RESUMEN
We introduce the Ontology of Craniofacial Development and Malformation (OCDM) as a mechanism for representing knowledge about craniofacial development and malformation, and for using that knowledge to facilitate integrating craniofacial data obtained via multiple techniques from multiple labs and at multiple levels of granularity. The OCDM is a project of the NIDCR-sponsored FaceBase Consortium, whose goal is to promote and enable research into the genetic and epigenetic causes of specific craniofacial abnormalities through the provision of publicly accessible, integrated craniofacial data. However, the OCDM should be usable for integrating any web-accessible craniofacial data, not just those data available through FaceBase. The OCDM is based on the Foundational Model of Anatomy (FMA), our comprehensive ontology of canonical human adult anatomy, and includes modules to represent adult and developmental craniofacial anatomy in both human and mouse, mappings between homologous structures in human and mouse, and associated malformations. We describe these modules, as well as prototype uses of the OCDM for integrating craniofacial data. By using the terms from the OCDM to annotate data, and by combining queries over the ontology with those over annotated data, it becomes possible to create "intelligent" queries that can, for example, find gene expression data obtained from mouse structures that are precursors to homologous human structures involved in malformations such as cleft lip. We suggest that the OCDM can be useful not only for integrating craniofacial data, but also for expressing new knowledge gained from analyzing the integrated data.
Asunto(s)
Biología Computacional , Anomalías Craneofaciales/genética , Bases de Datos Factuales , Investigación Biomédica Traslacional , Animales , Anomalías Craneofaciales/clasificación , Anomalías Craneofaciales/fisiopatología , Epigenómica , Genómica , Humanos , RatonesRESUMEN
H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.
Asunto(s)
Acidosis Tubular Renal/enzimología , Cromosomas Humanos Par 2 , Pérdida Auditiva Sensorineural/enzimología , Mutación , ATPasas de Translocación de Protón/genética , Acidosis Tubular Renal/complicaciones , Acidosis Tubular Renal/genética , Secuencia de Bases , Preescolar , Cóclea/metabolismo , Femenino , Genes Recesivos , Ligamiento Genético , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/genética , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , Linaje , ATPasas de Translocación de Protón/metabolismoRESUMEN
A transition matrix model of the population dynamics of the European house dust mite, Dermatophagoides pteronyssinus (Trouessart) (Acari: Pyroglyphidae), is described. It can model continuously varying conditions by forming transition matrices by interpolation between known transition matrices constructed from experimental data. Finite carrying capacity is modeled by modifying the population distribution vector at each time-step by using a form of the Skellam model, which is derived from the assumption that in competition each successful animal gets all it requires, and the unsuccessful animals get insufficient resources for survival or reproduction. The transition matrix model does not require all mites to have the same survivorship, life-stage durations, fecundity, and so on. Life table data to drive the model is taken from two sources, one source of which requires using the mean and standard deviation of the duration of each stage to synthesize a range of duration times and a range of transition probabilities to the next stage, thus ensuring variability between mites. Where synthesized data are used, significant long-lasting oscillations in dust mite levels are modeled, which does not happen when modeling with unsynthesized data, and is unlikely to occur in the field. Under conditions normally met with in the microenvironment (bedding, base of carpet, soft furnishing) of D. pteronyssinus, finite carrying capacity is essential to prevent unbounded population growth. The model is compared with other workers' field data with fair agreement. It is argued that shortcomings in the available data rather than the model are the principal reasons for differences between field and modeled results.
Asunto(s)
Dermatophagoides pteronyssinus/fisiología , Modelos Teóricos , Animales , Ambiente , Densidad de Población , Dinámica PoblacionalRESUMEN
Five adolescents received a multimedia CD-ROM containing a self-help treatment program for young people with an anxiety disorder. Participants used the 8-module Cool Teens CD-ROM over a 12-week period on a home computer. Every 2 weeks, they received a brief telephone call from a clinical psychologist to monitor symptoms and progress and to discuss any problems with understanding content or implementing techniques. Based on structured interviews, two participants (40%) no longer met diagnostic criteria (self-report ADIS) for at least one clinical anxiety disorder immediately following treatment and these same participants no longer met diagnostic criteria for any clinical anxiety disorder at 3-month follow-up. Two other participants failed to make gains based on diagnostic criteria, but showed improvement in anxiety symptoms for one main fear. Participants were generally satisfied with the multimedia content, the modules, and the delivery format of the program.
