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G Pelletier

Publications and source records attributed to G Pelletier.

At least 523 records · Page 29Linked to original sources
PubMed1985

Localization and characterization of brain somatostatin receptors as studied with somatostatin-14 and somatostatin-28 receptor radioautography.

The localization and characterization of receptors for somatostatin-14 (S-14) and somatostatin-28 (S-28) were studied in the rat brain using the iodinated agonists [Tyr0,D-Trp8]S-14 and [Leu8,D-Trp22,Tyr25]S-28 as tracers. Slide-mounted frozen sections were used for the radioautographic localization and biochemical characterization of somatostatin receptors. In the latter case counting was performed on scraped off serial sections from rostral regions of the brain. Specificity studies demonstrated that either tracer could be displaced with S-28, S-14 or their agonists. The N-terminus fragment (1-12) of S-28 as well as a number of unrelated peptides were unable to compete with either tracer, indicating that the binding capacity for ligand-receptor recognition is located in the C-terminal portion of S-28. Scatchard analysis of saturation curves gave a one-site interaction with Kd values of 0.42 +/- 0.09 nM and 0.32 +/- 0.04 nM for the S-14 and S-28 iodinated agonists, respectively. By radioautography, the distribution of receptors for both S-14 and S-28 appeared very similar with high levels of binding in the deep layers of the cortex, the cingulate cortex, the claustrum, the locus coeruleus and most structures of the limbic system. Treatment with cysteamine, which caused a somatostatin depletion in the brain, was required to observe labeling in the hypothalamus. In some caudal areas of the brain, especially in the cerebellar nuclei, the solitary tract nucleus and the nucleus of the vagus nerve, only labeling with the S-28 agonist could be detected. This S-28 binding could be displaced by native S-14 (10(-6) M). Generally, there was a correlation between the localization of somatostatin receptors and that of immunoreactive somatostatin, as evaluated by immunocytochemistry. However, in some areas, an inverse correlation between receptor and peptide concentrations was observed. These results are in agreement with previous data suggesting that somatostatin could act as a neurotransmitter or neuromodulator in several brain areas.

Animals↗
PubMed1985

Distribution of neuropeptide Y immunoreactivity in the basal forebrain and upper brainstem of the squirrel monkey (Saimiri sciureus).

The distribution of neuropeptide Y (NPY) immunoreactivity in the brain of the squirrel monkey (Saimiri sciureus) was studied by means of the indirect immunofluorescence, peroxidase-antiperoxidase, and avidin-biotin-complex methods. The antiserum used was raised in rabbits and did not show any significant crossreactivity with related peptides including peptide YY and avian pancreatic polypeptide. In the upper brainstem of the squirrel monkey a dense NPY-immunoreactive terminal field is seen in lateral parabrachial area, locus coeruleus, and interpeduncular nucleus. A small group of NPY-immunoreactive cell bodies is present in the lateral habenula and a moderate number of NPY-immunoreactive fibers occurs in periaqueductal gray and nucleus raphe pallidus. The substantia nigra (SN) appears mostly devoid of NPY immunoreactivity whereas the ventral tegmental area contains a few reactive fibers. In the hypothalamus the medial preoptic area as well as the arcuate and paraventricular nuclei receive a strikingly dense NPY innervation. In addition, numerous NPY-positive cell bodies are found within the dorsomedial half of the supraoptic nucleus but very few are seen in paraventricular nucleus. A large number of NPY-immunoreactive cell bodies is also present in arcuate nucleus. In the basal telencephalon NPY-immunoreactive cells abound mostly in striatum, but some are also found in the amygdala (particularly basal, central, and lateral amygdaloid nuclei), the claustrum, and in the bed nucleus of the stria terminalis. Intensely reactive network of NPY-immunoreactive fibers is also present in all of these structures. In striatum, the numerous, fine and non-varicose NPY-immunoreactive fibers, as well as the NPY-positive cell bodies, are slightly more abundant in caudate nucleus than in putamen. The globus pallidus (GP) is mostly devoid of NPY-immunoreactive fibers and terminals. The fact that the two major recipient structures of striatal outflow (SN and GP) do not receive significant NPY input suggests that the striatal NPY-containing neurons are intrinsically organized.

