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Neuroendocrine Cells (neuroendocrine + cell)
Terms modified by Neuroendocrine Cells Selected AbstractsA Study of Moderately Differentiated Neuroendocrine Carcinomas of the Larynx and an Examination of Non-Neoplastic Larynx Tissue for Neuroendocrine CellsTHE LARYNGOSCOPE, Issue 7 2004Jin-Haeng Chung MD Abstract Objectives/Hypothesis: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist. Study Design: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells. Methods: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells. Results: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin. Conclusions: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC. [source] Cell type-specific transgene expression of the prion protein in Xenopus intermediate pituitary cellsFEBS JOURNAL, Issue 4 2006Jos W. G. Van Rosmalen The cellular form of prion protein (PrPC) is anchored to the plasma membrane of the cell and expressed in most tissues, but predominantly in the brain, including in the pituitary gland. Thus far, the biosynthesis of PrPC has been studied only in cultured (transfected) tumour cell lines and not in primary cells. Here, we investigated the intracellular fate of PrPCin vivo by using the neuroendocrine intermediate pituitary melanotrope cells of the South-African claw-toed frog Xenopus laevis as a model system. These cells are involved in background adaptation of the animal and produce high levels of its major secretory cargo proopiomelanocortin (POMC) when the animal is black-adapted. The technique of stable Xenopus transgenesis in combination with the POMC gene promoter was used as a tool to express Xenopus PrPC amino-terminally tagged with the green fluorescent protein (GFP,PrPC) specifically in the melanotrope cells. The GFP,PrPC fusion protein was expressed from stage-25 tadpoles onwards to juvenile frogs, the expression was induced on a black background and the fusion protein was subcellularly located mainly in the Golgi apparatus and at the plasma membrane. Pulse,chase metabolic cell labelling studies revealed that GFP,PrPC was initially synthesized as a 45-kDa protein that was subsequently stepwise glycosylated to 48-, 51-, and eventually 55-kDa forms. Furthermore, we revealed that the mature 55-kDa GFP,PrPC protein was sulfated, anchored to the plasma membrane and cleaved to a 33-kDa product. Despite the high levels of transgene expression, the subcellular structures as well as POMC synthesis and processing, and the secretion of POMC-derived products remained unaffected in the transgenic melanotrope cells. Hence, we studied PrPC in a neuroendocrine cell and in a well-defined physiological context. [source] Serotonin content of normal and inflamed appendix: a possible role of serotonin in acute appendicitis,APMIS, Issue 11 2008MOHAMMAD VASEI The appendix is lined by a mucosa which has many neuroendocrine cells containing serotonin. Local release of serotonin can act as a mediator of inflammation. In this study we explored the serotonin content of the neuroendocrine cells of the appendixes removed for clinical diagnosis of appendicitis. Appendix specimens were divided into three groups: Acute appendicitis (AA), non-appendicitis (NA), and follicular hyperplasia (FH). Normal appendix specimens from patients undergoing elective abdominal surgery were used as the control group (NL). All sections were exposed to proteinase K, incubated with anti-serotonin, chromogranin A, and synaptophysin antibodies, and treated with the LSAB kit. Polygonal cells were seen within the crypt epithelium (enterochromaffin cell, EC) and within the lamina propria (subepithelial neuroendocrine cell, SNC). In AA, only 16 cases (64%) showed serotonin staining in non-destructed glands. There was a significant reduction in the number of ECs in AA compared to the FH (96%), NA (100%) and NL (100%) groups (P<0.001). Chromogranin and synaptophysin immunostaining also showed a significant reduction in the number of ECs in AA compared with the other three groups (P<0.001). SNC serotonin reactivity was lower in the AA group compared with the other groups (p<0.001). The inflamed appendix is markedly depleted of serotonin in the epithelium and lamina propria. Local serotonin release from ECs and SNCs in the appendix may act as an inflammatory mediator in appendicitis and is likely to be the source of raised blood serotonin in AA. [source] Cell type,specific expression of adenomatous polyposis coli in lung development, injury, and repairDEVELOPMENTAL DYNAMICS, Issue 8 2010Aimin Li Abstract Adenomatous polyposis coli (Apc) is critical for Wnt signaling and cell migration. The current study examined Apc expression during lung development, injury, and repair. Apc was first detectable in smooth muscle layers in early lung morphogenesis, and was highly expressed in ciliated and neuroendocrine cells in the advanced stages. No Apc immunoreactivity was detected in Clara or basal cells, which function as stem/progenitor cell in adult lung. In ciliated cells, Apc is associated mainly with apical cytoplasmic domain. In response to naphthalene-induced injury, Apcpositive cells underwent squamous metaplasia, accompanied by changes in Apc subcellular distribution. In conclusion, both spatial and temporal expression of Apc is dynamically regulated during lung development and injury repair. Differential expression of Apc in progenitor vs. nonprogenitor cells suggests a functional role in cell-type specification. Subcellular localization changes of Apc in response to naphthalene injury suggest a role in cell shape and cell migration. Developmental Dynamics 239:2288,2297, 2010. © 2010 Wiley-Liss, Inc. [source] Contribution of Kir3.1, Kir3.2A and Kir3.2C subunits to native G protein-gated inwardly rectifying potassium currents in cultured hippocampal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2003Joanne L. Leaney Abstract G protein-gated inwardly rectifying potassium (GIRK) channels are found in neurons, atrial myocytes and