Asunto(s)
Conducta del Adolescente/psicología , Trastornos de Ansiedad/terapia , Ansiedad/terapia , CD-ROM , Adolescente , Australia , Terapia Cognitivo-Conductual/métodos , Femenino , Humanos , Masculino , Multimedia , Satisfacción del Paciente , Proyectos Piloto , Escalas de Valoración Psiquiátrica , Calidad de Vida , Reproducibilidad de los Resultados , Autocuidado/métodos , Grupos de AutoayudaRESUMEN
House dust mites are found in almost all dwellings in New Zealand and are a major risk factor in the development of asthma and perennial allergic rhinitis. We studied the longevity, life stage length, and fecundity of a New Zealand strain of European house dust mite, Dermatophagoides pteronyssinus (Trouessart), at constant (23 degrees C, 75% RH) and the fluctuating conditions typically found in dry (18-25 degrees C, 60-38% RH) and damp (18-23 degrees C, 70-55% RH) New Zealand dust mite microhabitats in carpets. All the adult mites placed in the "dry" conditions died within 18 d. Mites in the "da conditions had developmental times, oviposition, and death rates that were not significantly different from constant conditions. These mites are tolerant of fluctuating temperatures, but they are more susceptible to environments that strongly fluctuate in humidity.
Asunto(s)
Dermatophagoides pteronyssinus/crecimiento & desarrollo , Humedad , Temperatura , Animales , Fertilidad , Longevidad , Oviposición , Factores de TiempoRESUMEN
Rapid effects of steroid hormones have been observed in neuronal cells for many years. We show here, that in the human neuroblastoma cell line SK-N-SH, the membrane impermeable conjugated 17beta-estradiol (E2BSA) activates mitogen activated protein kinase kinase (MAPKK or MEK) and induces the phosphorylation and activation of both ERK-1 and ERK-2 (mitogen activated protein kinase or MAPK). Additionally, E2BSA induces the transcription of a reporter gene construct driven by the promoter of the mouse c-fos proto-oncogene. The effects of this membrane impermeable estrogen on c-fos transcription are not inhibited by the estrogen receptor antagonists Tamoxifen or ICI 182,780, further excluding the involvement of the intracellular estrogen receptor. This is also illustrated by the observation that E2BSA does not activate estrogen response element (ERE) mediated transcription. This is the first report of rapid membrane effects of 17beta-estradiol on growth factor related signalling pathways in neuronal cells, and indicates a potential mechanism by which 17beta-estradiol might affect the expression of genes whose promoters do not contain EREs but are responsive to factors acting through other response elements such as AP-1 and SRE sites.
Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Membrana Celular/efectos de los fármacos , Estradiol/farmacología , Genes fos/genética , Neuronas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Membrana Celular/metabolismo , Activación Enzimática/efectos de los fármacos , Genes Inmediatos-Precoces , Humanos , Cinética , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos , Neuroblastoma , Neuronas/metabolismo , Fosforilación , Proteínas Quinasas/metabolismo , Proto-Oncogenes Mas , Transcripción Genética/efectos de los fármacos , Transfección , Células Tumorales CultivadasRESUMEN
Galanin-like peptide (GALP), which was recently isolated from the porcine hypothalamus, shares sequence homology with galanin and binds with high affinity to galanin receptors. To study the distribution and regulation of GALP-expressing cells in the brain, we cloned a 120 base-pair cDNA fragment of rat GALP and produced an antisense riboprobe. In situ hybridization for GALP mRNA was then performed on tissue sections throughout the forebrain of adult ovariectomized female rats. We found GALP mRNA-containing cells in the arcuate nucleus (Arc), caudal dorsomedial nucleus, median eminence and the pituitary. Because GALP mRNA in the Arc appeared to overlap with the known distribution of leptin receptor mRNA, we tested the hypothesis that GALP expression is regulated by leptin. Using in situ hybridization, we compared the number of GALP mRNA-containing cells among groups of rats that were fed ad lib or fasted for 48 h and treated with either leptin or vehicle. Fasting reduced the number of identifiable cells containing GALP mRNA in the Arc, whereas the treatment of fasted animals with leptin produced a 4-fold increase in the number of cells expressing GALP message. The presence of GALP mRNA in the hypothalamus and pituitary and its regulation by leptin suggests that GALP may have important neuroendocrine functions, including the physiological regulation of feeding, metabolism, and reproduction.
