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Biomedical subjects

F Roberge

Publications and source records attributed to F Roberge.

13 recordsLinked to original sources

Inhibition of S-antigen induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-antigen.

The ability to prevent the expression of retinal SAg induced experimental autoimmune uveitis (EAU) in Lewis rats by oral administration of the SAg and SAg fragments was investigated. Oral administration of the SAg molecule prevented or markedly diminished the clinical appearance of SAg-induced disease as measured by ocular inflammation. Furthermore, oral administration of the SAg also markedly diminished uveitis induced by the uveitogenic M and N fragments of the SAg. M and N fragments were not effective in preventing SAg-induced EAU, although feeding the M fragment prevented disease induced by the M fragment. Oral administration of the SAg did not prevent myelin basic protein induced experimental autoimmune encephalomyelitis, whereas feeding myelin basic protein did. In vitro studies demonstrated a significant decrease in proliferative responses to the SAg in lymph node cells draining the site of immunization from fed vs nonfed animals. Furthermore, the addition of splenocytes from SAg-fed animals to cultures of a CD4+ SAg-specific cell line profoundly suppressed the cell line's response to the SAg, whereas these splenocytes had no effect on a purified protein derivative-specific cell line. The Ag-specific in vitro suppression was blocked by anti-CD8 antibody (OX-8) demonstrating that this suppression is dependent on CD8+ T-cells. These experiments demonstrate that Ag-specific immunomanipulation can be achieved in the EAU model by oral administration of the SAg and raise the possibility that such an approach may have practical clinical implications in uveitis as well as other human autoimmune diseases.

Administration, Oral

Retinal glial cell proliferation and ion channels: a possible link.

Under a variety of pathological conditions, glial cells of the retina proliferate. Although glial cell proliferation may play a role in a number of important retinal disorders, the regulation of this proliferative response is understood poorly. We examined the possibility that the function of certain ion channels in retinal glial cells may be linked with the induction of proliferation. Experiments were performed on glial cells derived from the adult rat retina and maintained in culture. The cells stained positively by immunocytochemistry with antibodies specific for glial fibrillary acidic protein and for Muller cells. Patch clamp studies of these retinal glial cells demonstrated the presence of a large conductance, calcium-activated potassium channel that is sensitive to tetraethylammonium, a classical blocker of potassium channels. The activity of this type of potassium channel was monitored by patch clamp recordings in the cell-attached configuration before and after exposure of the glial cells to a mitogenic conditioned medium. Exposure to this conditioned medium was associated with a marked increase in the activity of the ion channel. A possible link between the activity of potassium channels and the action of mitogens was suggested further by the finding that tetraethylammonium significantly blocked the proliferative response of retinal glial cells to the conditioned medium. Our findings support the hypothesis that there is a link between the biophysical processes involved in ion channel activity and the proliferation of retinal glial cells.

Animals

Anisotropic conduction and functional dissociation of ischemic tissue during reentrant ventricular tachycardia in canine myocardial infarction.

We measured the conduction characteristics at the epicardial surface of the left anterior ventricular wall in the in situ canine heart before and 3 to 5 days (n = 9 dogs) after permanent occlusion of the left anterior descending coronary artery (LAD). During ventricular stimulation generating wavefronts conducted along the longitudinal or the transverse fiber direction, 61 unipolar electrograms were recorded with a fine-meshed plaque electrode. Before occlusion, the fastest conduction velocity was consistently found in a direction perpendicular to the nearby LAD segment (longitudinal direction), and the slowest velocity in a direction parallel to the LAD segment (transverse fiber direction). In 3- to 5-day-old infarct preparations, a layer of subepicardial muscle with 1 to 3 mm thickness survived over necrotic tissue. The velocities and directions of fast and of slow conduction measured in ischemic subepicardial muscle were not significantly different from preocclusion values during stimulation at a basic rate, but excitability was found to be depressed in response to premature stimuli. Premature impulses initiated in nonischemic myocardium and conducted into ischemic tissue in the longitudinal or in the transverse directions induced sustained (greater than 100 beats) monomorphic tachycardias during which figure-eight activation patterns were mapped with sock-array electrodes. During these tachycardias, the direction of the common reentrant wavefront of the figure-eight pattern was preferentially oriented along the longitudinal fiber direction, independently of the direction of the initiating impulse. When polymorphic beats were induced, tachycardia terminated spontaneously within 20 beats, or changed to a monomorphic pattern, as described above. In conclusion, the anisotropic organization of surviving subepicardial muscle overlying an infarct provides a spatial constraint that determines a preferential direction of reentrant propagation and may contribute to sustaining monomorphic tachycardia.

