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Biomedical subjects

G Pelletier

Publications and source records attributed to G Pelletier.

At least 271 records · Page 15Linked to original sources
PubMed1992

Structure and tissue-specific expression of 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase genes in human and rat classical and peripheral steroidogenic tissues.

The enzyme 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase (3 beta-HSD) catalyzes the oxidation and isomerization of 5-ene-3 beta-hydroxypregnene and 5-ene-hydroxyandrostene steroid precursors into the corresponding 4-ene-ketosteroids necessary for the formation of all classes of steroid hormones. We have recently characterized two types of human 3 beta-HSD cDNA clones and the corresponding genes which encode deduced proteins of 371 and 372 amino acids, respectively, and share 93.5% homology. The human 3 beta-HSD genes containing 4 exons were assigned by in situ hybridization to the p11-p13 region of the short arm of chromosome 1. We have also recently elucidated the structure of three types of rat 3 beta-HSD cDNAs as well as that of one type of 3 beta-HSD from bovine and macaque ovary lambda gt11 cDNA libraries which all encode 372 amino acid proteins. The human type I 3 beta-HSD is the almost exclusive mRNA species detected in the placenta and skin, while the human type II is the predominant mRNA species in the adrenals, ovaries and testes. The predicted rat type I and type II 3 beta-HSD proteins expressed in adrenals, gonads and adipose tissue share 94% homology while they share 80% similarity with the liver-specific type III 3 beta-HSD. Transient expression of human type I and type II as well as rat type I and type II 3 beta-HSD cDNAs in HeLa human cervical carcinoma cells reveals that 3 beta-ol dehydrogenase and 5-ene-4-ene isomerase activities reside within a single protein and these cDNAs encode functional 3 beta-HSD proteins that are capable of converting 3 beta-hydroxy-5-ene-steroids into 3-keto-4-ene derivatives as well as the interconversion of 3 beta-hydroxy and 3-keto-5 alpha-androstane steroids. We have found that the rat type III mRNA species was below the detection limit in intact female liver while, following hypophysectomy, its accumulation increased to 55% of the levels measured in intact or HYPOX male rats, an increase which can be blocked by administration of ovine prolactin (oPRL). In addition, in female rats, treatment with oPRL for 10 days starting 15 days after HYPOX, markedly decreased ovarian 3 beta-HSD mRNA accumulation accompanied by a similar decrease in 3 beta-HSD activity and protein levels. Treatment with the gonadotropin hCG reversed the potent inhibitory effect of oPRL on these parameters and stimulated 3 beta-HSD mRNA levels in ovarian interstitial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1992

Impaired functions of normal peripheral polymorphonuclear leukocytes in cirrhotic ascitic fluid.

The function of normal polymorphonuclear cells in the ascitic fluid of 32 patients with cirrhotic ascites and 17 patients with malignant ascites was studied independently of ascitic fluid heat-labile factors. Polymorphonuclear (PMN) function was assessed by a chemiluminescence method using preopsonized zymosan as stimuli. The chemiluminescence response was higher in malignant ascitic fluid than in cirrhotic ascitic fluid (0.84 and 0.15, respectively, p < 0.001). These results were confirmed by a microbiological assessment of phagocytosis. Suppressive factors were evidenced by making ascitic fluid dilutions and using cell-free chemiluminescence measurements. Addition of malignant ascitic fluid to cirrhotic ascitic fluid showed that there is also a deficiency in supportive factors other than C3. The impaired PMN production of oxidative metabolites we observed in cirrhotic ascitic fluid can partly explain the high susceptibility of cirrhotic patients to spontaneous bacterial peritonitis independently of C3 levels.

Adult↗
PubMed1992

Low early gallstone recurrence rate after successful extracorporeal lithotripsy in patients with solitary stones.