Asunto(s)
Hipotálamo/metabolismo , Leptina/farmacología , Proteínas del Tejido Nervioso/metabolismo , Animales , Ayuno/metabolismo , Femenino , Péptido Similar a Galanina , Hipotálamo/citología , Hipotálamo/efectos de los fármacos , Hibridación in Situ , Proteínas del Tejido Nervioso/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
Kisspeptins are products of the KiSS-1 gene, which bind to a G protein-coupled receptor known as GPR54. Mutations or targeted disruptions in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice, suggesting that kisspeptin signaling may be important for the regulation of gonadotropin secretion. To examine the effects of kisspeptin-54 (metastin) and kisspeptin-10 (the biologically active C-terminal decapeptide) on gonadotropin secretion in the mouse, we administered the kisspeptins directly into the lateral cerebral ventricle of the brain and demonstrated that both peptides stimulate LH secretion. Further characterization of kisspeptin-54 demonstrated that it stimulated both LH and FSH secretion, at doses as low as 1 fmol; moreover, this effect was shown to be blocked by pretreatment with acyline, a potent GnRH antagonist. To learn more about the functional anatomy of kisspeptins, we mapped the distribution of KiSS-1 mRNA in the hypothalamus. We observed that KiSS-1 mRNA is expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. We conclude that kisspeptin-GPR54 signaling may be part of the hypothalamic circuitry that governs the hypothalamic secretion of GnRH.
Asunto(s)
Hipotálamo/metabolismo , Hormona Luteinizante/metabolismo , Proteínas/genética , Proteínas/metabolismo , Animales , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/efectos de los fármacos , Inyecciones Intraventriculares , Kisspeptinas , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas/farmacología , ARN Mensajero/análisis , Receptores Acoplados a Proteínas G , Receptores de Kisspeptina-1 , Receptores de Neuropéptido/metabolismoRESUMEN
Galanin-like peptide (GALP) is a newly discovered molecule whose expression in the brain is confined to the arcuate nucleus and median eminence. In the rat, cellular levels of GALP mRNA are reduced by fasting and reversed by peripheral administration of leptin. The purpose of this investigation was 1) to clone and map the distribution of GALP mRNA in the brain of the mouse; 2) to compare the pattern and magnitude of GALP mRNA expression in the leptin-deficient obese (ob/ob) mouse with that of wild-type controls; and 3) to examine the effects of leptin delivered into the brain on the expression of GALP mRNA in the ob/ob mouse. We report the sequence of a mouse GALP cDNA and show that GALP mRNA is expressed in the arcuate nucleus, median eminence, infundibular stalk, and the neurohypophysis of this species. The expression of GALP mRNA in the brain was markedly reduced in the ob/ob mice, compared with wild-type animals. Intracerebroventricular infusion of leptin to ob/ob mice increased both the number of GALP mRNA-expressing neurons and their content of GALP mRNA, compared with vehicle-treated controls. These observations demonstrate that GALP mRNA is induced by leptin through a direct action on the brain.
Asunto(s)
Hipotálamo/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Animales , Encéfalo/metabolismo , Clonación Molecular , ADN Complementario/genética , Péptido Similar a Galanina , Leptina/deficiencia , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Obesidad/genética , ARN Mensajero/metabolismo , Valores de Referencia , Distribución TisularRESUMEN
Leptin acts as a metabolic activator of the neuroendocrine reproductive axis in several rodent species, but whether leptin plays a similar role in primates is unknown. To explore this question, we examined the effects of leptin on gonadotropin and testosterone secretion in male rhesus monkeys that were fasted for 2 days. Mean plasma levels of LH and FSH, LH pulse frequency, and LH pulse amplitude were significantly higher in leptin-treated animals compared with saline-treated controls during the second day of the fast. To identify targets for leptin's action, we used in situ hybridization and computerized imaging to map leptin receptor (Ob-R) messenger RNA (mRNA) distribution. Ob-R mRNA was observed in the anterior pituitary and several areas of the brain, including the arcuate and ventromedial nuclei of the hypothalamus. Ob-R mRNA was coexpressed in both POMC and neuropeptide Y neurons in the arcuate nucleus, whereas little or no coexpression of Ob-R mRNA was evident in GnRH neurons. These results suggest that leptin is a metabolic signal to the reproductive axis in primates and imply that both POMC and neuropeptide Y neurons are involved in mediating leptin's effects in the brain.
