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J Audet

Publications and source records attributed to J Audet.

At least 19 recordsLinked to original sources
PubMed2001

Distinct role of gp130 activation in promoting self-renewal divisions by mitogenically stimulated murine hematopoietic stem cells.

Previous studies have demonstrated hematopoietic stem cell amplification in vitro after the activation of three cell-surface receptors: flt3/flk2, c-kit, and gp130. We now show flt3-ligand and Steel factor alone will stimulate >85% of c-kit(+)Sca-1(+)lin(-) adult mouse bone marrow cells to proliferate in single-cell serum-free cultures, but concomitant retention of their stem cell activity requires additional exposure to a ligand that will activate gp130. Moreover, this response is restricted to a narrow range of gp130-activating ligand concentrations, above and below which hematopoietic stem cell activity is lost. These findings indicate a unique contribution of gp130 signaling to the maintenance of hematopoietic stem cell function when these cells are stimulated to divide with additional differential effects dictated by the intensity of gp130 activation.

Animals↗
PubMed2001

Cell cycle distribution of primitive haematopoietic cells stimulated in vitro and in vivo.

A novel approach is used to study the proliferating behaviour of primitive haematopoietic cell populations in response to different stimuli. A mathematical model based on the average proportion of apoptotic, dividing and quiescent cells in primitive haematopoietic cell populations is developed to describe the mitotic history of 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester-labelled cells. The cell cycle distributions in different cytokine-supplemented cultures of primitive human and mouse bone marrow cells are determined and compared with those found in vivo. The results indicate that a combination of flt-3 ligand, Steel factor and interleukin-11 or hyper-interleukin-6 provide a level of mitogenic stimulation similar to that existing in vivo after a myeloablative radiation dose. The comparison of the cell cycle distribution obtained for different cultures of human bone marrow CD34(+)(45RA/71)(-) cells demonstrates that the addition of flt-3 ligand in these cultures decreases apoptosis significantly but does not reduce quiescence. In addition, in vivo and in vitro, it was found that more than 3 days of stimulation are required to recruit a maximum number of quiescent cells into active cell cycle. These kinetics of cell cycle activation are found to be similar to those identified for the haematopoietic stem cells compartment in the same cultures. This mathematical analysis provides a useful tool for the development of haematopoietic stem cell culture processes for clinical applications.

Animals↗
PubMed2001

Characterization of human hematopoietic cells with short-lived in vivo repopulating activity.

Recent studies with purified hematopoietic stem cells in vitro support a model of stem cell self-renewal control that involves distinct mechanisms regulating permissiveness to and execution of lineage restriction. Such a model predicts the existence of phenotypically separable populations of hematopoietic cells that are pluripotent and either capable or incapable of extensive self-renewal. Such populations have been previously described in the mouse. We describe here the first evidence that such cells can now be identified in humans using different types of immunodeficient mice as hosts.

Animals↗
PubMed2000

High-resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro and in vivo.

The kinetics of proliferation of primitive murine bone marrow (BM) cells stimulated either in vitro with growth factors (fetal liver tyrosine kinase ligand 3 [FL], Steel factor [SF], and interleukin-11 [IL-11], or hyper-IL-6) or in vivo by factors active in myeloablated recipients were examined. Cells were first labeled with 5- and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and then incubated overnight prior to isolating CFSE(+) cells. After 2 more days in culture, more than 90% of the in vivo lymphomyeloid repopulating activity was associated with the most fluorescent CFSE(+) cells (ie, cells that had not yet divided), although this accounted for only 25% of the repopulating stem cells measured in the CFSE(+) "start" population. After a total of 4 days in culture (1 day later), 15-fold more stem cells were detected (ie, 4-fold more than the day 1 input number), and these had become (and thereafter remained) exclusively associated with cells that had divided at least once in vitro. Flow cytometric analysis of CFSE(+) cells recovered from the BM of transplanted mice indicated that these cells proliferated slightly faster (up to 5 divisions completed within 2 days and up to 8 divisions completed within 3 days in vivo versus 5 and 7 divisions, respectively, in vitro). FL, SF, and ligands which activate gp130 are thus efficient stimulators of transplantable stem cell self-renewal divisions in vitro. The accompanying failure of these cells to accumulate rapidly indicates important changes in their engraftment potential independent of accompanying changes in their differentiation status.