Animals↗
PubMed1985

Immunocytochemical localization of somatostatin-28 in the rat hypothalamus.

Somatostatin-28 (SS28) is considered as a precursor of somatostatin-14 (SS14) and also of the remaining NH2 terminus of SS28, the dodecapeptide SS28 which has been recently characterized. In order to study the cellular and subcellular localization of SS28 in the rat hypothalamus, we have conducted a light and electron microscopic immunocytochemical study, using both the peroxidase-antiperoxidase and the immunogold technique. Several antisera which selectively recognize one or more of these 3 somatostatin-related peptides were used. In serial paraffin sections, it was observed that SS28 was contained in the same neuronal cell bodies which also contain SS28. These neurons were exclusively located in the periventricular nucleus. All the antisera used also produced a strong staining in the external zone of the median eminence. At the electron microscopic level, the 3 peptides were exclusively localized in all the dense core vesicles in cell bodies and axons in the periventricular nucleus and terminals in the median eminence. These results strongly suggest that SS28 and SS14 originate from the precursor SS28 and that processing of the precursor occurs in the cell body. They also support the hypothesis that the 3 peptides are released simultaneously under appropriate stimulation.

Animals↗
PubMed1985

Localization and characterization of somatostatin-14 and somatostatin-28 receptors in the rat pituitary as studied by slide-mounted frozen sections.

The localization and characterization of somatostatin-14 (SS-14) and somatostatin-28 (SS-28) receptors were studied in the rat pituitary using the iodinated agonists [Tyr0, D-Trp8]-SS-14 and [Leu8, D-Trp22, Tyr25]-SS-28 as tracers. Slide-mounted frozen sections were used for the autoradiographic localization and biochemical characterization of somatostatin receptors. In the latter case, counting was performed on scraped off serial sections which contained both anterior and posterior pituitary. Specificity studies demonstrated that either tracer could be displaced with SS-28 and SS-14. A number of unrelated peptides were unable to compete with either tracer. Scatchard analysis of saturation curves gave one-site interactions with KD values of 0.53 +/- 0.08 nM and 0.22 +/- 0.03 nM for the SS-14 and SS-28 iodinated agonists, respectively. Using autoradiography, SS-14 and SS-28 receptors were shown to be distributed in the anterior pituitary only. Using densitometry, displacement and saturation curves could be also obtained.

Animals↗
PubMed1985

In vitro effect of cytochalasin B on adrenal steroidogenesis in frog.

In order to examine the role of microfilaments in adrenal steroidogenesis, we have studied the effect of cytochalasin B on corticosteroid secretion by frog interrenal tissue in vitro. Perifusion of interrenal fragments with increasing concentrations of cytochalasin B (ranging from 10(-8) to 10(-4) M) led to a dose-related inhibition of corticosterone and aldosterone secretion. Immunohistochemical examination of adrenocortical fragments, using specific anti-actin antibodies, showed that cytochalasin B (5 X 10(-5) M) was responsible for the disappearance of the microfilament network. Administration of 2 consecutive doses of cytochalasin B (5 X 10(-5) M) was responsible for a reproducible and reversible inhibition of corticosteroid secretion. In addition, cytochalasin B (5 X 10(-5) M) totally inhibited the stimulatory effect of angiotensin II, prostaglandin E1 and VIP. It also induced a marked decrease in both ACTH- and dbcAMP-induced stimulation of corticosteroidogenesis. These data indicate that cytochalasin B, which blocked the effect of all adrenal stimulating factors tested, interferes with a late step in the common pathway involved in the response of frog adrenocortical cells to all corticotropic stimuli.

