[Clinical and Biological Gastroenterology: evaluation of Hepatology division, 1995 to 1997].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G Pelletier.
Explore the source record for details and available documents.
Aspartate aminotransferase can exist as a macroenzyme, which has a higher molecular mass than the corresponding enzyme normally found in serum under physiologic or pathological conditions. This macroenzyme is often an immunoglobulin complexed-enzyme and induces persistently increased serum aspartate aminotransferase activity without any corresponding liver or muscle damage. We report 5 patients with isolated and persistent increased serum aspartate aminotransferase activity in whom a macroenzyme has been detected. Of these 5 cases, four were apparently healthy subjects and the last had chronic active hepatitis. Electrophoresis of aspartate aminotransferase isoenzymes of the subjects' serum showed an abnormal band migrating between mitochondrial and cytosolic aspartate aminotransferase. In 3 cases, the macrocomplex consisted of aspartate aminotransferase and immunoglobulin G, as shown by the immunoprecipitation method. In the patient with chronic active hepatitis, the macroenzyme disappeared after liver transplantation. As macroaspartate aminotransferase and others macroenzymes, may persist for months or even years, it is important for clinicians to be aware of their existence to avoid unnecessary invasive or costly procedures.
Explore the source record for details and available documents.
Pituitary adenylate cyclase-activating peptide (PACAP) is a 38-amino-acid polypeptide, first isolated from hypothalamus, which directly stimulates in vitro the production of cAMP as well as the release of several pituitary hormones, such as growth hormone and luteinizing hormone. In vivo, PACAP has been shown to stimulate ACTH release. The presence of PACAP receptors in several brain areas, including the hypothalamus, suggests that this peptide might play a role as a neurotransmitter/neuromodulator and might be involved in the regulation of hypophysiotropic neurohormones. In order to study the role of PACAP on corticotropin-releasing hormone (CRH) neuron, we have investigated the effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) injections of PACAP and the potent PACAP antagonist PACAP(6-38) on CRH gene expression in the hypothalamic paraventricular nucleus (PVN) in the male rat. The levels of CRH mRNA were evaluated by quantitative in situ hybridization. The i.c.v. injection of PACAP (4 microg/kg b.wt.) produced a 22% increase in the hybridization signal, an effect which was completely prevented by the concomitant injection of the PACAP antagonist (4 microg/kg b.wt.). On the other hand, the administration of the PACAP antagonist induced by itself a 40% decrease in the amounts of CRH mRNA. The i.v. injection of the same peptides (100 microg/kg. b.wt.) produced very similar results. These data strongly suggest that PACAP is involved in the positive regulation of CRH gene expression via specific central receptors and then can play a role as a neurotransmitter/neuromodulator. The effect observed after i.v. injection of PACAP also suggests that the circulating levels of PACAP can play a role in the modulation of CRH gene expression. PACAP might then be involved in the regulation of the HPA axis by a double mechanism: stimulation of CRH gene expression at the central level and direct effect on pituitary corticotrophs.
We have investigated the control of the expression of three different configurations of the mitochondrial gene orf138, whose expression is correlated with Ogura cytoplasmic male-sterility in rapeseed cybrids. These configurations, termed Nco2.5/13S, Nco2.7/13F and Bam4.8/18S, specific to the 13S (sterile), 13F (fertile) and 18S (sterile) cybrids respectively, have the same 5' regions but different 3' regions. The orf138 transcript from Bam4.8/18S is 10-fold more abundant than the one from Nco2.5/13S, while no orf138 transcript from Nco2.7/13F accumulates. However, transcriptional activity measurements show that the rate of transcription is equivalent for the three configurations. These results strongly suggest that the steady-state level of mRNA from the orf138 locus is determined post-transcriptionally, most likely by its 3' region. To determine the role of these 3' regions, we have established an in vitro decay and processing system. In the presence of rapeseed mitochondrial lysate, synthetic RNAs corresponding to the 3' region of the Nco2.7/13F transcript are, as expected, less stable than RNAs corresponding to the 3' regions of the Nco2.5/13S and Bam4.8/18S transcripts. We have also observed in vitro processing of synthetic RNAs at the sites corresponding to the 3' ends of the natural mRNAs from Nco2.5/13S and Bam4.8/18S. Further analysis of the role of these 3' regions in in vitro RNA stability should help us to better understand post-transcriptional control in plant mitochondria.
Mechanical prostheses induce artifacts that decrease the accuracy of conventional transthoracic echocardiographic imaging for the detection and quantitation of periprosthetic mitral regurgitation. In 15 patients undergoing transthoracic echocardiography, injection of sonicated albumin significantly enhanced the assessment of periprosthetic mitral regurgitation with an accuracy similar to that of transesophageal echocardiography.
