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Biomedical subjects

L Belanger

Publications and source records attributed to L Belanger.

At least 19 recordsLinked to original sources
PubMed2001

The mouse fetoprotein transcription factor (FTF) gene promoter is regulated by three GATA elements with tandem E box and Nkx motifs, and FTF in turn activates the Hnf3beta, Hnf4alpha, and Hnf1alpha gene promoters.

Fetoprotein transcription factor (FTF) is an orphan nuclear receptor that activates the alpha(1)-fetoprotein gene during early liver developmental growth. Here we sought to define better the position of FTF in transcriptional cascades leading to hepatic differentiation. The mouse FTF gene was isolated and assigned to chromosome 1 band E4 (one mFTF pseudogene was also found). Exon/intron mapping shows an mFTF gene structure similar to that of its close homologue SF1, with two more N-terminal exons in the mFTF gene; exon mapping also delimits several FTF mRNA 5'- and 3'-splice variants. The mFTF transcription initiation site was located in adult liver at 238 nucleotides from the first translation initiator codon, with six canonical GATA, E box, and Nkx motifs clustered between -50/-140 base pairs (bp) from the cap site; DNA/protein binding assays also pinpointed an HNF4-binding element at +36 bp and an FTF-binding element at -257 bp. Transfection assays and point mutations showed that the mFTF promoter is activated by GATA, HNF4alpha, FTF, Nkx, and basic helix-loop-helix factors, with marked cooperativity between GATA and HNF4alpha. A tandem GATA/E box activatory motif in the proximal mFTF promoter is strikingly similar to a composite motif coactivated by differentiation inducers in the hematopoietic lineage; a tandem GATA-Nkx motif in the distal mFTF promoter is also similar to a composite motif transducing differentiation signals from transforming growth factor-beta-like receptors in the cardiogenic lineage. Three genes encoding transcription factors critical to early hepatic differentiation, Hnf3beta, Hnf4alpha, and Hnf1alpha, each contain dual FTF-binding elements in their proximal promoters, and all three promoters are activated by FTF in transfection assays. Direct DNA binding action and cooperativity was demonstrated between FTF and HNF3beta on the Hnf3beta promoter and between FTF and HNF4alpha on the Hnf1alpha promoter. These combined results suggest that FTF is an early intermediary between endodermal specification signals and downstream genes that establish and amplify the hepatic phenotype.

Alternative Splicing↗
PubMed2000

Quantitative three-dimensional analysis of chondrocytic kinetic responses to short-term stapling of the rat proximal tibial growth plate.

Although it has been demonstrated clinically that controlled compression across a growth plate will slow the rate of endochondral ossification and thus can be used to correct angular limb deformities, the cellular-based mechanism by which altered growth is achieved is poorly understood. This study used short-term uniaxial stapling of the rat proximal tibial growth plate as an experimental system to study chondrocytic responses in the growth plate that account quantitatively for the decreased rate of growth. Growth plates were labeled with oxytetracycline to measure bone growth, and with bromodeoxyuridine to analyze proliferative cell kinetics. Multiple indicators of chondrocytic activity, measured by stereological parameters, were analyzed using growth rate as the primary dependent variable. The unique feature of this analysis was the creation of three-dimensional reconstructions that allowed analysis of data in all directions with distance from the staple. A significant observation was that for the entire operated limb after both 3 and 6 days, all chondrocytic kinetic parameters were affected, indicating that proliferative and hypertrophic responses both act to decrease growth rate in response to stapling. This contradicted our hypothesis that proliferative and hypertrophic responses could occur independently, and that small changes in rate would be attributed primarily to the former and large changes to the latter. The data from this study also demonstrate that volume regulation during hypertrophy can be affected by a primarily mechanical perturbation. Because changes in hypertrophic cell number and volume throughout the growth plate that occur by day 3 remain similar at day 6, the initial modulation of chondrocytic volume and shape may represent the limit of the response while maintaining a growth plate capable of continued growth.

Animals↗
PubMed1992

Molecular cloning of two C/EBP-related proteins that bind to the promoter and the enhancer of the alpha 1-fetoprotein gene. Further analysis of C/EBP beta and C/EBP gamma.

