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Biomedical subjects

G Pelletier

Publications and source records attributed to G Pelletier.

At least 109 records · Page 6Linked to original sources

Differential involvement of adrenal and gonadal steroids in anterior and intermediate pituitary pro-opiomelanocortin mRNA expression induced by the endogenous benzodiazepine, octadecaneuropeptide, in adult male rats.

The involvement of the endogenous benzodiazepine, octadecaneuropeptide (ODN), in the regulation of proopiomelanocortin (POMC) mRNA expression at the pituitary level, and the influence of adrenal and gonadal steroids, have been studied using a quantitative in situ hybridization technique. I.c.v. injection of ODN (4 micrograms/kg) in sham-operated rats induced a 17 and 7% decrease in the POMC mRNA expression in anterior and intermediate pituitary lobes respectively. To determine the reciprocal involvement of adrenal and gonadal steroids in this regulation, animals were adrenalectomized and/or castrated. Adrenalectomy significantly increased POMC mRNA expression by 48% at the anterior pituitary level, but induced a 10% decrease of hybridization signal at the intermediate pituitary lobe (vs control sham-operated). Adrenal ablation reversed the effect induced by ODN and increased POMC mRNA expression at the anterior and intermediate pituitary levels by 60 and 10% respectively, compared with control sham-operated. By contrast, castration, which produced a decrease in POMC mRNA in the anterior pituitary and an increase in the intermediate lobe, did not modify the negative influence of ODN observed in sham-operated animals. When rats were adrenalectomized and castrated, the adrenalectomy influence was predominant at the anterior pituitary level, since ODN increased significantly the hybridization signal (+68% vs control sham-operated), while the castration influence was predominant at the intermediate pituitary level, since ODN induced an 11% decrease in POMC mRNA signal compared with control sham-operated. These studies indicate that, in vivo, the decrease in POMC mRNA expression in the anterior and intermediate pituitary induced by an endogenous benzodiazepine is differently modulated by adrenal and gonadal steroids, with a predominant influence of adrenal steroids at the anterior pituitary level and gonadal steroids at the intermediate pituitary level.

Adrenal Cortex Hormones↗

[Endoscopic sphincteroclasy for choledocholithiasis of the principal bile duct. Short-term results and follow-up].

AIMS: The hydrostatic dilatation of the papilla of Vater, or sphincteroclasy, has been recently proposed as an alternative to endoscopic sphincterotomy. Our aim was to assess short term results and follow-up after sphincteroclasy for choledocholithiasis. METHODS: From August, 1994 to December, 1996, 52 patients were included for endoscopic therapy of choledocholithiasis (mean age 66 +/- 17 years). Patients were prospectively followed on the short term-period (24 h, 48 h and 30 days) and longer term after treatment (every 6 months) by clinical and biological controls. MAIN RESULTS: Forty-eight sphincteroclasies were performed successfully (92.3%). Thirty seven patients had a choledocolithiasis. Eleven were stone-free. Eight had undergone former gastric surgery and 8 had impaired coagulation test. Complete stone clearance was achieved in 98% of patients. Mild pancreatitis were observed in three patients (6.25%). Thirty-day mortality was nil. Long term follow-up (mean 21.4 +/- 7 months) revealed: 2 patients with cholecystitis 6 and 13 months after treatment, one of which was followed 8 months later by a fatal septic shock, and 3 patients with cholangitis, 2 of which in the same patient, 9, 12 and 24 months after sphincteroclasy. The global long term biliary complication rate was 8.4%, 4.2% of which were potentially related to the endoscopic procedure. CONCLUSION: Sphincteroclasy is an efficient procedure for the treatment of choledocholithiasis. Its short term results are similar to those of endoscopic sphincterotomy. Complications after 2 years appear to be scarce, but longer follow-up is required before routinely performing sphincteroclasy.

Adult↗

[Chronic acquired hepatocerebral degeneration: the role of manganese and treatment by endovascular occlusion of a porto-systemic shunt].

This case report describes a 74 year-old woman with cirrhosis who developed choreo-athetotic movements associated with elevated whole blood manganese and symmetric hyperintense pallidum on T1-weighted magnetic resonance imaging. The diagnosis was chronic acquired hepatocerebral degeneration. The endovascular occlusion of portal-systemic shunts was temporarily effective.

Aged↗

Development of amplified consensus genetic markers (ACGM) in Brassica napus from Arabidopsis thaliana sequences of known biological function.

A method for the development of consensus genetic markers between species of the same taxonomic family is described in this paper. It is based on the conservation of the peptide sequences and on the potential polymorphism within non-coding sequences. Six loci sequenced from Arabidopsis thaliana, AG, LFY3, AP3, FAD7, FAD3, and ADH, were analysed for one ecotype of A. thaliana, four lines of Brassica napus, and one line for each parental species, Brassica oleracea and Brassica rapa. Positive amplifications with the degenerate primers showed one band for A. thaliana, two to four bands in rapeseed, and one to two bands in the parental species. Direct sequencing of the PCR products confirms their peptide similarity with the "mother" sequence. By comparison of intron sequences, the correspondence between each rapeseed gene and its homologue in one of the parental species can be determined without ambiguity. Another important result is the presence of a polymorphism inside these fragments between the rapeseed lines. This variability could generally be detected by differences of electrophoretic migration on long non-denaturing polyacrylamide gels. This method enables a quick and easy shuttle between A. thaliana and Brassica species without cloning.

