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Biomedical subjects

G Pelletier

Publications and source records attributed to G Pelletier.

At least 19 recordsLinked to original sources
PubMed1995

Induction of apoptosis by excessive polyamine accumulation in ornithine decarboxylase-overproducing L1210 cells.

Deregulation of polyamine transport in L1210 cells overexpressing ornithine decarboxylase leads to a lethal accumulation of spermidine. We now provide evidence that over-accumulation of natural and synthetic polyamines, but not putrescine, rapidly induces apoptosis, as shown by hypercondensation of peripheral chromatin and internucleosomal cleavage, followed by nuclear fragmentation. Polyamine oxidation is not responsible for the apoptosis observed. Thus, abnormally high polyamine pools could be an important physiological trigger of apoptosis.

Animals↗
PubMed1995

Inhibitory effect of the potential endogenous benzodiazepine receptor ligand, octadecaneuropeptide (ODN), on gonadotropin-releasing hormone gene expression in the male rat brain.

It has been reported that activation of the GABAA receptor complex by different agents such as barbiturates and neurosteroids can negatively regulate the hypothalamopituitary-gonadal axis. Recently, an 86-amino acid polypeptide with high affinity for diazepam binding sites, termed diazepam-binding inhibitor (DBI), has been found in the rat brain. DBI as well as a peptide derived from DBI, the octadecaneuropeptide DBI[33-50] (ODN), can interact with the GABAA receptor complex. In order to investigate the role of these endogenous ligands for GABAA receptors on GnRH gene expression, we studied the effects of the acute administration (4 h before sacrifice) of ODN injected alone or in combination with the GABAA agonist muscimol on GnRH mRNA levels. Treatment with ODN produced a 31% decrease in the number of silver grains overlying labelled neurones. This effect was not modified by the concomitant administration of muscimol. The administration of the GABAA antagonist picrotoxin not only reversed the inhibitory effect of ODN but induced a 24% increase in the hybridization signal. This stimulating influence of picrotoxin was less striking (15% over control levels) when muscimol was administered with ODN. These data clearly indicate that a potential endogenous neuropeptide can positively interact with the GABAA receptor complex to modulate GnRH neuronal activity.

Animals↗
PubMed1995

Neuropeptide tyrosine in the brain of the African lungfish, Protopterus annectens: immunohistochemical localization and biochemical characterization.

Lungfishes, which share similarities with both fishes and amphibians, represent an interesting group in which to investigate the evolutionary transition from fishes to tetrapods. In the present study, we have investigated the localization and biochemical characteristics of neuropeptide Y (NPY)-immunoreactive material in the central nervous system of the African lungfish, Protopterus annectens. NPY-immunoreactive cell bodies were found in various regions of the brain, most notably in the telencephalon (septal area, ventral striatum, and nucleus accumbens), in the diencephalon (preoptic nucleus, periventricular region of the hypothalamus, and ventral thalamus), and in the tegmentum of the mesencephalon. A strong immunoreaction was also detected in cell bodies of the nervus terminalis. Immunoreactive nerve fibers were particularly abundant in the ventral striatum, the nucleus accumbens, the diagonal band of Broca, the hypothalamus, and the mesencephalic tegmentum. Positive fibers were also seen in the median eminence and in the neural lobe of the pituitary. The NPY-immunoreactive material localized in the brain and pituitary was characterized by combining high-performance liquid chromatography (HPLC) analysis and radioimmunological quantitation. The displacement curves obtained with synthetic porcine and frog NPY and serial dilutions of brain and pituitary extracts were parallel. Reversed-phase HPLC analysis of telencephalon, diencephalon, and pituitary extracts resolved a major NPY-immunoreactive peak that coeluted with frog NPY. The similarity between the distribution of NPY-containing neurons and the biochemical characteristics of the immunoreactive peptide in the brain of lungfish and frog strongly favors a close phylogenetic relationship between dipnoans and amphibians.

Animals↗
PubMed1995

Involvement of the Y2 receptor subtype in the regulation of prolactin gene expression by neuropeptide Y in the male rat.