Animals↗
PubMed1999

Introduction to stem cell biology in vitro. Threshold to the future.

Transplantable hematopoietic cells with multilineage reconstituting ability can be quantitated in suspensions of human or murine cells using similar assay procedures. The incorporation into these assays of stringently defined functional endpoints ensures a high degree of specificity for the cells detected. Application of these assays to stem cell-containing suspensions after they have been stimulated for several days with defined cytokines in vitro, or by a mixture of defined and/or undefined factors in vivo, has shown that net amplifications in these populations can be obtained under both circumstances. Such studies have allowed cytokine conditions that support stem cell self-renewal divisions to be identified and have also provided evidence that stem cell regeneration can be manipulated both in vitro and in vivo by altering the molecular milieu of the responding cells. These observations pave the way to future delineation of mechanisms that control the normal behavior, pathology and future clinical exploitation of hematopoietic stem cell populations.

Animals↗
PubMed1999

Relations of diabetes intrusiveness and personal control to symptoms of depression among adults with diabetes.

The generalizability of a model linking illness characteristics to psychosocial well-being was tested in a cross-sectional study of 237 adults with type 2 diabetes. It was hypothesized that diabetic complications increase illness intrusiveness, which in turn increases depressive symptomatology either directly or indirectly by reducing personal control over health outcomes. Illness intrusiveness was defined as the result of disruptions of valued activities and interests due to constraints imposed by the illness. An excellent fit of this model to the data was found using structural equation modeling. The model explained 65% of the variance in depressive symptomatology. Assessment of an alternative model excluding personal control suggested that the extent to which diabetes intrudes in life, rather than diabetic complications per se or personal control, is a key factor in relation to depressive symptomatology in individuals with diabetes.

Adult↗
PubMed1999

Cell division tracking and expansion of hematopoietic long-term repopulating cells.

The combined use of rigorous assays for quantitating transplantable stem cell numbers and precise cell labeling and tracking procedures have provided definitive evidence that stem cell self-renewal divisions can occur in vitro in the absence of stromal feeder layers. These findings set the stage for defining conditions that may alter the ability of these cells to maintain their primitive status when mitogenically activated.

Animals↗
PubMed1998

Advances in hematopoietic stem cell culture.

Recent advances in our understanding of the earliest stages of hematopoietic cell differentiation, and how these may be manipulated under defined conditions in vitro, have set the stage for the development of robust bioprocess technology applicable to hematopoietic cells. Sensitive and specific assays now exist for measuring the frequency of hematopoietic stem cells with long-term in vivo repopulating activity from human as well as murine sources. The production of natural or engineered ligands through recombinant DNA and/or combinatorial chemistry strategies is providing new reagents for enhancing the productivity of hematopoietic cell cultures. Multifactorial and dose-response analyses have yielded new insight into the different types and concentrations of factors required to optimize the rate and the extent of amplification of specific subpopulations of primitive hematopoietic cells. In addition, the rate of cytokine depletion from the medium has also been found to be dependent on the types of cell present. The discovery of these cell-type-specific parameters affecting cytokine concentrations and responses has introduced a new level of complexity into the design of optimized hematopoietic bioprocess systems.

Animals↗
PubMed1997

The assessment of diabetes-related cognitive and social factors: the Multidimensional Diabetes Questionnaire.