neuroendocrine cells. A characteristic feature is their activation by stimulation of Gi/o -coupled receptors. In central neurons, for example, they are activated by adenosine and GABA and, as such, they play an important role in neurotransmitter-mediated regulation of membrane excitability. The channels are tetrameric assemblies of Kir3.x subunits (Kir3.1,3.4 plus splice variants). In this study I have attempted to identify the channel subunits which contribute to the native GIRK current recorded from primary cultured rat hippocampal pyramidal neurons. Reverse transcriptase,polymerase chain reaction revealed the expression of mRNA for Kir3.1, 3.2A, 3.2C and 3.3 subunits and confocal immunofluorescence microscopy was used to investigate their expression patterns. Diffuse staining was observed on both cell somata and dendrites for Kir3.1 and Kir3.2A yet that for Kir3.2C was weaker and punctate. Whole-cell patch clamp recordings were used to record GIRK currents from hippocampal pyramidal neurons which were identified on the basis of inward rectification, dependence of reversal potential on external potassium concentration and sensitivity to tertiapin. The GIRK currents were enhanced by the stimulation of a number of Gi/o -coupled receptors and were inhibited by pertussis toxin. In order to ascertain which Kir3.x subunits were responsible for the native GIRK current I compared the properties with those of the cloned Kir3.1 + 3.2A and Kir3.1 + 3.2C channels heterologously expressed in HEK293 cells. [source] The C-terminal region of the proprotein convertase 1/3 (PC1/3) exerts a bimodal regulation of the enzyme activity in vitroFEBS JOURNAL, Issue 13 2007Nadia Rabah The proprotein convertase PC1/3 preferentially cleaves its substrates in the dense core secretory granules of endocrine and neuroendocrine cells. Similar to most proteinases synthesized first as zymogens, PC1/3 is synthesized as a larger precursor that undergoes proteolytic processing of its signal peptide and propeptide. The N-terminally located propeptide has been shown to be essential for folding and self-inhibition. Furthermore, PC1/3 also possesses a C-terminal region (CT-peptide) which, for maximal enzymatic activity, must also be cleaved. To date, its role has been documented through transfection studies in terms of sorting and targeting of PC1/3 and chimeric proteins into secretory granules. In this study, we examined the properties of a 135-residue purified bacterially produced CT-peptide on the in vitro enzymatic activity of PC1/3. Depending on the amount of CT-peptide used, it is shown that the CT-peptide increases PC1/3 activity at low concentrations (nm) and decreases it at high concentrations (µm), a feature typical of an activator. Furthermore, we show that, contrary to the propeptide, the CT-peptide is not further cleaved by PC1/3 although it is sensitive to human furin activity. Based on these results, it is proposed that PC1/3, through its various domains, is capable of controlling its enzymatic activity in all regions of the cell that it encounters. This mode of self-control is unique among members of all proteinases families. [source] Histogenesis of Abrikossoff tumour of the oral cavityINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 1 2010F Haikal Abstract:, Background:, Abrikossoff or granular cell tumour (GCT) is a relatively rare neoplasia, benign in most of the cases. It may occur in any part of the human body, but it has an oral location in 70% of the cases. Its origin has been discussed for decades, and it is not yet definitively determined. Immunohistochemical techniques suggest its origin in the Schwann cells, while more recent studies with new markers indicate an origin related to neuroendocrine cells. Objective:, Contribute to the clarification of histogenesis of oral Abrikossoff tumour studying immunohistochemical marking of 11 oral Brazilian cases. Materials and methods:, Samples of tissues from the oral mucosa, tongue and lips placed in paraffin blocks, from eleven patients with a histopathological diagnosis of benign GCT were studied. Four different anti-serums (S-100, vimentin, PGP9.5 and ENE) were used for immunoperoxydase technique. Results:, A clear positivity for S-100 protein and vimentin was observed, with markers indicating origin from the Schwann cells. Less intense positivity was found in some cases, for ENE and PGP9.5, which suggests a neuroendocrine origin. Conclusions:, The results obtained suggest an origin from Schwann cells, but also arise the possibility of neuroendocrine origin. New methods and more specific immunohistochemical markers are needed to elucidate the origin of the Abrikossoff tumour. [source] Primary carcinoid tumor of the bilateral testis associated with carcinoid syndromeINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004HYUN-YOUNG SON Abstract Carcinoid tumors derived from neuroendocrine cells can release serotonin and other vasoactive substances into the systemic circulation, resulting in carcinoid syndrome. Testicular carcinoid, a rare disease accounting for less than 1% of all testicular neoplasms, rarely manifests symptoms of carcinoid syndrome. We describe a case of carcinoid syndrome arising from a primary testicular carcinoid tumor. A 21-year-old male patient presented with facial flushing and diarrhea for 5 years. He had an enlarged left testis and a 1-cm, ill-defined, hard, non-tender mass in his right testis. His 24 h urinary excretion of 5-hydroxyindoleacetic acid was elevated (16.1 mg/day). Somatostatin receptor scintigraphy correlated with carcinoid tumor in both testes. Following bilateral orchiectomy, the patient's facial flushing and diarrhea disappeared. [source] Functions of erg K+ channels in excitable cellsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004Jürgen R. Schwarz Abstract Ether-à-go-go -related gene (erg) channels are voltage-dependent K+ channels mediating inward-rectifying K+ currents because of their peculiar gating kinetics. These characteristics are