In order to determine the influence of neuropeptide Y (NPY) on the biosynthesis of prolactin (PRL), we have studied the effects of NPY and some NPY analogs on PRL gene expression in the male rat anterior pituitary gland. The following peptides (4 micrograms/100 g body wt): NPY, peptide YY (PYY), NPY13-36 (a Y2 receptor agonist) and [Leu31,Pro34]NPY (a Y1 receptor agonist) were injected into the left lateral ventricle of adult male rats. Control animals received only the vehicle (0.9% NaCl). All the animals were perfused with 4% paraformaldehyde 4 h after injection and processed for in situ hybridization. The intracerebroventricular injection of NPY, PYY, and NPY13-36 induced a significant increase in the hybridization signal (22-40% over control). On the other hand, the Y1 receptor agonist [Leu31,Pro34]NPY did not influence PRL mRNA levels. These data then suggest that activation of the Y2 NPY receptor subtype at the central level can positively regulate PRL gene expression.

Animals↗
PubMed1995

Regulation of proopiomelanocortin gene expression by neuropeptide Y in the rat arcuate nucleus.

In the arcuate nucleus which is richly innervated by both proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons, it has been shown that NPY fibers are in synaptic contact with POMC cell bodies. In order to determine whether NPY could influence POMC neuronal activity, we have studied the effects of NPY and some NPY analogs on POMC gene expression using quantitative in situ hybridization. The following peptides NPY, [Leu31,Pro34]-NPY (a Y1 receptor agonist), and NPY13-36 (a Y2 receptor agonist) were injected into the left lateral cerebral ventricle of adult male rats 4 h before being perfused for histological procedures. The intracerebroventricular injection of NPY and NPY13-36 induced a significant decrease in the number of grains overlying the labelled neurons. On the other hand, the Y1 receptor agonist [Leu31,Pro34]-NPY did not modify POMC mRNA levels. These data then strongly suggest that NPY negatively regulates the genetic expression of POMC neurons via the Y2 NPY receptor subtype.

Animals↗
PubMed1995

[Medical treatment of chronic viral hepatitis].

alpha-interferon and vidarabine monophosphate are currently available for the treatment of chronic active hepatitis B. Treatment is indicated in patients with high transaminase levels, evidence of replicating virus and histological inflammation. Interferon or vidarabine suppress viral replication and normalize transaminase activity in 30 to 40% of the patients. The main predictive factors of response to therapy are a high transaminase level, a low replication level, and the absence of immunodepression. The response is usually sustained and the Ag HBs to anti-HBs seroconversion occurs a few years after treatment. No efficacious treatment is still available in patients with chronic hepatitis D. Standard treatment of chronic hepatitis C with alpha-interferon (3 millions units 3 times a week during 6 months) induces a complete response in only 15% of the patients. New modalities of interferon therapy and associated treatment are currently evaluated.

Chronic Disease↗
PubMed1995

The radiosensitivity of uveal melanoma cells and the cell survival curve.

BACKGROUND: No study of the radiosensitivity of uveal melanoma cells and their survival curve has been published. The purpose of this study was to investigate the sensitivity to different single radiation doses of SP6.5, a human uveal melanoma cell line. METHODS: Cells were irradiated with cobalt-60 at doses from 0 to 1200 cGy. Radiosensitivity was measured by three methods: soft-agar bilayer assay, tritiated thymidine incorporation, and bromodeoxyuridine (BrdU) incorporation. RESULTS: The soft-agar bilayer assay, by assessing the colony-forming units, showed that the D1 value was 470 cGy, the Dq value was 400 cGy, and the n value exceeded 10, thus indicating a broad, shoulder and relative radioresistance. The doubling time as estimated by [3H]thymidine incorporation was unaffected at doses below 600 cGy, another indication of radioresistance. BrdU incorporation revealed no significant increase between 0 and 1000 cGy, indicating that the cell cycle was not interrupted. CONCLUSION: Cell survival, doubling time, and cell phases are parameters of growth kinetics, and the results suggest that SP6.5 is radioresistant and virtually unaffected by single radiation doses lower than 600 cGy. Our data parallel published data for cutaneous melanomas.

Aged↗
PubMed1995

Trans fatty acid isomers in Canadian human milk.

