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Biomedical subjects

C Forest

Publications and source records attributed to C Forest.

At least 19 recordsLinked to original sources
PubMed2004

Removing tetrahedra from manifold tetrahedralisation: application to real-time surgical simulation.

This paper proposes an efficient method for removing tetrahedra from a tetrahedral mesh while keeping its manifold property. We first define precisely the notion of manifold tetrahedral mesh and stress its relevance in the context of real-time surgery simulation. We then provide a method for removing a tetrahedron that complies with the manifold definition. This removal may require in some cases the removal of neighboring tetrahedra. After providing an exhaustive description of the tetrahedron removal algorithm, its efficiency is evaluated for different mesh configurations. This algorithm is currently used in the context of real-time surgery simulation where the action of an ultrasonic lancet can be simulated by the removal of small set of tetrahedra from a tetrahedralisation.

Algorithms↗
PubMed2003

Deformable biomechanical models: application to 4D cardiac image analysis.

This article describes a methodology for creating a generic volumetric biomechanical model from different image modalities and segmenting time series of medical images using this model. The construction of such a generic model consists of three stages: geometric meshing, non-rigid deformation of the mesh in images of various modalities, and image-to-mesh information mapping through rasterization. The non-rigid deformation stage, which relies on a combination of global and local deformations, can then be used to segment time series of images, e.g. cine MRI or gated SPECT cardiac images. We believe that this type of deformable biomechanical model can play an important role in the extraction of useful quantitative local parameters of cardiac function. The biomechanical model of the heart will be coupled with an electrical model of another collaborative project in order to simulate and analyze a larger class of pathologies.

Algorithms↗
PubMed2003

Fatty acid recycling in adipocytes: a role for glyceroneogenesis and phosphoenolpyruvate carboxykinase.

FA (fatty acid) recycling in adipose tissue appears to be an important pathway for regulating FA release into the blood during fasting. Re-esterification requires G3P (glycerol 3-phosphate), which cannot be synthesized from glucose because glycolysis is much reduced under such circumstances. In addition, G3P can scarcely originate from glycerol since glycerol kinase has a very low activity in white adipose tissue. It was shown about 35 years ago that a metabolic pathway named glyceroneogenesis, which allows G3P synthesis from non-carbohydrate precursors like pyruvate, lactate or amino acids, is activated during fasting. The major enzyme in this pathway was shown to be PEPCK-C [cytosolic phosphoenolpyruvate carboxykinase (GTP); EC 4.1.1.32]. The present review analyses the mechanisms by which a series of hormones and nutrients affect PEPCK-C gene transcription and glyceroneogenesis and describes evidence for dysregulation of this pathway in type 2 diabetes.

Adipocytes↗
PubMed2001

Peroxisome proliferator-activated receptor gamma and chicken ovalbumin upstream promoter transcription factor II negatively regulate the phosphoenolpyruvate carboxykinase promoter via a common element.

A heterodimer of peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoid X receptor (RXR) is required for adipocyte differentiation. The gene encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK) is a PPARgamma/RXR target gene in adipose tissue. Of the two PPARgamma response elements, gAF1/PCK1 and PCK2, only PCK2 is required for PEPCK expression and responsiveness to the PPARgamma agonist, rosiglitazone, in adipose tissue even though both elements bind PPARgamma/RXR in vitro. In contrast, gAF1/PCK1 is essential for glucocorticoid inhibition of PPARgamma-induced PEPCK gene expression in adipocytes. We report that chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is the predominant nuclear receptor bound to gAF1/PCK1 in preadipocytes. COUP-TFII declines during adipogenesis in reciprocal fashion to PPARgamma. In transiently transfected fibroblasts COUP-TFII acts at gAF1/PCK1 to inhibit PPARgamma/RXR activation via PCK2. In contrast COUP-TFs are transcriptional activators of PEPCK in hepatocytes. PPARgamma/RXR occupies gAF1/PCK1 in adipocytes, and mutation of gAF1/PCK1 enhances PEPCK promoter transactivation by PPARgamma/RXR in fibroblasts, suggesting that this element is also a negative PPARgamma response element. These results indicate that gAF1/PCK1 is a pleiotropic element through which COUP-TFII inhibits premature PEPCK expression, and perhaps adipogenesis in general, and PPARgamma/RXR uses this same element in adipocytes to participate in PEPCK modulation by glucocorticoids.