Animals

Chemotaxis of rat retinal glia to growth factors found in repairing wounds.

Retinal glia migrate to sites in the vitreous body and on the inner and outer surfaces of the retina during a wide variety of pathological processes. Using in vitro cultures of rat retinal glia, we have evaluated an extensive list of homogeneous, well-characterized growth factors as chemoattractants for these cells. Humoral growth factors, fibroblast growth factors, extracellular matrix proteins and immune system cytokines all were without activity except for the platelet-derived growth factor (PDGF). Extracts of bovine ocular tissues including vitreous body and retina yielded significant activity.

Animals

The effect of cyclosporine on immunization with tetanus and keyhole limpet hemocyanin (KLH) in humans.

Eleven patients with chronic uveitis treated with Cyclosporine were immunized with keyhole limpet hemocyanin (KLH) and tetanus toxoid. Delayed cutaneous hypersensitivity responses, lymphocyte blastogenic responses, and antibody production were compared with those of similarly immunized control individuals. A significant decrease in delayed cutaneous hypersensitivity (P less than 0.001 for KLH and P less than 0.01 for tetanus toxoid) was observed. No significant differences in blastogenic or antibody responses were noted. These findings demonstrate that the majority of the Cyclosporine-treated patients had intact T cell-dependent antigen responses as measured by both proliferative response and antibody production to primary and secondary antigenic challenges but that other immune functions such as delayed cutaneous hypersensitivity are affected by therapeutic doses of systemic Cyclosporine.

Antibody Formation

Standardization of vitreal inflammatory activity in intermediate and posterior uveitis.

Standardization of observations is recognized as fundamental to clinical research. The methodology for the evaluation of anterior segment inflammatory disease has become well accepted, while the ocular inflammatory standardization of the posterior segment has not been so well described or accepted. A system for the evaluation of vitreal inflammatory activity in patients with intermediate and posterior uveitis is presented. A series of photographs representing various degrees of fundus vitreal haze is depicted. The observer examines the eye with an indirect ophthalmoscope, then chooses the photograph which most closely simulates what is being seen. This technique is rapid and its reproducibility is helpful in standardizing clinical observations.

Fundus Oculi

A microcomputer-based stimulator for clinical and experimental investigations in cardiac electrophysiology.

A cardiac stimulator is described which combines the ease of operation required in clinical investigations, particularly endocavitary studies of cardiac arrhythmias, and the versatility needed in a research context. This instrument uses a microcomputer to control two independent optically-isolated stimulation ports which can be addressed either independently or jointly to stimulate at two different sites. The main software module operates as a cascade of ten real time pulse generators with individually presettable parameters: amplitude, duration, period, initial delay, periodic and cyclic modifiers, triggering mode, etc. A simple interactive procedure allows the operator to define a stimulation protocol either by accessing the generator structure directly, or by calling any of five pre-programmed stimulation protocols. With this combination, the instrument can provide a large variety of pulse patterns. The operator can intervene at any time during stimulation to change parameter values or modify the pulse pattern. Concurrently with stimulation, the instrument generates time-codes to help relate cardiac responses recorded on paper chart and magnetic tape, and reference them to specific events. The instrument can be readily expanded by the addition of parallel microprocessor modules; other real time tasks such as acquisition and processing of cardiac responses can thus be incorporated.

Cardiac Pacing, Artificial

Effects of re-use on the physical characteristics of angiographic catheters.

Five types of angiographic catheters used in current radiological and haemodynamic clinical practice at Sacré-Coeur Hospital in Montreal were studied for their mechanical sturdiness, and also with respect to the possibility that re-use could be associated with blood contamination by loose particles. Samples were taken both from new catheters and from catheters re-used up to 10 times. Routine cleaning and sterilization procedures showed no adverse effects on the maximum tensile strength and elongation at break of catheters. While some biological debris were occasionally present in re-used catheters, they appeared to be firmly fixed to the lumen surface, and they seemed unlikely to be carried into the blood stream during catheterization. On the other hand, new catheters exhibited a substantially higher loose particicle count than catheters which had been properly cleaned and sterilized. It is concluded that properly handled re-used angiographic catheters are just as safe for the patient as new catheters. The limit on the number of re-uses may depend on the care taken to avoid damage to the lumen surface during cleaning, on ageing on the catheter material and on economic considerations.

Angiography