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Biomedical subjects

S Clavel

Publications and source records attributed to S Clavel.

17 recordsLinked to original sources

Lipoprotein lipase and endothelial lipase expression in mouse brain: regional distribution and selective induction following kainic acid-induced lesion and focal cerebral ischemia.

Lipoprotein and endothelial lipases are members of the triglyceride lipase gene family. These genes are expressed in the brain, where the encoded proteins are fulfilling functions that have yet to be elucidated. In this study, we examined the distribution of their respective mRNAs in the C57BL/6 mouse brain by in situ hybridization. In control mice, we observed widespread expression of lipoprotein lipase (LPL) mRNA mainly in pyramidal cells of the hippocampus (CA1, CA2 and CA3 areas), in the striatum and in several cortical areas. Endothelial lipase (EL) mRNA expression was restricted to CA3 pyramidal cells of the hippocampus, to ependymal cells in the ventral part of the third ventricle and to some cortical cell layers. To gain insight into the role played by lipases in the brain, neurodegeneration was induced by intraperitoneal injection of kainic acid (KA) or by occlusion of the middle cerebral artery (MCA). Upon injection of KA, a rapid increase in EL mRNA expression was observed in the piriform cortex, hippocampus, thalamus and neocortex. However, the levels of LPL mRNA were unaffected by KA injection. Remarkably, after focal cerebral ischemia, the expression of EL was unaffected whereas a dramatic increase in LPL expression was observed in neocortical areas of the lesioned side of the brain. These results show that LPL and EL transcripts are selectively upregulated in function of the type of brain injury. LPL and EL could thus fulfill a function in the pathophysiological response of the brain to injury.

Animals↗

Uncoupling protein 2 in the brain: distribution and function.

Uncoupling protein 2 (UCP2) mRNA is expressed in a panoply of tissues, including the brain, where it is widely distributed. In the mouse brain, it is expressed in the hypothalamus (suprachiasmatic, paraventricular, dorsomedial, ventromedial and arcuate nuclei), the thalamus (submedius nucleus) and the brain-stem (dorsal motor nucleus of the vagus nerve). In the rat brain, it is also expressed in the hippocampus. The presence of UCP2 mRNA in neurons expressing corticotropin-releasing factor and arginine-vasopressin suggests a role for UCP2 in the control of neuroendocrine and behavioural functions. We have recently demonstrated that UCP2-deficient mice can resist the lethal effect of toxoplasmosis through an enhanced production of reactive oxygen species (ROS) from the macrophages. This finding provides evidence that UCP2 can be part of a mechanism preventing ROS production. UCP2 could therefore be involved in protecting the brain against oxidative stress. The involvement of UCP2 in neuroprotection is also consistent with the recent observation that kainic acid, which promotes Ca(2+) uptake in the glutamate-activated neurons in the hippocampal CA1 field, can induce the UCP2 gene in the activated CA1 cells. The role of UCP2 in neuroprotection warrants further investigation.

Animals↗

High neonatal leptin exposure enhances brain GR expression and feedback efficacy on the adrenocortical axis of developing rats.

Leptin modifies the activity of the hypothalamic-pituitary-adrenal axis in adult rodents and inhibits the production of glucocorticoids from human and rat adrenals in vitro. During development, high levels of circulating leptin and low levels of corticosterone secretion are observed together with adrenal hyporesponsiveness to stress. As chronic neonatal leptin administration reduced stress-induced corticotropin-releasing factor mRNA expression and ACTH secretion in pups, we determined whether elevated leptin levels enhanced the feedback effect of glucocorticoids on the hypothalamic-pituitary-adrenal axis. In naive pups we found a highly significant inverse relationship between plasma levels of leptin and corticosterone (P < 0.01) during postnatal d 6-20. We tested the ability of dexamethasone (1 or 10 microg/kg BW, ip, -3 h before stress) to suppress ether-induced ACTH secretion in 10-d-old pups that were treated during the neonatal period (d 2-9) with either vehicle or leptin (1 or 3 mg/kg BW, ip, daily). The expressions of brain GR and MR in vehicle- or leptin-treated neonates were determined by in situ hybridization and Western blotting. Chronic leptin treatment enhanced the ability of dexamethasone to suppress ACTH secretion after stress, and the low dose of dexamethasone was discriminant. Leptin treatment increased GR mRNA levels in the hypothalamic paraventricular nucleus (P < 0.05) and in the dentate gyrus of the hippocampus in a dose-dependent fashion. Hippocampal GR protein concentrations were increased by leptin treatment (P < 0.05). Expression of MR mRNA was not modified. Thus, the ability of leptin to enhance glucocorticoid feedback in pups is mediated in part by changes in brain GR. The high circulating leptin concentrations found in developing pups might be critical to regulate glucocorticoid production, GR levels, and stress responses. As leptin levels in pups vary with maternal diet, leptin might represent an important mediator of the maternal environment on the infant.

