased; (3) expression of the CD4 cell surface marker was always significantly diminished in the FO groups, whereas other markers such as CD8, H2K, Thy-1 and LFA-1 were not affected. Similar results were obtained, whether fats constituted from 1% to 16% by weight of the food intake. Use of a recently selected line of the RDM-4 lymphoma, exhibiting higher CD4 marker expression, resulted in similar observations. On the other hand, CD4 expression on cells from lymphoid organs of healthy adult AKR mice was not detectably modulated by the dietary fats.

Animals↗

Protein quality and quantity in preterm infants receiving the same energy intake.

Fifteen low-birth-weight appropriate for gestational age infants, weighing 1.3 to 1.6 kg, were assigned to three isocaloric formulas differing in the quantity and form of nitrogen delivered. A balance study was done between 21 and 30 days after birth. Nitrogen retention expressed as milligram per kilogram per 100 kcal of metabolizable energy was greater with the 60:40 whey/casein and with the casein hydrolysate preparations than with the 20:80 whey/casein formula, which provided the same amount of energy (150 kcal/kg/day) but smaller quantities of protein (3.5 g/kg/day) than the two others (4.3 g/kg/day and 4.4 g/kg/day). Weight gain until discharge from the hospital and increment of height and head circumference over a three-month period showed an advantage of the two formulas providing higher intakes of protein. This study suggests that with high-energy intakes, protein quality does not affect nitrogen retention and growth unless the quantity of protein ingested falls below a critical level.

Caseins↗

Concentration and purification of influenza virus from allantoic fluid.

A simple procedure which enables the concentration and purification of influenza virus, using an angular rotor, is described. Virus is concentrated over a sucrose step gradient. The same gradients are reused and volumes up to 4 liters are concentrated in 1 day. The concentrated virus is further purified by a simplified density-gradient technique. No host cell protein is detectable in the final product. The technique offers a broad application potential for concentrating and purifying other viruses.

Allantois↗

[Behavioral treatment and prison discipline.].

This paper offers a descriptive and systematic review of behavior modification programs in penal settings. The following aspects are considered : the clinical relevance of behavior targetting, the problems related to the evaluative methodology and the limits of the effectiveness of these experiments. A brief historical overview points out the very special position of behavior modification programs in the field of prisoner rehabilitation.

English Abstract↗

Production of tissue-engineered three-dimensional human bronchial models.

We have reported morphological and functional features of cells isolated from human bronchial biopsies. Both epithelial and fibroblastic cells were isolated from the same biopsies using collagenase. A few models have been established to study normal bronchial response to various agents and to understand the mechanisms responsible for some disorders, such as asthma. We produced three-dimensional bronchial equivalents in culture, using human epithelial and fibroblastic cells. We previously showed that peripheral anchorage can prevent the dramatic collagen contraction in gels seeded with fibroblasts when properly adapted to the size and type of cultured tissues. Our bilayered bronchial constructs were anchored and cultured under submerged conditions and at the air-liquid interface. Three culture media were compared. Serum-free medium supplemented with retinoic acid (5 x 10(-8) M) was found to be the best for maintenance of bronchial cell properties in the reconstructed bronchial tissue. Immunohistological and ultrastructural analyses showed that these equivalents present good structural organization, allowing ciliogenesis to occur in culture. Moreover, human bronchial goblet cells could differentiate and secrete mucus with culture time. Laminin, a major constituent of the basement membrane and basal cells, was also detected at the mesenchymoepithelial interface. Such models will be useful for studying human bronchial properties in vitro.

Bronchi↗