Actin Cytoskeleton↗
PubMed1985

Comparison of clinical variables and variables derived from a limited predischarge exercise test as predictors of early and late mortality after myocardial infarction.

An exercise test limited to 5 METS or 70% of age-predicted maximal heart rate was performed 1 day before hospital discharge by 225 survivors of acute myocardial infarction, all of whom were subsequently followed up for at least 5 years. The mortality rate was 11.1% during the first year, but averaged only 2.9% per year from the second to fifth year. Over the entire follow-up period, the five variables that predicted mortality by multivariate analysis were QRS score, an exercise-induced ST segment shift, previous infarction, failure to achieve target heart rate or work load and ventricular arrhythmia during the exercise test. Because mortality differed markedly before and after 1 year, Cox regression analyses were performed separately for both of these periods. The factors that were predictive of mortality during the first year were an exercise-induced ST shift (p less than 0.0001, relative risk 7.8), failure to increase systolic blood pressure by 10 mm Hg or more during exercise (p = 0.0039, relative risk 4.3) and angina in hospital 48 hours or longer after admission (p = 0.0046, relative risk 3.4). None of these three variables was predictive of mortality after 1 year. Previous infarction (p = 0.0007), QRS score (p = 0.0042) and ventricular arrhythmia during the exercise test (p = 0.016) were predictive of mortality after the first year. Thus, clinical and exercise test variables are complementary predictors of mortality after myocardial infarction. An abnormal ST segment response during an early limited exercise test and angina in the hospital are common strong predictors of mortality to 1 year, but not thereafter. Late mortality correlates with markers of poor left ventricular function.

Adult↗
PubMed1985

Mononeuritis in acute viral hepatitis.

We describe the cases of 4 adults with acute viral hepatitis A or B in whom mononeuritis affecting a cranial nerve or a nerve of a limb developed. The features of this neuropathy were the following: (a) the prevalence of mononeuritis in patients with acute viral hepatitis was low; (b) this complication developed in the early phase of acute viral hepatitis in most of our patients; (c) the onset of mononeuritis was sudden in most of them; (d) the course of mononeuritis was protracted. Mononeuritis might be the consequence of ischemia resulting from vasculitis.

Acute Disease↗
PubMed1985

Immunohistochemical identification of the uncoupling protein in rat brown adipose tissue.

Brown adipose tissue mitochondria are characterized by the presence of an uncoupling protein that gives them an exceptional capacity for substrate-controlled respiration and thermogenesis. The specific localization of this protein in rat brown adipocytes was demonstrated using an immunohistochemical technique, the peroxidase-antiperoxidase (PAP) method. Light microscopy observations showed that serum antibodies raised against the uncoupling protein selectively reacted with multilocular brown adipocytes. No labeling could be detected in either unilocular adipocytes, capillaries, or muscle fibers (striated and vascular smooth muscle). Staining was more intensive in certain adipocytes than in others, suggesting the presence of cellular heterogeneity. The specificity of the staining technique was demonstrated by showing that treatment of the preparations with antiserum saturated with an excess of uncoupling protein almost entirely inhibited brown adipocyte labeling. The specificity and selectivity of the PAP method allow the clear differentiation of uncoupling protein-containing adipocytes from other cellular types, suggesting that this immunohistochemical technique will represent an extremely useful tool for studying adipocyte function and differentiation.

Adipose Tissue, Brown↗
PubMed1985

Ultrastructural autoradiographic localization of somatostatin-28 in the rat pituitary gland.