Adrenal Cortex↗

Anti TSH-receptor antibodies in pregnant patients with autoimmune thyroid disorder.

The study was designed to test further the usefulness of the radioreceptor assay of thyroid stimulating hormone (TSH) binding inhibitory immunoglobulins (TBII) and the bioassay of thyroid stimulating antibodies (TSAb) or TSH stimulated cAMP response inhibitory antibodies (TBkAb) in the prediction of neonatal thyroid dysfunction. Of 63 pregnant women with a current or past history of autoimmune thyroid disorder, 11 (one with active and six with a past history of Graves' disease and four with autoimmune thyroiditis) gave birth to a baby with transient hyper or hypo-thyroidism. Only high maternal titres (which could persist after partial thyroidectomy) of anti TSH-receptor antibodies (TRAb) led to neonatal hyperthyroidism. Both types of assay were able to detect the antibodies responsible for transitory neonatal autoimmune thyroid disease. TBII values reflected TSAb titres so that there was a significant correlation between the results of both assays in women with Graves' disease and in neonatal sera. Positive TBII and TBkAb activities were present in 5 of the 28 women with autoimmune thyroiditis. Therefore, when TBII is positive, the functional characterization of the antibodies warrants the use of the bioassay.

Autoantibodies↗

Additional factors associated with plantar ulcers in diabetic neuropathy.

Patients can only examine and handle their own feet if they have adequate visual acuity and joint mobility. We therefore studied the physical capacity of patients with neuropathy to perform the preventive footcare measures previously taught. The study included three groups of diabetic outpatients, comparable for age and duration of diabetes: (1) 38 patients with neuropathic ulcers; (2) 21 patients with neuropathy, but no ulcers; (3) 30 patients without neuropathy. Visual acuity and joint mobility, expressed as minimum eye-metatarsum and heel-buttock distances, did not differ between uncomplicated neuropathic and non-neuropathic patients: visual acuity was sufficient in 95% of neuropathic patients without ulceration and in 87% of non-neuropathic patients; joint mobility was in the normal range in both groups. However, 71% of complicated neuropathic patients had insufficient visual acuity for correct foot examination, and their joint mobility was reduced compared with uncomplicated neuropathic and non-neuropathic patients.

Aged↗

Blocking anti-thyrotropin receptor antibodies desensitize cultured human thyroid cells.

Stimulating anti-TSH receptor antibodies (TSAb) mimic TSH in the induction of refractoriness in cultured thyroid cells; TSAb and TSH desensitize one another. We investigated whether blocking anti-TSH receptor antibodies (TBkAb) have the same desensitizing effects in cultured human thyroid cells. Prolonged exposure of cells (20 h) to TBkAb followed by antigen-antibody dissociation by an acid wash step was required to induce refractoriness to subsequent stimulation of cAMP accumulation with TSH and TSAb. Cycloheximide prevented this desensitization effect. The cAMP response to forskolin was not reduced in cells pretreated by TBkAb and was increased in cells desensitized by TSH or TSAb. The pattern of the TSH dose-response curves suggested that desensitization by TSH or TSAb involved only a postreceptor mechanism but both receptor and postreceptor phenomena in the case of TBkAb. In conclusion, like TSH or TSAb, TBkAb may induce a homologous desensitization in human thyroid cells which is not mediated by cAMP.

Animals↗

[Extrarenal synthesis of calcitriol in sarcoidosis].

Mean plasma calcitriol was significantly increased in a patient with sarcoidosis and hypercalcemia without elevation of PTH. Recent studies provided evidence for an extrarenal production of calcitriol. To investigate this possibility, the conversion of calcidiol by a sarcoid lymph node homogenate was studied. After 2-hour incubation, a product was present in the incubation, which comigrated with synthetic calcitriol on two high performance liquid chromatography systems, was detected by ultraviolet absorption spectrometry and was bound with high affinity by the chick intestinal receptor for calcitriol. These results provide further evidence for an extrarenal synthesis of calcitriol, contributing to the excessive amounts of this metabolite found in the plasma of patients with sarcoidosis.

