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George Papaxoinis, Angela Lamarca, Anne Marie Quinn, Wasat Mansoor, Daisuke Nonaka
Pulmonary carcinoid tumors occur in both central and peripheral locations, and some differences in clinico-pathological features have long been observed. We investigated a large number of resected carcinoid tumors with the aim to further define the characteristics of tumors from both locations. One hundred sixty-six resected carcinoid tumors of the lung were analyzed for a variety of clinical and pathologic features, including histology subtype, mitotic rate, Ki67 index, necrosis, invasive pattern, architectural pattern, cell morphology, sustentacular cells, neuroendocrine hyperplasia, and orthopedia homeobox protein (OTP) and TTF-1 immunohistochemical expressions...
May 16, 2018: Endocrine Pathology
Philippe Hernigou, Jean Charles Auregan, Arnaud Dubory
The vitamin D history started early in the evolution of life (billion years ago) as a photochemical reaction producing an inert molecule. During the early evolution of vertebrates, this molecule became essential for calcium and bone homeostasis of terrestrial animals and arrived to the status of hormone. Phytoplankton, zooplankton, and most plants and animals that are exposed to sunlight have the capacity to make vitamin D. Vitamin D is critically important for the development, growth, and maintenance of a healthy skeleton from birth until death...
March 5, 2018: International Orthopaedics
Leslie A Slota, David R McClay
Correct patterning of the nervous system is essential for an organism's survival and complex behavior. Embryologists have used the sea urchin as a model for decades, but our understanding of sea urchin nervous system patterning is incomplete. Previous histochemical studies identified multiple neurotransmitters in the pluteus larvae of several sea urchin species. However, little is known about how, where and when neural subtypes are differentially specified during development. Here, we examine the molecular mechanisms of neuronal subtype specification in 3 distinct neural subtypes in the Lytechinus variegatus larva...
March 15, 2018: Developmental Biology
Krisztina Z Hanley, Zachary J Dureau, Cynthia Cohen, Dong M Shin, Taofeek K Owonikoko, Gabriel L Sica
BACKGROUND: Twenty-seven percent of neuroendocrine tumors (NETs) are associated with distant metastases, and in some patients, the primary site is unknown. Orthopedia homeobox protein (OTP) has been described as a useful marker for lung carcinoids (LCs) and for separating low-grade typical carcinoids (TCs) from intermediate-grade atypical carcinoids (ACs) in resection specimens. This study evaluated OTP, thyroid transcription factor 1 (TTF-1), and Ki-67 expression in fine-needle aspiration (FNA) samples of various NETs...
April 2018: Cancer Cytopathology
Lee Moir, Elena G Bochukova, Rebecca Dumbell, Gareth Banks, Rasneer S Bains, Patrick M Nolan, Cheryl Scudamore, Michelle Simon, Kimberly A Watson, Julia Keogh, Elana Henning, Audrey Hendricks, Stephen O'Rahilly, Inês Barroso, Adrienne E Sullivan, David C Bersten, Murray L Whitelaw, Susan Kirsch, Elizabeth Bentley, I Sadaf Farooqi, Roger D Cox
OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression...
November 2017: Molecular Metabolism
Daniela Biechl, Kristin Tietje, Soojin Ryu, Benedikt Grothe, Gabriele Gerlach, Mario F Wullimann
Zebrafish larvae imprint on visual and olfactory cues of their kin on day 5 and 6 postfertilization, respectively. Only imprinted (but not non-imprinted) larvae show strongly activated crypt (and some microvillous) cells demonstrated by pERK levels after subsequent exposure to kin odor. Here, we investigate the olfactory bulb of zebrafish larvae for activated neurons located at the sole glomerulus mdG2 which receives crypt cell input. Imprinted larvae show a significantly increased activation of olfactory bulb cells compared to non-imprinted larvae after exposure to kin odor...
March 14, 2017: Scientific Reports
Einav Wircer, Janna Blechman, Nataliya Borodovsky, Michael Tsoory, Ana Rita Nunes, Rui F Oliveira, Gil Levkowitz
Proper response to stress and social stimuli depends on orchestrated development of hypothalamic neuronal circuits. Here we address the effects of the developmental transcription factor orthopedia (Otp) on hypothalamic development and function. We show that developmental mutations in the zebrafish paralogous gene otpa but not otpb affect both stress response and social preference. These behavioral phenotypes were associated with developmental alterations in oxytocinergic (OXT) neurons. Thus, otpa and otpb differentially regulate neuropeptide switching in a newly identified subset of OXT neurons that co-express the corticotropin-releasing hormone (CRH)...