To identify the anterior pituitary cell type(s) containing somatostatin-28 (SS-28)-binding sites and to study the internalization processes of this peptide by the target cells, autoradiography was performed on rat anterior pituitaries removed at specific intervals (2-60 min) after iv injection of the [125I]iodo-SS-28 agonist [Leu8,D-Trp22,Tyr25]SS-28 into intact, adrenalectomized, or castrated male rats. At the light microscopic level, the silver grains were found in 75% of cells. Concomitant injection of an excess of unlabeled peptide prevented the binding of label, verifying the specificity of binding. No specific labeling could be detected in the adrenocorticotrophs of adrenalectomized rats or gonadotrophs (castration cells) of castrated rats. At the electron microscopic level, three cell types (somatotrophs, thyrotrophs, and mammotrophs) appear to contain radiolabeled SS-28. The time-course study in somatotrophs of intact animals showed that 2 min after injection, most silver grains were associated with the plasma membrane. Five to 15 min after injection, label was found over both the plasma membrane and cytoplasmic organelles, especially the Golgi apparatus, lysosomes, and secretory granules. At the longest time interval (60 min), labeling was mostly associated with the cytoplasmic organelles. These results indicate that SS-28-binding sites are present only in those cell types in which somatostatin is known to regulate secretory functions. The present data also show that a rapid internalization of the radiolabeled peptide occurs.

Animals↗
PubMed1985

Subcellular localization of thyroxine 5'-deiodinase activity in bovine anterior pituitary.

Bovine anterior pituitary glands were fractionated by differential centrifugation. T4 5'-monodeiodination to T3 was found predominantly in microsomal fractions (M2; 105,000 . g pellet) enriched in glucose-6-phosphatase and 5'-nucleotidase activities. T4 5'-deiodinase activity in M2 fraction was 85.2 fmol T3/min X mg protein and represented an 8.5-fold enrichment over homogenate specific activity (10.6 fmol T3/min . mg protein). Further subcellular localization of the T4 5'-deiodinase was effected by discontinuous sucrose density gradient centrifugation. Maximum T4 5'-deiodinase activity was found in fraction P5 at the interface of densities 1.18/1.20 (200 fmol T3/min . mg protein) and correlated with the profile of glucose-6-phosphatase and not with that of 5'-nucleotidase, the maximum activity of which was recovered in fraction P1 at the interface of densities 1.03/1.12. Electron microscopic examination of the fractions confirmed that P5 contained in excess of 90% rough membranes in contrast to 10% or less in P1. Characterization of T4 5'-deiodinase activity was carried out in M2 preparations. The reaction was thiol dependent, requiring the presence of 50 mM dithiothreitol or more (Km, 38 mM), with a maximum velocity of 55-150 fmol T3/min . mg protein (n = 8). Enzyme activity was substrate dependent, with a Km for T4 between 35-70 nM. 5'-Monodeiodination of T4 was abolished by heating to 70 C for 30 min and was unaffected by EDTA. Propylthiouracil and methimazole did not inhibit T3 generation. Iopanoic acid, on the other hand, was a competitive inhibitor of the 5'-monodeiodination reaction, abolishing T3 production in a dose-dependent manner with a Ki of 3 microM. These data indicate that the bovine anterior pituitary contains significant T4 5'-deiodinase activity, which shares many properties of the type II 5'-deiodinase of the rat. Bovine anterior pituitary T4 5'-deiodinase appears to be predominantly localized in the rough endoplasmic reticulum.

Animals↗
PubMed1985

[Role of alpha-MSH and related peptides in the central nervous system].