The neurotransmitter gamma-aminobutyric acid (GABA) exerts a tonic inhibitory influence on proopiomelanocortin (POMC) neurons in the hypothalamus as well as on the melanotrope cells of the intermediate lobe (IL) of the pituitary gland. Moreover, the activation of the GABAA receptor complex by different ligands has been shown to exert a negative influence on the POMC gene expression at the hypothalamic level. In order to elucidate the in vivo regulation of the POMC mRNA levels in the intermediate lobe of the pituitary by endogenous ligands of the GABAA receptor complex, we have studied the effect of intravenous (i.v.) and intracerebroventricular (i.c.v) injections of octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor (DBI). The possible involvement of neurosteroids in the action of ODN on melanotropic cells was evaluated following inhibition of two enzymes involved in the biosynthesis of neurosteroids known as activators of G3BAA receptor complex: trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), and MK-906, an inhibitor of 5 alpha-reductase. The i.v. injection of ODN produced a dose-dependent inhibition of POMC gene expression in the IL. The i.c.v. injection of ODN also depressed POMC mRNA. These effects were completely reversed by the concomitant administration of the GABAA antagonist picrotoxin. Similar results were obtained in POMC neurons in the arcuate nucleus (AN) of the hypothalamus. Trilostane administration induced an increase in POMC mRNA and also prevented the inhibitory influence of ODN. The neurosteroid pregnenolone-sulfate, a negative modulator of the GABAA receptor, also stimulated POMC gene expression. On the other hand, MK-906 produced a decrease in mRNA levels and could not reverse the effect of ODN. The results indicate that activation of the GABAA receptor complex by the endogenous benzodiazepine receptor ligand ODN can induce a negative regulation of POMC gene expression in the IL of the pituitary and neurons in the AN. The present results do not provide clear evidence that neurosteroids are involved in the action of ODN on POMC gene expression in the IL.
Dehydroepiandrosterone (DHEA) has been shown to exert a beneficial influence on some aging-associated deficits in rodents. It is well documented that in the rat, aging is associated with a decline in reproductive functions. In order to evaluate the effect of DHEA on GnRH gene expression in aged animals, we have studied the effect of 2.5-d administration of DHEA to young (50-54 d of age) and aged (18 mo of age) rats of both sexes. In the young males, DHEA induced an 18% reduction in the hybridization signal. In the aged animals, the mRNA levels were 10% lower than those observed in the young rats. DHEA completely restored the mRNA levels when compared to those detected in young male animals. In the young female, DHEA produced a 11% increase in GnRH mRNA, whereas, in the aged animals, hybridization signal was decreased by 28%. DHEA administration to aged females induced a 33% increase in the amount of mRNA, thus completely reversing the influence of aging. These results indicate that the decrease in GnRH gene expression which is likely involved in the loss of reproductive functions in aged rats can be totally reversed by a short term administration of DHEA which restored the GnRH neuronal activity. They also suggest that DHEA might play a role in the prevention and/or improvement of some deficits associated with aging through stimulation of GnRH biosynthesis.
Explore the source record for details and available documents.
We have recently demonstrated that the inhibitory influence of the endogenous benzodiazepine receptor ligand octadecaneuropeptide (ODN) on gonadotropin-releasing hormone (GnRH) gene expression could be prevented by specific inhibitors of 3 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase in adrenalectomized and castrated male rats, then suggesting an involvement of neurosteroids in the action of ODN on GnRH neurons. In order to study in detail the role of circulating steroids in the effect of ODN, we have evaluated the influence of adrenalectomy, castration and the combination of adrenalectomy and castration as well as the effect of dexamethasone administration in the response of GnRH gene expression to ODN in the male rat. The intracerebroventricular injection of ODN (4 h before sacrifice) produced a 36% decrease in the hybridization signal. Adrenalectomy induced a 21% decrease in GnRH mRNA levels. In the adrenalectomized rats, the injection of ODN increased by 11% the amounts of mRNA. As previously reported by our group, castration was found to enhance GnRH mRNA (15% over control values). In castrated animals, ODN produced an inhibitory effect in the hybridization signal which was of the same amplitude as that observed in sham-operated animals. Finally, the combination of adrenalectomy and castration resulted in a small but significant decrease in the hybridization signal, the values being intermediary between those observed after adrenalectomy and those obtained after castration. In these animals, ODN induced a 38% decrease in the amounts of GnRH mRNA. In animals that had been castrated and adrenalectomized, dexamethasone treatment during 4 days produced a 19% increase in hybridization signal. In these dexamethasone-treated animals, ODN produced the usual decrease (33%) in GnRH mRNA. These results demonstrate that gonadal hormones do not play a major role in the activation of the GABAA receptor complex by ODN. On the other hand, it clearly appears that glucocorticoids exert a tonic stimulatory influence on GnRH neuronal activity and are involved in the inhibitory effect of ODN. The mechanism of action of glucocorticoids, which seems complex since the influence of adrenalectomy on the ODN action can be prevented by orchidectomy, remains to be fully elucidated.
