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Biomedical subjects

G Pelletier

Publications and source records attributed to G Pelletier.

At least 469 records · Page 26Linked to original sources

Immunohistochemical localization of a prostatic secretory protein of 94 amino acids in normal prostatic tissue, in primary prostatic tumors and in their metastases.

Using the immunoperoxidase technique, we have studied in normal, hyperplastic and adenocarcinomatous prostates the tissue localization of an abundant 94 amino acid protein secreted by prostatic epithelial cells. In normal and hyperplastic prostates, strong immunoreactivity was found exclusively in glandular epithelial cells. No reaction was observed over the stroma. In well differentiated adenocarcinoma, the acinar cells were generally stained less intensely than in benign prostatic hyperplasia while in poorly differentiated tissue, strongly positive immunoperoxidase staining was found in some cancer cells scattered in the stroma. All prostatic cancer tissues examined (N = 21), with the exception of one, exhibited at least a few positive immunoreactive areas for the 94 amino acid secretory protein. In addition, immunoperoxidase staining was observed in lung and bone marrow metastases respectively in two patients with prostatic carcinoma. All other normal tissues and non-prostatic cancers studied to date were negative. These results suggest that this new marker could be a useful addition to prostatic acid phosphatase and prostate specific antigen.

Adenocarcinoma↗

Influence of pregnancy, lactation, litter size and diet energy density on the stomach and intestine of sows.

In the first experiment, 52 sows, each having raised one litter, were randomly assigned to the five following groups: control (nongravid) for pregnancy (CP), 110 d pregnancy (P110), control (nongravid) for lactation (CL), 4-wk lactation with 8 (L8) and with 12 (L12) piglets. In a second experiment, 36 sows, each having raised three litters, were randomly assigned to the following groups: control group (nongravid) fed a low-energy-density, 1% tallow diet (CLED) and two lactating groups, one fed the low-energy-density diet (LLED) and one fed a high-energy-density, 10% tallow diet (LHED). At slaughter, the stomach, small and large intestine and cecum were excised, emptied and freed from fat. Lengths and pre- and post-defatting weights were measured. Portions of tissues were homogenized and analyzed for protein, pepsin, maltase, RNA and DNA. Pregnancy had no effect on the weights of the different components of the gastrointestinal tract. Liver and small intestine weights were larger in lactating sows than in the CL group. Sows nursing 12 piglets had heavier livers than those nursing 8. The fundic mucosa of the latter had higher total pepsin activity and total protein and RNA contents than that of L12 sows. LHED sows had heavier small intestine and lower total pepsin content of the fundic mucosa than LLED sows.

Animals↗

Demonstration of epidermal growth factor binding sites in the adult rat pancreas by light microscopic autoradiography.

The distribution of epidermal growth factor (EGF) receptors was studied in the pancreas using light microscopic autoradiography, which was performed at different time intervals (2-60 min) after injecting 125I-labeled EGF intravenously into the adult rat. In the exocrine pancreas, a labeling was found to occur over the pyramidal cells of the acini and cells lining the intercalated ducts. Moreover, substantial binding of EGF to cells of the islets of Langerhans was also revealed. At the 2-min time interval, most silver grains were found at the periphery of the target cells. The localization, as well as the diminution of silver grains over the cytoplasm of these cells, between 7 and 60 min, suggested the internalization and degradation of 125I-labeled EGF. Control experiments indicated that the autoradiography reaction was due to specific interaction of 125I-labeled EGF with its receptor. These results clearly indicate that EGF receptors are present in the acinar cells and the cells of intercalated ducts of the exocrine pancreas, as well as the cells of the endocrine pancreas. Finding that there are EGF binding sites in pancreatic acinar cells supports the physiological role of EGF in the regulation of pancreatic exocrine function. The presence of EGF receptors in cells of the islets of Langerhans suggests that EGF may play a role in the regulation of the endocrine pancreas.

Animals↗

Demonstration of contacts between neurons staining for LHRH in the preoptic area of the rat brain.

It has been recently demonstrated that luteinizing hormone-releasing hormone (LHRH) can inhibit LHRH release by the hypothalamus, suggesting an ultrashort feedback of LHRH on LHRH neurons. In order to test this hypothesis, immunocytochemical localization of LHRH was conducted in the preoptic area of the rat brain. Contacts between endings and neuronal cell bodies staining for LHRH were observed. This direct interaction between LHRH neurons might be well the morphological basis for an autoregulation of the LHRH system in the rat brain.

Animals↗

Localization of glycoproteins in insulin secretory granules by ultrastructural autoradiography.

