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Biomedical subjects

M Couvreur

Publications and source records attributed to M Couvreur.

13 recordsLinked to original sources
PubMed2002

Nitric oxide is involved in interleukin-1alpha-induced cytotoxicity in polarised human thyrocytes.

Nitric oxide (NO) is a well-known mediator of autoimmune processes. In the thyroid gland, it is produced in response to interleukin 1 (IL-1) and may mediate cytokine action at an early stage of autoimmune thyroiditis. In this study, we have investigated whether NO is involved in cytokine-induced cytotoxic effects and epithelial barrier alterations in thyrocytes. Human thyroid epithelial cells were cultured as tight polarised monolayers on a permeable support and exposed or not to IL-1alpha (100 U/ml), alone or in combination with interferon-gamma (IFN-gamma; 100 U/ml) added to the basal compartment. NO production was not detected in control thyrocytes, but was significantly induced by the combination of IL-1alpha with IFN-gamma, in a time-dependent fashion. Similarly, expression of the inducible isoform of nitric oxide synthase (NOSII), determined by immunoblot and immunofluorescence confocal microscopy, was not detected in control cells, but was markedly induced after 48-h exposure to both cytokines. This treatment significantly increased the release of cytosolic lactate dehydrogenase (LDH) in the apical and basolateral media and decreased transepithelial electrical resistance. Although IFN-gamma was not sufficient to induce NO production, it could by itself decrease transepithelial resistance and synergised the IL-1alpha effect on LDH release. The NOS inhibitor, L-nitro-arginine-methyl ester, suppressed the cytokine-induced NO production and decreased the LDH release, but failed to prevent the loss of transepithelial resistance. These results indicated that human thyrocytes express NOSII and produce NO in response to IL-1alpha+IFN-gamma and suggest that NO acts as a mediator of cytokine-induced cytotoxicity in the thyroid gland and may promote the exposure of autoantigens to the immune system. In contrast, NO does not appear to mediate the cytokine-induced disruption of the thyroid epithelial barrier.

Cell Death↗
PubMed2000

MR diagnosis of a congenital abnormality of the thoracic aorta with an aneurysm of the right subclavian artery presenting as a Horner's syndrome in an adult.

Congenital abnormality of the aortic arch is a diagnosis made most of the time incidentally in childhood, unless dysphagia or respiratory disorders occur before. A case of a complex aortic arch anomaly with an aneurysm of the right subclavian artery presenting as an isolated Horner's syndrome in an adult is reported herein. Magnetic resonance imaging led to this very unusual diagnosis.

Adult↗
PubMed1998

Posttranslational modifications affect the activity of the human monocyte chemotactic proteins MCP-1 and MCP-2: identification of MCP-2(6-76) as a natural chemokine inhibitor.

Chemokines are important mediators in infection and inflammation. The monocyte chemotactic proteins (MCPs) form a subclass of structurally related C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors. Recombinant and synthetic MCP-1 variants have been shown to function as chemokine antagonists. In this study, posttranslationally modified immunoreactive MCP-1 and MCP-2 were isolated from mononuclear cells. Natural forms of MCP-1 and MCP-2 were biochemically identified by Edman degradation and mass spectrometry and functionally characterized in chemotaxis and Ca2+-mobilization assays. Glycosylated MCP-1 (12 and 13.5 kDa) was found to be two- to threefold less chemotactic for monocytes and THP-1 cells than nonglycosylated MCP-1 (10 kDa). Natural, NH2-terminally truncated MCP-1(5-76) and MCP-1(6-76) were practically devoid of bioactivity, whereas COOH-terminally processed MCP-1(1-69) fully retained its chemotactic and Ca2+-inducing capacity. The capability of naturally modified MCP-1 forms to desensitize the Ca2+ response induced by intact MCP-1 in THP-1 cells correlated with their agonistic potency. In contrast, naturally modified MCP-2(6-76) was devoid of activity, but could completely block the chemotactic effect of intact MCP-2 as well as that of MCP-1, MCP-3, and RANTES. Carboxyl-terminally processed MCP-2(1-74) did retain its chemotactic potency. Although comparable as a chemoattractant, natural intact MCP-2 was found to be 10-fold less potent than MCP-1 in inducing an intracellular Ca2+ increase. It can be concluded that under physiologic or pathologic conditions, posttranslational modification affects chemokine potency and that natural MCP-2(6-76) is a functional C-C chemokine inhibitor that might be useful as an inhibitor of inflammation.

Amino Acid Sequence↗
PubMed1998

Age delays thyroglobulin progression towards dense lysosomes in the cream hamster thyroid.