In an attempt to identify proteins that may regulate alpha 1-fetoprotein (AFP) gene expression, we screened a cDNA expression library from neonatal rat liver with two essential cis-elements of the AFP promoter and enhancer. We isolated two cDNAs which were found to correspond to leucine zipper proteins of the CC-AAT/enhancer binding protein (C/EBP) family: C/EBP beta and C/EBP gamma. The three related proteins C/EBP alpha, beta and gamma bind with indistinguishable specificity to multiple DNA sites in the promoter and the enhancer of the AFP gene. In addition, C/EBP beta and C/EBP gamma readily heterodimerize with each other as well as with C/EBP alpha. The mRNAs coding for C/EBP beta and C/EBP gamma are expressed in a wider variety of rat tissues than C/EBP alpha mRNA, including yolk sac and fetal liver. The steady-state levels of C/EBP alpha, beta and gamma mRNAs increase during liver development, in parallel with their respective gene transcriptional rates. The high levels of C/EBP beta and gamma mRNAs in rat yolk sac and fetal liver, where C/EBP alpha is poorly expressed, suggest that C/EBP beta and/or gamma could be preponderant or early regulators of the AFP gene in these tissues.

Amino Acid Sequence↗
PubMed1992

Biochemical changes in bull spermatozoa during capacitation in vitro.

To evaluate the metabolic changes of bull spermatozoa (SPZ) during capacitation in vitro, SPZ were incubated for 0, 5 or 10 hours in the presence (co-culture) and absence (control) of monolayers of bovine oviduct epithelial cells, which promote capacitation-like changes in vitro. There was little change in the oxygen uptake of the SPZ after 5 hours, but after 10 hours there was a decrease, particularly in the co-cultured sample. After 5 hours there was little change in the cyclic adenosine monophosphate (cAMP) concentration of the co-culture or control SPZ, but by 10 hours the levels of cAMP decreased in both the co-cultured and control SPZ (P=0.06). The concentration of adenosine triphosphate (ATP) was somewhat decreased after 5 hours in both the co-cultured and control SPZ and the percentage of decline was much higher after 10 hours. Overall, there was no significant change in oxygen uptake or cAMP and ATP levels specifically associated with capacitation of bull SPZ.

Journal Article↗
PubMed1990

Characterization of the wheat mitochondrial orf25 gene.

The wheat mitochondrial orf25 nucleotide sequence of 576 bp has been determined. Its derived protein sequence shares 88% and 75% amino acid identity with those of maize and tobacco mitochondria, respectively. The wheat and tobacco orf25 sequences lack four inserts, of 6 bp to 36 bp, that are present in the maize homologue. The wheat orf25 gene is actively transcribed and is preceded by a regulatory sequence block very similar to those located upstream of the wheat coxII and atp6 genes. Our observations support the view that orf25 sequences encode a functional polypeptide in plant mitochondria.

Amino Acid Sequence↗
PubMed1983

Oncodevelopmental and hormonal regulation of alpha 1-fetoprotein gene expression.

The main features of the oncodevelopmental biology of alpha 1-fetoprotein (AFP) are reviewed. Progress made in the molecular biology of AFP gene regulation is discussed and we present our recent data on the mechanisms of AFP suppression by glucocorticoid hormones. The relationship between AFP gene transcription and cell replication is examined, and it is suggested that the degree of methylation of the AFP gene (or of co-methylated regulatory DNA sequences) conditions its response to hormones.

Albumins↗
PubMed1982

Sensitivity for Telemed diagnosis of myocardial infarction by use of 12-lead electrocardiogram derived from Frank XYZ leads.

Another comparison of sensitivity for diagnosis of myocardial infarction in conventional and derived 12-lead ECGs processed by the computer diagnostic program of the Telemed Cardio-Pulmonary System is reasonably consistent with the original trial of these two methods of recording ECG signals reported earlier by Dower and Machado. Other similarities and disparities are cited, together with brief comments about the theoretical and clinical implications of those findings and the relationship to a more rigorous analysis from this laboratory.

Computers↗
PubMed1982

Treadmill test responses to an early exercise program after myocardial infarction: a randomized study.