To determine whether or not the secretory granules of insulin-secreting cells contained glycoproteins, isolated rat pancreatic islets were incubated for 2 and 4 hr in a medium containing L-[3H]-fucose. Quantitative analysis of high-resolution electron microscopic autoradiographs of the insulin-secreting beta cells demonstrated that glycoproteins with fucose residues are contained within the insulin secretory granule.

Animals↗

Morphological studies of the canine pituitary luteinizing hormone (LH) cells after long-term treatment with the LH-releasing hormone (LHRH) agonist [D-Trp6]LHRH ethylamide.

Since treatment with LHRH agonists (LHRH-A) cause changes in LH secretion which are similar in both man and dog, we have studied cytological changes occurring in canine LH cells after chronic administration of an LHRH-A, [D-Trp6] LHRH ethylamide. At the light microscopic level, LH cells were distributed evenly in the gland, but showed a decrease in cell surface area of 10% after 1 month and 23% after 4 months of daily injection of 50 micrograms LHRH-A. At the electron microscopic level, the gonadotrophs from control animals were characterized by the presence of two types of secretory granules and a dilatation of the rough endoplasmic reticulum. Immunostaining for LH was localized only to secretory granules. LHRH-A administration caused the appearance of glycogen in the cytoplasm. Four months after cessation of the treatment, the gonadotrophs showed a normal cytological appearance, thus indicating full reversibility of the morphological changes induced by long-term treatment with an LHRH-A.

Animals↗

Ovarian adrenergic nerves directly participate in the control of luteinizing hormone-releasing hormone and beta-adrenergic receptors during puberty: a biochemical and autoradiographic study.

The rat ovary receives sympathetic innervation from the superior ovarian nerve (SON) and the plexus nerve (OP). To examine the possibility of a direct adrenergic mechanism controlling ovarian receptor distribution during the onset of puberty, we have studied the acute (48-h) effect of unilateral nervotomy (combined section of SON and OP nerves) on ovarian LHRH and beta-adrenergic receptor concentrations and distribution using both radioreceptor assays and in vitro autoradiography. Ovarian LHRH receptor concentration increased sharply between 12 and 20 days of age. At this time receptors were mostly associated with follicles and interstitial cells, whereas at 37 days of age, when a measurable loss in the receptor concentration was observed, light and diffuse autoradiographic labeling of receptors was also found in the corpora lutea. Complete removal of adrenergic input to the gland produced a sharp decrease in LHRH-binding activity within the denervated ovary at each time interval studied, with no effect in the innervated contralateral gland. Autoradiographic data also revealed a decrease in both the number of labeled follicles and the intensity of the labeling. beta-Adrenergic receptor concentration increased progressively between days 12 and 27, reaching a peak value at 37 days of age. Labeling was very weak at 12 days of age and increased progressively at 20 and 27 days of age. At this time, receptors were mostly localized by autoradiography in the interstitial cells, while at 37 days of age corpora lutea were strongly labeled. Ovarian beta-adrenergic receptors showed a marked drop when acutely deprived of their neural tone, as illustrated by the 2- to 3-fold decrease in receptor-binding capacity within the denervated gland. The autoradiographic data also showed marked changes in beta-adrenergic receptor distribution, specially at 37 days of age. At this time, the labeling of corpora lutea was markedly decreased in denervated ovaries. The present results clearly demonstrate that complete removal of ovarian adrenergic tone produces a profound decrease in the concentrations of LHRH and beta-adrenergic receptors within the ovary, although it cannot be excluded that peptidergic factors also arriving via the SON and OP could have some influence on the regulation of these receptors. The results support the concept of a direct involvement of the central nervous system in ovarian function. They also suggest that during ovarian development a neural efferent system might be involved in the adjustment of ovarian responsiveness to stimulation by the gonadotropins via changes in receptor content and/or distribution in the different ovarian compartments.

Animals↗

Morphological study of the effects of an GnRH agonist on the canine testis after 4 months of treatment and recovery.

After 4 months of treatment of adult male dogs with the GnRH agonist (GnRH-A) [D-Trp6]GnRH ethylamide, the seminiferous tubules contained only type A and B spermatogonia, Sertoli cells, and rare primary spermatocytes, thus causing a 64% decrease in testis weight. At the electron microscope level, Sertoli cells showed an increase in phagosomes and lipid droplets. Leydig cells were markedly atrophied with the accumulation of lipid droplets and showed a predominance of mitochondria with lamellar instead of vesicular cristae. Four months after cessation of treatment with GnRH-A, a complete return to normal spermatogenesis and Leydig cell morphology was observed. The full reversibility of spermatogenesis in the dog after chronic GnRH-A treatment suggests that this well-tolerated peptide could be used as a reversible method of male contraception.

