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Biomedical subjects

A Fournier

Publications and source records attributed to A Fournier.

At least 793 records · Page 44Linked to original sources
PubMedDate not supplied

Endothelin-1 (ET)-induced mobilization of intracellular Ca2+ stores from the smooth muscle facilitates sympathetic cotransmission by potentiation of adenosine 5'-triphosphate (ATP) motor activity: studies in the rat vas deferens.

Endothelin-1 (ET) enhances nerve-stimulated contractions in epididymal (E) and prostatic (P) halves of the rat vas deferens, in addition to raising the basal tone in E. Whereas the peak increase in basal tone occurs in about 30 s, the maximal enhancement of neurotransmission is observed within 5 min. The latter effect is long lasting and is maintained even after extensive tissue washout. Furthermore, ET potentiates, in a concentration-dependent fashion, the adenosine 5'-triphosphate (ATP) or the adenylylimidodiphosphate (AMP-PNP) but not the noradrenaline (NA)-induced motor activity. The ATP motor response is partially blocked in media without Ca2+ plus 0.1 mM EGTA or following tissue incubation in buffer containing 10-50 nM nifedipine. However, these procedures do not modify significantly the ET-induced potentiation of the ATP contractions. The ET-induced potentiation of the ATP motor response is not modified by tissue preincubation in Ca(2+)-free buffer plus 10-30 microM ryanodine or 5-20 mM caffeine. The ET-induced rise in E basal tension is significantly reduced in the absence of external Ca2+ or by nifedipine; ryanodine does not modify this effect. Surgical denervation of the tissues does not obliterate the ET-induced potentiation of the ATP motor responses nor the ET increase in E basal tension in tissues superfused in Ca(2+)-free media or buffer with 2.5 mM Ca2+. Endothelin-1 does not significantly modify the overflow of 3H-NA, following transmural electrical depolarization of tissue nerve terminals. Hoe 140 did not interfere with the ET activity.

Adenosine Triphosphate↗
PubMedDate not supplied

Endothelin derivatives showing potent effects in the guinea pig trachea.

Endothelin (ET-1) was synthesized by solid-phase peptide synthesis. To prevent side reactions with tryptophan residue, a formyl group was used to protect the beta-indole moiety. The two disulfide bridges were formed selectively using S-methylbenzyl for the cysteine residues in positions 3 and 11, and S-acetamidomethyl for positions 1 and 15. Crude synthetic ET-1 was obtained after deprotection and cleavage from the resin by HF, followed respectively by potassium ferricyanide and iodine oxidations, in order to generate sequentially the monocyclic and bicyclic forms of the peptide. Finally, Trp(For) was deprotected by a treatment with piperidine. After each step, a sample of peptide was isolated and purified by RP-HPLC. The biological activity of these synthetic peptides was evaluated on guinea pig tracheal strips. The results suggest that oxidation of Met-7 and/or formylation of Trp-21 do not affect the biological activity of ET-1 in the guinea pig trachea. Moreover, although a decrease of potency and intrinsic activity was observed, the monocyclic analog containing Cys(Acm) residues at positions 1 and 15 exhibited substantial constrictor activity. This result, contrasting with that observed with several vascular preparations, suggests that the guinea pig trachea contains a distinct ET receptor population.

Animals↗
PubMedDate not supplied

Role of the cytoskeleton in the secretory response of the frog adrenal gland to calcitonin gene-related peptide.

We have previously shown that calcitonin gene-related peptide (CGRP) stimulates the secretion of corticosterone and aldosterone from the frog adrenal gland in vitro. The aim of the present study was to investigate the role of cytoskeletal elements in the stimulatory effect of CGRP on corticosteroid production. Perifusion of adrenal explants with the microfilament-disrupting agent cytochalasin B (5 x 10(-5) M) induced a reversible inhibition of the spontaneous secretion of corticosterone and aldosterone, and markedly reduced the stimulatory effect of frog CGRP (3 x 10(-7) M) on corticosteroid release. In contrast, administration of the antimicrotubular agent vinblastine (10(-5) M) and the intermediate filament inhibitor beta-beta' iminodipropionitrile (10(-3) M) had no significant effect on either spontaneous or CGRP-evoked steroid secretion. Taken together, these data provide the first evidence for the involvement of microfilaments in CGRP-induced corticosteroid secretion. In contrast, microtubules and intermediate filaments are not implicated in the mechanism of action of CGRP.