Piezoelectric lithotripsy with the EDAP LT-01 machine combined with adjuvant bile acid therapy results in complete clearance of radiolucent gallstones in selected patients. We assessed stone recurrence rate in 84 patients with complete clearance of stone fragments and followed up at least 12 months after cessation of bile acid therapy (mean 17 months, range 12-33). Fifty-four patients had a solitary stone and 30 multiple stones. Bile acid therapy was continued for 3 months after complete fragment stones clearance which was ascertained by two consecutive ultrasound examinations. Stone recurrence was assessed by ultrasonography at 6 and 12 months, and then at least once a year. Gallstone recurrence occurred in 5 patients (6%) between 9 and 12 months with no further recurrence up to 33 months. The rate of recurrence at one year was 3.7% in patients with a solitary stone and 10% in patients with multiple stones. Only one patient with stone recurrence had recurrent biliary pain. We concluded that early gallstone recurrence rate after successful lithotripsy seems to be low in patients with solitary stones.

Adolescent↗
PubMed1992

Treatment of symptomatic cholelithiasis in France. A decision analysis comparing cholecystectomy and biliary lithotripsy.

To determine the potential role of extracorporeal shock wave lithotripsy (ESWL) in the treatment of symptomatic gallstone patients in France, a simulation model evaluated the health and economic effects of three different treatment strategies. Decision analysis of conventional cholecystectomy alone and either of two strategies using a combination of biliary lithotripsy and conventional cholecystectomy reveals that a strategy employing biliary ESWL results in a significant number of successfully treated patients, thus avoiding the risks and costs of abdominal surgery. Moreover, cost analysis shows that expanding the use of lithotripsy to all patients for whom the procedure is indicated increases the average cost per successfully treated patient, but, more importantly, decreases the overall costs incurred by the cohort. From a societal viewpoint, a policy using biliary ESWL in appropriate patients is superior to one of cholecystectomy alone, from both clinical and economic perspectives.

Adolescent↗
PubMed1992

Association of juxtapapillary diverticula with choledocholithiasis but not with cholecystolithiasis.

Juxtapapillary diverticula are often associated with biliary lithiasis. The aim of this study was to compare the prevalence of juxtapapillary diverticula in choledocholithiasis and in cholecystolithiasis without common bile duct stones. The results of 520 consecutive retrograde cholangiographies were retrospectively analysed. The prevalence of juxtapapillary diverticula was higher in patients with biliary lithiasis than in patients without: 26.0% vs 10.5% (p less than 0.001). However, juxtapapillary diverticula were more frequently encountered in patients with choledocholithiasis than in those with gallbladder lithiasis or previous cholecystectomy and a stone-free common bile duct: 40.0% vs 10.2% (p less than 0.001). There was no significant difference between the patients with cholecystolithiasis alone and those without biliary lithiasis. Among the patients with previous cholecystectomy or with gallbladder lithiasis, common bile duct stones were more frequently found in patients with juxtapapillary diverticula than in those without: 80.3% vs 40.6% (p less than 0.001). These data suggest that juxtapapillary diverticula are associated only with choledocholithiasis and not with gallbladder lithiasis.

Aged↗
PubMed1992

Ontogeny and cellular localization of 125I-labeled basic fibroblast growth factor and 125I-labeled epidermal growth factor binding sites in ovaries from bovine fetuses and neonatal calves.

We have recently reported that although specific 125I-FSH receptors are present in granulosa cells from primary and secondary follicles, gonadotropin responsiveness is very low in ovaries from bovine fetuses, which consist mainly of preantral follicles with few early antral follicles. It is well established that a number of polypeptide growth factors show pronounced mitogenic effects on follicular cells. Therefore, we have compared autoradiographically the ontogeny and cellular localization of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) binding activities to assess their possible involvement in the regulation of early follicular growth in fetuses and neonatal calves. Follicular growth was initiated around Day 180 of gestation in fetuses. 125I-bFGF binding values were high in granulosa cells from preantral follicles (mean +/- SEM, 7.8 +/- 1.1-9.8 +/- 0.7 grains/cell, 0.05-0.15-mm diam.) but decreased in early antral follicles (0.16-3.0 mm) to a constant level (5.7 +/- 1.2 grains/cell). Specific 125I-EGF binding values were low in preantral follicles but showed a 2.5- and 5.0-fold increase in both granulosa cells and the theca interna from antral I (0.16-0.5 mm) and antral II follicles (0.6-3.0 mm), respectively. In atretic follicles, 125I-bFGF specific binding values were high (10.4 +/- 0.8 grains/cell), whereas 125I-EGF binding levels were significantly reduced or absent. None of the radioligands tested bound significantly to primordial follicles. There was no age-related difference in any ligand binding to follicles of comparable size. These results provide novel evidence that bFGF, a potent mitogen, is involved in the regulation of granulosa cell function as early as the preantral stage in cattle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Ontogeny and cellular localization of 125I-labeled insulin-like growth factor-I, 125I-labeled follicle-stimulating hormone, and 125I-labeled human chorionic gonadotropin binding sites in ovaries from bovine fetuses and neonatal calves.