Animals↗

Dose response of two synthetic human growth hormone-releasing factors on growth hormone release in heifers and pigs.

This study was undertaken to evaluate the biological potency of two synthetic human growth hormone-releasing factors, hGRF (1-44)NH2 and hGRF (1-29)NH2, on growth hormone (GH) release in young dairy heifers (n = 10) and pigs (n = 10). In each species, the GH response to an iv injection (0, .067, .2, .6 and 1.8 nmol.kg-1 body weight) of each peptide was evaluated in a double 5 X 5 Latin square design. In each square, there were five animals injected with either hGRF (1-44)NH2 or hGRF (1-29)NH2. Main effects were doses (n = 5) of hGRF and days (n = 5) of injection. In both species, data indicated that hGRF (1-44)NH2 and hGRF (1-29)NH2 equally stimulate GH secretion at all doses. In dairy heifers, average peak concentrations (81.7, 94.7, 84.5 and 93.7 ng.ml-1 vs 91.5, 81.0, 94.3 and 91.6 ng.ml-1) and area under the GH response curve (3,661, 4,541, 7,196 and 6,788 ng.ml-1.min vs 3,000, 3,982, 5,639 and 6,724 ng.ml-1.min) were not different (P greater than .05) between hGRF(1-44)NH2 and hGRF(1-29)NH2 at .067, .2, .6 and 1.8 nmol.kg-1, respectively. Similarly, in pigs, average peak concentrations (35.6, 38.6, 76.5 and 73.8 ng.ml-1 vs 28.7, 30.0, 41.3 and 80.8 ng.ml-1) and area under the GH curve (1,576, 1,567, 3,299 and 3,622 ng.ml-1.min vs 1,115, 1,658, 1,482 and 2,528 ng.ml-1.min) were not different (P greater than .05) between both peptides. A biphasic release of GH after hGRF (1-44)NH2 and hGRH (1-29)NH2 injection was observed at the highest dose in heifers. The GH response to hGRF injection was much more variable in pigs as compared with dairy heifers. In conclusion, hGRF (1-44)NH2 and its (1-29)NH2 fragment are equipotent in stimulating GH release in dairy heifers and pigs.

Animals↗

Release of leukotrienes and histamine by the isolated anaphylactic heart.

The purpose of this study was to demonstrate the ability of heart tissue to release the mediators of anaphylaxis after antigenic challenges. Guinea pigs were sensitized with ovalbumin. Hearts were excised, perfused in a langendorff apparatus, and challenged with a bolus injection of ovalbumin. Analysis of the perfusates demonstrated the presence of histamine as determined by radioenzymatic assay. Histamine release was observed to be maximum after 2 min (8 +/- 1 nmol) of perfusion, then decreased to baseline level. The heart also released LTB4, LTC4, LTD4, and LTE4 as determined by high performance liquid chromatography and bioassays. The release of LTC4 occurred rapidly, reaching maximum after 2 min (4.2 +/- 1 pmol) and then returned to baseline level. Although the release of LTD4 paralleled the release of LTC4, it reached a maximum after 5 min (7.7 +/- 2 pmol). LTE4 was detected after 10 min and was undetectable after 15 min. Maximum release of LTB4 was observed after 5-10 min (15 +/- 3 pmol) and was no longer detectable after 15 min. These results indicate that the isolated sensitized heart undergoing antigenic challenge releases leukotrienes and histamine suggesting the cardiac anaphylaxis might occur by the locally released mediators.

Anaphylaxis↗

Injection of synthetic human growth hormone-releasing factors in dairy cows. 1. Effect on feed intake and milk yield and composition.

Eighteen multiparous Holstein cows in the second half of their lactation were used to determine the effect of human growth hormone-releasing factor (1-44)NH2 and a fragment of growth hormone-releasing factor (1-29)NH2 on lactational performance and feed intake. Saline, the 44-amino acid peptide or the 29-amino acid fragment, at the same dose per injection (.2 nmol.kg-1) was injected intravenously at 4-h intervals for 10 d. Average milk yield, milk composition, feed intake, and feed efficiency were compared for the second half of each 10-d preinjection, injection, and post-injection period. Injections of the 44-amino acid peptide and the 29-amino acid fragment increased milk yield 18.6 and 14.6%, respectively. Feed intake was not changed, but feed efficiency was increased 23.9 and 18.8% over control following 44-amino acid peptide and the 29-amino acid fragment injection, respectively. The lactational response was not different between the two peptides for any of the variables measured. This study demonstrates the feasibility of using a growth hormone-releasing factor fragment as an alternative method of elevating milk yield in cattle via somatotropins.

