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Biomedical subjects

G Pelletier

Publications and source records attributed to G Pelletier.

At least 163 records · Page 9Linked to original sources
PubMed1997

Localization of BRCA1 gene expression in adult cynomolgus monkey tissues.

The breast and ovarian cancer susceptibility gene BRCA1 encodes a phosphoprotein of 1863 amino acids containing a highly conserved N-terminal RING finger domain and a C-terminal acidic region typical of several transcription factors. BRCA1 acts as a tumor suppressor that may inhibit the proliferation of breast and ovarian cancer cells. To gain knowledge and to further understand the biological function of BRCA1, we examined its localization and expression in various tissues from 20-year-old male and female cynomolgus monkeys (Macaca fascicularis) by in situ hybridization using a 35S-labeled human BRCA1 DNA probe fragment derived from exon 11. In mammary glands, BRCA1 expression was primarily located in the duct and acinar epithelial cells. In the ovary, strong BRCA1 expression was detected in granulosa cells in maturing follicles and in luteal cells of the corpus luteum, as well as in the epithelial cells overlying the tunica albuginea. Specific signal was also observed in epithelial cells of the oviduct, endometrium, cervix, and vagina. Moreover, BRCA1 was strongly expressed in the germinal epithelium of the seminiferous tubules as well as over interstitial cells of the testis, in the epithelium of the epididymis, and in epithelial cells bordering the glandular lumen of the seminal vesicles. Signal was also detected in both the anterior and posterior lobes of the pituitary. In the adrenal glands, the signal was greater in the zona glomerulosa compared to the two other cortical zones, whereas the medullary cells were weakly labeled. In the stomach, and in small and large intestine, epithelial cells of the crypts usually exhibited stronger positive reaction than that observed over surface epithelial lining cells. BRCA1 expression was also found in diverse types of epithelial cells of the thyroid, pancreas, salivary glands, trachea, urinary bladder, and kidneys. In addition to demonstrating widespread tissue- and cell-specific expression of the BRCA1 gene in primate tissues, primarily in the epithelia, we observed a weaker but specific signal in various other cell types, suggesting a generalized biological function of BRCA1.

Animals↗
PubMed1997

Downregulation of IGF-I mRNA expression during postnatal pancreatic development and overexpression after subtotal pancreatectomy and acute pancreatitis in the rat pancreas.

Insulin-like growth factors (IGFs) are important peptides involved in the regulation of cell growth and differentiation in many tissues. The ontogeny of IGF-I was examined in pancreata from 19-day rat fetuses, newborns and 5-, 11-, 26- and 70-day-old rats. For the regeneration studies two models were used: (i) 90% pancreatectomy was carried out and the rats were killed at 1, 2, 3 and 6 days after resection; (ii) acute pancreatitis was induced with caerulein (12 micrograms/body weight three times a day every 8 h for 2 days) and the rats were killed at 1, 2, 5, 7 and 9 days after the first injection. Total RNA was extracted by the guanidinium isothiocyanate method and Northern blots were performed using total RNA and labeled cRNA probes. Abundance of the different mRNA transcripts was estimated by densitometric scanning and normalized to the abundance of 18 S rRNA for each time point. Northern blot analysis during ontogeny showed four (0.8-1.2, 1.9, 4.7 and 7.5 kb) major transcripts in the rat pancreas and liver. Total IGF-I mRNA was 40-fold higher in the adult liver than in the adult pancreas. Moreover, in the liver, IGF-I mRNA levels were higher in the adult than in the fetus, whereas in the pancreas, the highest levels were observed around birth. During the first 3 days after pancreatectomy, a peak of maximal expression was observed after the second day. Densitometric analysis of each IGF-I mRNA species showed concomitant increases in all transcripts. After 6 days, all transcripts had returned to near-control values. IGF-I mRNA expression 2 days after pancreatectomy was 3.5-fold higher than in the newborn. During the first 2 days of acute pancreatitis induction, overexpression of IGF-I mRNA was observed. However, soon after the second day of caerulein treatment, the 7.5 kb transcripts remained elevated whereas those of the others regressed toward control values. Our results show that IGF-I mRNA is overexpressed in both models of pancreatic regeneration but downregulated in the normal adult pancreas.