Aging is frequently associated with changes in physiological and cognitive processes. Among these changes, it has been shown that aging has a profound impact on the hypothalamo-pituitary-adrenocortical (HPA) axis. Since there is controversy about the influence of aging on the HPA axis, the first objective of the present study was to clarify the effects of aging on the HPA axis using the genetic expression of hypothalamic corticotropin-releasing hormone (CRH). Changes in the CRH mRNA expression were quantified in the hypothalamic paraventricular nucleus (PVN) using in situ hybridization, in young (50 days) and old (18 months) rats of both sexes. The second objective was to determine the effects of dehydroepiandrosterone (DHEA) treatment on the age-related changes in CRH mRNA in both sexes. In aged animals of both sexes, CRH mRNA levels in PVN were significantly reduced by 20%. DHEA treatment increased the CRH mRNA expression in young rats and reversed the decrease in the CRH mRNA expression in old rats. Young males were more sensitive to DHEA than young females (+15% vs. +9%) whereas in old animals females showed more striking changes than males (+38% vs. +24%). These findings clearly demonstrate that in old apparently healthy rats of both sexes aging process induced a significant decrease in basal CRH mRNA levels and that DHEA treatment which exerts a positive influence on CRH gene expression completely reversed the decrease of the CRH mRNA levels associated with aging.
It is well documented that in the rat of both sexes aging is associated with a decline in reproductive functions. We have recently shown that melatonin exerts a positive influence on GnRH gene expression in the adult male rats. In order to evaluate the effect of aging as well as melatonin on GnRH mRNA levels, we have studied the effect of 2.5-day administration of melatonin to young (50-55 day of age) and aged (18 month of age) rats of both sexes. In the young males melatonin induced a 11% increase in the hybridization signal. In the aged males, the GnRH mRNA levels were 13% lower than those observed in the young animals. Melatonin administration to aged animals completely restored GnRH mRNA levels when compared to those observed in the young untreated male rats. In contrast, melatonin did not modify the hybridization signal in young female rats, while aging induced a 20% decrease in mRNA levels. Melatonin administration to aged female induced a 18% increase in GnRH mRNA levels, thus completely reversing the influence of aging. These results indicate that the decrease in GnRH gene expression which is likely involved in the decline of reproductive functions in aging can be totally reversed by a short term administration of melatonin, then suggesting that the pineal hormone may be involved in the decrease of GnRH neuronal activity during aging.
Epidermal growth factor (EGF), EGF receptor (EGFR), and basic fibroblast growth factor (bFGF) messenger RNA (mRNA) levels were examined by Northern blot analysis in four tissues (pancreas, liver, kidney, and skeletal muscle) of pig from fetal 90 d to postnatal 180 d of age. The present study shows for the first time that EGF mRNA increased with advancing age in the kidney and skeletal muscle of pig. A high level of EGF mRNA was observed in the kidney compared with the liver and skeletal muscle. In the pancreas, high levels of EGF mRNA were found in fetuses and newborns and were low in older pigs. Pancreatic EGFR mRNA level parallelled its EGF mRNA, whereas in the kidney and skeletal muscle, patterns of EGFR mRNA were reversed to their EGF mRNA levels. In the liver, EGFR mRNA was abundant but EGF mRNA was undetected. In the pancreas and skeletal muscle, the highest levels of bFGF mRNA were found in fetuses of 90 d of age and then decreased with advancing age. In the liver and kidney, there were no major changes in bFGF mRNA levels during the examined developmental periods. These results show that EGF, EGFR, and bFGF mRNA levels are developmentally and tissue specifically regulated in pig. In the pancreas, mRNA levels of EGF, EGFR and bFGF were high in fetal and neonatal life and low thereafter. In the kidney and skeletal muscle, EGF mRNA increased with advancing age. EGF may play a role in muscle growth and maintenance in growing pigs during the later stage of development.
We investigated the influence of the fatty acid composition of the diet on the number of hepatic metastases and the ganglioside profile of the primary tumor and metastases. C57BL/6 female mice were fed different diets containing either no fats (TEK) or 8% of fish oil (POL), linseed oil (LIN), safflower oil (SAF) or beef tallow (BT) and were injected subcutaneously in the dorsum with H59 cells, a variant of the Lewis lung carcinoma (3LLc) that metastasizes preferentially to the liver. The omega3 polyunsaturated fatty acid (PUFA)-rich diets (LIN and POL) elicited more metastases than the omega6 PUFA-rich (SAF), fat-free (TEK), or saturated fats (BT) diets. However, dietary fat did not influence the ganglioside composition of either the primary tumors or the metastases, at least in the glucidic part. However, comparison of diets with low (TEK, SAF, and BT) and high (LIN and POL) number of metastases showed that the levels of G3 (which could be a second band of GM2) were greater in metastases of the latter group. This study showed that the H59 hepatic metastases contained more GM2 than the s.c. tumors, irrespective of diet or the number of metastases produced. The small differences in the ganglioside profiles observed in this study could have resulted from the limitations of the HPTLC method. A detailed analysis of the lipid chains, as well as glycolipids other than gangliosides, could give more information on changes resulting from different lipid diets.
