Biomedical subjects

M Garin

Publications and source records attributed to M Garin.

4 recordsLinked to original sources

PubMed2007

Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.

The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) largely relies on the graft-versus-leukemia (GvL) effect exerted by donor T cells. CD4(+)CD25(high) regulatory T cells (T(regs)) have been shown to downregulate antitumor responses but their role on GvL has not been evaluated. We performed a cross-sectional study in which we enumerated and characterized CD4(+)CD25(high) T(regs) in the peripheral blood of CML patients undergoing allogeneic SCT. We documented higher frequencies of T(regs) in patients after transplant as compared to normal controls and newly diagnosed patients. The increment was particularly evident in patients who had received their SCT 18 months before. In vitro functional studies demonstrated that the T(regs) purified from SCT patients exhibited a more potent suppressive activity than T(regs) isolated from healthy volunteers. Patients in whom T(regs) numbers were higher than controls more than 18 months after SCT showed evidence of disease relapse. Although the increment in T(regs) might have an advantageous effect on graft rejection in the early phase post-transplant, our data suggest that T(regs) exert an inhibitory effect on GvL.

Adolescent↗

PubMed2006

[Performing saccadic eye movements modifies postural control organisation].

AIMS OF THE STUDY: To assess to which extent performing saccadic eye movements modifies the postural strategies aimed at maintaining balance. MATERIALS AND METHODS: Twelve healthy adults were tested on a force platform in several conditions including one in which they were required to stare a visual target and four in which small and larger saccadic eyes movements were performed vertically and horizontally. The displacements of the centre of pressure (CP) were then processed through frequency analysis and modelled as fractional Brownian motion (fBm). Through the latter, one may objectively assess from which distance and after which delay corrective process are initiated. In addition, the degree with which the CP movement is successively controlled is determined. RESULTS: A decrease of the magnitudes of the CP trajectories is observed during saccades, especially along the anteroposterior axis. The fBm modelling emphasises the setting of a particular postural strategy whose main effect consists in more delayed corrective processes associated with a better capacity to control the corrective CP displacements. CONCLUSION: This particular strategy could be linked to the difficulty for the subjects to detect pertinent visual information in this very axis and/or an increased cognitive constraint due to the saccades. On the whole, these data underline the necessity, when performing postural protocols, to ask the patients to stare a visual target in order to limit their eye movements.

Adult↗

PubMed2001

Elimination of the truncated message from the herpes simplex virus thymidine kinase suicide gene.

Introduction of the Herpes simplex virus thymidine kinase (HSV-tk) gene into target cells renders them susceptible to killing by ganciclovir (GCV). We are studying the use of HSV-tk-transduced T lymphocytes in the context of hematopoietic stem cell transplantation. We have previously shown, in vitro and in vivo, the occurrence of transduced cells resistant to GCV due to a deletion within HSV-tk. This deletion, a consequence of the presence of cryptic splice donor and acceptor sites, originates in the retroviral producer cell. Here we adopt two different methods that introduce third-base degenerate changes at the cryptic splice sites and so prevent splicing. Consequently, the HSV-tk protein is unaltered and the sensitivity of the target cells to GCV is preserved. The use of this mutated HSV-tk should reduce the likelihood of the development of resistant genetically modified cells during clinical trials.

Antiviral Agents↗

PubMed1995

Lactate catabolism by enzyme-loaded red blood cells.

Two different enzymes that metabolize lactate in the presence of oxygen, either to acetate plus CO2 (lactate 2-mono-oxygenase; Lmox) or to pyruvate plus H2O2 (lactate oxidase; Lox) were encapsulated in human and murine red blood cells (RBCs). Lmox shows a low affinity for lactate (Km 22 mM) and thus works at a low rate at the lactate concentrations found in hyperlactataemia (5-20 mM). Encapsulation of Lox provides a constant catabolic rate under the same range of blood lactate concentrations, but generates H2O2, which is toxic to the enzyme-loaded RBCs. Co-encapsulation of both enzymes at a ratio of 20 units of Lmox/unit of Lox results in significant rates of lactate metabolism over a wide range (1-30 mM) of lactate concentrations with modest methaemoglobin formation (5-8.5%) and normal cellular ATP concentrations (1.1-1.23 mM). In vitro experiments with [1-14C]glucose and [U-14C]glucose have shown that Lmox/Lox-loaded RBCs counteract the production of H2O2 by increasing the amount of glucose metabolized in the pentose phosphate pathway. In vivo attempts to prove the efficacy of these engineered RBCs in removal of blood lactate in mice have failed because of the high aerobic capacity and high lactate metabolism of these animals. However, the results obtained in vitro suggest that the encapsulation of lactate-catabolizing enzymes may be useful in the treatment of hyperlactataemia.

Acetates↗