3T3 Cells↗
PubMed2001

A single element in the phosphoenolpyruvate carboxykinase gene mediates thiazolidinedione action specifically in adipocytes.

Phosphoenolpyruvate carboxykinase (PEPCK) is the key enzyme in glyceroneogenesis, an important metabolic pathway that functions to restrain the release of non-esterified fatty acids (NEFAs) from adipocytes. The antidiabetic drugs known as thiazolidinediones (TZDs) are thought to achieve some of their benefits by lowering elevated plasma NEFAs. Moreover, peroxisome proliferator activated receptor gamma (PPARgamma) mediates the antidiabetic effects of TZDs, though many TZD responses appear to occur via PPARgamma-independent pathways. PPARgamma is required for adipocyte PEPCK expression, hence PEPCK could be a major target gene for the antidiabetic actions of TZDs. Here we used tissue culture and transfection assays to confirm that the TZD, rosiglitazone, stimulates PEPCK gene transcription specifically in adipocytes. We made the novel observation that this effect was by far the most rapid and robust among several other genes expressed in adipocytes. Adipocytes were transfected with a PEPCK/chloramphenicol acetyltransferase chimeric gene, in which either of the two previously discovered PPARgamma/retinoid X receptor alpha response elements, PCK2 and gAF1/PCK1, had been inactivated by mutagenesis. We demonstrate that PCK2 alone is a bona fide thiazolidinedione response element. We show also that the regulation of PEPCK by PPARs is cell-specific and isotype-specific since rosiglitazone induces PEPCK gene expression selectively in adipocytes, and PPARalpha- and PPARbeta-specific activators are inefficient. Hence, TZDs could lower plasma NEFAs via PPARgamma and PEPCK by enhancing adipocyte glyceroneogenesis.

3T3 Cells↗
PubMed2001

Acting, behaving, and the selfless basis of metaperception.

The desire to create a particular impression of oneself to others is a fundamental interpersonal motive that should be followed by an assessment of the success of the self-presentation. The authors integrate the areas of self-presentation and metaperception in the present research by assigning participants to enact roles during 2 dyadic interactions and measuring the actors' metaperceptions and their partners' trait judgments. They found a high level of accuracy in actors' metaperceptions but no accuracy in partners' trait judgments of the actors. Instead, partners' trait judgments corresponded closely to the actors interpersonal behavior, indicating that there was little or no "personality leakage" in the actors' behavior. Random assignment to role created a situation in which private self was uncorrelated with public self. Results indicate that actors were able to disregard their self-concepts when determining the impressions they created.

Affect↗
PubMed2001

The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance.

Protease inhibitors used in the treatment of HIV infection have been causally associated with lipodystrophy and insulin resistance and were shown to alter adipocyte differentiation in cultured cells. We aimed to delineate the mechanism by which indinavir impaired adipocyte function. We report that indinavir altered neither the growth nor insulin sensitivity of 3T3-F442A preadipocytes, nor did it alter the initial step of their differentiation, i.e., clonal proliferation. However, adipose conversion was inhibited by indinavir (by 50-60%), as shown by 1) the decrease in the number of newly formed adipocytes; 2) the lower level of the adipogenic protein markers, sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and the insulin receptor (IR); and 3) the lack of SREBP-1 and PPAR-gamma immunoreactivity in the nucleus of most indinavir-treated cells. Partial adipose conversion also correlated with an accumulation of SREBP-1 at the nuclear periphery and an alteration in its electrophoretic mobility. Defective expression and nuclear localization of PPAR-gamma probably resulted from the decreased level of nuclear SREBP-1. Indinavir also rendered 3T3-F442A adipocytes resistant to insulin for mitogen-activated protein kinase activation at a step distal to IR substrate-1 tyrosine phosphorylation. Hence, indinavir impairs differentiation at an early step of adipose conversion probably involving the process controlling SREBP-1 intranuclear localization.

3T3 Cells↗
PubMed2000

Subcutaneous adipose tissue expression of plasminogen activator inhibitor-1 gene during very low calorie diet in obese subjects.