In a previous study we reported that ovaries from bovine fetuses, which consist mainly of preantral follicles with few antral follicles, are weakly responsive to gonadotropins (FSH and LH). Insulin-like growth factor-I (IGF-I) is known to enhance gonadotropin responsiveness in vitro, but there is a lack of consistent data on the involvement of IGF-I, FSH, and LH during early stages of folliculogenesis in cattle. In the study reported here, we assessed autoradiographically the ontogeny of 125I-gonadotropin and 125I-IGF-I binding activities during preantral and early antral stages in cattle. Follicular growth was initiated around Day 180 of gestation in fetuses. The density of 125I-FSH binding was high in granulosa cells from primary (mean +/- SEM 10.5 +/- 0.7 grains/cell, 0.05-mm diam.) and secondary follicles (10.8 +/- 0.8 to 13.6 +/- 1.2 grains/cell, 0.06-0.15 mm) but increased significantly (p < 0.05) in early antral follicles (18.2 +/- 1.1 grains/cell, 0.16-3.0 mm). Specific 125I-IGF-I binding levels were low in granulosa cells from preantral follicles, averaging 2.5 +/- 0.6-3.1 +/- 0.9 grains/cell. However, after antrum formation, the density of 125I-IGF-I binding increased significantly (p < 0.05) with follicular diameter in granulosa cells and was 5.7 +/- 0.7 and 9.1 +/- 0.6 grains/cell for antral I (0.16-0.5 mm) and antral II (0.6-3.0 mm) follicles, respectively. 125I-FSH and 125I-IGF-I binding densities were low in theca cells from preantral and early antral follicles as well as in the interstitial tissue and granulosa cells from atretic follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Variations of pre-proNPY mRNA in the arcuate nucleus during the rat estrous cycle.

In order to assess the role of sex steroids on the regulation of neuropeptide Y (NPY), levels of pre-proNPY mRNA were measured by in situ hybridization in the rat arcuate nucleus during the estrous cycle. Pre-proNPY mRNA levels were quite stable during diestrus I, diestrus II and the morning of the proestrus, and were 25-30% higher during the afternoon of the proestrus and during the day of the estrus. These data suggest that NPY synthesis is modulated by variations in the circulating levels of sex steroids. Also the excellent correlation between the variations in the levels of pre-proNPY mRNA and those of luteinizing hormone-releasing hormone (LHRH) mRNA observed throughout the estrous cycle supports the hypothesis that NPY might be involved in the regulation of LHRH secretion.

Animals↗
PubMed1992

Enhancement of Naphthaleneacetic Acid-Induced Rhizogenesis in T(L)-DNA-Transformed Brassica napus without Significant Modification of Auxin Levels and Auxin Sensitivity.

Determination of the abscisic acid and indoleacetic acid (IAA) contents of floral stem segments of nontransformed and pRi A(4) T(L)-DNA-transformed rape (Brassica napus L. var oleifera, cv Brutor) using a high performance liquid chromatography-enzyme-linked immunosorbent assay procedure and mass spectrometry controls showed that IAA levels were not modified. The regeneration abilities of the in vitro cultured explants were compared on media supplemented with several plant growth regulator combinations. No regeneration occurred on hormone-free media, and shoot production was similar in both genotypes when supplemented with benzyladenine. In the presence of naphthaleneacetic acid (NAA), transformed explants were characterized by faster root regeneration and reduced shoot organogenesis. The optimum for root formation was the same in nontransformed and transformed plants, but the sensitivity threshold was slightly lower in the latter. The NAA inductive period was shorter (14 versus 22 h) with transformed tissue. Root neoformation occurred about 72 h earlier on transformed explants. Our results suggest mainly that there is an acceleration of the auxinic signal transduction and/or that the events preliminary to the formation of roots occur faster in the transformed tissues than in the normal ones.

