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T Coche

Publications and source records attributed to T Coche.

9 recordsLinked to original sources
PubMed2001

Using in silico transcriptomics to search for tumor-associated antigens for immunotherapy.

Immunotherapy approaches to fight cancer are based on the principle of mounting an immune response against a self-antigen expressed by the tumor cells. In order to reduce potential autoimmunity side-effects, the antigens used should be as tumor-specific as possible. A complementary approach to experimental tumor antigen discovery is to screen the human genome in silico, particularly the databases of "Expressed Sequence Tags" (ESTs), in search of tumor-specific and tumor-associated antigens. The public databases currently provide a massive amount of ESTs from several hundreds of cDNA tissue libraries, including tumoral tissues from various types. We describe a novel method of EST database screening that allows new potential tumor-associated genes to be efficiently selected. The resulting list of candidates is enriched in known genes, described as being expressed in tumor cells.

Antigens, Neoplasm↗
PubMed2001

Applied genome research in the field of human vaccines.

Prophylactic vaccination has made an essential contribution to the improvement of human health over the 20th century. However, we still lack efficient vaccines against major human diseases such as malaria or tuberculosis. Today, the design of therapeutic vaccines referred to as 'pharmaccines' is actively investigated in order to treat diseases such as cancer. In that context, novel ways to rationalize and accelerate vaccine discovery are needed. A series of advances in the fields of molecular biology and computer science, have greatly accelerated the rate at which candidate vaccine antigens can be discovered. In this review, we will present and discuss how applied genome research may facilitate antigen discovery and the design of new prophylactic and therapeutic vaccines.

Antigens↗
PubMed1998

Multiple delta genes and lateral inhibition in zebrafish primary neurogenesis.

In Drosophila, cells are thought to be singled out for a neural fate through a competitive mechanism based on lateral inhibition mediated by Delta-Notch signalling. In tetrapod vertebrates, nascent neurons express the Delta1 gene and thereby deliver lateral inhibition to their neighbours, but it is not clear how these cells are singled out within the neurectoderm in the first place. We have found four Delta homologues in the zebrafish--twice as many as reported in any tetrapod vertebrate. Three of these--deltaA, deltaB and deltaD--are involved in primary neurogenesis, while two--deltaC and deltaD--appear to be involved in somite development. In the neural plate, deltaA and deltaD, unlike Delta1 in tetrapods, are expressed in large patches of contiguous cells, within which scattered individuals expressing deltaB become singled out as primary neurons. By gene misexpression experiments, we show: (1) that the singling-out of primary neurons, including the unique Mauthner cell on each side of the hindbrain, depends on Delta-Notch-mediated lateral inhibition, (2) that deltaA, deltaB and deltaD all have products that can deliver lateral inhibition and (3) that all three of these genes are themselves subject to negative regulation by lateral inhibition. These properties imply that competitive lateral inhibition, mediated by coordinated activities of deltaA, deltaB and deltaD, is sufficient to explain how primary neurons emerge from proneural clusters of neuroepithelial cells in the zebrafish.

Amino Acid Sequence↗
PubMed1991

Saturation of hepatic transport of taurocholate in rats in vivo.

A single intravenous injection of [14C]taurocholate was followed up in blood and bile of rats submitted to steady intravenous infusions of taurocholate (TC) at rates of 0.0, 0.5, 1.0, and 1.5 mumol.min-1.100 g body wt-1 for at least 30 min. The transport rate constants and the amounts of TC in different compartments were estimated by weighted least-squares adjustment of a six-compartment model to the experimental data (3 compartments for TC distribution in blood, 2 compartments for liver, and 1 compartment for sinusoidal blood space). The saturation of the TC excretion rate was reached at 0.8 mumol.min-1.100 g body wt-1. It was characterized by a decrease of both the uptake and excretion rate constants, by an increase of the ratio of the amounts of TC in the two intrahepatic compartments (H'/H), and by an intrahepatic TC concentration of approximately 2 mM. When tauroursodeoxycholate (TUDC) was infused at a rate of 0.5 mumol.min-1.100 g body wt-1 together with TC at a rate of 1.5 mumol.min-1.100 g body wt-1, the TC excretion rate increased to 1.2 mumol.min-1.100 g body wt-1, and the excretion rate constant and H'/H decreased toward control values. These results support the hypothesis that the saturation of the transport of TC is due to TC hepatotoxicity and can be reduced by TUDC. Michaelis-Menten parameters, derived from saturation curves for both uptake and excretion steps, closely matched earlier results, thus confirming the good descriptive capacity of the model.

Animals↗
PubMed1991

Compartmental analysis of steady-state taurocholate transport kinetics by isolated rat hepatocytes.

We used compartmental modeling to describe taurocholate transport by isolated rat liver cells in suspension. Cells are preincubated in the presence of unlabeled taurocholate. When a steady-state for taurocholate is reached, radiolabeled taurocholate is added to the medium and its exchange kinetics between the medium and the cells are followed over time. Because the studies are performed under steady-state conditions, the kinetics can be described by linear compartmental models. We found a closed two-compartment model sufficient to describe the steady-state transport data. Simulations reveal that if the pools of free and bound intracellular taurocholate exchange rapidly, the cells will behave as a single, kinetically homogeneous compartment and intracellular events will not influence the exchange kinetics of taurocholate between the medium and the cells. The two-compartment model was used to study the concentration dependence of taurocholate transport by isolated cells. Steady-state transport rates and taurocholate concentrations in the medium and the cells were calculated using the model equations. Taurocholate influx, accumulation and efflux processes were studied simultaneously by examining the relationship between appropriate combinations of these variables. Application of this approach to study the inhibition of taurocholate transport by taurochenodeoxycholate is illustrated. In conclusion, this method provides a complementary approach to initial rate studies, which are generally used to investigate bile acid transport by isolated cells.

Animals↗
PubMed1989

Compartmental modeling of the hepatic transport of taurocholate in the rat in vivo.

Compartmental analysis was used to study the hepatobiliary transport of taurocholate (TC) in the rat in vivo. The available data are the following: [14C]TC kinetics in blood and bile, weighting factors associated with these data and computed from a theoretical variability model, and TC excretion rate in bile. The lumped model that best fits the data contains five compartments: three compartments for TC distribution in blood and two compartments for the liver. It includes a compartmental representation of the laminar flow of bile in the collecting catheter. This model overestimates TC concentration in blood. A perfusion model that includes a compartment representing explicitly the sinusoidal TC concentration gradient was developed. TC concentration in blood estimated by this model is in good agreement with direct measurements, showing that the perfused model has a better descriptive capacity than the lumped model. The amounts of TC estimated in the two hepatic compartments are similar to values previously published.

Animals↗