The effects of an exercise program started early after myocardial infraction and the added effects of an outpatient teaching-counseling program were studied. At random, 84 patients were allocated to a control group (A), 88 patients to an exercise group (B1) and 86 patients to an exercise and teaching-counseling group (B2). The same exercise program was prescribed for patients in groups B1 and B2 and was started about 4.5 days after myocardial infarction and continued for 3 months. The outpatient teaching-counseling program consisted of eight group sessions pertaining to risk factor reduction and psychosocial adjustment to myocardial infraction. A low-level treadmill test and an exercise test were performed at 3 months and the exercise test was repeated at 6 months. The clinical, hemodynamic and electrocardiographic responses to these tests were not different among the three groups. However, by the end of 3 months, patients in group B1 and B2 reported walking greater distances than patients in group A. The incidence of morbidity and mortality was not different between the groups. No deleterious or beneficial physiologic effects of an exercise program either by itself or combined with a teaching-counseling program were demonstrated. Routine medical care and our interventions were equally effective in permitting the spontaneous hemodynamics improvements after myocardial infraction. More than 3 months after myocardial infarction, the group as a whole manifested spontaneous recovery in the form of a significant decrease in resting heart rate (p less than 0.001) and a significant increase in systolic and diastolic blood pressure at rest and with submaximal exercise (p less than 0.001). No further improvements were observed between 3 and 6 months.

Blood Pressure↗
PubMed1981

A computer terminal program to evaluate cardiovascular functional limits and estimate coronary event risks.

A system of computer terminals was set up in a group of office practices, industrial medical departments and hospitals and connected to a central computer. This service provides a means of analyzing treadmill exercise results, which are displayed graphically on the computer printout. The system also provides estimates of probabilities of primary or secondary coronary heart disease events developing based on the exercise responses.

Adult↗
PubMed1980

Alpha-fetoprotein concanavalin A-binding variants in the diagnosis of neural tube defects and other communicating fetal abnormalities.

We have extended our initial observations (Smith et al., 1979) on th use of determining the alpha-fetoprotein (AFP) concanavalin A-binding variant patterns in amniotic fluid for the detection of certain fetal malformations. We report here our complete series of amniotic fluids between 14 and 36 weeks of gestation from 52 normal pregnancies and 28 abnormal pregnancies including anencephaly, open spina bifida, Turner's syndrome, omphalocele, osteogenesis imperfecta congenita, meningomyelocele, meningocele, spinal cysts, spontaneous abortion and fetal death. The percentage of the total amniotic fluid AFP which was not reactive with concanavalin A was significantly lower in the presence of a communicating fetal abnormality (mean = 4.8%, P less than 0.001), one in which the fetal/amniotic fluid barrier is defective, than in the presence of a normal fetus (mean = 24.7%) (or of a noncommunicating fetal abnormality. We applied the concanavalin A-binding assay to two of the above amniotic fluids from pregnancies in progress and correctly classified the gestations as abnormal. Our results indicate that measurement of the percentage of concanavalin A-non-reactive amniotic fluid AFP is a valuable adjunct in the diagnosis of a communicating fetal abnormality, especially when the elevation of amniotic fluid AFP concentration is equivocal (between 2 and 5 S.D. above the mean), when gestational aging is uncertain or when the total amniotic fluid AFP concentration and ultrasonographic data are inconsistent.

Amniotic Fluid↗
PubMed1977

Rat iso-alpha1-fetoproteins. Purification and interaction with estradiol-17beta.

The combination of polyacrylamide gel electrophoresis and Concanavalin-A-Sepharose affinity chromatography has permitted the isolation on a preparative scale, of four molecular forms of rat alpha 1-fetoprotein: a "slow" and a "fast" fraction, each separable into Concanavalin-A-adsorbed ("high carbohydrate", i.e. rich in accessible alphaD-Mannosyl and alphaD-Glu-cosyl residues) and a Concanavalin-A-non adsorbed ("low carbohydrate") fractions. These four iso-alpha 1-fetoproteins (iso-AFP) bind estradiol-17beta. However, they disclose differences in both their association constants and number of binding sites for this hormone. Very high affinity sites (10(9) are mainly located on the "slow-low carbohydrate" form. Low affinity, high capacity sites are preferentially located on the "high carbohydrate" form. These results confirm the molecular and functional heterogeneity of rat AFT and suggest that the carbohydrate moiety of the protein may have a role in estrogen-AFP interactions.

Animals↗