We have recently demonstrated that different activators of the GABAA receptor complex including reduced progesterone metabolites and the endozepine octodecaneuropeptide (ODN) exert an inhibitory influence on GnRH gene expression. In order to investigate the possible involvement of neurosteroids, especially progesterone metabolites in the effect of ODN, we have evaluated in adrenalectomized and castrated male rats the influence of pretreatment with an inhibitor of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) trilostane (TRIL) and an inhibitor of 5 alpha-reductase MK-906 on GnRH mRNA levels in ODN-treated rats. TRIL completely prevented the inhibitory influence of ODN on GnRH mRNA. It was also found that the inhibitor of 3 beta-HSD as well as pregnenolone sulfate (PREG-S), which has been shown to be increased following TRIL treatment, could induce an increase in GnRH mRNA. MK-906 could also completely reverse the negative influence of ODN. When administered alone, this antagonist of 5 alpha-reductase induced an increase in GnRH mRNA. These results clearly indicate that the inhibition of two key enzymes for the synthesis of reduced progesterone metabolites can completely prevent the inhibitory influence of the endozepine ODN, suggesting that the effect of this endogenous ligand might be completely or partially mediated by an activation of the synthesis of active progesterone metabolites. On the other hand, it remains possible that, as a consequence of enzymatic inhibition, an increase in some precursors known as antagonists of GABAA may play a role in the prevention of the ODN effect by the two enzyme antagonists.
BACKGROUND AND STUDY AIMS: Endoscopic exploration of the common bile duct is generally more difficult and hazardous in patients with a Billroth II gastrectomy than in patients with normal anatomy. Hydrostatic dilation of the papilla, which we term "endoscopic sphincteroclasy", provides a useful alternative to sphincterotomy in such patients. PATIENTS AND METHODS: Endoscopic sphincteroclasy was carried out in five patients with a Billroth II anastomosis. There were four men and one woman, aged 58 to 90 years. One patients was cirrhotic, with impaired coagulation. Four presented with typical cholangitis, and one had pain and jaundice. The common bile duct was dilated in all five patients. Four had choledocholithiasis and one had a cholangiocarcinoma. RESULTS: Sphincteroclasy was carried out with balloon dilators mounted on 0.035-inch guide wires. Immediate extraction of stones was achieved in three of the four patients with choledocholithiasis. In one case, a control endoscopic retrograde cholangiopancreatography was necessary to remove residual stones, without additional dilation. Insertion of the endoprosthesis was possible without difficulty in the patient with a malignant stricture. None of the patients required a sphincterotomy. No complications were observed up to six months after the sphincteroclasy. CONCLUSIONS: We recommend the use of endoscopic sphincteroclasy in patients with a Billroth II gastrectomy who require endoscopic therapy, as well as in patients in need of emergency bile duct decompression who have impaired coagulation.
BACKGROUND AND STUDY AIMS: This study was carried out to establish the indications for biliary endoscopy due to biliary complications after laparoscopic cholecystectomy (LC). PATIENTS AND METHODS: One hundred nineteen patients (36 men, 86 women; median age 59, range 16-93) were referred for endoscopic retrograde cholangiopancreatography (ERCP) to five centers between 1990 and 1994, and included in the study. The delay between LC and ERCP was 105 +/- 21 days. RESULTS: Four types of complications were observed. a) Fifty-seven patients had residual stones or clip migration into the common bile duct (CBD); all were successfully treated with endoscopic sphincterotomy (ES). b) Twelve major injuries to the CBD were diagnosed by ERCP; successful surgical repair was carried out in most of these cases. c) Twenty patients had a partial biliary stricture; endoscopic stenting was attempted as a primary procedure in eight patients, with a satisfactory outcome in five (63%). d) Thirty patients had a bile leak; endoscopic therapy (26 patients) led to recovery in 18 (69%). The benefit of endoscopic treatment was less clear in five (19%); ES failed to bring about improvement in three patients (12%). CONCLUSIONS: ERCP is indicated when a biliary complication is suspected after laparoscopic cholecystectomy. Endoscopic sphincterotomy is effective for the treatment of retained stones, clip migration, and bile leakage. Endoscopic stenting may be offered as a primary option in partial CBD strictures.
Explore the source record for details and available documents.