Journal Article↗
PubMed1992

Characterization, expression, and immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in human skin.

Three beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyses an obligatory step in the biosynthesis of all classes of hormonal steroids, namely, the oxidation/isomerization of 3 beta-hydroxy-5-ene steroids into the corresponding 3-keto-4-ene steroids in gonadal as well as in peripheral tissues. Because humans are unique with some primates in having adrenals that secrete large amounts of the steroid precursors dehydropiandrosterone (DHEA) and its sulfate (DHEA-S) and its exceptionally large volume makes the skin an important site of steroid biosynthesis, we have isolated and characterized cDNA clones encoding 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase from a human skin lambda gt11 library. The longest clone obtained contains the entire coding sequence for type I 3 beta-HSD (372 amino acids) as well as an additional 131 nucleotides in the 5'-untranslated region. The insert of 1647 bp containing the entire coding region has been inserted in a pCMV expression vector and transfected into human cervical carcinoma cells (HeLa). The expressed enzyme efficiently catalyzes the transformation of pregnenolone, DHEA, and dihydrotestosterone into progesterone, 4-androstenedione, and 5 alpha-androstane-3 beta, 17 beta-diol, respectively. Using the enzyme expressed in HeLa cells, we have shown cyproterone acetate, a progestin used in the treatment of acne and hirsutism, as well as norgestrel and norethindrone, two steroids widely used as oral contraceptives, to be relatively potent inhibitors, with Ki values of 0.38 microM, 1.3 microM, and 1.2 microM, respectively. Immunohistochemical localization of 3 beta-HSD, illustrated by using an antibody raised against human placental 3 beta-HSD, shows that the enzyme is localized in sebaceous glands.

Amino Acid Sequence↗
PubMed1992

Interleukin-4 and nerve growth factor can act as cofactors for interleukin-3-induced histamine production in human umbilical cord blood cells in serum-free culture.

In order to better define the role of recombinant interleukins and growth factors in supporting histamine production by histamine-producing-cells (HPC), namely basophils or mast cells, we have conducted experiments in which we compared the abilities of IL-3, IL-4, IL-6 and nerve growth factor (NGF), either alone or in various combinations, to stimulate histamine production from human umbilical cord blood mononuclear cells cultured in either the presence or absence of serum. Over a period of 15 d, IL-3 was able to support intracellular histamine production, in both serum-supplemented and serum-free medium, although the effectiveness of IL-3 was lower in the serum-free cultures. IL-4, NGF and IL-6 taken individually, exhibited little, if any, histamine-promoting activity regardless of whether or not the cells were cultured in serum. Moreover, none of these cytokines significantly enhanced the effect of IL-3 in serum-supplemented cultures. In contrast, IL-3-promoted histamine production in serum-free cultures was significantly enhanced by IL-4 and NGF. These results demonstrate that both IL-4 and NGF can function as cofactors with IL-3 in the support of histamine production in human umbilical cord blood cells.

Cells, Cultured↗
PubMed1992

Enhancement of normal polymorphonuclear cells respiratory burst in ascitic fluid by fibronectin. Comparison between cirrhotic and malignant ascitic fluids.

The chemiluminescence (CL) response of normal peripheral blood polymorphonuclear cells (PMN) in ascitic fluids (cirrhotic = 32; malignant = 17) was studied independently of the ascitic fluid complement activity. CL response and fibronectin levels were higher in malignant ascitic fluid than in cirrhotic ascitic fluid (p less than 0.001). Addition of pure fibronectin or malignant ascitic fluids to cirrhotic ascitic fluids increased the CL response of normal PMN. These findings suggest that the susceptibility of cirrhotic patients to spontaneous bacterial peritonitis (SBP) is a multifactorial defect involving factors distinct from low C3 levels. Fibronectin is an important factor in the promotion of the respiratory burst of normal PMN stimulated by opsonized zymosan or PMA in ascitic fluid. Our results suggest that low levels of ascitic fluid fibronectin could partly explain the high susceptibility of cirrhotic patients to spontaneous bacterial peritonitis.