The fatty acid composition, total trans content (i.e., sum of all the fatty acids which may have one or more trans double bonds) and geometric and positional isomer distribution of unsaturated fatty acids of 198 human milk samples collected in 1992 from nine provinces of Canada were determined using a combination of capillary gas-liquid chromatography and silver nitrate thin-layer chromatography. The mean total trans fatty acid content was 7.19 +/- 3.03% of the total milk fatty acids and ranged from 0.10 to 17.15%. Twenty-five of the 198 samples contained more than 10% total trans fatty acids, and thirteen samples contained less than 4%. Total trans isomers of linoleic acid were 0.89% of the total milk fatty acids with 18:2 delta 9c,13t being the most prevalent isomer, followed by 18:2 delta 9c,12t and 18:2 delta 9t,12c. Using the total trans values in human milk determined in the present study, the intake of total trans fatty acids from various dietary sources by Canadian lactating women was estimated to be 10.6 +/- 3.7 g/person/d, and in some individuals, the intake could be as high as 20.3 g/d. The 18:1 trans isomer distribution differed from that of cow's milk fat but was remarkably similar to that in partially hydrogenated soybean and canola oils, suggesting that partially hydrogenated vegetable oils are the major source of these trans fatty acids.

Canada↗
PubMed1995

Involvement of serotonin in the regulation of GnRH gene expression in the male rat brain.

The role of serotonin (5-HT) in the regulation of the hypothalamo-pituitary-gonadal axis is still controversial. In order to evaluate the influence of 5-HT on gonadotropin-releasing hormone (GnRH) neurons, we have investigated the effects of repeated administration (during 2 days) of 5-HT, the 5-HT1+2 receptor antagonist methysergide, the 5-HT2 receptor antagonist ketanserin, and the 5-HT3 receptor antagonist ondansetron on GnRH mRNA levels in the male rat medial preoptic area (MPOA), as measured by quantitative in situ hybridization. The treatment with 5-HT decreased by 32% the number of silver grains overlying labelled neurons. The administration of methysergide and ketanserin increased the hybridization signal by 32% and 29%, respectively. On the other hand, the 5-HT3 receptor antagonist did not modify GnRH mRNA levels. The present results clearly indicate that the serotoninergic system exerts a negative tonic influence on the biosynthesis of GnRH as evaluated by mRNA level measurements. They also strongly suggest that the influence of 5-HT in the regulation of GnRH neuronal activity is mediated via activation of 5-HT2 receptor, although an involvement of 5-HT1 receptors cannot be totally excluded.

Animals↗
PubMed1995

Effects of dehydroepiandrosterone (DHEA) on GnRH gene expression in the rat brain as studied by in situ hybridization.

Dehydroepiandrosterone (DHEA) is an adrenal androgen that is converted into potent androgens and/or estrogens in peripheral tissues. To further investigate the potential role of DHEA in reproductive functions in the rat, we have studied the effect of 2-day administration of DHEA on GnRH gene expression in brain of sham-operated and castrated animals of both sexes. In the male rat, orchiectomy induced an increase in the hybridization signal. In sham-operated animals, DHEA decreased GnRH mRNA levels induced by orchiectomy. In orchiectomized rats, DHEA also depressed the amount of mRNA levels and then reversed the increase in mRNA levels induced by orchiectomy. In female animals, as observed in the male, castration produced an increase in the hybridization signal. In both sham-operated and ovariectomized animals, DHEA administration increased mRNA levels. These data clearly indicate that DHEA administration can modify neuronal GnRH gene expression in adult rats of both sexes, the effect being inhibitory in the male and stimulating in the female. This modulation of GnRH neuronal activity, which is probably exerted following the conversion of DHEA into active sex steroids, might be at least partly responsible for modifications of the activity of the hypothalamo-pituitary-gonadal axis induced by DHEA.

Animals↗
PubMed1995

Investigation of the effect of coffee lipids on serum cholesterol in hamsters.