essential for repolarization of the cardiac action potential. Inherited and acquired malfunctioning of erg channels may lead to the long QT-syndrome. However, erg currents have also been recorded in many other excitable cells, like smooth muscle fibres of the gastrointestinal tract, neuroblastoma cells or neuroendocrine cells. In these cells erg currents contribute to the maintenance of the resting potential. Changes in the resting potential are related to cell-specific functions like increase in hormone secretion, frequency adaptation or increase in contractility. [source] Merkel cell carcinoma with squamous and sarcomatous differentiationJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2008June H. K. Hwang Merkel cell carcinoma is an aggressive neuroendocrine tumor historically thought to arise from neural crest-derived cutaneous neuroendocrine cells. Recent evidence supports an epidermal origin. We present a case of Merkel cell carcinoma arising on the upper arm of a 94-year-old woman that had multiple morphologic patterns: small cells typical of Merkel cell carcinoma, malignant cells with squamous differentiation and malignant poorly differentiated spindle cells. Subsequent metastatic disease in regional lymph nodes showed only the small cells and the malignant spindle cells. To our knowledge, this is the first case of Merkel cell carcinoma showing these three patterns of differentiation at first presentation. This morphology raises the possibility that Merkel cell carcinomas may arise from epidermal stem cells that can differentiate along different lines. [source] Magnetic resonance imaging in the detection of pancreatic neoplasmsJOURNAL OF DIGESTIVE DISEASES, Issue 3 2007Liang ZHONG Recently, with the rapid scanning time and improved image quality, outstanding advances in magnetic resonance (MR) methods have resulted in an increase in the use of MRI for patients with a variety of pancreatic neoplasms. MR multi-imaging protocol, which includes MR cross-sectional imaging, MR cholangiopancreatography and dynamic contrast-enhanced MR angiography, integrates the advantages of various special imaging techniques. The non-invasive all-in-one MR multi-imaging techniques may provide the comprehensive information needed for the preoperative diagnosis and evaluation of pancreatic neoplasms. Pancreatic neoplasms include primary tumors and pancreatic metastases. Primary tumors of the pancreas may be mainly classified as ductal adenocarcinomas, cystic tumors and islet cell tumors (ICT). Pancreatic adenocarcinomas can be diagnosed in a MRI study depending on direct evidence or both direct and indirect evidence. The combined MRI features of a focal pancreatic mass, pancreatic duct dilatation and parenchymal atrophy are highly suggestive of a ductal adenocarcinoma. Most cystic neoplasms of the pancreas are either microcystic adenomas or mucinous cystic neoplasms. Intraductal papillary mucinous tumors are the uncommon low-grade malignancy of the pancreatic duct. ICT are rare neoplasms arising from neuroendocrine cells in the pancreas or the periampullary region. ICT are classified as functioning and non-functioning. The most frequent tumors to metastasize to the pancreas are cancers of the breast, lung, kidney and melanoma. The majority of metastases present as large solitary masses with well-defined margins. [source] The polybasic sequence in the C2B domain of rabphilin is required for the vesicle docking step in PC12 cellsJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Takashi Tsuboi Abstract Rabphilin is generally thought to be involved in the regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, and it has recently been hypothesized that the C2B domain of rabphilin promotes the docking of dense-core vesicles to the plasma membrane through simultaneous interaction with a vesicle protein, Rab3A/27A, and a plasma membrane protein, SNAP-25 (synaptosome-associated protein of 25 kDa). However, the physiological significance of the rabphilin,SNAP-25 interaction in the vesicle-docking step has never been elucidated. In this study we demonstrated by a mutation analysis that the polybasic sequence (587 KKAKHKTQIKKK 598) in the C2B domain of rabphilin is required for SNAP-25 binding, and that the Asp residues in the Ca2+ -binding loop 3 (D628 and D630) of the C2B domain are not required. We also investigated the effect of Lys,Gln (KQ) mutations in the polybasic sequence of the C2B domain on vesicle dynamics by total internal reflection fluorescence microscopy in individual PC12 cells. A rabphilin(KQ) mutant that completely lacks SNAP-25-binding activity significantly decreased the number of plasma-membrane-docked vesicles and strongly inhibited high-KCl-induced dense-core vesicle exocytosis. These results indicate that the polybasic sequence in the C2B domain functions as an effector domain for SNAP-25 and controls the number of ,releasable' vesicles docked to the plasma membrane. [source] Increased synthesis but decreased processing of neuronal proCCK in prohormone convertase 2 and 7B2 knockout animalsJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Jens F. Rehfeld Abstract In addition to its role as a gut hormone, cholecystokinin (CCK) is a widespread and potent neurotransmitter. Its biosynthesis requires endoproteolytic cleavage of proCCK at several mono- and dibasic sites by subtilisin-like prohormone convertases (PCs). Of these, PC1 and PC2 are specific for neuroendocrine cells. We have now examined the role of PC2 and its binding protein, 7B2, in the neuronal processing of proCCK by measurement of precursor, processing-intermediates and bioactive end-products in brain extracts from PC2- and 7B2-null mice and from corresponding controls. PC2-null mice displayed a nine-fold increase of cerebral proCCK concentrations, and a two-fold increase in the concentrations of the processing-intermediate, glycine-extended CCK, whereas the concentrations of transmitter-active (i.e. ,-amidated and O -sulfated) CCK peptides were reduced (61%). Chromatography showed that O -sulfated CCK-8 still is the predominant transmitter-active CCK in PC2-null brains, but that the fraction of intermediate-sized CCK-peptides (CCK-58, -33 and -22) was eight-fold increased. 