Adult↗
PubMed1992

Prolactin regulation of pro-opiomelanocortin gene expression in the arcuate nucleus of the rat hypothalamus.

It is well known that the opiate peptides, especially the pro-opiomelanocortin (POMC)-related peptide beta-endorphin, stimulate the release of prolactin (PRL) in the rat. In order to evaluate the involvement of PRL on the activity of POMC neurons in the arcuate nucleus, we have studied the effects of the injection of PRL into the third ventricle of intact and hypophysectomized rats as well as the effects of hyperprolactinemia induced by pituitary implants under the kidney capsule on POMC gene expression. The amounts of POMC mRNA in the arcuate nucleus were measured by in situ hybridization using a [35S]-labelled cDNA probe encoding for POMC. Hypophysectomy performed 2 weeks previously decreased by 24% the number of silver grains/unit of surface of labelled neurons. Intracerebroventricular injection of 3 micrograms of PRL 4 h before sacrifice induced a significant decrease in the hybridization signal of 32 and 20% in the intact and hypophysectomized rat, respectively. Hyperprolactinemia achieved by pituitary implants also led to a significant decrease in POMC mRNA levels. The present data show that hypophysectomy depresses hypothalamic POMC mRNA levels and that this effect is not related to the suppression of PRL secretion since this hormone exerts an inhibitory action on POMC gene expression. They suggest that the regulation of PRL secretion by short loop feedback mechanism might be well mediated by beta-endorphin which has already been shown to inhibit dopaminergic neuron activity in the arcuate nucleus.

Animals↗
PubMed1992

Carcass composition and resistance to fasting in neonatal piglets born of sows immunized against somatostatin and/or receiving growth hormone-releasing factor injections during gestation.

Thirty-eight gestating sows were either immunized against somatostatin (SRIF) and/or injected with growth hormone-releasing factor (GRF). Treatment effects on carcass composition and resistance of newborn piglets to a 60-hour fast were investigated. Protein content of carcasses at birth was increased in piglets of sows receiving GRF or immunized against SRIF, however, when sows received both treatments there was a reduction in carcass protein content (p = 0.01). Other carcass components were unaltered by treatments, and none of the treatments affected metabolic or endocrine profiles of piglets at birth. Concentrations of GH, IGF-I (p less than 0.01), glucagon and cortisol (p less than 0.05) increased linearly with duration of fast, whereas glucose values decreased. Resistance to fasting was unaltered in piglets from any treatment thereby suggesting that exogenous GRF and/or SRIF immunization of sows during gestation are unlikely to improve survival of newborn piglets.

Animals↗
PubMed1992

Role of dopamine in the regulation of gonadotropin-releasing hormone in the male rat brain as studied by in situ hybridization.

The effects of the dopaminergic antagonist haloperidol (HAL) as well as the D2 dopamine receptor agonist bromocriptine (BRO) on GnRH messenger RNA (mRNA) levels in the male rat were investigated by quantitative in situ hybridization. Since it had already shown that androgens could induce a decrease in GnRH mRNA levels in castrated rats, the involvement of the dopaminergic system in the inhibitory effect of dihydrotestosterone (DHT) was also investigated. In situ hybridization was performed on paraformaldehyde-fixed cryostat sections through an area extending from the preoptic area to the anterior hypothalamus using a 35S-labeled 48-base oligodeoxynucleotide complementary to the GnRH coding region of the GnRH DNA. The corresponding mRNA levels were assessed by counting the number of silver grains overlying labeled neurons. In intact animals, a 14-day treatment with BRO increased by 67% the number of silver grains per neuron while HAL decreased by 31% the value of this parameter. Hypophysectomy which induced a 22% decrease in the hybridization signal could not prevent the effects of BRO or HAL. Gonadectomy performed 14 days earlier increased by 54% the mean number of silver grains while a 14-day treatment of gonadectomized animals with DHT decreased the hybridization signal by 48%. On the other hand, the concomitant administration of HAL and DHT did not prevent the inhibitory effect of DHT but rather resulted in a decrease of the hybridization signal which was more marked than that induced by DHT or HAL alone. The present data clearly demonstrate that GnRH mRNA levels are positively regulated by dopamine and that the effects of BRO and HAL on GnRH mRNA are not mediated by variations in pituitary hormone secretion. Moreover, our results suggest that the effect of DHT on GnRH gene expression is probably not mediated by the dopaminergic system.