The purpose of this study was to examine the psychometric properties of the recently developed Multidimensional Diabetes Questionnaire (MDQ). The MDQ, which is theoretically linked to a social learning perspective of diabetes, was designed to provide a comprehensive assessment of diabetes-related cognitive and social factors. It includes 41 items grouped into three sections: (1) perceptions related to diabetes and related social support, (2) positive and misguided reinforcing behaviors related to self-care activities, and (3) self-efficacy and outcome expectancies. Confirmatory factor analyses, conducted on a sample of 249 patients with non-insulin-dependent diabetes mellitus, supported the construct validity of the MDQ. Adequate internal consistency and significant demographic, psychological, behavioral, and disease-related correlates were found. The MDQ may prove valuable in understanding individual differences in adjustment to diabetes.

Adult↗
PubMed1991

Rheological properties of the human lumbar spine ligaments.

The purpose of this study is to provide a better understanding of the rheological properties of the lumbar spinal ligaments under subfailure physiological loads. Non-destructive tests including an hysteresis experiment, stress-relaxation and stepwise load-relaxation tests were used to investigate the time-dependent properties of the interspinous-supraspinous ligament complex. Using a reduced relaxation function, the viscoelastic behaviour over the experimental time-scale was described by a linear function of the logarithm of time. Internal damping of ligament substance dissipates about 36% of the mechanical energy applied during physiological loading. Local elastic stiffness is found to be two to four times global stiffness of the bone-ligament-bone complex. These physical parameters (stiffness, energy dissipation, hysteresis, relaxation, etc) can be used to improve computer models of the lumbar spinal column.

Adult↗
PubMed1982

Evidence that reduced growth hormone secretion observed in monosodium glutamate-treated rats is the result of a deficiency in growth hormone-releasing factor.

The present experiments were designed to examine various aspects of GH secretion in adult male rats given monosodium glutamate (MSG; 4 mg/g BW, sc) during the neonatal period. MSG-treated animals sustained lesions localized to the hypothalamic arcuate nuclei (ARC) and had reduced nasal-anal lengths and body weights. Anterior pituitary (AP) weights were decreased, but AP concentrations of GH and PRL were not significantly altered. Analysis of pulsatile GH secretion showed depressed GH pulses and prolonged GH trough periods. Mean 5-h plasma GH levels were reduced, whereas PRL levels were not affected. Morphine sulfate (MS) at doses of 0.01, 0.1, 1.0, and 3.0 mg/kg induced a prompt rise in GH during the 45 min after drug administration in controls. MSG-treated animals showed a significant rise in GH only with 1.0 and 3.0 mg/kg MS. A significant elevation in PRL was found in both control and MSG-treated animals after 1.0 and 3.0 mg/kg MS. The pentobarbital-induced rise in GH was also blunted in MSG-treated animals. MSG-treated animals which were administered antisomatostatin serum showed elevated GH trough and mean GH levels, with no apparent effect on GH peak levels. In view of the mechanisms by which MS and pentobarbital act to increase GH secretion, the present data suggest that the GH regulatory deficit observed in MSG-treated rats is due to a relative loss of GH-releasing factor secondary to ARC damage.

Animals↗
PubMed1982

Microwave thermography--characteristics of waveguide applicators and signatures of thermal structures.

In this paper, we study the problem of the interpretation of the signals provided by microwave thermography, which allows the detection of the thermal gradients in living tissues. These signals correspond to the thermal noise measured by a radiometer when the probe scans the surface of the tissues (passive process). We describe how these signals can be computed by means of a new method based on the antenna reciprocity principle. This process requires a knowledge of the electrical field distribution in the lossy medium when the applicator is radiating a microwave signal (active process). Examples of computations of the thermal signals and experimental verifications are presented. Then, we introduce a new concept of 'thermal signature' and show how it is possible to reach a quantitative interpretation of the thermal signals such as those obtained in clinical investigations (thermal pattern recognition).

Microwaves↗
PubMed1980

Electrical characteristics of waveguide applicators for medical applications.

