No description available.

Neuroendocrine tumors (NETs) are a rare type of malignancy, however, their incidence and prevalence have markedly increased over the past several decades. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), NETs of the gastrointestinal (GI) tract, account for the majority of these tumors. Data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI), as well as from multiple cancer registries in Canada and Europe, indicate that the small intestine is one of the most common primary sites of GEP-NET development in Caucasian populations. Smaller studies from Asian countries, however, report a significantly lower proportion of small intestinal NETs (SI-NETs) in those countries’ populations. Interestingly, this finding persists in a study of Asians living in the United States, which, therefore, may suggest that genetics, and not environment, play a predominant role in driving this difference. Multiple studies exploring the genetics of SI-NETs in Caucasians have been published and have identified several genetic alterations implicated in tumorigenesis. However, the most consistently reported finding is chromosome 18 loss of heterozygosity (chr18 LOH), which has been detected in 61-78% of SI-NETs. Unfortunately, these studies have yet to be performed in a strictly Asian cohort. The proposed study, therefore, is a multicenter, cross-sectional study that will compare the proportion of SI-NETs with chr18 LOH in Asian versus Caucasian populations by performing a fluorescence in-situ hybridization (FISH) analysis of SI-NET tissue from both Asian and Caucasian samples. Overall, the results of this study may help to identify possible mechanisms driving the difference in proportion of SI-NETs between Asians and Caucasians, which in turn, may help to better characterize the genetic events leading into SI-NET tumorigenesis.

BACKGROUND: Kisspeptin has recently been deemed the critical central regulatory factor for gonadotropin releasing hormone (GnRH) release. Through the control of GnRH release, kisspeptin is also responsible for the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), both downstream and regulated by GnRH. Kisspeptin is released from kisspeptin, neurokinin B, dynorphin A (KNDy) neurons within the hypothalamus’ arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). As the most prominent regulator of GnRH release, KNDy neurons directly influence the hypothalamic pituitary gonadal (HPG) axis. The HPG axis primarily regulates reproduction and can be inhibited by the presence of stress hormones, glucocorticoids (GCs), and activation of the hypothalamic pituitary adrenal cortex (HPA) axis. It was found that exposure to stress before and during puberty can lead to short-term pubertal delay and long-term physiological and behavioral alterations. It is known that a large portion of kisspeptin neurons contain glucocorticoid receptors (GR) which bind GCs. However, the exact pathway that allows HPA axis activation to inhibit the HPG axis is still unknown. OBJECTIVE: The objective of this study is to understand how kisspeptin neurons mediate the relationship between the HPG and HPA axis and if the lack of GR from kisspeptin neurons alters pubertal development. METHODS: A mouse model with the targeted deletion of GR from Kiss1 expressing neurons GRflox/flox; Kiss1-Cre (Kiss1GRKO) was compared to control (GRflox/flox) mice in phenotypic pubertal development studies. To determine if the removal of GR from Kiss1 expressing neurons affected pubertal development we began data recording of male and female mice phenotypes beginning on postnatal day (PND) twenty-one after weaning. We collected data assessing the body weight of the animal and age and body weight of preputial separation (PS), vaginal opening (VO), and first estrus, markers of pubertal development in mice. RESULTS: The removal of GR from Kiss1 expressing neurons did not cause a significant difference in pubertal development. Male and female Kiss1GRKO and GRflox/flox mice did not have significantly different ages or body weights at PS or VO, nor was age and body weight significantly altered at first estrus. CONCLUSION: The removal of GR and therefore the loss of the ability for Kiss1 expressing neurons to bind GCs does not appear to significantly alter pubertal development in male and female Kiss1GRKO mice. Further research and studies are necessary to determine if GR in kisspeptin neurons mediate the effects of stress on pubertal development.

Neuroendocrine cell populations were systematically studied and characterized in the thymus, an avian primary immune organ. The expression of the specific mRNAs for both Chromogranin A (CgA) and Carboxypeptidase E (CpE) in the thymus was first verified by RT-PCR. Additional evidence using immunofluorescent dual labeling, has demonstrated for the first time the co-existence of CgA and CpE in identical neuroendocrine cells at the protein level in a vetebrate primary lymphoid organ. These CpE- and CgA-positive cells were primarily found in the transition zone between the cortex and the medulla of the thymic lobules, an area known to contain numerous arterioles and to be heavily innervated by the autonomic nervous system, suggesting that these cell population can potentially receive input from each other, from the autonomous nervous system, from the circulation, or all of the above. (Neuro)endocrine messenger molecules produced by the thymic microenvironment, such as somatostatin (SST), seem to play a potentially important immunomodulatory role with regard to cell proliferation, differentiation, and migration, as well as cytokine production. The results showed that both SST and its receptor, SSTR2, are expressed locally within chicken thymus. The in vitro study showed that SST significantly inhibits IL-2 and concanavalin A (ConA) induced proliferation of thymocytes. In comparison with controls (medium containing IL-2 and ConA but without SST), addition of SST at 10-9 M and 10-6 M resulted in a nearly 20% decrease in proliferation (P < 0.01). The effects of somatostatin (SST) on the immune system, the role of SST on the gene expression of cytokines (IL-1, TGF, INF), chemokine receptors (CXCR4) as well as MHC-I components was assessed by real-time PCR. The question as to exactly which stimuli trigger the release of mediators such as somatostatin remains for future study. In addition, a complete inventory of all substances stored in the thymic LDCV and their effects on the developing T-cells when released in the microenvironment of the thymus are also questions that warrant further investigation.