7B2-null brains displayed a similar pattern but with less pronounced precursor accumulation. In contrast with the cerebral changes, PC2 deficiency was without effect on proCCK synthesis and processing in intestinal endocrine cells, whereas 7B2 deficiency halved the concentration of bioactive CCK in the intestine. The results show that PC2 plays a major neuron-specific role in the processing of proCCK. [source] Glial Limitans Elasticity Subjacent to the Supraoptic NucleusJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2004A. K. Salm Abstract Two previous studies from our laboratory have indicated that the ventral glial limitans subjacent to the hypothalamic supraoptic nucleus (SON-VGL) undergoes a reversible thinning upon chronic activation of the magnocellular neuroendocrine cells (MNCs) of the supraoptic nucleus (SON). Numerous other studies have shown that MNC somata hypertrophy with activation. One aim of the current study was to understand better how SON-VGL thinning occurs. A second aim was to quantify overall changes of the MNC somata region due to cellular hypertrophy to compare relative changes in dimensions. Here, we undertook a light microscopic stereological investigation of the SON and the subjacent SON-VGL of Nissl stained material under basal and activated conditions. Astrocyte numbers in the underlying SON-VGL remained stable across hydration state as did the overall volume of the SON-VGL and dendritic zone reference area. How these data are consistent with our earlier observations of SON-VGL thinning was resolved by the finding of a highly significant, 30% increase in the mediolateral dimension of the SON-VGL in dehydrated rats. These observations fit well with previous work from our laboratory that demonstrates a reorientation of SON-VGL astrocytes, from vertical to horizontal, which occurs in the activated SON-VGL. We found a significant, approximately 54%, increase in the overall volume of the MNC region of the SON. No significant rostrocaudal lengthening of the SON was detected, although a trend was evident. All the observed changes reversed with rehydration. These data indicate that elasticity of the SON-VGL acts to accommodate the volume expansion of the MNCs and enables the SON-VGL to continue as an interface between the underlying cerebrospinal fluid in the subarachnoid space and the expanded SON above. [source] The Hypothalamic Insulin-Like Growth Factor-1 Receptor and Its Relationship to Gonadotropin-Releasing Hormones Neurones During Postnatal DevelopmentJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2004S. S. Daftary Abstract Reproduction in vertebrates is controlled by hypophysiotropic gonadotropin-releasing hormone (GnRH) neurones. Pulsatile GnRH release increases during reproductive development, resulting in the onset and progression of puberty and, ultimately, the acquisition and maintenance of adult reproductive function. These changes in GnRH release are largely due to inputs to GnRH cells from other factors, including the neurotrophic factor, insulin-like growth factor-1 (IGF-1). Here, molecular studies were undertaken to quantify expression of IGF-1 receptor (IGF-1R) mRNA in the preoptic area-anterior hypothalamus (POA-AH) and mediobasal hypothalamus (MBH)-median eminence (ME), the sites of GnRH perikarya and neuroterminals, respectively. Immunocytochemical studies were also carried out to study the anatomical relationship between the IGF-1R and GnRH neurones. Experiments were performed in a developmental context using neonatal (P5), peripubertal (,P30) and adult (P60) male and female mice. We found that IGF-1R mRNA levels in the POA-AH were significantly different among all age groups, with levels higher at P60 then P5 or ,P30. Levels of IGF-1R mRNA in the MBH-ME were lower at P5 than ,P30 or P60. Qualitative observations suggested that IGF-1R immunoreactivity in POA-AH increased from P5 through P60. Quantitative double-label immunocytochemistry studies showed that GnRH perikarya expressed IGF-1R. Taken together, the results demonstrate expression of, and developmental changes in, IGF-1R gene and protein in brain regions containing GnRH and other neuroendocrine cells. Moreover, the novel finding that the IGF-1R is expressed on GnRH perikarya in vivo suggests a potential direct anatomical locus where IGF-1 can regulate reproductive development and function. [source] Development of Luteinizing Hormone Releasing Hormone NeuronesJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2001S. Wray Abstract This review concentrates on some of the recent discoveries and future questions relevant to the development of the neuroendocrine luteinizing hormone releasing hormone (LHRH) cells. Neuroendocrine LHRH cells originate outside the central nervous system, in the nasal placode, and thereafter migrate into the forebrain during prenatal development. It is this population of LHRH cells that is responsible for reproductive function, becoming integral members of the hypothalamo-pituitary-gonadal axis postnatally. Disruption of the development of this system results in reproductive dysfunction. Increasing our understanding of LHRH neuroendocrine cells establishes conditions where we can look with greater precision at the mechanisms controlling reproductive development, both activation and failure. In addition, the ability to manipulate the molecular and cellular biology of the LHRH system opens the route to understanding critical neurobiological issues such as phenotypic commitment, axonal path finding and mechanisms involved in neuronal migration. Each of the topics is discussed in turn and potential mechanisms controlling the development of the neuroendocrine LHRH system are indicated. [source] Effects of Chronic Oestrogen Replacement on Stress-Induced Activation of Hypothalamic-Pituitary-Adrenal