This work concerns the electrical properties of waveguide applicators consisting of flanged rectangular waveguides filled with a dielectric, used in medical applications (microwave thermography and local hyperthermia). The reflection coefficient and the near field configuration in lossy materials were obtained in some cases analytically and in some other cases numerically. The validity of these methods was verified experimentally. The study shows that the matching of the applicator and the penetration depth in a lossy material, such as a living tissue, depend not only on the tissue characteristics but also on the characteristics of the applicator itself.

Electromagnetic Fields↗
PubMed1978

Neuropharmacological regulation of episodic growth hormone and prolactin secretion in the rat.

The effects on GH and PRL secretion of several pharmacological agents known to modify central neurotransmitter action were determined in unanesthetized male rats. Phenoxybenzamine, an alpha-adrenergic blocker (5 mg/kg iv), abolished episodic GH secretion and caused elevation of serum PRL levels. Propranolol, a beta-adrenergic blocker (5 mg/kg iv), had no effect on GH secretion and caused a small but significant depression in PRL levels. Parachlorophenylalanine methyl ester, an inhibitor of tryptophan hydroxylase (300-350 mg/kg ip), resulted in significant inhibition of GH pulsatile secretion and suppressed PRL levels. Methysergide hydrogen maleinate (25 mg/kg iv), a serotonin receptor antagonist, also inhibited GH secretion, but produced a transient stimulation in PRL levels. Atropine sulfate (2 mg/kg iv) caused significant suppression in GH secretion, but had no effect on PRL. Picrotoxin, a gamma-aminobutyric acid antagonist, in a subconvulsive dose of 1-3 mg/kg iv, also depressed GH episodic secretion but did not affect PRL levels. These results indicate that several neurotransmitters, i.e., norepinephrine, serotonin, acetylcholine, and gamma-aminobutyric acid, found in high concentration in the hypothalamus, influence GH and PRL secretion.

Animals↗
PubMed1977

Haemodynamic changes due to clamping of the abdominal aorta.

Haemodynamic changes due to aortic cross-clamping were examined in 18 patients. It has been shown that the distal occlusion of the abdominal aorta induces an increased impedance to ejection. Because the mechanisms controlling the auto-regulation of cardiac output and the circulatory reflexes are damped by anaesthesia, the augmentation of resistance is not followed by any increase in contractility or vasomotor tone and thus the cardiac output falls. Patients with chronic obstructive disease (Leriche) did not differ significantly from subjects with more acute obstruction (aneurysm), though the latter have a tendency to show more important changes in their haemodynamic response.

Adult↗
PubMed1977

Physiologic secretion of growth hormone and prolactin in male and female rats.

Growth hormone and prolactin are secreted episodically in man and experimental animals. To investigate physiologic mechanisms of GH and PRL secretion, a series of experiments were performed in individual, unanaesthetized male and female rats. GH secretion in the male rat is characterized by intermittent surges that occur approximately every 3 h and are entrained to the light-dark cycle. Peaks reach 200--400 ng/ml and troughs are unmeasurable. PRL is secreted in more frequent episodes with a pattern distinct from GH. In the female rat, GH surges occur more frequently--approximately once each hour. PRL levels are low (less than 15 ng/ml) except on the afternoon of pro-oestrous when they surge to levels of 100--300 ng/ml. Prolactin rises 4--6 h before delivery. Levels decline rapidly at the onset of parturition and surge with each episode of suckling in the post-partum period. Growth hormone and corticosterone rise during delivery and remain elevated for several hours after delivery. Reinstitution of suckling after removal of pups causes an immediate rise in PRL and GH. The PRL response is sustained for 3--4 h, whereas the GH response is brief with return to baseline within 1 h. The time courses of the two responses are clearly independent. Stress in the male rat causes a rapid rise in PRL and suppression in GH. The PRL surge to stress is brief with return to baseline by 1 h. GH pulses are suppressed for up to 5 h after stress. These studies indicate that separate neuroendocrine control mechanisms exist for regulation of the episodic release of GH and PRL in the rat.

Animals↗