OBJECTIVE: To determine whether changes in subcutaneous adipose tissue plasminogen activator inhibitor-1 (PAI-1) expression influence plasma PAI-1 level during weight loss in obese humans. DESIGN: Study of the variations of PAI-1 levels both in plasma and in subcutaneous abdominal adipose tissue in 15 volunteer non-diabetic obese subjects, body mass index (BMI) 40.4.+/-1.9 kg/m2, aged 48+/-3 y, before and after a 3 week very low calorie diet (VLCD) programme (3.9+/-0.1 MJ/day). MEASUREMENTS: Plasma and adipose tissue PAI-1 protein levels were measured by enzyme-linked immunosorbent assay and PAI-1 mRNA levels were quantified by quantitative RT-competitive PCR. RESULTS: VLCD induced weight loss (5.8+/-0.8 kg) and decreased plasma PAI-1 concentration (-26% (P<0. 01)). Surprisingly, PAI-1 mRNA and protein abundance in subcutaneous adipose tissue increased by 87% (P<0.05) and by 44% (P<0.01), respectively. CONCLUSION: These data indicate thus that changes in subcutaneous adipose tissue PAI-1 expression are not involved in the decrease of plasma PAI-1 levels during VLCD in obese subjects. International Journal of Obesity (2000)24, 70-74

Abdomen↗
PubMed2000

Formation of glycine receptor clusters and their accumulation at synapses.

The glycine receptor is highly enriched in microdomains of the postsynaptic neuronal surface apposed to glycinergic afferent endings. There is substantial evidence suggesting that the selective clustering of glycine receptor at these sites is mediated by the cytoplasmic protein gephyrin. To investigate the formation of postsynaptic glycine receptor domains, we have examined the surface insertion of epitope-tagged receptor alpha subunits in cultured spinal cord neurons after gene transfer by polyethylenimine-adenofection. Expression studies were also carried out using the non-neuronal cell line COS-7. Immunofluorescence microscopy was performed using wild-type isoforms and an alpha mutant subunit bearing the gephyrin-binding motif of the beta subunit. In COS-7 cells, transfected glycine receptor alpha subunits had a diffuse surface distribution. Following cotransfection with gephyrin, only the mutant subunit formed cell surface clusters. In contrast, in neurons all subunits were able to form cell surface clusters after transfection. These clusters were not colocalized with detectable endogenous gephyrin, and the GlyR beta subunit could not be detected in transfected cells. Therefore, exogenous receptors were not assembled as heteromeric complexes. A quantitative analysis demonstrated that newly synthesized glycine receptor progressively populated endogenous gephyrin clusters, since association of both proteins increased as a function of time after the onset of receptor synthesis. This phenomenon was accelerated when glycine receptor contained the gephyrin-binding domain. Together with previous results, these data support a two-step model for glycinergic synaptogenesis whereby the gephyrin-independent formation of cell surface clusters precedes the gephyrin-mediated postsynaptic accumulation of clusters.

Animals↗
PubMed1999

Isolation and characterization of the mouse cytosolic phosphoenolpyruvate carboxykinase (GTP) gene: evidence for tissue-specific hypersensitive sites.

A 72 kilobase pair DNA fragment that contains the mouse phosphoenolpyruvate carboxykinase (PEPCK) gene locus, pck1, was isolated from a genomic bacterial artificial chromosome library. The region from approximately -5.5 to +6.6 kilobase pairs relative to the pck1 transcription start site was sequenced and exhibits a high degree of homology to the rat and human genes. Additionally, the chromatin structure of the PEPCK gene in mouse liver resembles that seen in rat. Backcross panel analysis of a microsatellite sequence confirms that the gene is located on chromosome 2. Hypersensitive site analysis was performed on nuclei isolated from the adipocyte cell line 3T3-F442A in the preadipose and adipose states. Several hypersensitive sites are present in the undifferentiated 3T3-F442A cells, before PEPCK mRNA is detected. The same sites are present after differentiation, however, the sensitivity of mHS 3 increases relative to the others. We conclude that the chromatin is open in 3T3-F442A cells and that factors are able to bind in the undifferentiated state but that something else is required for transcription.

3T3 Cells↗
PubMed1998

Glucocorticoids repress induction by thiazolidinediones, fibrates, and fatty acids of phosphoenolpyruvate carboxykinase gene expression in adipocytes.