Asunto(s)
Sistemas Neurosecretores/efectos de los fármacos , Proteínas/farmacología , Reproducción/efectos de los fármacos , Animales , Química Encefálica/efectos de los fármacos , Hormona Folículo Estimulante/biosíntesis , Hormona Liberadora de Gonadotropina/biosíntesis , Hormonas/biosíntesis , Hormonas/sangre , Hibridación in Situ , Leptina , Hormona Luteinizante/biosíntesis , Macaca mulatta , Masculino , Proopiomelanocortina/biosíntesis , Sondas ARN , ARN Mensajero/biosíntesis , Estimulación QuímicaRESUMEN
Leptin is a secretory product of adipocytes that has been shown to affect food intake, metabolism, and reproduction. One site of leptin's action is the central nervous system, where the leptin receptor (Ob-R) messenger ribonucleic acid (mRNA) and protein are expressed in discrete areas. In both the rat and monkey, Ob-R mRNA has been localized in the Raphe nuclei of the brainstem. Neurons in the Raphe nuclei are the primary source of serotonin in the brain. Serotonergic pathways influence both feeding and reproduction, and these cells are plausible direct targets for leptin's action. We used double label in situ hybridization and computerized image analysis to determine whether serotonergic neurons in the brainstem of the female pigtailed macaque (Macaca nemestrina) express Ob-R mRNA. We observed that many cells in the Raphe nuclei express serotonin transporter mRNA, a marker of serotonergic cells, and Ob-R mRNA. Based on quantitative analysis, the highest number of cells that express both serotonin transporter and Ob-R mRNAs were found in the caudal dorsal Raphe and median Raphe nuclei; fewer double labeled cells were situated in the caudal linear nucleus and rostral median Raphe, whereas double labeled cells occurred infrequently in the rostral dorsal Raphe. These observations suggest that leptin may act on serotonergic cells to mediate some of its effects on ingestive behavior, metabolism, and reproduction.
Asunto(s)
Leptina/fisiología , Neuronas/fisiología , Núcleos del Rafe/metabolismo , Receptores de Superficie Celular , Serotonina/fisiología , Animales , Proteínas Portadoras/genética , Femenino , Hibridación in Situ , Macaca nemestrina , ARN Mensajero/metabolismo , Núcleos del Rafe/citología , Receptores de Leptina , Serotonina/genéticaRESUMEN
Pulsus paradoxus is a key physical finding in patients with cardiac tamponade. This report describes a 38-year-old woman with metastatic adenocarcinoma who had cardiac tamponade confirmed by cardiac catheterization. Pulsus paradoxus was notably absent. No evidence could be found for an atrial septal defect, significant aortic regurgitation, elevated left ventricular diastolic pressure, or localized tamponade, previously described disorders in which pulsus paradoxus may not be seen when tamponade occurs. The lack of pulsus paradoxus in this case was attributed to right ventricular pressure overload due to mechanical obstruction of the pulmonary artery.
Asunto(s)
Adenocarcinoma/secundario , Taponamiento Cardíaco/diagnóstico , Neoplasias Pulmonares/secundario , Arteria Pulmonar , Pulso Arterial , Adenocarcinoma/complicaciones , Adulto , Taponamiento Cardíaco/etiología , Constricción Patológica/complicaciones , Ecocardiografía , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , ReologíaRESUMEN
OBJECTIVE: To determine the proper treatment of children and adolescents with foreign bodies of the external auditory canal (EAC). DESIGN: Retrospective case series. SETTING: Specialty care referral hospital. PATIENTS: All patients younger than 18 years of age who presented in the emergency ward or office setting with a foreign body of the EAC during a 5-year period. RESULTS: One hundred ninety-one patients with aural foreign bodies were identified. Age at presentation ranged from 10 months to 17 years with 141 patients (74%) younger than 8 years old. Twenty-seven different objects were encountered with pebbles, beads, insects, and plastic toys the most common. Fifty-seven (30%) of the patients required surgical removal of the aural foreign body under general anesthesia. CONCLUSION: Adequate immobilization and proper instrumentation allow the uncomplicated removal of many EAC foreign bodies in the pediatric population. The use of general anesthesia is preferred in very young children and in children of any age with aural foreign bodies whose contour, composition, or location predispose to traumatic removal in the ambulatory setting. Criteria for otolaryngologic referral and consideration of operative microscopic removal are outlined.
