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Biomedical subjects

R Winand

Publications and source records attributed to R Winand.

At least 19 recordsLinked to original sources
PubMed2001

Plasticity of skeletal myosin in endurance-trained rats (I). A quantitative study.

The aim of this study was to quantify modifications in the expression of skeletal myosin light chain (MLC) and myosin heavy chain (MHC) isoforms of five muscles, according to their fiber composition and function, following endurance training in rats. Rodents were assigned randomly to one of two groups: caged sedentary controls (C) or endurance-trained rats (T). In T rats, three out of the four fast and mixed muscles studied exhibited a significant increase in the expression of MLC1s, 1f and 2s and a significant decrease in MLC2f and 3f, the exception being the plantaris muscle. In two out of the four muscles we observed a significant increase in MHCI and IIa, the exception being both gastrocnemii, where the expression of MHCI did not change. In the soleus of T rats, the expression of MLC1s, 2f and 3f decreased significantly, while that of MLC2s increased significantly, compared with those of C rats. The expression of MHCIIa in T rats decreased significantly compared with that of C rats, while the expression of MHCI increased significantly. In all muscles studied, a significant slowing of myosin isoforms was observed after endurance training.

Animals↗
PubMed1994

Plasma glycosaminoglycans in endocrine ophthalmopathy.

With evidence on the important role of glycosaminoglycans (GAG) in the pathogenesis of endocrine ophthalmopathy (EO) having accumulated, the present study focused on the biochemical assessment of plasma GAG content in 37 EO patients as compared to 20 controls. Glycosaminoglycans were isolated from plasma samples by protein elimination, dialysis, and precipitation with ethanol and cetylpyridinium chloride. Patients (9.71, 5.09, 15.09 mg/100 ml; median, 25th, 75th percentile) exhibited significantly (p = 0.0021) higher plasma GAG levels than controls (4.6, 3.38, 6.8 mg/100 ml). Plasma GAG content was unrelated to age, sex, or antithyroid treatment. However, an even higher level of significance (p = 0.0001) was reached when discriminating between untreated patients with EO of recent onset (14.16, 10.35, 15.51 mg/100 ml) and controls. By contrast, steroid therapy of EO led to values (3.82, 1.85, 6.52 mg/100 ml) indistinguishable from those of the controls. Further statistical analysis of the results, based on a specificity of 95% for the control group, revealed a sensitivity of 91% for patients with untreated EO of recent onset, and a specificity of 100% for patients receiving steroid therapy. In comparison, plasma GAG content was determined in 8 untreated and in 6 treated EO patients by a second method already published. All untreated patients exhibited high GAG levels (median 2.23 mg/100 ml) whereas in treated EO patients normal plasma GAG values (0.17-0.34 mg/100 ml) were found. Follow-up determination of plasma GAG content in 7 patients undergoing steroid treatment unveiled a marked decrease of initially elevated values. These findings correlated well with clinical improvement of thyroid eye disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cytotoxic assay of circulating thyroid peroxidase antibodies.

This study describes an assay for the detection of cytotoxicity for thyroid cells in serum of patients with autoimmune thyroiditis. Quantitative measurement may be performed by DNA or [3H] leucine incorporation determinations. The cytotoxic effect is localized in the gamma-globulin fraction, and is complement-mediated. It is thyroid specific i.e. it is not observed with fibroblasts and patients with other autoimmune diseases (patients with lupus erythematosis or glomerulonephritis) do not have cytotoxic antibodies directed against thyroid cells. The thyroid cytotoxicity is related to the presence of antimicrosomal antibodies and the effect of circulating antibodies is inhibited by human thyroid peroxidase. These results strengthen the possible implication of circulating antithyroid peroxidase antibodies in thyroid damage observed in autoimmune thyroiditis.

Animals↗
PubMed1989

[Personal experience in the study of thyroid autoimmunity and endocrine exophthalmos].

