Mixed neuroendocrine-non-neuroendocrine neoplasms of the right colon: a case report

Mixed neuroendocrine-non neuroendocrine neoplasm (MiNENs) is a rare gastrointestinal neoplasm that has been redefined by the World Health Organization (WHO) in 2017 as the association of two types of components, neuroendocrine and non-neuroendocrine, each of them present in at least 30% of the tumour mass. Small case reports and case series have demonstrated the occurrence of this neoplasm in the colon. We here report the case of a 47-year-old man undergoing colonscopy for anemia. This showed impassable polypoidal tumor budding in the right colic flexure. Computerized tomography (CT) scan and magnetic resonance imaging (MRI) showed the presence of liver metastases. As the tumor was hemorrhagic, right hemicolectomy with lymph node dissection was performed. The histological examination showed MiNEN of the ascending colon. The patient received adjuvant chemotherapy

Targeted expression of a dominant-negative fibroblast growth factor (FGF) receptor in gonadotropin-releasing hormone (GnRH) neurons reduces FGF responsiveness and the size of GnRH neuronal population

Increasing evidence suggests that fibroblast growth factors (FGFs) are neurotrophic in GnRH neurons. However, the extent to which FGFs are involved in establishing a functional GnRH system in the whole organism has not been investigated. In this study, transgenic mice with the expression of a dominant-negative FGF receptor mutant (FGFRm) targeted to GnRH neurons were generated to examine the consequence of disrupted FGF signaling on the formation of the GnRH system. To first test the effectiveness of this strategy, GT1 cells, a GnRH neuronal cell line, were stably transfected with FGFRm. The transfected cells showed attenuated neurite outgrowth, diminished FGF-2 responsiveness in a cell survival assay, and blunted activation of the signaling pathway in response to FGF-2. Transgenic mice expressing FGFRm in a GnRH neuron-specific manner exhibited a 30% reduction in GnRH neuron number, but the anatomical distribution of GnRH neurons was unaltered. Although these mice were initially fertile, they displayed several reproductive defects, including delayed puberty, reduced litter size, and early reproductive senescence. Overall, our results are the first to show, at the level of the organism, that FGFs are one of the important components involved in the formation and maintenance of the GnRH system

Influence de l'anisotropie initiale et induite sur l'instabilité plastique en emboutissage

The intented result of this thesis is to elaborate a model of the influence of the initial and the induced anisotropy onto the development of plastic instabilities during the deep-drawing process. The thesis is divided into three parts : the first part is a summary of biography concerning models of the influence of the plastic instability using structural criteria like localized or diffused necking. The second part is deduced to initial anisotropical hardening law. The solution procedure can be divided into three steps : linearized analysis of the plastic instability; the model of Marciniak-Kuczinski combined with the rotational effects; the application to strongly anisotropic materials (Ti-Zr). The third part considers the induced anisotropy simulated by a kinematic hardening model which also considers the rotational effectLe but de ce travail est de modèliser l'influence de l'anisotropie initiale et induite sur le développement des instabilités plastiques. Le travail est divisé en trois parties : la première partie est une étude bibliographique de la modélisation de l'instabilité plastique, en faisant appel aux critères d'apparition de striction localisée et diffuse. La deuxième partie consacrée à des matériaux ayant une forte anisotropie initiale et dont l'évolution est régie par une loi d'écrouissage isotrope. Cette partie comprend trois étapes : analyse linéarisée de l'instabilité plastique; étude de l'approche Marciniak-Kuczunski combinée à l'effet de rotation; application au zirconium et au titane. Dans la troisième partie, on fait intervenir l'anisotropie induite, modélisée par l'écrouissage cinématique, en tenant compte de l'effet de rotatio

Influence de l'anisotropie initiale et induite sur l'instabilite plastique en emboutissage

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Localization of Olfactory Cyclic Nucleotide-Gated Channels in Rat Gonadotropin-Releasing Hormone Neurons

The GT1 GnRH cell lines express all three subunits of the cyclic nucleotide-gated (CNG) channels (CNG2, 4.3 and 5) expressed in olfactory neurons. We investigated using in situ hybridization and double immunofluorescence whether endogenous GnRH neurons in therat also express CNG channel subunits. Sections from male and female adult rats were hybridized with a digoxigenin-labeled riboprobe made to regions of rat GnRH, CNG2, CNG4.3 or CNG5 cDNAs. In both sexes, 70–80% of GnRH neurons contained mRNAs for CNG2, CNG4.3 and CNG5. Similarly, double immunofluorescence staining for GnRH and CNG2, CNG4.3 or CNG5 confirmed that 70–80% of GnRH perikarya contained all three CNG subunit proteins. Moreover, the distribution of the immunostaining of CNG subunits in the external layer of the median eminence overlapped with GnRH with the presence of functional cAMP-gated cation channels. The presence of CNG channel subunits in the median eminence supports the notion that coordination of the excitability of the scattered GnRH perikarya may occur at the level of the nerve terminals

Changes in Hypothalamic Gene Expression Associated with the Arrest of Pulsatile Gonadotropin-Releasing Hormone Release during Infancy in the Agonadal Male Rhesus Monkey (Macaca mulatta)