Phosphoenolpyruvate carboxykinase (PEPCK) exerts a glyceroneogenic function in adipocytes in which transcription of its gene is increased by unsaturated fatty acids and fibrates. We used cultured rat adipose tissue fragments and 3T3-F442A adipocytes to show that the antidiabetic thiazolidinedione BRL 49653, a ligand and an activator of the gamma isoform of peroxisome proliferator activated receptors (PPARgamma), is a potent inducer of PEPCK mRNA. In 3T3-F442A adipocytes, the effect of BRL 49653 is rapid and concentration dependent, with a maximum reached at 1 microM and a half-maximum at 10-100 nM. PEPCK mRNA is similarly induced by the natural ligand of PPARgamma, the 15-deoxy-delta(12-14) prostaglandin J2. These observations strongly suggest that PPARgamma is a primary regulator of PEPCK gene expression in adipocytes. Dexamethasone at 10 nM repress induction of PEPCK mRNA by 1 microM BRL 49653, 0.32 mM oleate, or 1 mM clofibrate, in a cycloheximide-independent manner. The antiglucocorticoid RU 38486 prevents dexamethasone action, demonstrating involvement of the glucocorticoid receptor. Stable transfectants of 3T3-F442A adipocytes bearing -2100 to +69 base pairs of the PEPCK gene promoter fused to the chloramphenicol acetyltransferase (CAT) gene respond to 1 microM BRL 49653 or 1 mM clofibrate by a large increase in CAT activity, which is prevented by the simultaneous addition of 10 nM dexamethasone. Hence, in adipocytes, glucocorticoids act directly through the 5'-flanking region of the PEPCK gene to repress, in a dominant fashion, the stimulation of PEPCK gene transcription by thiazolidinediones and fibrates.

3T3 Cells↗
PubMed1998

Cytosolic aspartate aminotransferase gene is a member of the glucose-regulated protein gene family in adipocytes.

Stress controls the expression of a cohort of genes. Among these, the glucose-regulated protein (GRP) genes are specifically activated by glucose deprivation, reducing agents, glycosylation block, intracellular calcium or ex vivo incubations of tissues or cells. We demonstrate that these stimuli induce the expression of the cytosolic aspartate aminotransferase gene in adipocytes by a process involving the region of the promoter between -2405 and -26 bp. Therefore this transaminase is a new member of the GRP family.

3T3 Cells↗
PubMed1998

Identification of an adipocyte-specific negative glucose response region in the cytosolic aspartate aminotransferase gene.

Cytosolic aspartate aminotransferase (cAspAT) participates in gluconeogenesis in the liver and is expected to exert a glyceroneogenic function in the adipose tissue when the supply of glucose is limited. Here we demonstrate that adipose cAspAT messenger RNA (mRNA) is increased when rats are fed a low carbohydrate diet. In the 3T3-F442A, BFC-1 adipocyte cell lines and differentiated adipocytes in primary culture, a 24 h glucose deprivation induces approximately a 4-fold increase in cytosolic AspAT (cAspAT) mRNA, whereas mitochondrial AspAT mRNA remains unchanged. cAspAT activity is also increased in a weaker but reproducible manner. Addition of glucose within a physiological range of concentrations reverses the increase of cAspAT mRNA in 8 h (EC50 = 1.25 g/liter). Such a regulation requires protein synthesis and is specific for adipocytes differentiated in culture. It does not occur in Fao or H4IIE hepatoma cells, in C2 muscle cells, or in 293 kidney cells. 2-deoxyglucose mimicks glucose, while 3-orthomethyl-glucose has no effect, suggesting that glucose-6-phosphate is the effector. cAspAT mRNA stability is not affected by glucose deprivation. To ascertain the transcriptional nature of the glucose effect, we have stably transfected 3T3-F442A adipoblasts with constructs containing the chloramphenicol acetyltransferase reporter gene under the control of either 5'-deletions of the cAspAT gene promoter or internal fragments in an heterologous context. We demonstrate that a glucose response element(s) is present in the region between -1838 and -1702 bp relative to the translation start site. In this region, three DNA sequences bind nuclear proteins from adipocytes as shown by footprinting experiments. Our results indicate that cAspAT gene transcription is repressed by glucose selectively in adipocytes.

Adipocytes↗
PubMed1997

Mechanism of adenovirus improvement of cationic liposome-mediated gene transfer.