Animals↗
PubMed1992

Immunocytochemical localization of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human ovary.

The enzyme complex 3 beta-hydroxy-5-ene-steroid dehydrogenase and steroid delta 5----4-ene-isomerase (3 beta HSD) is involved in the biosynthesis of all classes of active steroids, namely glucocorticoids, mineralocorticoids, progesterone, and sex steroids. To obtain more information about the age-specific expression of 3 beta HSD in the human ovary, we have localized this enzyme by immunocytochemistry at the light microscopic level during fetal and postnatal periods of development in the human. Immunocytochemical localization was achieved using specific polyclonal antibodies developed against purified human placental 3 beta HSD. In the fetal ovary of 28-34 weeks, specific immunostaining for 3 beta HSD was exclusively detected in thecal cells surrounding primary follicles and in interstitial cells. From birth until puberty, no significant immunostaining for 3 beta HSD could be observed, while from puberty to menopause, staining was detected in theca interna cells as well as granulosa cells of growing follicles. The intensity of staining in the theca interna cells was always much higher than that in granulosa cells. Immunostaining was also found in the cytoplasm of luteinized granulosa and theca interna cells of the corpus luteum. Interestingly, there was an absence of immunoreactivity for 3 beta HSD in one to several layers of theca interna cells lying just beneath the basement membrane. These negative cells may correspond to fibroblast-like cells that are devoid of 3 beta HSD activity. In postmenopausal ovaries, immunolabeling was only found in dispersed interstitial cells, thus suggesting that the ovaries of postmenopausal women might be involved in sex steroid hormone secretion.

Aged↗
PubMed1992

Immunohistochemical localization of 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5----delta 4 isomerase in human placenta and fetal membranes throughout gestation.

The regulation of steroid production by the placenta and fetal membranes is important for both the maintenance of pregnancy and the timing of parturition. 3 beta-Hydroxy-5-ene-steroid dehydrogenase/delta 5----delta 4-isomerase (3 beta HSD) catalyzes an obligatory step in the biosynthesis of steroid hormones. We have determined the localization of 3 beta HSD in the human placenta, fetal membranes, and umbilical cord throughout gestation by immunohistochemical analysis, using a polyclonal antibody raised in rabbits against a purified preparation of human placental 3 beta HSD. In placenta, immunoreactive (IR-) 3 beta HSD was localized in the syncytiotrophoblast and intermediate trophoblast cells at both villous and extravillous sites, but not in cytotrophoblast cells from 6 weeks gestation to term. At 6-7 weeks gestation, IR-3 beta HSD was distributed in the cytoplasm of syncytiotrophoblast in about half of placental villi. By 12-14 weeks, the syncytiotrophoblast of all placental villi stained positively for 3 beta HSD. In the fetal membranes, strong IR-3 beta HSD staining was found in the trophoblast and reticular layers of chorion and in invasive trophoblast cells in decidua, and weakly in decidual stromal cells and amniotic epithelium. No IR-3 beta HSD was found in amnion on the placental plate, but in the umbilical cord, IR-3 beta HSD was present in the amniotic epithelium and also in fibroblast cells in Warton's jelly. These observations demonstrate that the localization of 3 beta HSD immunoreactivity and, therefore, the presumed sites of delta 5- to delta 4-steroid interconversion throughout gestation are principally the syncytiotrophoblast and intermediate trophoblast cells in placenta and the trophoblast cells in chorion and decidua in fetal membranes.

Extraembryonic Membranes↗