The effect of coffee total lipids (CTL), coffee non-saponifiable matter (NSM) and coffee diterpene alcohols (DTA) extracted from Coffea arabica beans on serum cholesterol in adult male Syrian hamsters was examined. The animals were fed either a commercial laboratory chow diet (study 1), containing 5% fat and low in saturated fat (1.46 g/100 g diet) and cholesterol (0.03 g/100 g diet) or a semi-synthetic diet (study 2) set in gelatine, containing 10% fat and high in saturated fat (4 g/100 g diet) and cholesterol (0.5 g/100 g diet). The coffee lipid extracts were dissolved in olive oil (concentration either 5 mg CTL, 0.5 mg NSM or 0.5 mg DTA per 250 microliters olive oil) in study 1 and in coconut oil (concentration either 20 mg CTL, 2 mg NSM or 2 mg DTA per 250 microliters) in study 2. A dose of 250 microliters of these solutions was administered daily to hamsters by gavage. Control animals received 250 microliters vehicle only. For serum lipid analysis, blood samples were obtained on days 0, 7 and 14 in study 1 and on days 0, 7, 14 and 21 in study 2. Statistical analyses of the data in Study 1 indicated a tendency for serum total cholesterol and high density lipoprotein-cholesterol to increase with administration of CTL, NSM and DTA. In contrast, in study 2 there were no significant differences in serum lipid levels between control and coffee lipid-treated groups across time. In either study, total serum cholesterol levels of the three coffee lipid groups were not significantly different from each other. These results support the concept that coffee lipids may be hypercholesterolaemic and indicate that diterpenes could be the lipid component responsible for such an effect. However, it appears that this hypercholesterolaemic effect is apparent only when the background diet is low in saturated fat and cholesterol. A high saturated fat/high cholesterol diet may mask the hypercholesterolaemic effect of coffee lipids.

Animals↗
PubMed1995

Case study: dreamy state and temporal lobe dysfunction in a migrainous adolescent.

Symptoms of migraine can be very atypical during childhood and adolescence. This article describes a case in which the symptoms of migraine were mainly psychiatric: dreamy state, intermittent confusion, partial amnesia, and childlike regressive behavior with depressive features. Although the results from neurological examinations and electroencephalographic recordings were normal when the individual was symptomatic or not, temporal lobe dysfunction, determined by 99mTc-hexamethyl-propyleneamine oxamine single-photon emission computed tomography, was evident during the migraine.

Adolescent↗
PubMed1995

Role of neuropeptide Y in the regulation of tyrosine hydroxylase messenger ribonucleic acid levels in the male rat arcuate nucleus as evaluated by in situ hybridization.

Neuroanatomical data have clearly demonstrated the existence of synaptic contacts between neuropeptide Y (NPY) endings and tuberoinfundibular dopaminergic (TIDA) neurons in the rat arcuate nucleus. In order to determine the influence of NPY in the biosynthesis of dopamine, we have studied the effects of NPY and some NPY analogs on tyrosine hydroxylase (TH) gene expression in TIDA neurons in the male rat. The following peptides: NPY, PYY, [Leu31, Pro34]-NPY (a Y1 receptor agonist) and NPY13-36 (a Y2 receptor agonist) were injected into the left lateral ventricle of adult male rats. All the animals were perfused with 4% paraformaldehyde 4 h after injection. Cryostat sections through the arcuate nucleus were processed for quantitative in situ hybridization. The intracerebroventricular injection of NPY, PYY and [Leu31, Pro34]-NPY induced an increased of 43, 33 and 42%, respectively, in the number of grains overlying TH neurons. On the other hand, the Y2 receptor agonist NPY13-36 did not influence mRNA levels. These data then strongly suggest that NPY positively regulates the genetic expression of TH in rat TIDA neurons via the Y1 NPY receptor subtype.

Animals↗
PubMed1995

Antibodies against p53 protein in serum of patients with benign or malignant pancreatic and biliary diseases.

Specific markers for pancreatic or biliary cancer have been developed in the past few years. Ca 19-9 has a good sensitivity but it is also increased in benign cholestasis. Mutations in the p53 gene are commonly reported in pancreatic cancer and can be detected by a serological analysis. The aim of this work was to find out the sensitivity and specificity of this new assay in diagnosing cancer of the pancreas or of the bile ducts. The presence of antibodies against p53 was determined by an enzyme linked immunosorbent assay (ELISA) in 29 patients with pancreatic cancer, 33 with biliary tract cancer, and 33 with benign biliary or pancreatic diseases as controls. p53 Antibodies were detected in eight of 29 patients with pancreatic cancer (28%), in five of 33 patients with biliary tract (15%), and in one patient (3%) with stones of the common bile duct. The sensitivity and the specificity for the diagnosis of malignant biliary or pancreatic diseases were 21% and 96% respectively. It is concluded that the presence of p53 antibodies in the serum of patients with pancreatic and biliary diseases is specific for malignancy and independent from the presence of cholestatic disease.

Aged↗
PubMed1995

Role of neuropeptide Y in the regulation of tyrosine hydroxylase gene expression in rat adrenal glands.