Adult↗

[Transient neonatal hypothyroidism in a neonate born of a mother with Hashimoto's thyroiditis].

Transient neonatal hypothyroidism was found in a boy whose mother was treated for hypothyroidism due to Hashimoto's thyroiditis. During the neonatal period the infant had antithyroid microsomal and antithyroglobulin antibodies and immunoglobulins inhibiting cyclic AMP production by thyroid cells in vitro. After one year of treatment, all antibodies disappeared. Thyroid scintiscan and fixation in the neonatal period was negative and became positive 2 months after stopping treatment with normal fixation and cervical thyroid picture. The mother's serum contained the same antibodies: they crossed the placental barrier and were responsible for neonatal pathological manifestations.

Autoantibodies↗

Effects of antituberculosis and antileprosy drugs on mycobacteriophage D29 growth.

The minimal inhibitory concentrations of antituberculosis and antileprosy drugs were determined for Mycobacterium aurum. The concentrations that reduced the final yield of bacteriophage D29R1 by 50% and the time during the replication cycle at which the drugs completely inhibited phage production were estimated. THe 50% inhibitory concentration/minimal inhibitory concentration ratios were close to 1.0 for clofazimine, colistin, rifampin, and streptomycin; these ratios were high for dapsone (diaminodiphenylsulfone) and isoniazid. Ethambutol (minimal inhibitory concentration, 1.0 micrograms/ml) was without effect on viral growth.

Antitubercular Agents↗

Stability of bacteriophage type of Mycobacterium tuberculosis: absence of variation caused by experimental chemotherapy in mice and analysis of spontaneous variation.

The bacteriophage typing of 54 strains isolated from the tissues of mice infected with the strain H37Rv of Mycobacterium tuberculosis and treated with isonazid and rifampin showed that the bacteriophage type did not change. The fluctuation analysis of populations of the tubercle bacilli demonstrated that the rate of mutation from sensitivity to resistance in respect to the bacteriophage DS6A was less than 1.3 X 10(-8) mutations per bacterium per generation.

Analysis of Variance↗

Interaction of Mycobacterium leprae and mycobacteriophage D29.

This study of the interaction between Mycobacterium leprae and the mycobacteriophage D29 showed that the viruses caused a patchy damage of cell wall structure and the accumulation in the host of internal crystalline structures. Whether the observed ultrastructural alterations were caused by the replication of D29 was not clear. Mitomycin C also caused the accumulation of crystalline structures in M. leprae.

Cell Wall↗

[Lipidic constituents of "Mycobacterium leprae" isolated from experimentally infected armadillo (author's transl)].

Mycobacterium leprae (obtained from experimentally infected armadillo) was submitted to saponification. The liposoluble part was methylated and fractionated by chromatographic methods. Each fraction was studied by gas-liquid chromatography. Cholesterol (from the infected host) and the main fatty acids were identified. Mycolic acids were isolated, and their structures determined, using mass spectrometry. These structures are useful to make a comparison of M. leprae with some other mycobacteria. Some of these comparisons are discussed here. The absence-or, at least, the very low level-of tuberculostearate suggests comparative studies of M. leprae and M. gordonae.

Animals↗

Paracrystalline inclusions in Mycobacterium leprae.

The occurrence of paracrystalline inclusions of Mycobacterium leprae infected with the mycobacteriophage D29 or treated with mitomycin C was reported before [5, 6]. In pursuing these studies we have now documented by electron micrography a number of paracrystals we thought sufficient to further describe these inclusions, and to show that they appeared to be formed in association with the intracellular membranous structures of the leprosy bacilli.

Animals↗

Adsorption of mycobacteriophages on Mycobacterium leprae: taxonomic significance.

The following bacteriophages were shown to adsorb on Mycobacterium leprae: BK1, Clark, Sedge, Baits, Watson and D29. Bacteriophages that did not adsorb on the leprosy bacilli were Bg1, Legendre, Marshall, Panetti, Leo and Wiseman. The taxonomic significance of these findings and some prospective consequences of these investigations are discussed.

Adsorption↗