Most of the thyroid disorders are considered as being autoimmune diseases. It is the case for autoimmune thyroiditis where various antibodies are found. In Graves' Basedow disease, one or several immunoglobulin(s) which stimulate(s) the thyroid were found. In simple goitre, autoimmune origin is probable. We have measured the presence of anti-alpha-galactosyl antibody in various thyroid disorders. An increase titre was observed in progressive Graves' ophthalmopathy, untreated Graves' disease, progressive simple goitres and in autoimmune thyroiditis. Therefore, we think that the measure of anti-alpha-galactosyl antibodies represents reproducible parameter in order to know if the thyroid disease is or not in progression.

Autoantibodies↗
PubMed1988

Beneficial effects of intensive plasma exchange followed by immunosuppressive therapy in severe Graves' ophthalmopathy.

Nine patients with severe Graves' ophthalmopathy were treated by intensive plasma exchange, followed by immunosuppression. Severity of ocular involvement and response to therapy were evaluated by numerical scoring (ophthalmopathy index) and clinically. Serum thyroid stimulating immunoglobulins (TSI) and urinary excretion of glycosaminoglycans (GAG) were measured immediately before and immediately after plasmapheresis. Plasma exchange was rapidly accompanied by marked clinical improvement in 8/9 patients. The most marked effects were on soft tissue involvement, proptosis, intraocular pressure, and visual acuity. The ophthalmopathy index decreased from 9.7 +/- 4.1 to 5.7 +/- 2.2 (p less than 0.001) after plasmapheresis. Serum TSI levels were initially elevated in 6 patients and remained positive in 3 patients after treatment. Urinary GAG excretion was initially 2- to 12-fold normal levels and was decreased by 60%. After plasmapheresis, patients received immunosuppressive drugs for 3-6 months. The follow-up period, after withdrawal of drugs, ranged from 5 to 38 months with a median of 17 months. The ocular condition remained stable in 6 patients. Three patients had a relapse 1 year after plasmapheresis: they were treated a second time by plasma exchange with subsequent improvement. In conclusion, intensive plasma exchange provided prompt and effective improvement in patients with severe progressive Graves' ophthalmopathy. This therapeutic procedure, followed by immunosuppression, gave long lasting results. Relapses were responsive to plasmapheresis therapy. The data suggest that plasma exchange may represent the best primary treatment for severe progressive Graves' ophthalmopathy.

Adult↗
PubMed1987

Elevated anti-alpha-galactosyl antibody titres. A marker of progression in autoimmune thyroid disorders and in endocrine ophthalmopathy?

The titres of anti-alpha-galactosyl antibodies were measured by passive haemagglutination in 50 control subjects and in 128 patients presenting with various thyroid disorders. Titres of control subjects ranged from 1/10 to 1/80, regardless of age and blood group. Elevated titres (greater than 1/80) were constantly noted in 6/6 patients with progressive exophthalmos, in 5/5 patients with untreated Graves' disease, and in 11/12 patients with progressive nontoxic goitre. By contrast, the titres were within the normal range in primary myxoedema (17 patients) and in residual exophthalmos (11 patients), whereas they were only erratically increased in 1/31 patients with treated or cured Graves' disease and in 5/36 patients with nonprogressive nontoxic goitre. Finally, elevated titres were also found in 3/7 patients presenting with autoimmune thyroiditis. No correlations could be established between elevated titres and the thyrotropin binding inhibiting immunoglobulin activity, the antithyroglobulin antibody titres or the antimicrosomal antibody titres. As in the control subjects, the anti-alpha-galactosyl antibodies mainly belonged to the IgG class. Affinity purified anti-alpha-galactosyl antibodies were capable of binding to trypsinized human and porcine thyroid cells in culture, as shown by indirect immunofluorescence. On the other hand, they were not able to react with untreated thyroid cells. The data show that the measurement of anti-alpha-galactosyl antibody titres could represent an easy and useful tool to determine whether an autoimmune thyroid disorder is in progression. Besides, they suggest that some of the antigenic determinants implicated in the enhanced production of anti-alpha-galactosyl antibodies are present, but normally hidden, within the cell surface of thyroid cells.