Axis Control PathwaysJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2000C. V. Dayas Abstract Oestrogen replacement therapy reportedly suppresses hypothalamic-pituitary-adrenal (HPA) axis responses to an emotional stressor in postmenopausal women. However, most studies in the rat suggest a facilitatory role for oestrogen in the control of HPA axis function. One explanation for this difference may be the regimen of oestrogen replacement: during oestrogen replacement therapy, oestrogen levels are low and constant whereas most animal studies examined the HPA axis response when oestrogen levels are rising. In the present study, we assessed HPA axis stress responses in mature ovariectomized rats after plasma oestrogen levels had been maintained at physiological levels for a prolonged period (25 or 100 pg/ml for 7 days). In the case of both an emotional stressor (noise) and a physical stressor (immune challenge by systemic interleukin-1, administration), oestrogen replacement suppressed stress-related Fos-like immunolabelling, in hypothalamic neuroendocrine cells and plasma adrenocorticotropin hormone responses. From the present data, and past reports, it appears unlikely that these effects of oestrogen are due to a direct action on corticotropin-releasing factor or oxytocin cells. Therefore, to obtain some indication of oestrogen's possible site(s) of action, Fos-like immunolabelling was mapped in the amygdala and in brainstem catecholamine groups, which are neuronal populations demonstrating substantial evidence of involvement in the generation of HPA axis stress responses. In the amygdala, oestrogen replacement suppressed central nucleus responses to immune challenge, but not to noise. Amongst catecholamine cells, oestrogen replacement was more effective against responses to noise than immune challenge, suppressing A1 and A2 (noradrenergic) and C2 (adrenergic) responses to noise, but only A1 responses to immune challenge. These data suggest that, as in postmenopausal women on oestrogen replacement therapy, chronic low-level oestrogen replacement can suppress HPA axis stress responses in the rat. Moreover, oestrogen appears to exert effects at multiple sites within putative HPA axis control pathways, even though most of the relevant neuronal populations do not contain genomic receptors for this gonadal steroid and the pattern of oestrogen action differs for an emotional vs a physical stressor. [source] Deletion of N-terminus of human tyrosine hydroxylase type 1 enhances stability of the enzyme in AtT-20 cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Akira Nakashima Abstract Wildtype human tyrosine hydroxylase (TH) type 1 and 4 mutants (del-52, a form with the first 52 amino acid residues deleted; del-157, one with the first 157 amino acid residues deleted; RR-EE, one in which Arg37 -Arg38 was replaced by Glu37 -Glu38; and S40D, one in which Ser40 was replaced by Asp40) were expressed in AtT-20 mouse neuroendocrine cells in order to clarify how deeply the N-terminus of TH is involved in the efficient production of dopamine (DA) in mammalian cells. The amounts of DA that accumulated in AtT-20 cells expressing these human TH type 1 (hTH1) phenotypes were in the following order: del-52 = del-157 = RR-EE > S40D > wildtype, although the enzyme activities of del-52 and del-157 were lower than those of wildtype, RR-EE, and S40D. The observation on immunoblot analyses that the N-terminus-deleted hTH1 mutants were much more stable than wildtype can reconcile the discrepant results. Computer-assisted analysis of the spatial configuration of hTH1 identified five newly recognized PEST motifs, one of which was located in the N-terminus sequence of Met1 -Lys12 and predicted that deletion of the N-terminus region would alter the secondary structure within the catalytic domain. Collectively, the high stability of the N-terminus-deleted hTH1 mutants can be generated by the loss of a PEST motif in their N-termini and the structural change in the catalytic domain, which would promise an efficient production of DA in mammalian cells expressing N-terminus deleted hTH1. © 2005 Wiley-Liss, Inc. [source] Regulation of gene expression for neurotransmitters during adaptation to hypoxia in oxygen-sensitive neuroendocrine cellsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2002Waltke R. Paulding Abstract Reduced oxygen tension (hypoxia) in the environment stimulates oxygen-sensitive cells in the carotid body (CB). Upon exposure to hypoxia, the CB immediately triggers a reflexive physiological response, thereby increasing respiration. Adaptation to hypoxia involves changes in the expression of various CB genes, whose products are involved in the transduction and modulation of the hypoxic signal to the central nervous system (CNS). Genes encoding neurotransmitter-synthesizing enzymes and receptors are particularly important in this regard. The cellular response to hypoxia correlates closely with the release and biosynthesis of catecholamines. The gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine biosynthesis, is regulated by hypoxia in the CB and in the oxygen-sensitive cultured PC12 cell line. Recently, genomic microarray studies have identified additional genes regulated by hypoxia. Patterns of gene expression vary, depending on the type of applied hypoxia, e.g., intermittent vs. chronic. Construction of a hypoxia-regulated, CB-specific, subtractive cDNA library will enable us to further characterize regulation of gene expression in the CB. Microsc. Res. Tech. 59:178,187, 2002. © 2002 Wiley-Liss, Inc. [source] Small cell carcinoma of the extrahepatic bile duct: Case report and immunohistochemical analysisPATHOLOGY INTERNATIONAL, Issue 12 2003Kazuya Kuraoka A small cell carcinoma of the extrahepatic bile duct in a 75-year-old Japanese man is reported. The patient suffered from obstructive jaundice, and percutaneous transhepatic cholangiography-drainage (PTCD) revealed a massive lesion in the lower common bile duct. Because it