Acute Disease↗
PubMed1997

Remnants of the right valve of the sinus venosus presenting as a right atrial mass on transthoracic echocardiography.

Three patients were referred for suspicion of intracardiac tumour on transthoracic echocardiography. In all patients, the mass appeared as a nonobstructive oval structure measuring approximately 12 x 4 mm, located near the posterior third of the interatrial septum in the right atrium in the apical four-chamber view. The characteristics of the mass were not those of a Eustachian valve or a Chiari network. Multiplane transesophageal echocardiography performed in each of these patients did not reveal a tumour but rather a fibrous band in the right atrium, extending from the inferior to the superior vena cava. These findings are consistent with remnants of the right valve of the sinus venosus. Inclusion of a persistent right valve of the sinus venosus in the differential diagnosis of a right atrial mass can alleviate concern and spare an unnecessary transesophageal examination when the typical transthoracic echocardiographic characteristics are identified.

Adult↗
PubMed1997

[Diagnosis of cystic lesions of the liver].

Many cystic lesions of the liver are found during ultrasonography of the abdomen. Most of these lesions are simple hepatic cysts that require no further investigation and no treatment. The diagnostic problem would be to fail to recognize a lesion that requires a specific treatment such as a cystadenoma or hydatid cyst, or a lesion that could modify the patient's treatment such as metastasis. In most cases, the sonographic pattern and the clinical context are sufficient to make a correct diagnosis. If the diagnosis remains doubtful, cytologic analysis and determination of tumor marker levels in the cystic fluid obtained by sonographic needle aspiration are often the key tests.

Cysts↗
PubMed1997

[Intra-corporeal shockwave lithotripsy in the treatment of complex lithiasis of the bile ducts. Comparison of endoscopic techniques and long-term results].

OBJECTIVES: About 2% of common bile duct stones and most intra-hepatic stones cannot be removed by conventional endoscopy. Intra-corporeal lithotripsy is an alternative technique for these patients. Contact lithotripsy can be obtained by a pulsed dye laser or by electro-hydraulic shockwaves. We compared and assessed the results of these two methods. METHODS: Thirty-seven patients (79 +/- 9.8 years, 25 women and 12 men) underwent laser lithotripsy (n = 21), electro-hydraulic lithotripsy (n = 9) or both methods consecutively (n = 7) for common bile duct stones (n = 31), intra-hepatic stones (n = 3) or diffuse lithiasis (n = 3). The mean diameter of the largest stone was 23 +/- 12 mm. Lithotripsy was performed by a retrograde approach in 35 cases and a combined, retrograde and transhepatic approach in 2 cases. RESULTS: The mean number of lithotripsy sessions was 1.5 +/- 0.65. The overall success rate (free bile ducts with patent drainage) was 95%. In 2 patients, stones were not fully extracted: one underwent surgery, the other one was treated conservatively with antibiotics. The duration of the hospital stay was 9.3 +/- 4.5 days. Morbidity at 30 days was 27% and only one case of major morbidity (hemorrhage after sphincterotomy, 2.7%) was observed. There were no procedure-related mortality. Electro-hydraulic and laser groups did not differ significantly for success rate, morbidity and time spent at hospital. Follow-up information was obtained in 34 patients (91.8%) a median of 17 months after lithotripsy (range: 4.52 months). Ten patients died of non-biliary diseases. Two patients (5.8%) developed biliary symptoms 24 and 34 months after lithotripsy, one after unsuccessful lithotripsy. CONCLUSION: Intra-corporeal lithotripsy is a valuable tool for the most complex cases of duct stones, and with an acceptable morbidity. The results of the two techniques are similar. Late biliary complications after intra-corporeal lithotripsy appear to be rare.

Aged↗
PubMed1996

Ontogeny of hepatocyte growth factor and c-met/hgf receptor in rat pancreas.

