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Biomedical subjects

S Gignac

Publications and source records attributed to S Gignac.

4 recordsLinked to original sources

Glucocorticoids decrease endothelin-A- and -B-receptor expression in the kidney.

Glucocorticoids play an important role in circulatory homeostasis and in excess they cause hypertension. These corticosteroids affect the expression of many genes involved in blood pressure control including preproendothelin-1 (PPET-1), the precursor of endothelin-1 (ET-1), a potent vasoactive peptide. We have previously shown that glucocorticoids increase PPET-1 mRNA levels in rat aorta. Moreover, they also affect ET(A)- and ET(B)-receptor expression in various in vitro and in vivo situations. Both ET-1 and glucocorticoids exert direct effects in the kidney and are involved in vascular resistance and sodium balance. We therefore sought to determine the effects of glucocorticoids on renal PPET-1, ET(A)- and ET(B)-receptor expression in an animal model of glucocorticoid-induced hypertension. Wistar rats were given 2.5 mg/l of dexamethasone, a glucocorticoid agonist, in their drinking water for 1 or 5 days. Our data reveal that dexamethasone administration increases systolic blood pressure (SBP) in rats. SBP rose from 120 +/- 3 to 139 +/- 4 and 150 +/- 5 mmHg after 1 and 5 days treatments, respectively (p < 0.05). Furthermore, dexamethasone administration decreased ET(A) and ET(B)-receptor expression in the rat kidney. This effect was observed after 1 day of dexamethasone treatment with ET(A) and ET(B)-receptor mRNA levels decreasing to 83 +/- 2% and 80 +/- 5% of control values. respectively (p < 0.01). Both ET(A)- and ET(B)-receptor mRNA levels further declined to 67 +/- 3 and 65 +/- 6% of control values after 5 days of dexamethasone treatment, respectively (p < 0.001). Interestingly, kidney PPET-1 expression was not affected by dexamethasone administration. Our results suggest a contribution of renal ET receptors in glucocorticoid actions on blood pressure control.

Animals↗

Tyramine amplification technique in routine immunohistochemistry.

Signal amplification in immunohistochemistry via binding of biotinylated tyramine to proteins near the site of peroxidase-labeled antibodies is a promising new technique, but studies investigating a wide range of markers are lacking. The tyramine amplification technique (TAT) was investigated on 85 antibodies using a simple and fast protocol, and TAT results were compared to those obtained with conventional immunohistochemistry. Using TAT, most of the markers could be 5- to 50-fold further diluted and still showed identical staining results compared with standard stainings (maximal 500-fold). However, the variable reactivity of the different markers with TAT underlines the need for individual testing of every antibody to determine the optimal dilution. Some antibodies against cell adhesion molecules could be demonstrated for the first time in archival, formalin-fixed tissue sections. TAT, if carefully evaluated, offers a revolutionary improvement for modern immunostaining, either to increase sensitivity or primary antibody dilutions (cost reduction). From a methodological point of view, immunohistochemistry has not reached its limits by far and TAT is an important progressive step in this developmental process.

Antibodies, Monoclonal↗

High concordance between marker profiles of 22 human leukemia-lymphoma cell lines tested with the same monoclonal antibodies before and during the second international workshop on human differentiation antigens.

Our laboratory participated in the Second International Workshop and Conference on Human Leucocyte Differentiation Antigens. In this international study the reactivity profiles of monoclonal antibodies were analyzed on normal and malignant hematopoietic cells. The Workshop was divided into three categories: the T-cell, B-cell and myelomonocytic cell studies. We blindly tested 159 coded monoclonal antibodies of the panel for the T-cell study on 22 permanently established leukemia cell lines. The monoclonal antibodies were provided by the Workshop Committee and their reactivity with the target cells was visualized by standardized indirect immunofluorescence. After decoding it was recognized that 11 monoclonal antibodies had been examined on these cell lines prior to the Workshop. The reactivity of these 11 monoclonal antibodies was analyzed and compared with the earlier results. From a total of 217 paired tests done blindly in the Workshop study and prior to the Workshop, 191 tests (88%) did not show significantly different data. The possible reasons for discrepancies include nonspecific Fc-receptor-binding on some cell lines and a relatively nonspecific reactivity of some monoclonal antibodies. This analysis demonstrates the stability of the antigen expression on human leukemia-lymphoma cell lines grown at consistently optimal conditions, for the tests, using the same monoclonal antibodies as in the Workshop, had been performed 0.5-5 years prior to the Workshop study. On the other hand, nonspecific Fc-binding, wide "specificity" of monoclonal antibodies and a shift in antigen expression of the cells (due to poor growth conditions, involuntary induction of differentiation and other factors) must be taken into consideration upon immunological analysis.

Antibodies, Monoclonal↗

An experimental histopathologic study of surgical glove powders.

Tissue reactions to surgical glove powders, ie, talc (magnesium silicate) and Keoflo (low cross-linked cornstarch) were studied histologically from day 1 to 16 weeks. These materials were tested as a contaminant on the surface of surgical suture or in a pellet form implanted in abdominal muscle of rat. Use of Keoflo resulted in an intense acute inflammatory response, with a progressive decrease in the amount of starch with time after implant. By the fourth week, most of the starch had disappeared with minimal tissue damage and scar formation. Rats implanted with talc showed an initial mild to moderate acute inflammation followed by chronic inflammatory response and granuloma formation by the third day. From the fourth week on, granulomas showed talc crystals within the giant cells surrounded by histiocytes, lymphocytes, some collagen, and fibroblasts. This study indicates that talc molecules are not absorbed, whereas low cross-linked cornstarch is an absorbable substance; therefore the latter is a safe material for use as surgical glove powder.

Drug Implants↗