Amino Acid Sequence↗

Conversion of cyclosporine A to tacrolimus following heart transplantation.

BACKGROUND: Cyclosporine A (CyA) is ususally the immunosuppressive drug of choice in organ transplantation; however, some side effects have limited its use. Tacrolimus is a novel immunosuppressive drug that is more potent than CyA, and has been used as a rescue agent following heart transplantation when the use of CyA is undesirable or inefficient. PATIENTS AND METHODS: Since 1996, 14 heart transplant recipients under CyA were switched to tacrolimus therapy, for refractory rejection or intolerance, to conventional immunosuppression. RESULTS: After a mean of 35+/-7 months of treatment, tacrolimus was substituted for CyA therapy. The reason for substitution was refractory rejection in six patients, gingival hypertrophy in five patients, hypertrichosis in one patient, severe arterial hypertension in one patient and hepatotoxicity in one patient. Five patients underwent a successful rescue therapy and one patient died of refractory rejection despite the use of tacrolimus. All patients with CyA side effects recovered with tacrolimus. After conversion from CyA to tacrolimus, the number of episodes of acute rejection decreased from a mean of 0.42+/-0.17 to 0.14+/-0.09 episodes/patient/month under CyA and tacrolimus therapy (P=0.11), respectively. The mean dose of prednisone was 0.18+/-0.06 mg/kg/day before compared with 0.06+/-0.01 mg/kg/day after conversion from CyA to tacrolimus (P=0.09). Creatinine serum levels averaged 124+/-7 mmol/L under CyA treatment compared with 113+/-7 mmol/L with tacrolimus therapy (P=0.002). CONCLUSION: In patients with refractory rejections or intolerance to CyA after heart transplantation, conversion to tacrolimus-based immunosuppression is safe and effective.

Adult↗

Differential distribution of inward rectifier potassium channel transcripts in human atrium versus ventricle.

BACKGROUND: The inward rectifier K+ current (IK1) plays an important role in governing cardiac electrical activity and is well known to have different properties in the atrium compared with the ventricle. Several inward rectifier K+ channel (IRK) subunits (hIRK, HH-IRK1, HIR, and TWIK-1) with different properties have been cloned from human tissues, but their relative expression in cardiac tissues has not been quantified. The present study was designed to define the relative levels of mRNA for various IRKs in human atrium and in failing and nonfailing ventricle. METHODS AND RESULTS: Competitive reverse transcription-polymerase chain reaction was used to quantify in human atrium and ventricle the mRNA levels of hIRK, HH-IRK1, HIR, and TWIK-1. The absence of important noncardiac contamination was confirmed by demonstrating a lack of detectable mRNA markers for neuronal (acetylcholine receptor) and vascular (maxi-K channel) tissue. mRNA of HIR was more abundant in normal atrium (7.1+/-1.3 amol/ microg total RNA) than ventricle (0.6+/-0.1 amol/ microg, P<0. 05), whereas TWIK-1 mRNA was more concentrated in ventricle (18. 1+/-4.3 amol/ microg) than atrium (1.4+/-0.3 amol/ microg, P<0.05). Concentrations of hIRK (42.7+/-6.7 amol/ microg in atrium vs 57. 1+/-9.2 amol/ microg in ventricle) and HH-IRK1 (2.0+/-0.5 amol/ microg in atrium vs 1.5+/-0.5 amol/ microg in ventricle) were comparable. No significant differences in IRK subunit transcript concentrations were found between normal and failing ventricles. CONCLUSIONS: mRNAs for all 4 IRKs are detected in human atrium and ventricle, but the mRNA copy number of a low-conductance subunit (HIR) is larger in atrium and the copy number of a weakly rectifying subunit (TWIK-1) is larger in ventricle. These differences in relative message levels may provide a potential molecular basis for different properties of IK1 in human atrium compared with ventricle.

Atrial Function↗

Role of nitric oxide in the regulation of gonadotropin-releasing hormone and tyrosine hydroxylase gene expression in the male rat brain.