Hepatocyte growth factor has several activities in epithelial cells, including mitogenesis, dissociation of epithelial sheets, stimulation of motility, and promotion of matrix invasion. HGF is the ligand of a dimeric transmembrane tyrosine kinase receptor encoded by the met proto-oncogene. The objective of this study was to characterize by Northern blot the HGF and c-met mRNA expression in rat pancreas during development. Our findings show that simultaneous expression of both messengers occurs during the early development of the rat pancreas. Pancreatic HGF and c-met mRNA levels were higher between late fetal and 11 post-natal days and then decreased to a very low level at 26 days. This low level was maintained until the adult age. We conclude that HGF gene expression and c-met pancreatic gene expression are age dependent with the highest expression before weaning. These new data demonstrate that HGF and its receptor may be implicated in normal pancreas development and maturation.

Age Factors↗
PubMed1996

[Endoscopic treatment in acute biliary pancreatitis].

Overall mortality in acute pancreatitis is over 10%, but exceeds 40% in acute forms. In France, it has been estimated that 40 to 60% of the acute forms are of biliary origin, usually by obstruction of the pancreatic duct. Endoscopic sphincterotomy can liberate the main bile duct and separate the bile ducts from the pancreatic ducts in a minimally invasive procedure. Nevertheless, the decision to use an endoscopic treatment rather than conservative medical treatment raises several questions. Can the endoscopic technique alleviate the obstacle causing pancreatitis? Can it improve the prognosis of acute biliary pancreatitis? Which patients can best benefit from the procedure? Based on a review of the current literature, it can be concluded that endoscopic treatment improves prognosis in patients with severe pancreatitis at admission. Retrograde opacification should reasonably be associated with sphincterotomy in order to avoid leaving small stones. Endoscopy should be performed within a short delay, preferably within 24 hours following admission, by an experienced operator. Inversely, patients with less severe disease, less than 4 of Ranson's modified criteria, could benefit more from conservative management. In all cases, the diagnosis of acute biliary pancreatitis should be made on the basis of evidence of gall bladder lithiasis or sludge and/or elevated transaminase or bilirubin levels and in the absence of severe alcoholic intoxication. Obviously, in the clinical practice, these criteria may be difficult to establish, especially at admission. If the delay should exceed 72 hours, the clinical course must be taken into consideration. It is probably preferable to propose an endoscopic treatment when the situation worsens and conservative therapy if the clinical situation tends to improve.

Acute Disease↗
PubMed1996

Gangliosides in human uveal melanoma metastatic process.

The inability of current therapy to prevent metastases arising from uveal melanoma often results in patient mortality. With the goal of developing a treatment for metastasis, gangliosides were studied as potential tumor-associated antigens. Our report describes the production of a metastatic liver variant (MH) from a human uveal melanoma cell line (SP6.5). Cells were injected into nude mouse spleens and liver metastases collected 2 months later. After 21 days of in vitro subculture, the cells were re-injected into normal nude mice spleen; 10 cycles (MH10) were performed. Gangliosides were extracted, purified, chromatographed on HPTLC plates and sprayed with a resorcinol-HCl reagent, the sialic acid spots being quantified by densitometry. Gangliosides were analyzed in each metastatic liver variant and compared with the SP6.5 s.c. tumor. The results showed a significant increase in GM3 and a significant decrease in GD3 and GD2 in the last metastatic variants obtained (MH5, MH8, MH9 and MH1O) compared with the primary s.c. tumor, SP6.5. Such evolution in the ganglioside pattern was maintained throughout the progression of the different liver variants. Our results indicate that precursor ganglioside GM3 and gangliosides GD3 and GD2 could be associated with neoplastic evolution of malignancy of human uveal melanoma in nude mice.

Animals↗
PubMed1996

Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on gonadotropin-releasing hormone and somatostatin gene expression in the rat brain.