Neuroendocrine cell populations were systematically studied and characterized in the thymus, an avian primary immune organ. The expression of the specific mRNAs for both Chromogranin A (CgA) and Carboxypeptidase E (CpE) in the thymus was first verified by RT-PCR. Additional evidence using immunofluorescent dual labeling, has demonstrated for the first time the co-existence of CgA and CpE in identical neuroendocrine cells at the protein level in a vetebrate primary lymphoid organ. These CpE- and CgA-positive cells were primarily found in the transition zone between the cortex and the medulla of the thymic lobules, an area known to contain numerous arterioles and to be heavily innervated by the autonomic nervous system, suggesting that these cell population can potentially receive input from each other, from the autonomous nervous system, from the circulation, or all of the above. (Neuro)endocrine messenger molecules produced by the thymic microenvironment, such as somatostatin (SST), seem to play a potentially important immunomodulatory role with regard to cell proliferation, differentiation, and migration, as well as cytokine production. The results showed that both SST and its receptor, SSTR2, are expressed locally within chicken thymus. The in vitro study showed that SST significantly inhibits IL-2 and concanavalin A (ConA) induced proliferation of thymocytes. In comparison with controls (medium containing IL-2 and ConA but without SST), addition of SST at 10-9 M and 10-6 M resulted in a nearly 20% decrease in proliferation (P < 0.01). The effects of somatostatin (SST) on the immune system, the role of SST on the gene expression of cytokines (IL-1, TGF, INF), chemokine receptors (CXCR4) as well as MHC-I components was assessed by real-time PCR. The question as to exactly which stimuli trigger the release of mediators such as somatostatin remains for future study. In addition, a complete inventory of all substances stored in the thymic LDCV and their effects on the developing T-cells when released in the microenvironment of the thymus are also questions that warrant further investigation.

No description available.

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 5 uppsatser.

Aims: Test the putative contribution of 17-beta-estradiol in the development of spreading depression (SD) events and head pain in awake, non-restrained rats. Main Methods: Female, Sprague-Dawley rats were intact or underwent ovariectomy followed one week later by surgery to place electrodes onto the dura to detect epidural electroencephalographic activity (dEEG). dEEG activity was recorded two days later for 12 hours after systemic administration of 17-beta-estradiol (180 mu g/kg, i.p.). A separate set of rats were observed for changes in exploratory, ambulatory, fine, and rearing behaviors; periorbital allodynia was also assessed. Key Findings: A bolus of 17-beta-estradiol significantly elevated serum estrogen levels, increased SD episodes over a 12-hour recording period and decreased rearing behaviors in ovariectomized rats. Pre-administration of ICI 182,780, an estrogen receptor antagonist, blocked 17-beta-estradiol-evoked SD events and pain behaviors; similar results were observed when the antimigraine therapeutic sumatriptan was used. Significance: These data indicate that an estrogen receptor-mediated mechanism contributes to SD events in ovariectomized rats and pain behaviors in both ovariectomized -and intact-rats. This suggests that estrogen plays a different role in each phenomenon of migraine where intense fluctuations in concentration may influence SD susceptibility. This is the first study to relate estrogen peaks to SD development and pain behaviors in awake, freely moving female rats, establishing a framework for future preclinical migraine studies.

Concurrence of adenocarcinoma and large-cell neuroendocrine carcinoma of the stomach is a rare condition. Here, we report a case of gastric collision tumour with large-cell neuroendocrine carcinoma and adenocarcinoma. A 71-year-old Peruvian man presented with nausea, epigastric pain, and weight loss for seven months. An Endoscopic evaluation revealed a huge ulcerative and infiltrative mass in the upper and middle third of the stomach. The patient underwent a D2 total gastrectomy. Microscopically, two separated and attached ulcerative lesions were recognised. The proximal to the cardial lesion showed neuroendocrine morphology and immunoreactivity for synaptophysin, and the other a moderated tubular adenocarcinoma Borrmann type III. Both lesions invaded serosa and lymph nodes metastases were found in 17 of 41 lymph nodes retrieved (one lymph node with neuroendocrine metastatic deposits).

No description available.