Asunto(s)
Conducto Auditivo Externo , Cuerpos Extraños/terapia , Adolescente , Niño , Preescolar , Conducto Auditivo Externo/cirugía , Femenino , Cuerpos Extraños/complicaciones , Cuerpos Extraños/cirugía , Humanos , Lactante , Masculino , Otolaringología/instrumentación , Derivación y Consulta , Estudios RetrospectivosRESUMEN
Vocal cord paralysis is a common cause of neonatal stridor. Familial vocal cord dysfunction, however, is unusual. All three siblings in one family had neonatal stridor. Vocal cord dysfunction was confirmed after endoscopic examination in two of the children; a temporary tracheotomy was required by one child. Results of evaluation, including pulmonary function tests, suggest discrete dysfunction localized to the neuromuscular pathway responsible for vocal cord abduction. Endoscopy is of prime importance in the diagnosis of vocal cord dysfunction. In considering therapy, the physician must weigh both the potentially life-threatening nature of vocal cord paralysis, as well as the likelihood of eventual spontaneous resolution of many familial and idiopathic cases.
Asunto(s)
Obstrucción de las Vías Aéreas/etiología , Ruidos Respiratorios/etiología , Parálisis de los Pliegues Vocales/genética , Obstrucción de las Vías Aéreas/diagnóstico , Obstrucción de las Vías Aéreas/genética , Femenino , Humanos , Hipertensión/etiología , Recién Nacido , Masculino , Pruebas de Función Respiratoria , Parálisis de los Pliegues Vocales/complicacionesRESUMEN
To characterize the extent of early activation of the hemostatic system following angioplasty, we obtained blood samples from the involved coronary artery of 11 stable angina patients during the procedure and measured sensitive markers of thrombin formation (fibrinopeptide A, prothrombin fragment 1.2, and soluble fibrin) and of platelet activation (beta-thromboglobulin). Levels of hemostatic markers in venous blood obtained from 14 young individuals with low pretest probability for coronary artery disease were not significantly different from levels in venous blood or intracoronary samples obtained prior to angioplasty. Also, there was no translesional (proximal and distal to the lesion) gradient in any of the hemostatic markers before or after angioplasty in samples obtained between 18 and 21 min from the onset of the first balloon inflation. Furthermore, no significant difference was noted between angioplasty and postangioplasty intracoronary concentrations. We conclude that intracoronary hemostatic activation does not occur in the majority of patients during and immediately following coronary angioplasty when high doses of heparin and aspirin are administered.
Asunto(s)
Angioplastia Coronaria con Balón , Vasos Coronarios/metabolismo , Adulto , Anciano , Biomarcadores/sangre , Femenino , Fibrina/análisis , Fibrinopéptido A/análisis , Hemostasis , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/análisis , Protrombina/análisis , Sensibilidad y Especificidad , Trombina/biosíntesisRESUMEN
1,3-Butadiene and two major genotoxic metabolites 3,4-epoxybutene (EB) and 1,2:3,4-diepoxybutane (DEB) were used as model compounds to determine if genetic toxicity findings in animal and human cells can aid in extrapolating animal toxicity data to man. Sister chromatid exchange (SCE) and micronucleus induction results indicated 1,3-butadiene was genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats to 1,3-butadiene carcinogenicity. However, 1,3-butadiene did not induce unscheduled DNA synthesis (UDS) in the rat or mouse hepatocytes following in vivo exposure. Likewise, UDS in rat and mouse hepatocytes in vitro was not induced by EB or DEB. Salmonella typhimurium gene mutation (Ames) tests of 1,3-butadiene using strains TA1535, TA97, TA98, and TA100 and employing rat, mouse, and human liver S9 metabolic systems were barely 2-fold above background only in strain TA1535 at 30% 1,3-butadiene in air with induced and uninduced rat S9 and mouse S9 (uninduced). 1,3-Butadiene was negative in in vitro SCE studies in human whole blood lymphocytes cultures treated in the presence of rat, mouse, or human liver S9 metabolic activation. In general, 1,3-butadiene is genotoxic in vivo but is a weak in vitro genotoxin.
Asunto(s)
Butadienos/farmacología , Mutágenos , Animales , Médula Ósea/efectos de los fármacos , Butadienos/metabolismo , Butadienos/toxicidad , Carcinógenos , ADN/biosíntesis , Humanos , Técnicas In Vitro , Ratones , Pruebas de Mutagenicidad , Ratas , Salmonella typhimurium/efectos de los fármacos , Intercambio de Cromátides Hermanas/efectos de los fármacosRESUMEN
Lateral sinus thrombosis (LST) is an infrequent complication of otitis media and mastoiditis in the antibiotic era. A recent case of LST in a 7-year-old boy, the third such case at our institutions in the past 5 years, prompted a review of the modern day English literature concerning LST in pediatric patients. Our goal was to highlight the clinical findings suggestive of LST in the antibiotic era as well as to analyze retrospectively the diagnostic and therapeutic modalities of greatest benefit based on the outcomes reported in the reviewed studies.