Pituitary adenylate cyclase-activating peptide (PACAP) is a 38-amino acid polypeptide, first isolated from ovine hypothalamus, which directly stimulates the release of several pituitary hormones, including GH, ACTH, and LH. The presence of PACAP receptors in several brain areas, including the hypothalamus, suggests that this peptide might play a role as neurotransmitter/neuromodulator. We have thus investigated the effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) injections of PACAP and the potent PACAP antagonist PACAP(6-38) on gonadotropin-releasing hormone (GnRH) and somatostatin (SS) gene expression in the male rat hypothalamus. The levels of mRNA were measured at the cellular level by quantitative in-situ hybridization. The i.c.v. injection of PACAP produced a 12.5% increase in the GnRH mRNA levels, an effect which was completely prevented by the concomitant administration of the PACAP antagonist. The administration of the PACAP antagonist induced by itself a 12.9% decrease in the hybridization signal. The i.v. administration of the same peptides induced modifications in GnRH gene expression which were completely opposite to those produced by i.c.v. administration. In somatostatinergic neurons located in the periventricular nucleus, the i.c.v. injection of the peptides induced modification in SS gene expression which were very similar to those observed for GnRH gene expression, although the changes were less striking. The i.v. administration of PACAP or its antagonist did not induce any change in the levels of SS mRNA. These results then strongly suggest that PACAP might be involved in a positive regulation of two neuropeptides involved in the control of anterior pituitary secretion via central specific receptors. The inverse influence of PACAP on GnRH gene expression after the i.v. injection might be explained by the short feedback effect induced by the direct stimulation of gonadotropin hormone release following the systemic injection of the peptide.

Animals↗
PubMed1996

The DNA supercoiling architecture induced by the transcription factor xUBF requires three of its five HMG-boxes.

The formation of a near complete loop of DNA is a striking property of the architectural HMG-box factor xUBF. Here we show that DNA looping only requires a dimer of Nbox13, a C-terminal truncation mutant of xUBF containing just HMG-boxes 1-3. This segment of xUBF corresponds to that minimally required for activation of polymerase I transcription and is sufficient to generate the major characteristics of the footprint given by intact xUBF. Stepwise reduction in the number of HMG-boxes to less than three significantly diminishes DNA bending and provides an estimate of bend angle for each HMG-box. Together the data indicate that a 350 +/- 16 degree loop in 142 +/- 30 bp of DNA can be induced by binding of the six HMG-boxes in an Nbox13 dimer and that DNA looping is probably achieved by six in-phase bends. The positioning of each HMG-box on the DNA does not predominantly involve DNA sequence recognition and is thus an intrinsic property of xUBF.

Binding Sites↗
PubMed1996

Localization of 17beta-hydroxysteroid dehydrogenase and characterization of testosterone in the brain of the male frog.

Several enzymes involved in the formation of steroids of the pregnene and pregnane series have been identified in the brain, but the biosynthesis of testosterone has never been reported in the central nervous system. In the present study, we have investigated the distribution and bioactivity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) (EC 1.1.1.62; a key enzyme that is required for the formation of testosterone and estradiol) in the brain of the male frog Rana ridibunda. By using an antiserum against human type I placental 17beta-HSD, immunoreactivity was localized in a discrete group of ependymal glial cells bordering the telencephalic ventricles. HPLC analysis of telencephalon and hypothalamus extracts combined with testosterone radioimmunoassay revealed the existence of two peaks coeluting with testosterone and 5alpha-dihydrotestosterone. After HPLC purification, testosterone was identified by gas chromatography/mass spectrometry. Incubation of telencephalon slices with [3H]pregnenolone resulted in the formation of metabolites which coeluted with progesterone, 17alpha-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, and 5alpha-dihydrotestosterone. The newly synthesized steroid comigrating with testosterone was selectively immunodetected by using testosterone antibodies. These data indicate that 17beta-HSD is expressed in a subpopulation of gliocytes in the frog telencephalon and that telencephalic cells are capable of synthesizing various androgens, including dehydroepiandrosterone, androstenedione, testosterone, and 5alpha-dihydrotestosterone.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

C2-ceramide primes specifically for the superoxide anion production induced by N-formylmethionylleucyl phenylalanine (fMLP) in human neutrophils.