Alpha-melanocyte stimulating hormone (alpha-MSH) is a tridecapeptide secreted by intermediate lobe cells and synthesized in the brain as well. As a hormonal peptide, the physiological function of alpha-MSH consists mainly in the control of pigment movements within dermal melanophores. At the pituitary level, alpha-MSH secretion is under multifactorial control: it is inhibited by dopamine and GABA and stimulated by corticoliberin (CRF), thyroliberin (TRH), beta-adrenergic agonists and (or) serotonin. Identification of alpha-MSH containing neurons in the hypothalamus and other brain regions (septum, thalamus, mid-brain, striatum, hippocampus, cerebral cortex and spinal cord) has been carried out by means of immunological and biochemical techniques combined with bioassays. In the central nervous system (CNS) as in the hypophysis, alpha-MSH is synthesized from a high molecular weight precursor, pro-opiomelanocortin (POMC). Maturation of this protein yield similar end products in the hypothalamus and the intermediate lobe. Several peptides chemically related to alpha-MSH are generated including the desacetyl and monoacetyl (authentic alpha-MSH) forms; the latter has the greatest behavioral activity. The demonstration that alpha-MSH has numerous central nervous system effects has raised the possibility that this neuropeptide acts as a neuromodulator or a neurotransmitter. In the rat, intra-cerebroventricular administration of ACTH/MSH peptides induces the stretching-yawning syndrome (SYS) which is frequently preceded by excessive grooming. This excessive grooming is blocked by neuroleptics indicating that the central dopaminergic neurons are implicated in this behavioral effect of the peptide. alpha-MSH is involved in memory, arousal and attention; in hypophysectomized animals, the learning ability is restored after administration of MSH or related peptides. Injection of alpha-MSH delays also extinction of passive avoidance behavior and affects performances motivated by hunger as well as aggressive behavior. Recent studies concerning the role of alpha-MSH have been undertaken in human beings. The effects of MSH-related peptides favour a role of these peptides in arousal: they maintain a high level of vigilance and improve visual discrimination. These behavioral changes were accompanied by marked changes in CNS electrophysiology. Current studies, which aim at establishing a neurotransmitter function for alpha-MSH, concern the distribution and characterization of alpha-MSH receptors in the central nervous system and the mechanism controlling the release of neuronal alpha-MSH.

Aggression↗
PubMed1985

[Hepatocellular carcinoma in France. Clinical, biological and virological aspects in 197 patients].

The authors report the clinical and biological features in 197 patients with hepatocellular carcinoma seen in two French hospitals. Mean age was 63 +/- 12 years. Eighty-nine per cent were men. Cirrhosis was present in 88 p. 100. Alcoholic liver disease was associated with hepatocellular carcinoma in 71.5 p. 100. At the time of diagnosis, ascites was present in 62 p. 100 of the patients, jaundice in 49 p. 100, encephalopathy in 20 p. 100 and gastrointestinal bleeding in 12.5 p. 100. Twenty patients (10 p. 100) did not have any of these complications. An increase in serum gammaglutamyl transpeptidase and ASAT was the most frequent biological abnormality observed in 96 and 94 p. 100 of patients respectively. Hypercalcemia and a high hematocrit were present in 5 and 6 p. 100 of patients respectively. Serum HBs Ag (RIA) was present in 17.5 p. 100 of patients, anti-HBc in 50 p. 100 and anti-HBs in 33.5 p. 100; 38.5 p. 100 of patients had no serum HBV marker. Serum alphafetoprotein levels were higher than 20 ng/ml, 250 ng/ml and 1,000 ng/ml in 76.5 p. 100, 43.5 p. 100 and 33 p. 100 of patients respectively. There were no relationships between the presence of serum markers of HBV or high alphafetoprotein levels and clinical and biological data. These results confirm that the clinical, biological and virological aspects of hepatocellular carcinoma in France are similar to those reported in other western countries.

Adult↗
PubMed1985

[Propranolol prevention of hemorrhagic recurrence caused by rupture of esophageal varices: worsened prognosis in ascites and jaundice].