Adrenal Glands↗
PubMedDate not supplied

Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene.

The expression of class I transplantation antigens encoded in the major histocompatibility complex (H-2 in mouse, HLA in man) can be induced by alpha-, beta- and gamma-interferons. Both transcriptional and post-transcriptional mechanisms have been postulated. Recently, a common sequence has been found in the promoter region of several human genes responsive to IFN-alpha. The promoters of H-2Kb and several other mouse class I genes contain a similar interferon response sequence. We show here, in a transient assay, that the H-2Kb promoter can be induced by all three types of interferon and that the interferon response sequence is necessary for induction to occur. However, the response sequence is active only when associated with a functional enhancer sequence which we have recently identified in the promoter of H-2Kb and other class I genes. The combination of these two sequences can render a heterologous promoter responsive to interferon, irrespective of its orientation relative to the cap site.

Animals↗
PubMedDate not supplied

Application of phorbol ester to mouse skin causes a rapid and sustained loss of protein kinase C.

It is now widely accepted that tumour-promoting phorbol esters activate a Ca2+- and phospholipid-dependent protein kinase (protein kinase C) both in vitro and in intact cells, and that the kinase represents a major cellular phorbol ester-binding protein. The phorbol esters act as analogues of diacylglycerol, a natural regulator of protein kinase C, and stabilize the membrane-association of the kinase. Although other molecular targets may exist, protein kinase C activation is probably important in mediating the diverse responses of cultured cells to phorbol esters and in promoting in vivo tumours. The enzyme comprises a family of closely related proteins and has been detected in extracts from mouse epidermal cells, the likely targets for two-stage carcinogenesis in mouse skin. In this report we show that application of a single dose of TPA (12-O-tetradecanoyl phorbol-13-acetate) to mouse skin results in a rapid and complete loss of protein kinase C activity which is maintained for 3-4 days. This is associated with a loss of immunologically detectable protein kinase C and the accumulation of a smaller protein detectable by antibodies recognizing the regulatory domain of protein kinase C.

Animals↗
PubMedDate not supplied

Mechanism of action of endothelins on adrenocortical cells.

Endothelins (ETs) play a pivotal role in the control of various endocrine and neuroendocrine tissues. In this review, we discuss the involvement of ETs as possible regulators of steroid secretion and we describe the mechanism of action of ETs on adrenocortical cells. The occurrence of ETs has been demonstrated in the human, porcine and rat adrenal gland. In humans, immunohistochemical and biochemical techniques have reported that ETs are localized exclusively in the cortex but the presence of ETs has also been detected in pheochromocytomas. In vitro studies have shown that ETs stimulate aldosterone secretion by adrenal tissues in various mammalian and amphibian animal models. The receptor subtype involved in the corticotropic action of ETs clearly differs among the various vertebrate species studied. In rat, the effect of ETs is mediated through an ET(B) receptor subtype while, in frog, an ET(A) receptor is implicated in the stimulatory action of ETs. In human adrenocortical cells, both ET(A) and ET(B) receptor subtypes are involved in the corticotropic effect of ETs. Activation of adrenal receptors causes an elevation of inositol trisphosphates associated with an increase in cytosolic calcium concentration. In addition, ETs induce an elevation of prostaglandin E2 (PGE2) and prostacyclin PGI2 production in the adrenal tissue, indicating that prostanoids may act as second messengers of ETs. It thus appears that ETs present in the adrenal gland may act as paracrine factors to stimulate the secretory activity of adrenocortical cells.

Adrenal Cortex↗
PubMedDate not supplied

Method for the quantification of alginate in microcapsules.