We have shown that large lysosomes appear in thyroids of aging male cream hamsters. To investigate the role of this lysosomal change in the age-dependent reduction in hormone secretion, thyroids of young (<4 months of age) and old (>22 months of age) male and female hamsters were labeled with 125I at near isotopic equilibrium. Changes in thyroid morphology were analyzed by light- and electron-microscopic morphometry. Changes in thyroglobulin processing were analyzed by subcellular fractionation and identification of 125I-compounds by sucrose gradients and reverse-phase high-pressure liquid chromatography (HPLC). Sexual dimorphism present in thyroids of young animals became more marked upon aging. The parallel increase in thyroid weight and thyroglobulin content was more conspicuous in old females than in old males. Two morphological observations were specific to old females: (1) large follicles with flat epithelium and evenly labeled colloid and (2) deposits of amyloid material (possibly immunoglobulin light chain-related) between follicles. Although lysosomes were enlarged in female and male aged thyroids, they did not accumulate iodine. However, after isopycnic centrifugation of crude lysosomal fractions in Percoll gradients, 125I in old thyroids was not distributed mainly in the dense fraction L1 (lysosomes) as in young thyroids, but partly in particles of lower density (light L2 and buoyant fractions). 125I in the lighter particles was mostly found in intact thyroglobulin and in large iodopeptides. This 125I shift towards less dense particles was more marked in females than in males. These results indicate that age delays thyroglobulin progression towards dense lysosomes and suggest that the slower traffic of thyroglobulin in the endocytic pathway contributes to the reduction in thyroid hormone secretion in the aged cream hamster.

Aging↗
PubMed1995

T4 accumulation in lysosomes of rat thyroid remnants after subtotal thyroidectomy.

In chronically stimulated rat thyroids after subtotal thyroidectomy, lysosomes increased in number and volume. They contained iodocompounds and did not appear in iodine-deficient animals. In this study, we analyzed the subcellular localization and the nature of these intracellular iodocompounds. Classical subcellular fractions were isolated from homogenates of rat thyroids and remnants 14 weeks after sham-operation or subtotal thyroidectomy. Two lysosome subpopulations of increasing density, a light fraction, lysosomes 2 (L2, density 1.065-1.08 g/ml) and a dense fraction, lysosomes 1 (L1, density > 1.08 g/ml) were separated from crude lysosomal particulate fractions (ML) by centrifugation in Percoll gradients. Results obtained with thyroids of normal rats were used as controls. In TSH-stimulated thyroid remnants, total activities of three lysosomal enzymes and iodine concentration were increased by 1.6-fold compared with thyroids of sham-operated rats. Total iodoprotein-derived T3 and T4 concentrations, measured after pronase hydrolysis, were slightly decreased. Thyroglobulin (Tg) concentration in the supernatant was reduced by 50%. Iodine, T3 and T4 contents of Tg were not modified. After differential centrifugation, the iodine excess of remnants sedimented with subcellular particulate fractions. The concentration of iodine in dense lysosomes (L1) was 6 times that in sham L1. Intact Tg did not accumulate in L1. Two thirds of the iodine in L1 was soluble in methanol, double the normal proportion, with twice as much iodine included in hydrophobic peptides eluted after T4 by reverse-phase HPLC. Although iodoprotein-derived T4 and T3 concentrations were decreased in the remnant homogenate, they were increased in particles, particularly in L1 where they were increased by 8 and 4-fold, respectively. In contrast, specific activities of lysosomal enzymes in ML and L1 remained unchanged. It is concluded that the chronic TSH stimulation of thyroid remnants in subthyroidectomized rats receiving a normal iodine supply induces the endocytosis of a normal Tg with iodine kept in dense lysosomes. The expansion of the lysosomal compartment resulted from a limitation in iodopeptides degradation as though secondary lysosomes would be overloaded with Tg. The accumulation in L1 of hydrophobic iodopeptides and of more iodoprotein-derived T4 than T3 suggests that exopeptidases involved in the liberation of T4 become rate-limiting.

Animals↗
PubMed1982

A new mechanism for the reabsorption of thyroid iodoproteins: selective fluid pinocytosis.

Rat thyroid hemilobes were incubated in presence of exogeneous, heterologous and homologous thyroglobulins. The median density of the thyroglobulin molecules originally added to the medium was compared with that of the molecules remaining at the end of a three-hour incubation period (37 degrees C). A certain degree of specificity in the reabsorption process of thyroglobulin was found: the uptake of homologous molecules (rat) was higher than heterologous (hog) molecules. The median density of the iodoproteins remaining after the incubation did not change for the heterologous whereas it shifted towards lower density for the homologous thyroglobulins (equilibrium labelled, 35 iodine atoms/molecule). In addition, rat follicular cells display selectivity in the endocytosis of homologous thyroglobulin. Among the rat molecules, the normally iodinated are taken up more actively than the lowly iodinated or newly synthesized ones. Dissimilarity in the median density of the thyroglobulin molecules before and after endocytosis was only evident for the equilibrium-labelled, normally iodinated rat preparation: the disappearance from the medium of 25-30% of exogenous iodoproteins was sufficient to lower significantly the median density of the remaining molecules. This means that the thyroglobulin molecules having higher density are taken up preferentially by the tissue. A mechanism involving specific interactions between the iodoproteins and the surface of thyroid cell is suggested.

Animals↗
PubMedDate not supplied

Strangulated transomental hernia: CT findings.

We report a case of surgically confirmed strangulation of small bowel through a defect in the greater omentum. Computed tomography demonstrated the presence and the location of this very unusual internal abdominal hernia. Those findings are presented.

Aged↗