Animals↗

[Pro-opiomelanocortin neuronal systems].

Proopiomelanocortin (POMC) is a glycoprotein which serves as a multihormonal precursor for corticotropin (ACTH), lipotropins (beta and gamma-LPH), melanotropins (alpha, beta- and gamma-MSH) and endorphins (alpha-, beta- and gamma-endorphins). This precursor protein is primarily synthesized in corticotrophs of the anterior lobe and in melanotrophs of the intermediate lobe of the pituitary, as well as in other organs or tissues such as the genitourinary tract, the gastrointestinal tract and leukocytes. POMC is also present in the central nervous system (CNS) and numerous studies have been conducted to determine the localization, biosynthesis and functions of POMC-derived peptides. The identification of POMC-neuronal systems has been achieved by combining immuno histochemical studies, biochemical analysis, bioassays and radioimmunoassays. Three groups of perikarya containing various POMC-related peptides have been identified. One of these is located in the arcuate nucleus in the basal hypothalamus and projects towards the septum, thalamus and telencephalon. Some fibers originating from the arcuate nucleus terminate in the nucleus of the solitary tract in the brainstem where a second group of POMC-containing nerve cells are located. The latter innervates both the mesencephalon, the brainstem and the spinal cord. A third group of neurons, which contain alpha-MSH but not other POMC-derivates, has been identified in the zona incerta in the dorso-lateral hypothalamus. Processing of POMC in the cell bodies of the arcuate nucleus follows a similar pattern as in the pituitary intermediate lobe. Endopeptidases called "acid-thiol-arginyl-proteases" cleave the prohormone at paired basic amino acids. The basic residues remaining on the resulting peptides are subsequently eliminated by the joint action of the less specific B-type carboxypeptidases and B-type aminopeptidases. alpha-MSH and beta-endorphin are among the major end products. Enzymatic modifications including N-alpha-acetylation by opiomelanotropin-acetyltransferase (OMAT) and/or C-terminal amidation by peptidyl-glycine alpha-amidating monooxygenase (PAM) occur after proteolytic processing. However, the rate of acetylation observed in hypothalamic POMC neurons is much lower than in the melanotrophs of the pars intermedia. Acetylation of MSH and endorphin is crucial in determining the biological potency of these peptides. Desacetyl alpha-MSH is far less active than alpha-MSH (monoacetyl alpha-MSH), whereas acetylated beta-endorphin has no opiate activity. The mechanisms regulating the activity of POMC-containing neurons are still unknown.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Dupuytren's contracture, alcohol consumption, and chronic liver disease.

This prospective study was undertaken to assess the prevalence of Dupuytren's contracture (DC) and its relationship with possible causes, especially alcohol consumption and chronic liver disease. Four hundred thirty-two consecutively hospitalized patients were examined for evidence of DC. They were divided into five groups based on the following clinical, biologic, and histologic criteria: alcoholic cirrhosis (89 patients), noncirrhotic alcoholic liver disease (55 patients), chronic alcoholism without liver disease (46 patients), nonalcoholic chronic liver disease (68 patients), and a control group (174 patients). The prevalence of DC in these five groups of patients was 32.5%, 22%, 28%, 6%, and 12%, respectively; the prevalence of DC was higher in patients with cirrhotic or noncirrhotic alcoholic liver disease (25.5%) than it was in patients with nonalcoholic liver disease (6%), but it was not significantly different in alcoholic patients with or without liver disease. The relationship between DC and age, sex, manual labor, previous hand injuries, diabetes mellitus, alcohol consumption, and cigarette smoking was assessed by univariate and logistic regression methods. Nine variables were significantly different in patients with or without DC: age, sex, manual labor, previous hand injuries, diabetes mellitus, daily alcohol consumption, duration of alcohol consumption, total alcohol consumption, and duration of cigarette smoking. In our patients, variables that could explain DC were, in decreasing order, age, total alcohol consumption, sex (male), and previous hand injuries. In alcoholic patients, these variables were age and previous hand injuries; in nonalcoholic patients, these variables were age and cigarette smoking. These results emphasize the high prevalence of DC in alcoholic patients and the absence of a correlation between DC and chronic liver disease. Age and alcohol consumption are the best explanatory variables of DC in hospitalized patients.

Adolescent↗