Activated sphingomyelinases release ceramide molecules believed to be involved in intracellular signalling. The present study investigated whether soluble C2-ceramide modulates some of the effects of N-formylmethionylleucyl phenylalanine (fMLP) and other agonists on human neutrophils (or polymorphonuclear leukocytes-PMN); principally superoxide anion (O2-) production. The preincubation of PMN for 15 min with C2-ceramide increased by up to almost 3-fold the amounts of O2- generated in response to 0.1 and 1 microM fMLP. Priming was detected at C2-ceramide concentrations of 2 microM to 4 microM per million PMN. Though less potent than C2-ceramide, C6-ceramide (N-hexanoylsphingosine) could prime for O2- generated in response to 0.1 microM fMLP, with maximal effects obtained at 10-20 microM. In contrast, micromolar concentrations of sphingosine, dihydroceramide, and ceramide-phosphate, failed to exert any potentiating effect on fMLP-induced O2- generation. As expected, TNF-alpha (1000 U/ml), also primed for fMLP-induced O2- production; however, the combination of TNF-alpha and C2-ceramide showed no additive effect. Moreover, S. aureus sphingomyelinase (0.1 U/ml), was unable to reproduce the priming effects of C2-ceramide and TNF-alpha. C2-ceramide at 2 microM did not enhance the production of O2- induced by 100 nM recombinant human interleukin-8 (IL-8), leukotriene B4 (LTB4), platelet-activating factor (PAF) or 20 mM sodium fluoride (NaF). Furthermore, C2-ceramide (2 microM) did not enhance the mobilization of calcium, the release of arachidonic acid or the accumulation of phosphatidylethanol, induced by 100 nM fMLP. This suggests that probably neither phospholipases C, A2 or D (PLC, PLA2, PLD) were involved in the priming effect by C2-ceramide. However, C2-ceramide inhibited in a dose-related manner the production of O2- induced by phorbol 12-myristate 13-acetate (PMA) and mezerein. Furthermore, PMA-stimulated PLD activity was also significantly reduced by a preincubation of PMN with C2-ceramide. The priming of O2- production by C2-ceramide could involve yet unidentified mechanisms specific for fMLP, or it might imply that cytokines such as TNF-alpha have different mechanisms than C2-ceramide.

Arachidonic Acid↗
PubMed1996

Prospective controlled study of endoscopic ultrasonography and endoscopic retrograde cholangiography in patients with suspected common-bileduct lithiasis.

BACKGROUND: Endoscopic sphincterotomy is sometimes done unnecessarily in patients with suspected choledocholithiasis. Our aims were to assess the diagnostic accuracy of endoscopic ultrasonography and endoscopic retrograde cholangiography (ERC) and to find out whether endoscopic ultrasonography may help to prevent unnecessary sphincterotomy or surgical explorations. METHODS: We recruited 119 patients aged 70.4 (SD 16.1) years with strongly suspected choledocholithiasis who presented to our endoscopy unit between January, 1994, and January, 1995. During the same spell of sedation or within 2 h of each other, endoscopic ultrasonography and ERC were carried out by investigators unaware of the patient's history. Endoscopic sphincterotomy with instrumental exploration was then done as the gold standard for the presence or the absence of stones. FINDINGS: 78 (66%) patients had choledocholithiasis; 17 (14%) had other bileduct diseases; 24 (20%) had a clear bileduct or did not require an invasive endoscopic procedure. The sensitivity of endoscopic ultrasonography was 93%, specificity 97%, positive predictive value 98%, and negative predictive value 88%. The corresponding values for ERC were 89%, 100%, 100%, and 83%. There were five false-negative cases by endoscopic ultrasonography (of which three were also negative with ERC) and one false-positive. The morbidity rate was 4.1%. INTERPRETATION: We conclude that endoscopic ultrasonography is at least as sensitive as ERC. Endoscopic ultrasonography may prevent inappropriate invasive explorations of the common bileduct.

Adult↗
PubMed1996

Endoscopic sphincterotomy in patients with liver cirrhosis.