was diagnosed as a malignant tumor, pancreaticoduodenectomy was performed. A nodular infiltrating tumor measuring 4.5 × 3.0 × 2.0 cm was located in the intrapancreatic portion of the extrahepatic bile duct. Histologically, the tumor was composed of a dense proliferation of small atypical cells with a little region of high-grade dysplasia in the adjacent epithelium of the common bile duct. Tumor cells were immunoreactive to neuroendocrine markers such as chromogranin A, synaptophysin, CD56, and Leu7. Although carcinoma cells invaded into pancreas and duodenum, there were no histological findings that indicated the carcinoma arose from the mucosa of either the pancreatic duct or duodenum. These results indicated that the tumor was a small cell carcinoma derived from the epithelium of the extrahepatic bile duct; a rare neoplasm with only a few cases reported. A few neuroendocrine cells were recognized in the adjacent epithelium of the extrahepatic bile duct, suggesting that the tumor cells might be derived from them. Using immunohistochemical examination, no p53 abnormality was found. Tumor cells showed positive nuclear staining for p16, while negative for cyclin D1, suggesting that functional retinoblastoma protein (pRB) might be lost in the p16/pRB pathway, as in small cell lung cancer. [source] Overexpression of keratinocyte growth factor in cancer cells and enterochromaffin cells in human colorectal cancerPATHOLOGY INTERNATIONAL, Issue 5 2000Masanori Watanabe Keratinocyte growth factor (KGF) is a mitogenic polypeptide that is mainly synthesized by mesenchymal cells. Its actions are dependent on its binding to a specific cell-surface KGF receptor (KGFR), which is localized in epithelial cells. In the present study, the expression level of KGF and KGFR messenger RNA (mRNA), and the localization of these mRNA and proteins in tumor specimens obtained from 12 human colorectal cancer cases were estimated. Competitive reverse transcriptase,polymerase chain reaction (RT-PCR) revealed the expression of KGF and KGFR mRNA in both colorectal cancer and normal colorectal tissues. In specimens from 10 of the 12 cancer cases, the KGF mRNA level was higher in the specimens obtained from the cancerous portions than in those obtained from non-cancerous tissues of the same cases. KGFR mRNA was higher in cancerous tissues in eight of 12 cases. To localize the KGF protein in normal and cancerous human colorectal tissues, immunohistochemistry was employed. In normal colorectal tissue, faint KGF immunoreactivity was present in a few fibroblasts. In contrast, strong KGF immunoreactivity was present in many of the neuroendocrine cells present in close proximity to cancer cells, and moderate immunoreactivity was recognized in the cancer cells themselves and adjacent fibroblasts. KGF-positive neuroendocrine cells also showed serotonin immunoreactivity, indicating that they were enterochromaffin cells. By in situ hybridization, both KGF and KGFR mRNA were co-overexpressed in these colorectal cancer cells, and KGF mRNA was recognized in neuroendocrine cells lying in close proximity to the cancer cells. These findings indicate the possibility that KGF acts in both a paracrine and autocrine manner to induce colorectal cancer cell growth in vivo. [source] Familial neuroendocrine cell hyperplasia of infancy,,PEDIATRIC PULMONOLOGY, Issue 8 2010J. Popler MD Abstract Background Neuroendocrine cell hyperplasia of infancy (NEHI) is a recently described children's interstitial lung disease (chILD) disorder of unknown etiology. It manifests clinically with tachypnea, retractions, hypoxemia, and crackles. The characteristic radiographic appearance consists of pulmonary hyperexpansion and ground-glass densities on high-resolution computed tomography (HRCT). Lung histology shows hyperplasia of bombesin-immunopositive neuroendocrine cells within distal bronchioles and alveolar ducts without other identifiable lung pathology or developmental anomaly. Methods We describe four families with multiple siblings diagnosed with NEHI. Cases were identified at three pediatric centers. Inclusion criteria included clinical findings consistent with NEHI, lung biopsy confirmation in the index case, and a diagnostic HRCT or biopsy in other siblings. Results Each family had a proband diagnosed with NEHI based upon pathologic review, and at least one additional sibling diagnosed either by pathologic review or HRCT. All patients presented between 2 and 15 months of age. Both male and female children were affected. The majority of the patients underwent both HRCT and lung biopsy. There were no deaths among affected children. No environmental exposures or other potential etiologies were identified as a cause of presenting symptoms. Conclusions The familial occurrence of NEHI suggests the possibility of a genetic etiology for this disorder and highlights the importance of taking a complete family medical history for infants presenting with a suggestive clinical picture. Identification of familial NEHI patients allows for the opportunity to further our understanding of this disorder, its natural history, the phenotypic spectrum, and potential genetic causes. Pediatr. Pulmonol. 