It is well known that the adrenal medulla contains high concentrations of neuropeptide Y (NPY) where it coexists with epinephrine and norepinephrine. In order to evaluate the possible involvement of NPY in the regulation of the chromafin cells of the rat adrenal medulla, we have studied the effects of NPY and some NPY analogs on the concentrations of tyrosine hydroxylase (TH) mRNA. The following peptides, NPY, PYY, [Leu31, Pro34]-NPY (a Y1 receptor agonist) and NPY13-36 (a Y2 receptor agonist) were administered intravenously at the dose of 40 micrograms/100 g body weight. All the animals were perfused with 4% paraformaldehyde 4 h after injection and cryostat sections of adrenals were processed for in situ hybridization using a 35S-labelled oligonucleotide probe encoding for rat TH. Optical density measurements performed in adrenal medulla demonstrated that the administration of NPY, PYY, and [Leu31, Pro34]-NPY induced a marked increase in the hybridization signal while the Y2 receptor agonist NPY13-36 did not affect TH mRNA levels. Then, these data clearly indicate that NPY positively regulates the genetic expression of TH probably via the Y1 NPY receptor subtype. They suggest that variations in the levels of circulating NPY or in the release of NPY by the chromaffin cells themselves (in autocrine and/or paracrine way) can increase the biosynthesis of catecholamines in rat adrenals.

Adrenal Medulla↗
PubMed1995

Evidence for the involvement of chromaffin cells in the stimulatory effect of tachykinins on corticosteroid secretion by the frog adrenal gland.

The adrenal gland of the frog is innervated by a network of fibers containing two tachykinins (ranakinin and [Leu3,Ile7]neurokinin A), which both stimulate corticosteroid secretion from frog adrenal tissue. The aim of the present study was to determine the mode of action of tachykinins on the frog adrenal gland. Double immunolabeling of tissue sections with a monoclonal antibody to tyrosine hydroxylase and an antiserum to substance P showed that tachykinin-containing fibers are preferentially apposed onto chromaffin cells. Immunocytochemical labeling at the electron microscope level revealed that tachykinin-immunoreactive fibers establish close contacts only with adrenochromaffin cells. Ranakinin stimulated corticosterone and aldosterone secretion from perifused adrenal slices, but had no stimulative effect on dispersed adrenal cells. Cytoautoradiographic labeling of frog adrenal cells in primary culture with [3H]substance P revealed the existence of specific binding sites located exclusively on chromaffin cells. Microfluorimetric measurement of cytosolic calcium concentrations ([Ca2+]i) in cultured adrenal cells showed that ranakinin induced a dose-dependent increase in [Ca2+]i in chromaffin cells (ED50 = 2 x 10(-7) M). In contrast, ranakinin did not affect [Ca2+]i in adrenocortical cells. The present results indicate that in the frog adrenal gland, tachykinin-containing fibers make preferential contacts with chromaffin cells, and tachykinins directly activate chromaffin cells. These data suggest that the stimulative effect of tachykinins on corticosteroid secretion is mediated via presynaptic activation of adrenochromaffin cells.

Adrenal Cortex Hormones↗
PubMed1995

The effect of feed intake and growth hormone-releasing factor on lactating dairy cows.

Twenty-four lactating dairy cows, averaging 30.0 kg/d of milk and 159 d of lactation, were used to study the effect of feed intake and growth hormone-releasing factor in a 2 x 2 factorial arrangement. For the first 10-d period, cows had free access to a TMR and received a fixed amount of high moisture corn, protein supplement, and hay. In the second 10-d period, 12 cows were maintained on this high intake, and 12 cows received 70% of their previous intake (low intake). During the following 10-d period, each intake group was divided, and each of two subgroups (n = 6) received twice daily s.c. injections of saline or growth hormone-releasing factor (10 micrograms/kg of BW per injection). Feed restriction decreased milk production by 24%. Milk production increase was not different following growth hormone-releasing factor treatment for cows maintained at high intake (4.6 kg/d) or low intake (3.4 kg/d). Feed restriction increased concentration of growth hormone but did not affect IGF-I concentration. Growth hormone-releasing factor increased IGF-I concentration similarly for both intake groups but increased concentrations of insulin and IGF-binding proteins-1 and -3 only in the high intake group. Low intake did not affect growth hormone, IGF-I, or milk responses to growth hormone-releasing factor, but suppressed the increase in concentrations of insulin and IGF-binding proteins-1 and -3 following treatment with growth hormone-releasing factor for cows on high intake.

Animal Feed↗