It has been recently demonstrated that nitric oxide (NO), a free radical gas which may act as neurotransmitter in the brain, can stimulate the in vivo release of luteinizing hormone as well as the in vitro hypothalamic release of gonadotropin-releasing hormone (GnRH). In order to study the influence of NO on GnRH mRNA expression, two inhibitors of NO synthase (NOS) NG-monomethyl-l-arginine (NMMA) and HP-228, were microinjected into the left lateral ventricle of sham-operated and castrated male rats 4 h before sacrifice. Since the dopaminergic system can positively influence GnRH gene expression, we have also measured in the same animals tyrosine hydroxylase (TH) mRNA in tuberoinfundibular dopamine (TIDA) neurons. GnRH and TH mRNA levels were measured at the cellular level by quantitative in situ hybridization. The injection of HP-228 or NMMA induced a similar decrease (-19.5%) in GnRH mRNA. In castrated animals, the hybridization signal was 88% higher than that observed in sham-operated animals. Both HP-228 and NMMA produced in castrated animals a 39% decrease in GnRH mRNA. In contrast the injection of NOS inhibitors resulted in an increase in the amount of TH mRNA in TIDA neurons. The stimulating effect was more striking in HP-228-treated (+60%) than in NMMA-treated (+32%) animals. Castration did not induce any changes in the number of silver grains overlying TIDA neurons, while the administration of either HP-228 or NMMA induced a 43% increase in castrated animals. These results together with previous ones on GnRH release in vitro suggest that NO exerts a positive influence not only on the secretion but also on the biosynthesis of GnRH. Since NO appears to play a role in the negative regulation of dopamine, it is likely that the increase in GnRH mRNA expression is not mediated by the TIDA system.

Animals↗

Low-copy-number molecules are produced by recombination, actively maintained and can be amplified in the mitochondrial genome of Brassicaceae: relationship to reversion of the male sterile phenotype in some cybrids.

A PCR analysis of mitochondrial (mt) genomes of cybrid rapeseed plants revealed substoichiometric concentrations of molecules bearing different configurations of the gene (orf138) responsible for Ogura cytoplasmic male sterility (CMS). These substoichiometric molecules are also present in plants bearing the unmodified Ogura cytoplasm. In one cybrid family, which shows reversion of the male sterile phenotype, we observed changes in the respective proportions of these molecules. The phenotypic (sterility-fertility) reversion occurs as a result of a modification of the equilibrium state between the different forms of the orf138 gene and is very probably determined by the level of expression of this gene. Stable situations are always characterized by one predominant form; the others, when present, exist in substoichiometric amounts. We report results indicating that the different forms of the orf138 gene are continuously interconverted by recombination and that an active mechanism is involved in the maintenance of some substoichiometric molecules.

Base Sequence↗

T-DNA mediated disruption of essential gametophytic genes in Arabidopsis is unexpectedly rare and cannot be inferred from segregation distortion alone.

Many genes are thought to be expressed during the haploid phase in plants, however, very few haploid-specific genes have been isolated so far. T-DNA insertion mutagenesis is a powerful tool for generating mutations that affect gametophyte viability and function, as disruption of a gene essential for these processes should lead to a defect in the transmission of the gametes. Mutants can therefore be screened on the basis of segregation distortion for a reporter resistance gene contained in the T-DNA. We have screened the Versailles collection of Arabidopsis transformants for 1:1 KanR:KanS segregation after selfing, focussing on gametophyte mutations which show normal transmission through one gametophyte and cause lethality or dysfunction of the other. Only 1.3% (207) of the 16,000 lines screened were scored as good candidates. Thorough genetic analysis of 38 putative T-DNA transmission defect lines (Ttd) identified 8 defective gametophyte mutants, which all showed 0 to 1% T-DNA transmission through the pollen. During the screen, we observed a high background of low-penetrance mutations, often affecting the function of both gametophytes, and many lines which were likely to carry chromosomal rearrangements. The reasons for the small number of retained lines (all male gametophytic) are discussed, as well as the finding that, for most of them, residual T-DNA transmission is obtained through the affected gametophyte.

Arabidopsis↗

A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct.

BACKGROUND: Although metallic stents remain patent longer than plastic stents, the optimal palliation of inoperable malignant biliary strictures remains controversial because of the high cost of metallic stents and short patient survival. METHODS: A total of 101 patients (mean age 72.5+/-12.9 years) with malignant strictures of the common bile duct were included in this study, after three exclusions for technical failure (n = 3) and one for noncompliance with study design. The etiology of the strictures included pancreatic cancer (65), cholangiocarcinoma (21), ampullary tumor (3), and metastatic lymph nodes (12). Patients were randomized to receive either an 11.5F polyethylene stent to be exchanged in case of dysfunction (group 1, n = 33), an 11.5F stent to be exchanged every 3 months (group 2, n = 34), or a self-expanding metallic Wallstent (group 3, n = 34). RESULTS: Endoscopic procedures were successful (including complete relief of jaundice) in 97.1 % of cases. Procedure-related morbidity was 11.9%, and mortality was 2.9%. Bilirubinemia after 48 hours (37.2%+/-21.7% decrease from the preoperative level) did not differ between groups. Patients were followed for a mean of 166 days (median 143, range 0 to 596 days). Overall survivals were not different between groups, but complication-free survival for groups 2 and 3 was longer than that of group 1 (p < 0.05). Cumulated hospital days were 7.4+/-1.5, 10.6+/-1.7, and 5.5+/-1.4 (groups 1, 2, and 3, respectively) (p < 0.05; analysis of variance). Cost analysis showed that metallic stents were advantageous in patients surviving more than 6 months, whereas a plastic stent was advantageous in patients surviving 6 months or less. CONCLUSIONS: Metallic stents and plastic stents exchanged every 3 months are valuable alternatives for increasing complication-free survival in patients with malignant strictures of the common bile duct. Metal stents are advantageous in patients with the longest life expectancy.

Adult↗