2010; 45:749,755. © 2010 Wiley-Liss, Inc. [source] Correlation-associated peptide networks of human cerebrospinal fluidPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2005Jens Lamerz Dr. Abstract Profiling of peptides and small proteins from either human body fluids or tissues by chromatography and subsequent mass spectrometry reveals several thousand individual peptide signals per sample. Any peptide is an intermediate in the course of biosynthesis, post-translational modification (PTM), proteolytic processing and degradation. Changes in the concentration of one peptide often affects the concentration of the other, hence a challenge consists in the development of suitable tools to turn this large amount of data into biologically relevant information. Comprehensive statistical analysis of the peptide profiling data allows associating peptides, which are closely related in terms of peptide biochemistry. Here, the bioinformatic concept of peptide networks, correlation-associated peptide networks (CANs), is introduced. Peptides with statistical similarity of their concentrations are grouped in form of networks, and these networks are interpreted in terms of peptide biochemistry. The spectrum of functional relationships found in cerebrospinal fluid CAN covers PTM and proteolytic degradation of peptides, clearance processing in the complement cascade, common secretion of peptides by neuroendocrine cells as well as ubiquitin-mediated degradation. Our results indicate that CAN is a powerful bioinformatic tool for the systematic analysis and interpretation of large peptidomics and proteomics data and helps to discover novel bioactive and diagnostic peptides. [source] A Study of Moderately Differentiated Neuroendocrine Carcinomas of the Larynx and an Examination of Non-Neoplastic Larynx Tissue for Neuroendocrine CellsTHE LARYNGOSCOPE, Issue 7 2004Jin-Haeng Chung MD Abstract Objectives/Hypothesis: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist. Study Design: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells. Methods: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells. Results: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin. Conclusions: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC. [source] Protein tyrosine phosphatase PTP1B is involved in neuroendocrine differentiation of prostate cancerTHE PROSTATE, Issue 11 2006Chengyu Wu Abstract BACKGROUND Prostate cancer (PC) contains a minor component of neuroendocrine (NE) cells that may stimulate androgen-independent growth of the tumor. The mechanism of neuroendocrine differentiation remains unknown. METHODS The expression of PTP1B, a protein tyrosine phosphatase, was studied in LNCaP cells induced to show neuroendocrine phenotype by androgen withdrawal. Wild-type PTP1B and its dominant-negative mutant were transfected into LNCaP cells to study their effects on neuroendocrine differentiation. In vivo expression of PTP1B in human prostate cancer was studied by immunohistochemistry. RESULTS Androgen withdrawal of LNCaP cells led to increased expression of PTP1B with a corresponding increase in its tyrosine phosphatase activity. Overexpression of PTP1B in LNCaP cells led to neuroendocrine differentiation while expression of its dominant-negative mutant inhibited neuroendocrine differentiation. Immunohistochemical study showed that PTP1B was exclusively expressed in neuroendocrine cells of human prostate cancer tissue. Conclusion Our findings suggest that PTP1B plays an important role in neuroendocrine differentiation, and therefore, may possibly be involved in the progression of prostate cancer. Prostate © 2006 Wiley-Liss, Inc. [source] Morphological Studies on the Development of the Bronchial Epithelium of the Fetal Camel LungANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005G. Kamel Light microscopic observations revealed that in camel foetuses of 25 mm crown-to-rump length (CRL) the primordial tubular system of the prospective lung was formed of several tubules lined by undifferentiated columnar epithelium. Intra-epithelial neuroendocrine cells were the first elements to be differentiated in the lining epithelium of the primordial tubular system of the prospective lung as early as 25 mm CRL. On reaching 50,67 mm CRL, the primordial tubular system started to differentiate into two systems of primordial tubules, the prospective bronchial or light tubules and the future respiratory or dark tubules. The lining epithelium of the prospective bronchial tubules revealed a clear evidence of ciliogenesis as early as 80 mm CRL. From 800 mm CRL onwards, the bronchial epithelium demonstrated ciliated and non-ciliated secretory cells. The non-ciliated secretory cells of the bronchial epithelium of fetal camel lung showed moderate reaction to AB/PAS technique, for the first time, in fetuses reaching 600 mm CRL. [source] Serotonin content of normal and inflamed appendix: a possible role of serotonin in acute appendicitis,APMIS, Issue 11 2008MOHAMMAD VASEI The appendix is lined by a mucosa which has many neuroendocrine cells containing serotonin. Local release of serotonin can act as a mediator of inflammation. In this study we explored the serotonin content of the neuroendocrine cells of the appendixes removed for clinical diagnosis of appendicitis. Appendix specimens were divided into three groups: Acute appendicitis (AA), non-appendicitis (NA), and follicular hyperplasia (FH). Normal appendix specimens from patients undergoing elective abdominal surgery were used as the control group (NL). All sections were exposed to proteinase K, incubated with anti-serotonin, chromogranin A, and synaptophysin antibodies, and treated with the LSAB kit. Polygonal cells were seen within the crypt epithelium (enterochromaffin cell, EC) and within the lamina propria (subepithelial neuroendocrine cell, SNC). In AA, only 16 cases (64%) showed serotonin staining in non-destructed glands. There was a significant reduction in the number of ECs in AA compared to the FH (96%), NA (100%) and NL (100%) groups (P<0.001). Chromogranin and synaptophysin immunostaining also showed a significant reduction in the number of ECs in AA compared with the other three groups (P<0.001). SNC serotonin reactivity was lower in the AA group compared with the other groups (p<0.001). The inflamed appendix is markedly depleted of serotonin in the epithelium and lamina propria. Local serotonin release from ECs and SNCs in the appendix may act as an inflammatory mediator in appendicitis and is likely to be the source of raised blood serotonin in AA. [source] Differential cytotoxicity of novel somatostatin and dopamine chimeric compounds on bronchopulmonary and small intestinal neuroendocrine tumor cell linesCANCER, Issue 4 2008Mark Kidd PhD Abstract BACKGROUND. Survival rates for gastrointestinal (GI) and bronchopulmonary (BP) neuroendocrine tumors (NETs) have not significantly altered (overall 67%, 5-year survival) in 30 years (1973-2004), whereas the incidence has increased (, 1000%) in the same time frame. No effective or specific antineoplastic agent is available for treatment, although somatostatin analogs inhibit tumor secretion. Given the coexistence of somatostatin and dopamine regulatory receptors on NET cells, the antiproliferative efficacy as well as the signaling and transcriptional targets of their ligands were evaluated. METHODS. The cytotoxic effects of 12 somatostatin/dopamine compounds were evaluated in 3 NET cell lines, and real-time polymerase chain reaction and enzyme-linked immunoadsorbent assay studies were performed to delineate antiproliferative signaling pathways. RESULTS. The atypical BP-NET, NCI-H720, was most sensitive to the sst5 analog BIM23206 (half-maximal concentration, 2.4 pM) and demonstrated similar sensitivity to lanreotide and the sst2 analog BIM23120. The typical BP-NET, NCI-H727, was most sensitive to BIM23120 (0.7 nM) and to the pan-somatostatin receptor analog (BIM23A779). The GI-NET, KRJ-I, was most sensitive to sst2,5 analogs lanreotide (1 nM) and BIM23244 (7.4 nM). Lanreotide activated extracellular signal regulated kinase-1/2 phosphorylation and p21WAF1/CIP1 transcription, but inhibited Ki-67 transcription. NCI-H720 was most sensitive to the sst2,5 - and D2 -selective compound BIM23A761 (4.2 nM), as was NCI-H727 (5.5 nM). KRJ-I did not respond to any chimeric analog. BIM23A761 activated c-Jun N-terminal kinase signaling and caused inhibition of Ki-67 transcription. P21WAF1/CIP1 transcription was activated only in NCI-H727 cells. CONCLUSIONS. The different responses of each individual cell line suggested that NETs from different locations arising from different neuroendocrine cells may require cell-specific antiproliferative agents based on the unique receptor profile of individual lesions. Cancer 2008. © 2008 American Cancer Society. [source] Role of 5-HT2A, 5-HT4 and 5-HT7 receptors in the antigen-induced airway hyperresponsiveness in guinea-pigsCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2010P. Segura Summary Background A possible role of 5-hydroxytryptamine (5-HT) in the origin of antigen-induced airway hyperresponsiveness (AI-AHR) has been scarcely investigated. Objective To explore the participation of different 5-HT receptors in the development of AI-AHR in guinea-pigs. Methods Lung resistance was measured in anaesthetized guinea-pigs sensitized to ovalbumin (OVA). Dose,response curves to intravenous (i.v.) acetylcholine (ACh) were performed before and 1 h after antigenic challenge and expressed as the 200% provocative dose (PD200). Organ bath experiments, confocal microscopy and RT-PCR were additionally used. The 5-HT content in lung homogenates was measured by HPLC. Results Antigenic challenge significantly decreased PD200, indicating the development of AI-AHR. This hyperresponsiveness was abolished by a combination of methiothepin (5-HT1/5-HT2/5-HT5/5-HT6/5-HT7 receptors antagonist) and tropisetron (5-HT3/5-HT4 antagonist). Other 5-HT receptor antagonists showed three different patterns of response. Firstly, WAY100135 (5-HT1A antagonist) and ondansetron (5-HT3 antagonist) did not modify the AI-AHR. Secondly, SB269970 (5-HT7 antagonist), GR113808 (5-HT4 antagonist), tropisetron or methiothepin abolished the AI-AHR. Thirdly, ketanserin (5-HT2A antagonist) produced airway hyporresponsiveness. Animals with bilateral vagotomy did not develop AI-AHR. Experiments in tracheal rings showed that pre-incubation with LP44 or cisapride (agonists of 5-HT7 and 5-HT4 receptors, respectively) induced a significant increase of the cholinergic contractile response to the electrical field stimulation. In sensitized lung parenchyma strips, ketanserin diminished the contractile responses to ACh. Sensitization was associated with a ninefold increase in the 5-HT content of lung homogenates. Confocal microscopy showed that sensitization enhanced the immunolabelling and co-localization of nicotinic receptor and 5-HT in airway epithelium, probably located in pulmonary neuroendocrine cells (PNECs). RT-PCR demonstrated that neither sensitization nor antigen challenge modified the 5-HT2A receptor mRNA levels. Conclusions Our results suggested that 5-HT was involved in the development of AI-AHR to ACh in guinea-pigs. Specifically, 5-HT2A, 5-HT4 and 5-HT7 receptors seem to be particularly involved in this phenomenon. Participation of 5-HT might probably be favoured by the enhancement of the PNECs 5-HT content observed after sensitization. Cite this as: P. Segura, M. H. Vargas, G. Córdoba-Rodríguez, J. Chávez, J. L. Arreola, P. Campos-Bedolla, V. Ruiz, L. M. García-Hernández, C. Méndez and L. M. Montaño, Clinical & Experimental Allergy, 2010 (40) 327, 338. [source] Epidemiology of non-gastroenteropancreatic (neuro)endocrine tumoursCLINICAL ENDOCRINOLOGY, Issue 1 2007P. Ferolla Summary The widespread availability and reliability of immunohistochemical techniques in the last three decades have allowed researchers to identify cells with common neuroendocrine markers in virtually every organ. As a whole, these neuroendocrine cells form the so-called diffuse neuroendocrine system. Tumours arising from the cells of the diffuse neuroendocrine system are defined as (neuro)endocrine tumours (NETs). NETs have been increasingly described in recent years. However, despite the increase in the number of published papers focused on NET, we still lack adequate epidemiological data, particularly for non-gastroenteropancreatic (GEP) NETs. Furthermore, the real incidence of neuroendocrine differentiation for most sites is not completely known and is probably underestimated. As a consequence, data on the clinical features of many NET subgroups are not well known or confusing. For all of these reasons, we have attempted to evaluate the epidemiology of non-GEP NETs, reviewing the limited data available in the literature. [source] | ||||||||||||||||