BACKGROUND: Nonsurgical alternatives in biliary diseases have not been studied in large series of patients with cirrhosis. Our aim was to determine the indications and results of endoscopic treatment in this subset of patients. METHODS: Fifty-two patients (36 men, 16 women-Child-Pugh Class A, 18; B, 22; C, 12) aged 63 +/- 18 years underwent endoscopic sphincterotomy (ES) between 1988 and 1993. Antibiotic prophylaxis was routinely carried out and coagulopathy was corrected before ES when required. The data were collected retrospectively up to 30 days after ES. RESULTS: ES succeeded in 98% of the patients (12 cases of needle-knife papillotomy). Twenty-nine patients (55.7%) had choledocholithiasis, 18 had biliary strictures (12 malignant), and 5 had pancreatic or other biliary diseases. Five days after ES, morbidity was 13.5% and mortality was 7.7%. At 1 month, morbidity was 22.9% and mortality 12.5%. Only endoscopic procedures and Ineffective drainage were seen to be significant risk factors or morbidity. The results of the subgroup of cirrhotic patients with choledocholithiasis (n = 29) were compared with those of matched noncirrhotic patients (n = 58). The cirrhotic and noncirrhotic patients treated for choledocholithiasis showed similar results for stone clearance, morbidity, and mortality. CONCLUSION: ES is a safe and effective procedure for treating choledocholithiasis in cirrhotic patients. ES can therefore be considered as an alternative to surgery in Child class A and B patients and must be preferred for Child class C patients with life-threatening biliary complications.

Adult↗
PubMed1996

In vivo and in vitro evidence for the biosynthesis of testosterone in the telencephalon of the female frog.

Neurons and glial cells are capable of synthesizing various steroid hormones, but biosynthesis of testosterone in the CNS has never been reported. The aim of the present study was to demonstrate the synthesis of testosterone in the frog brain. The presence of 17beta-hydroxysteroid dehydrogenase (17beta-HSD)-like immunoreactivity was detected in a population of glial cells located in the telencephalon. Reversed-phase HPLC analysis of brain tissue extracts combined with radioimmunoassay detection revealed the presence of substantial amounts of testosterone and 5alpha-dihydrotestosterone (5alpha-DHT) in the telencephalon where 17beta-HSD-positive cells were visualized. In male frogs, castration totally suppressed testosterone and 5alpha-DHT in the blood and in the rhombencephalon but did not affect the concentration of these two steroids in the telencephalon. Chemical characterization of testosterone in female frog telencephalon extracts was performed by coupling HPLC analysis with gas chromatography-mass spectrometry. Using the pulse-chase technique with [3H]pregnenolone as a precursor, the formation of a series of metabolites was observed, including dehydroepiandrosterone, androstenedione, testosterone, 5alpha-DHT, and estradiol. These data demonstrate the existence of an active form of 17beta-HSD in the frog telencephalon, which is likely involved in testosterone biosynthesis within the brain.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

Biliary symptoms and complications more than 8 years after endoscopic sphincterotomy for choledocholithiasis.

BACKGROUND & AIMS: Although long-term results of endoscopic sphincterotomy (ES) have been poorly estimated, extended indications of ES have been proposed, especially in young patients. The aim of this study was to assess late biliary complications of ES. METHODS: Between 1981 and 1986, 169 patients younger than age 70 (55+/-11.8 years; range, 24-70 years; male-female sex ration, 0.55) underwent ES for choledocholithiasis. One hundred fifteen patients (68%) underwent cholecystectomy. Long-term data were obtained retrospectively from the patients and general practitioners. RESULTS: Information was obtained for 156 patients, 2 of whom died within 1 month (one ES-related death). The mean follow-up for 154 patients was 9.6+/-3.3 years (range 8-13 years); 138 patients had no biliary symptoms. During follow-up, 16 patients experienced biliary symptoms; 2 of these patients underwent elective cholecystectomy, 3 had malignant strictures, 1 had a complicated cirrhosis, and 1 had a benign stricture related to the previous cholecystectomy. Nine patients developed potentially ES-related biliary symptoms. Second endoscopic exploration showed papillary stenosis in 3 patients (with stones in 2 patients) and recurrent bile duct stones in 3 others. Two patients had sine materia cholangitis, and 1 patient developed liver abscesses. CONCLUSIONS: Long-term ES-related complications seem to be rare, ES could reasonably be included in management strategies of choledocholithiasis, even in young patients.

Adult↗