Between October 1981 and December 1983, 46 consecutive unselected cirrhotic patients who had been admitted for variceal hemorrhage were assigned to propranolol for the prevention of variceal rebleeding and followed for a mean period of 13.3 months (ranges: 1 day, 45 months). At the time of inclusion, 87 p. 100 of patients had alcoholic cirrhosis: ascites was present in 43 p. 100, jaundice in 43 p. 100 and encephalopathy in 33 p. 100 of cases. The goal of this retrospective study was to assess the effectiveness of propranolol in these unselected patients and to determine variables associated with a high rebleeding rate. Twenty-four patients (52 p. 100) rebled from esophageal varices within a mean time of 8.2 months (range: 6 days, 39 months) and 12 of these patients died. The percentage of patients who rebled from varices was 27 p. 100 at 6 months, 43 p. 100 at 1 year, 52 p. 100 at 18 months. Patients with ascites at the time of inclusion were 3.5 times more likely to rebleed than patients without ascites (p = 0.007). Patients with jaundice (total bilirubin greater than or equal to 50 mumol/l) were 3.1 times more likely to rebleed than patients without jaundice (p = 0.01). One year after the beginning of this treatment, the probability of rebleeding was 19 p. 100 in the 17 Pugh-Child class A cirrhotic patients, 60 p. 100 in the 15 class B patients, 55 p. 100 in the 14 class C patients. Neither proper acceptance in taking propranolol nor alcohol withdrawal were associated with significantly modified risks of rebleeding in these unselected alcoholic patients.

Ascites↗
PubMed1985

[Intermediate lobe of the amphibian pituitary gland: an endocrine gland with multiple secretions and under multi-hormonal control].

The cells of the frog pars intermedia synthesize a 36 000 (36K) protein called proopiomelanocortin (POMC). After [3H]glucosamine incorporation, separation of newly synthesized products by SDS-polyacrylamide gel electrophoresis showed that this 36K protein was glycosylated. Tryptic mapping revealed only one site of glycosylation and showed that the carbohydrate side-chain was located in the N-terminal region of POMC. The 36K protein was not released by the melanotrophs, but it generated, through specific intracellular proteolytic cleavage, a number of smaller peptides which were subsequently released. These peptides were identified by various methods including selective amino-acid incorporation, HPLC purification, acid-urea gel electrophoresis, tryptic and chymotryptic mapping, assay of melanotropic activity, radioimmunoassays and immunoprecipitations. Some of the newly synthesized N-terminal (18K) fragment of the POMC was secreted intact while a portion of it was further processed, via an intermediate peptide, to give mature gamma-MSH. All three of these peptides were glycosylated. In addition, the mature peptide (gamma-MSH) exhibited a low but significant melanotropic activity. The C-terminal portion of the prohormone was very rapidly processed to give des N alpha-acetyl alpha-MSH, corticotropin-like-intermediate lobe peptide (CLIP) and beta-endorphin. Authentic alpha-MSH was always absent in cellular extracts: acetylation to give rise to alpha-MSH was a late enzymatic process strictly linked to hormonal release. Since acetylation of alpha-MSH is required for full biological activity of this peptide, it is possible to conceive that this later step could be under neuroendocrine control. Using the perifusion technique we have been able to show the complexity of the control mechanisms regulating amphibian melanotrophs. It is generally accepted that the aminergic innervation of the intermediate lobe of the pituitary is involved in the hypothalamic control of melanotropin release. We have demonstrated that, in amphibians, dopamine inhibits alpha-MSH secretion through D2-type dopaminergic receptors whereas norepinephrine and (or) epinephrine stimulate alpha-MSH secretion via beta-adrenergic receptors. The existence of peptidergic fibers within parenchymal cells of the pars intermedia has been demonstrated. Evidence for TRH-containing fibers has been obtained by immunohistochemistry. Using a specific radioimmunoassay for TRH, we have confirmed the presence of TRH in the neurointermediate lobe of the frog. We have shown that TRH is a powerful MSH-releasing factor in these animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphibians↗
PubMed1984

Serotonin-secreting and insulin-secreting ileal carcinoid tumor and the use of in vitro culture of tumoral cells.

The authors report the case of a patient with a typical carcinoid syndrome and a severe hypoglycemia due to hyperinsulinism. He was found to have an ileal carcinoid tumor with hepatic metastasis and no evidence of pancreatic insulinoma at surgery and autopsy. By assaying serotonin and insulin in the tumor and in the supernatants of the culture derived from hepatic metastasis, the authors have been able to show that both hormones were produced by the carcinoid tissue. Cultured cells also synthesized minute amounts of gastrin and thyrocalcitonin.

Blood Glucose↗