Adult↗
PubMed1986

Effects of thyrotropin and thyroid stimulating immunoglobulins on gangliosides labelling of human thyroid cultured pathological cells.

Gangliosides are known to play an important role in different cell processes. We have investigated the effect of TSH on [14C] glucosamine incorporation into gangliosides of cultured pathological cells isolated from colloid nodular goiter, follicular adenoma, and toxic adenoma. The effect of thyroid stimulating immunoglobulins (TSI) has also been similarly studied on primary cultures from colloid nodular goiter and from porcine thyroid cells. Immunoglobulins were purified from sera of Graves' disease patients. Cells were cultured with or without either stimulator and labelled with [14C] glucosamine during 24 h. Total lipid extracts were fractionated on DEAE Sephadex A 25. Eluted gangliosides were analysed by thin layer chromatography, detected by autoradiography and scraped off for radioactivity measurement. Radioactivity was related to the free cholesterol content. The ganglioside pattern of human thyroid cells in primary cultures is found to vary and to closely reflect the ganglioside pattern of the corresponding gland. No ganglioside pattern could be related to a specific thyroid disorder. When cells are treated with TSH, the amount of [14C] glucosamine incorporated in total gangliosides varies according to diseases. The radioactivity incorporated in gangliosides from colloid nodular goiter cells is not similarly affected by TSH and TSI. In porcine thyroid cells, TSH and TSI have the same effect on glucosamine incorporation into gangliosides. Thus it appears that TSH and TSI may differently affect the gangliosides labelling according to the origin of the thyroid cells.

Animals↗
PubMed1986

Metabolic changes in the extracellular matrix during differentiation of myoblasts of the L6 line and of a Myo- non-fusing mutant.

In the present study we have characterized by biochemical and immunochemical methods the changes which take place in collagen, laminin and fibronectin biosynthesis during the differentiation of clonal skeletal myoblasts of the L6 line. Time-course experiments showed that the relative rate of synthesis of collagen increased significantly during the cell-cell contact step of myogenesis and decreased later on. The major collagens synthesized were types I and III, found mainly as soluble precursors in the culture medium. Types IV and V collagens were detected exclusively in the cell layer. The relative amounts of types I and III collagens remained unchanged during myogenesis, while types IV and V collagens increased as the cells of the L6 line fused. In a non-fusing alpha-amanitin-resistant mutant of the L6 line (Ama 102), the rate of collagen synthesis was largely depressed and its rate of degradation was increased as compared with the fusing wild type. The synthesis of laminin was very low in cells of the fusing wild type, but abundant and associated with the cell layer of the Myo- mutant. The appearance of a muscle-specific extracellular matrix is a complex process involving changes in the organization, the biosynthesis and remodelling of its macromolecules of the extracellular matrix.

Animals↗
PubMed1986

Beneficial effects of intensive plasma exchange followed by immunosuppressive therapy in severe Graves' ophthalmopathy.