Substantial effort has been focused on the development of highly efficient gene transfer strategies. Although viral and non-viral methods have been elaborated, mechanisms of gene delivery are still poorly understood. We exploited our recent observation that replication-deficient type 5 adenovirus dramatically enhances lipofectAMINE-mediated gene transfer (lipoadenofection) in differentiated cells to elucidate the mechanism of adenovirus action in this process. Heat-induced denaturation of viral capsid abolishes adenovirus action whereas inactivation of viral genome by short treatment with UV has no effect. Electron microscopic observations reveal the formation of a complex containing adenovirus and lipofectAMINE which probably carries DNA into cells via endocytosis. Anti-adenovirus antiserum or monoclonal anti-alpha(v)beta3 integrin antibody inhibits lipoadenofection, at least partially. Neutralization of endosomal compartments with chloroquine, ammonium chloride or monensin does not prevent adenovirus improvement of gene transfer. Hence, adenovirus-lipofectAMINE-DNA complexes in which viral particles are each encompassed by three lipid layers, penetrate cells via an endocytic pathway involving probably the adenovirus receptor and alpha(v)beta3 integrin. The resulting efficient transfer and expression of plasmid DNA proceeds from a mechanism in which adenoviral endosomolytic activity appears to be required while viral genome is not essential.

Adenoviridae↗
PubMed1997

Transcriptional and posttranscriptional mechanisms of glucocorticoid-mediated repression of phosphoenolpyruvate carboxykinase gene expression in adipocytes.

Glucocorticoids exert pleiotropic effects, among which negative regulation of transcription has been recognized as of crucial importance. While glucocorticoids induce phosphoenolpyruvate carboxykinase (PEPCK) gene expression in liver cells, it represses gene activity in adipose cells. We used the 3T3-F442A adipocytes to analyze the underlying mechanisms in these cells, the synthetic glucocorticoid dexamethasone exerts a dominant repression either on basal or on beta-agonist stimulation of PEPCK gene expression. To determine whether glucocorticoid action required protein synthesis, we employed cycloheximide, anisomycin, and puromycin, three different translation inhibitors. None of these affected induction by isoprenaline or repression by dexamethasone of isoprenaline stimulation. In contrast, dexamethasone inhibitory action on basal PEPCK mRNA was totally prevented by the three translation inhibitors. Time courses of glucocorticoid action on basal and on induction by beta-agonist were similar. Half-maximal effect of dexamethasone on isoprenaline-induced PEPCK mRNA was obtained at about 10 nM, a tenfold higher concentration than that observed for the reduction of basal mRNA. Using the transcription inhibitor DRB, we showed that dexamethasone did not alter mRNA half-life, while isoprenaline strongly stabilized mRNA. In a 3T3-F442A stable transfectant bearing -2,100 base pairs of the PEPCK promoter fused to the chloramphenicol acetyltransferase (CAT) gene, isoprenaline stimulated CAT activity, whereas dexamethasone reduced basal and isoprenaline-induced CAT expression. Hence, beta-agonists exert both transcriptional and posttranscriptional regulation, while glucocorticoid action is purely transcriptional. However, mechanisms of glucocorticoid repression of basal and of beta-agonist stimulation appear different.

Adipocytes↗
PubMed1997

Glucocorticoids use a positive liver element to repress fibrate-induced adipose transcription of the phosphoenolpyruvate carboxykinase gene.

Glucocorticoids inhibit basal and hormone-induced phosphoenolpyruvate carboxykinase (PEPCK) gene transcription in adipocytes whereas beta-adrenergic agonists and fibrates are stimulatory. Here we show that dexamethasone inhibits the induction of PEPCK mRNA by isoprenaline or clofibrate in 3T3-F442A adipocytes. RU 38486 antagonizes dexamethasone effect, suggesting the involvement of the glucocorticoid receptor. In H4IIE hepatoma cells, glucocorticoids enhance PEPCK gene transcription through a complex region which encompasses an element, AF1, with a direct repeat 1-type sequence. Mutations in the AF1 sequence abolish binding of nuclear factors from liver and from 3T3-F442A adipocytes. We transiently transfected 3T3-F442A cells with a wild type or an AF1-mutated PEPCK-CAT construct comprising -2100 to +69 base pairs of the promoter fused to the chloramphenicol acetyltransferase (CAT) gene. With both constructs, CAT activity is decreased by dexamethasone and is increased by isoprenaline or by clofibrate. However, dexamethasone is unable to inhibit clofibrate induction of CAT activity in cells transfected with the AF1-mutated construct whereas it prevents isoprenaline action on both constructs. Hence, although a single hormone can repress stimulations originating from different intracellular routes, sites in the promoter which mediate inhibition of a specific stimulation are distinct.

3T3 Cells↗