This study examined whether changes in the levels of the messenger RNAs (mRNAs) encoding the g-aminobutyric acid (GABA) synthesizing enzymes, glutamate decarboxylase (GAD)65 and GAD67 and transforming growth factor-a (TGFa) in the hypothalamus are correlated with the arrest of pulsatile GnRH release during infancy in the agonadal male monkey. This experiment also provided the opportunity to examine changes in hypothalamic GnRH gene expression during this critical phase of primate development. Male rhesus monkeys were castrated at 1 week of age: four were killed 4–7 weeks after orchidectomy while pulsatile GnRH release was robust as reflected by high circulating LH levels, and four were killed at 12–15 months of age after establishing that pulsatile GnRH release had been arrested. GAD65, GAD67, TGFa, and GnRH mRNA levels were estimated using RNase protection assays employing homologous probes and the results were expressed relative to cyclophilin mRNA levels. GnRH peptide was measured by RIA. GAD65 and GAD67 mRNA levels in the hypothalamus of juveniles were significantly greater than those in neonatal monkeys. On the other hand, hypothalamic TGFa and GnRH mRNA (and peptide) levels in agonadal neonate and juvenile monkeys were indistinguishable. These results indicate that the molecular concomitants associated with bringing the hypothalamic GnRH pulse generator into check in agonadal neonatal males are not a mirror image of those previously reported at the time this neuronal network is reactivated at puberty when TGFa and GnRH gene expression increase and GAD65 and GAD67 mRNA levels remain unchanged. Thus, the neurobiological mechanism that reactivates pulsatile GnRH release at puberty is likely to involve more than a simple reversal of that underlying inhibition of the same network in late infancy. (Endocrinology 141: 3273–3277, 2000

Neuropeptide Y: A hypothalamic brake restraining the onset of puberty in primates

The adult reproductive axis is driven by an intermittent discharge of gonadotropin-releasing hormone (GnRH) generated by a network of hypothalamic neurons known as the GnRH pulse generator. Although this signal generator is operational in infant primates, puberty in these species is delayed by activation shortly after birth of a central neural mechanism that holds GnRH release in check during juvenile development. Here, we show that, in the male rhesus monkey, the postnatal pattern in GnRH pulse generator activity is inversely related to that in neuropeptide Y (NPY) gene and protein expression in the mediobasal hypothalamus and that central administration of an NPY Y1 receptor antagonist to juvenile animals elicits precocious GnRH release. Cell imaging indicated that the developmentally regulated NPY neurons may be located in regions dorsal to the arcuate nucleus. These findings lead us to propose that NPY is a fundamental component of the neurobiological brake restraining the onset of puberty in primates

Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats

Experiments in the GT1 gonadotropin-releasing hormone (GnRH) cell line have shown that the cAMP signaling pathway plays a central role in regulating the excitability of the cells. Lowering cAMP levels by expressing the constitutively active cAMP-specific phosphodiesterase PDE4D1 in GT1 cells inhibited spontaneous Ca2+ oscillations and intrinsic pulsatile GnRH secretion. To address the role of cAMP levels in endogenous GnRH neurons, we genetically targeted expression of PDE4D1 (P) to GnRH neurons in transgenic rats (R) by using the GnRH gene promoter/enhancer regions (G). Three lines of transgenic rats, GPR-2, -4, and -5, were established. In situ hybridization and RT-PCR studies demonstrated that transgene expression was specifically targeted to GnRH neurons. Decreased fertility was observed in female but not in male rats from all three lines. The mean luteinizing hormone (LH) levels in ovariectomized rats were significantly reduced in the GPR-4 and -5 lines but not in the GPR-2 line. In castrated male and female GPR-4 rats, the LH pulse frequency was dramatically reduced. Six of twelve GPR-4 females studied did not ovulate and had polycystic ovaries. The remaining six females ovulated, but the magnitude of the preovulatory LH surge was inhibited by 63%. These findings support the hypothesis that cAMP signaling may play a central role in regulating excitability of GnRH neurons in vivo. The GPR-4 line of transgenic rats provides a genetic model for the understanding of the role of pulsatile gonadotropin release in follicular development

Development and organization of the hypophysiotropic hypothalamus driving the pituitary-gonadal axis in the rhesus monkey

Abstract Le but de cette revue est de décrire, tout particulièrement chez le singe rhésus, l\u27ontogenèse et l\u27organisation fonctionnelle du générateur de pulse à GnRH au niveau de l\u27hypothalamus. Cette fonction est assurée chez les primates, par un groupe d\u27environ 1 000 neurones répartis diffusément dans l\u27ensemble de l\u27hypothalamus. Le GnRH, initialement produit sous forme d\u27une préhormone, est déversé dans la circulation porte-hypothalamo-hypophysaire et va permettre la libération de FSH et LH. Abstract The purpose of the present review is to describe, with particular emphasis on the rhesus monkey, the ontogeny and functional organisation of the hypothalamic GnRH pulse generator. Control of pituitary-gonadal axis in higher primates is provided by a group of some 1,000 GnRH neurons that are diffusely distributed throughout the hypothalamus. After synthesis of a prehormone and formation of the mature decapeptide, GnRH is released in the hypophysial portal circulation and stimulates FSH and LH production