Nine patients with severe Graves' ophthalmopathy were treated by intensive plasma exchange, followed by immunosuppression. Severity of ocular involvement and response to therapy were evaluated clinically by numerical scoring (ophthalmopathy index). Serum thyroid stimulating immunoglobulins (TSI) and urinary excretion of glycosaminoglycans (GAG) were measured immediately before and immediately after plasmapheresis. Plasma exchange was rapidly accompanied by marked clinical improvement in 8/9 patients. The most marked effects were on soft tissue involvement, proptosis, intraocular pressure, and visual acuity. The ophthalmopathy index decreased from 9.7 +/- 4.1 to 5.7 +/- 2.2 (P less than 0.001) after plasmapheresis. Serum TSI levels were initially elevated in 6 patients and remained positive in 3 patients after treatment. Urinary GAG excretion was initially 2- to 12-fold normal levels and was decreased by 60%. After plasmapheresis, patients received immunosuppressive drugs for 3-6 months. The follow-up period, after withdrawal of drugs, ranged from 5 to 38 months with a median of 17 months. The ocular condition remained stable in 6 patients. Three patients had a relapse 1 year after plasmapheresis: they were treated a second time by plasma exchange with subsequent improvement. In conclusion, intensive plasma exchange provided prompt and effective improvement in patients with severe progressive Graves' ophthalmopathy. This therapeutic procedure, followed by immunosuppression, gave long lasting results. Relapses were responsive to plasmapheresis therapy. The data suggest that plasma exchange may represent the best primary treatment for severe progressive Graves' ophthalmopathy.

Adult↗
PubMed1985

Synthesis of basement membrane components by differentiated thyroid cells.

Morphological studies indicate that basement membrane formation or maintenance can be achieved in cultures of thyroid cells. In the present investigation we have studied the biosynthesis of this extracellular matrix by differentiated porcine thyroid cells in culture. They were prepared by two procedures: (1) thyroid cells isolated by dispase digestion of the thyroid gland were maintained in serum-free medium on poly(L-lysine) coated dishes; (2) thyroid follicles released by collagenase treatment of the gland were isolated by differential filtration and cultured in suspension on agarose-coated dishes. In both cases, functional follicular-like structures were obtained as shown by their ability to organify Na125I and to respond to thyrotropin stimulation (250 microU/ml). After incubating the cells with radiolabeled proline or methionine, collagen synthesis was observed with the two types of culture, as shown by the formation of radioactive hydroxyproline and by the synthesis of peptides with electrophoretic properties identical to those of authentic collagen molecules and susceptible to collagenase. Besides variable amounts of type I and type III collagen-like peptides, significant proportions of labeled peptides migrated with type IV collagen chains and were precipitated by anti-type IV collagen antibody; thyrotropin had no significant effect either on the total collagen synthesis or on the relative amounts of the different collagen peptides. When thyroid cells were incubated with [35S]sulfate, a labeled glycosaminoglycan with chromatographic properties analogous to that of heparan sulfate could be obtained in both culture conditions; here again, no effect of thyrotropin was observed. The ability of differentiated porcine thyroid cells to synthesize basement membrane was suggested by their production of type IV collagen and heparan sulfate, two of its potential components. Thyrotropin, which drastically enhanced the functional property of the cells, did not seem to regulate this synthesis.

Animals↗
PubMed1983

The site of leakage of intrafollicular thyroglobulin into the blood stream in simple human goiter.

Serum thyroglobulin is increased in many thyroid diseases, including simple goiter. We followed thyroglobulin levels in 19 patients with diffuse and nodular euthyroid goiters by serial measurements of 80 samples over 2 yr. The large intraindividual variations suggested episodic release of thyroglobulin in this thyroid disease. To test the hypothesis that the phenomenon was due to sporadic release of colloid from diseased follicles, we studied 98 multinodular goiters by conventional histological techniques. Sixty-four surgical samples were auto-radiographed. Focal necrosis of single follicles as well as large necrotic areas, involving multiple follicles together with interstitial stroma, were found in 42% of the goiter specimens. The earliest stage of necrosis was focal death of epithelial cells, often followed by hemorrhages. Through the epithelial gaps, colloid leaked out into the interstitial space. In later stages, granulation tissue containing numerous macrophages invaded damaged follicles. Fibrous scars remained as ultimate witness of repair processes. In one chance observation, acute release of highly labeled thyroglobulin from follicular lumina into the interfollicular interstitium was autoradiographically documented. We conclude that the varying concentrations of thyroglobulin in serum of patients with simple goiter may result from episodic necrosis of follicles, permitting leakage of colloid into the interfollicular space.

Epithelium↗