Alginate is a key reagent in the preparation of microcapsules for cell transplantation. To address the question of the intracapsular alginate concentration, a sensitive assay has been developed to quantify the alginate content of microcapsules. The method is based on the metachromatic change induced by alginate binding to the dye, 1,9-dimethyl methylene blue (DMMB). The assay has a high sensitivity and precision. It covers a wide concentration range enabling the measurement of alginate in dilute supernatants as well as in microcapsules. For the latter, the membrane is initially dissolved by incubating the microcapsules in an alkaline medium. The effect of potentially interfering substances (poly-L-lysine (PLL), citrate, chloride, sodium) and of pH has been studied. Poly-L-lysine interfered with the assay at pH 6.5 but not at pH 13. Interference by sodium augmented with increasing sodium concentration and reached a plateau at 200 mM. This problem was overcome by routinely adjusting all samples to 500 mM sodium. The other substances tested had a negligible effect on the assay. The reliable measurement of alginate with this new assay will allow the optimization of the intracapsular alginate concentration.

Alginates↗
PubMedDate not supplied

[Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?].

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.

Angiotensin II↗
PubMedDate not supplied

Liver granulomatosis is not an exceptional cause of hypercalcemia with hypoparathyroidism in dialysis patients.

In 4 of our patients on chronic dialysis, we were intrigued by the association of hypercalcemia +/- hyperphosphatemia and normal intact PTH, with anicteric cholestasis without cytolysis. This picture occurred in 2 patients after they resumed dialysis because of a transplant rejection and in a third one after discontinuation of corticosteroids, prescribed for an idiopathic thrombocytopenia. No patient was under calcitriol, CaCO3 therapy, and their hypercalcemia persisted on a low calcium dialyzate (1.25 mmol/l). Obvious etiologies of hypercalcemia were not found: vitamin D or A intoxication, hyperparathyroidism, aluminum intoxication, hemopathy, HIV infection. The hypothesis of a granulomatous disease was made and a liver biopsy was performed showing granulomas with giant epitheloid cells. In one case foreign material (silicon ?) was present in the macrophages. Extensive investigations for sarcoidosis, tuberculosis and mycosis were negative. In 2 cases the so-called "dialysis" granulomatosis actually occurred in transplanted patients, suggesting the role of a transplantation related factor (toxic or virus). In the last case HCV seroconversion was present. In the 4 cases, corticotherapy led to the disappearance of hypercalcemia and to an increase of PTH. Our patients had the biological pattern of low bone turnover disease (hypercalcemia and normal intact PTH) and bone biopsy performed in 2 showed osteomalacia or ABD without aluminum. The association of this pattern with cholestasis should evoke liver granulomatosis, which should be confirmed by a liver biopsy and lead to a treatment by corticosteroids. The masking effect of previous corticoid therapy for transplantation should be pointed out. In 2 cases serial monitoring of plasma calcitriol showed a relation between decreasing high normal calcitriol with prednisone and normalization of calcemia, suggesting the role of inappropriate synthesis of calcitriol by the granuloma. In conclusion, liver granulomatosis should be looked for in dialysis patients on the association of unexplained hypercalcemia and normal PTH with anicteric cholestasis, and confirmed by a liver biopsy. Although still of unknown etiology, its evolution is favourable under corticotherapy.

Adult↗
PubMedDate not supplied

[Study of 52 cases of diphtheria observed over a period of ten years in the North of France (author's transl)].

Over a period of ten years, 88 cases of diphtheria were diagnosed in the North of France especially in the area of Lille, Roubaix and Tourcoing. 25 p. cent of the patients had been correctly vaccinated within less than five years, and among the latter 25 p. cent died from their diphtheria. The clinical presentation was typical but delay in diagnosis is frequent.

Adolescent↗
PubMedDate not supplied

[Primary hyperparathyroidism. Current aspects of its diagnosis apropos of a case with digestive and neuropsychiatric manifestations].

On the basis of a dramatic hypercalcemia revealed by digestive and neuropsychic symptoms and related to a primary hyperparathyroidism, the authors recall all the clinical circumstances which should lead to determination of plasma calcium as well as the clinical and biological particularities which, in front of a hypercalcemia, suggest a primary hyperparathyroidism. The stress the usefulness and the limits of the dosage of plasma immunoreactive parathyroid hormone as well as the difficulties to differentiale primary from paraneoplasic hyperparathyroidism. The recent pathophysiological concepts of malignant hypercalcemia reviewed.

Aged↗