January 17, 2017: ELife
George Papaxoinis, Daisuke Nonaka, Ciara O'Brien, Benjamin Sanderson, Piotr Krysiak, Wasat Mansoor
CD44 and orthopedia homeobox protein (OTP) expressions have shown to be predictive of overall survival in pulmonary carcinoid (PC) tumours. The scope of the present study was to validate their role in PC patients and investigate potential application in clinical practice. Data was collected from patients presenting to a tertiary cancer centre diagnosed with PC between 2003 and 2015. Diagnosis was confirmed by central pathology review. Formalin-fixed paraffin-embedded (FFPE) tissue samples collected at diagnosis were scored using immunohistochemistry (H score) for standard CD44 and nuclear and cytoplasmic OTP protein expression...
March 2017: Endocrine Pathology
Alexandra Kerbl, José M Martín-Durán, Katrine Worsaae, Andreas Hejnol
BACKGROUND: Annelida is a morphologically diverse animal group that exhibits a remarkable variety in nervous system architecture (e.g., number and location of longitudinal cords, architecture of the brain). Despite this heterogeneity of neural arrangements, the molecular profiles related to central nervous system patterning seem to be conserved even between distantly related annelids. In particular, comparative molecular studies on brain and anterior neural region patterning genes have focused so far mainly on indirect-developing macrofaunal taxa...
2016: EvoDevo
Daisuke Nonaka, George Papaxoinis, Wasat Mansoor
Recently, Orthopedia Homeobox (OTP) was described as a prognostic marker for pulmonary carcinoid tumors; however, little is known about the function and distribution pattern of this transcription factor in normal organs/tissues and in tumors. Consequently, OTP expression was investigated in a variety of tumors, with special interest in pulmonary and nonpulmonary neuroendocrine tumors (NETs) and high-grade neuroendocrine carcinomas. OTP immunohistochemical analysis was performed on a total of 162 pulmonary carcinoid tumors, 31 pulmonary neuroendocrine hyperplasias, 104 pulmonary high-grade neuroendocrine carcinomas (large cell neuroendocrine and small cell neuroendocrine), 102 nonpulmonary NETs (G1/G2 NETs, small cell and large cell neuroendocrine carcinomas, and Merkel cell carcinomas), 150 endocrine tumors (thyroid, parathyroid, adrenocortical, and pheochromocytomas/paragangliomas), 279 adenocarcinomas, and 88 squamous cell carcinomas of various organs, including those of the lungs and others...
June 2016: American Journal of Surgical Pathology
Jose Arturo Gutierrez-Triana, Ulrich Herget, Patrick Lichtner, Luis A Castillo-Ramírez, Soojin Ryu
BACKGROUND: The homeodomain transcription factor orthopedia (Otp) is an evolutionarily conserved regulator of neuronal fates. In vertebrates, Otp is necessary for the proper development of different regions of the brain and is required in the diencephalon to specify several hypothalamic cell types, including the cells that control the stress response. To understand how this widely expressed transcription factor accomplishes hypothalamus-specific functions, we performed a comprehensive screening of otp cis-regulatory regions in zebrafish...
2014: BMC Developmental Biology
Dorian R A Swarts, Robert-Jan van Suylen, Michael A den Bakker, Matthijs F M van Oosterhout, Frederik B J M Thunnissen, Marco Volante, Anne-Marie C Dingemans, Marc R M Scheltinga, Gerben P Bootsma, Harry M M Pouwels, Ben E E M van den Borne, Frans C S Ramaekers, Ernst-Jan M Speel
Pulmonary carcinoids are neuroendocrine tumors histopathologically subclassified into typical (TC; no necrosis, <2 mitoses per 2 mm) and atypical (AC; necrosis or 2 to 10 mitoses per 2 mm). The reproducibility of lung carcinoid classification, however, has not been extensively studied and may be hampered by the presence of pyknotic apoptosis mimicking mitotic figures. Furthermore, prediction of prognosis based on histopathology varies, especially for ACs. We examined the presence of interobserver variation between 5 experienced pulmonary pathologists who reviewed 123 originally diagnosed pulmonary carcinoid cases...
October 2014: American Journal of Surgical Pathology
Sinem Sarı, Osman Nuri Aydın
Stellate ganglion block (SGB) is one of the most often used sympathetic blockade procedure. Despite performed by experienced physicians some complications may occur. The right brachial plexus injury was diagnosed in the patient who admitted to orthopedia clinic, with weakness in the right arm, and pain after motor vehicle accident. There was no response to medical treatment of fortyfour-years-old female patient and there was loosing of sensation from dis the right elbow joint to fingers on the radial and median nerve tracing...
2014: Aǧrı: Ağrı (Algoloji) Derneği'nin Yayın Organıdır, the Journal of the Turkish Society of Algology
Soojin Ryu, Julia Mahler, Dario Acampora, Jochen Holzschuh, Simone Erhardt, Daniela Omodei, Antonio Simeone, Wolfgang Driever
No abstract text is available yet for this article.
February 26, 2008: Current Biology: CB
Alida Filippi, Thomas Mueller, Wolfgang Driever
Throughout the vertebrate lineage, dopaminergic neurons form important neuromodulatory systems that influence motor behavior, mood, cognition, and physiology. Studies in mammals have established that dopaminergic neurons often use γ-aminobutyric acid (GABA) or glutamatergic cotransmission during development and physiological function. Here, we analyze vglut2, gad1b and gad2 expression in combination with tyrosine hydroxylase immunoreactivity in 4-day-old larval and 30-day-old juvenile zebrafish brains to determine which dopaminergic and noradrenergic groups may use GABA or glutamate as a second transmitter...
June 15, 2014: Journal of Comparative Neurology
Ulrich Herget, Andrea Wolf, Mario F Wullimann, Soojin Ryu
The paraventricular nucleus (PVN) in mammals is the main hypothalamic nucleus controlling hormone release in the pituitary and plays pivotal roles in homeostasis. While the location of a PVN-homologous region has been described in adult fish as the neurosecretory preoptic area (NPO), this region has not been clearly defined in larval zebrafish due to the difficulty in defining cytoarchitectonic nuclear boundaries in the larval brain. Here we identify the precise location of the larval zebrafish NPO using conserved transcription factor and neuropeptide gene expressions...
May 1, 2014: Journal of Comparative Neurology
António M Fernandes, Erin Beddows, Alida Filippi, Wolfgang Driever
The homeodomain transcription factor Orthopedia (Otp) is an important regulator for specification of defined subsets of neuroendocrine cells and dopaminergic neurons in vertebrates. In zebrafish, two paralogous otp genes, otpa and otpb, are present in the genome. Neither complete loss of Otp activity nor differential contributions of Otpa and Otpb to specification of defined neuronal populations have been analyzed in detail. We characterized zebrafish embryos and early larvae mutant for null alleles of otpa, otpb, or both genes to determine their individual contributions to the specification of th expressing dopaminergic neuronal populations as well as of crh, oxt, avp, trh or sst1...
2013: PloS One
Dorian R A Swarts, Mieke E R Henfling, Leander Van Neste, Robert-Jan van Suylen, Anne-Marie C Dingemans, Winand N M Dinjens, Annick Haesevoets, Martina Rudelius, Erik Thunnissen, Marco Volante, Wim Van Criekinge, Manon van Engeland, Frans C S Ramaekers, Ernst-Jan M Speel
PURPOSE: Pulmonary carcinoids are well-differentiated neuroendocrine tumors showing usually a favorable prognosis. However, there is a risk for late recurrence and/or distant metastasis. Because histologic classification in typical and atypical carcinoids is difficult and its reliability to predict disease outcome varies, we evaluated three genes as potential prognostic markers, that is, orthopedia homeobox (OTP), CD44, and rearranged during transfection (RET). EXPERIMENTAL DESIGN: These genes were analyzed in 56 frozen carcinoids by quantitative real-time PCR (qRT-PCR)...
April 15, 2013: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Takao Kaji, Katsunori Nonogaki
Homeobox genes contribute to the regionalization, patterning and cell differentiation during embryogenesis and organ development. During mammalian embryonic development, homeobox genes, including orthopedia (Otp), a brain-specific homeobox transcription factor (Bsx) and a thyroid transcription factor-1 (TTF-1), are expressed in the hypothalamus. The genetic ablation of these genes indicated that Otp and TTF-1 are essential for the normal morphological development of the hypothalamus, including the arcuate nucleus (ARC), whereas Bsx is not required...
2013: Frontiers in Bioscience (Landmark Edition)
Aaron M Lambert, Joshua L Bonkowsky, Mark A Masino
The most conserved part of the vertebrate dopaminergic system is the orthopedia (otp)-expressing diencephalic neuronal population that constitutes the dopaminergic diencephalospinal tract (DDT). Although studies in the neonatal murine spinal cord in vitro suggest an early locomotor role of the DDT, the function of the DDT in developing vertebrates in vivo remains unknown. Here, we investigated the role of the DDT in the locomotor development of zebrafish larvae. To assess the development of the behavioral and neural locomotor pattern, we used high-throughput video tracking in combination with peripheral nerve recordings...
September 26, 2012: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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