Asunto(s)
Antibacterianos , Quimioterapia Combinada/uso terapéutico , Mastoiditis/complicaciones , Otitis Media/complicaciones , Trombosis de los Senos Intracraneales/etiología , Niño , Terapia Combinada , Quimioterapia Combinada/administración & dosificación , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Mastoiditis/diagnóstico , Mastoiditis/terapia , Otitis Media/diagnóstico , Otitis Media/terapia , Pronóstico , Estudios Retrospectivos , Trombosis de los Senos Intracraneales/líquido cefalorraquídeo , Trombosis de los Senos Intracraneales/diagnóstico , Trombosis de los Senos Intracraneales/terapia , Tomografía Computarizada por Rayos XRESUMEN
Galanin-like peptide (GALP) is a hypothalamic neuropeptide that binds and activates galanin receptors in vitro. Following the discovery of GALP, researchers have attempted to properly place it in the context of galanin receptor physiology. Central injections of GALP have revealed some common actions with galanin, such as acutely increased food intake and suppression of the thyroid axis. Other actions are unique to GALP, such as long-term inhibition of food intake and stimulation of luteinizing hormone (LH) secretion in male rats. GALP and galanin also produce differential effects on expression of the immediate early gene product Fos in the brain. Determining which of these actions are dependent on galanin receptors (versus a putative GALP-specific receptor), as well as which actions represent the authentic physiology of endogenous GALP will require continued experimentation. GALP gene expression is positively regulated by several hormones involved in the control of energy balance and metabolism, namely leptin, insulin and thyroid hormone. Based on current evidence, GALP neurones may serve as a hypothalamic relay, transmitting information from the periphery to circuits within the brain involved in the physiological control of metabolism and reproduction.
Asunto(s)
Metabolismo Energético/fisiología , Péptido Similar a Galanina/fisiología , Reproducción/fisiología , Secuencia de Aminoácidos , Animales , Regulación de la Expresión Génica , Homeostasis/fisiología , Humanos , Hipotálamo/metabolismo , Ratones , Datos de Secuencia Molecular , Ratas , Receptores de Galanina/metabolismo , Homología de Secuencia de Aminoácido , Porcinos , Termogénesis/fisiología , Glándula Tiroides/fisiologíaRESUMEN
Galanin-like peptide (GALP) mRNA is expressed in neurones of the hypothalamic arcuate nucleus and within pituicytes in the neurohypophysis. Several neuropeptides that are expressed in the arcuate nucleus participate in the neuroendocrine regulation of pituitary hormone secretion. Our objective was to determine the extent to which GALP might be a target for regulation by pituitary hormones or their downstream targets in the rat. The expression of GALP mRNA in the arcuate nucleus was reduced by hypophysectomy as determined by in situ hybridization. However, this did not appear to be attributable to the loss of either gonadal or adrenal steroids because castrated, ovariectomized and adrenalectomized rats had GALP mRNA expression that was indistinguishable from their respective controls. Next, we investigated the effects of growth hormone deficiency on GALP mRNA expression by studying dwarf rats and found that GALP gene expression was not different between dwarf rats and controls. We found that thyroidectomy led to a significant reduction in GALP mRNA expression compared to intact controls, and thyroidectomized rats implanted with thyroxine pellets had GALP mRNA expression that was similar to intact controls. Thus, the reduction of GALP mRNA expression seen in hypophysectomized animals may reflect, in part, a selective loss of thyroid hormone. We also found that the expression of GALP mRNA was increased in the neurohypophysis of lactating rats compared to nonlactating rats, whereas GALP mRNA expression in the arcuate nucleus was unaffected by lactation. This suggests that the induction of GALP gene expression in pituicytes is physiologically associated with activation of oxytocin and vasopressin secretion during lactation.
Asunto(s)
Núcleo Arqueado del Hipotálamo/metabolismo , Péptido Similar a Galanina/metabolismo , Lactancia/metabolismo , Neurohipófisis/metabolismo , Adrenalectomía , Animales , Castración , Péptido Similar a Galanina/genética , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/fisiología , Hipofisectomía , Lactancia/genética , Hormona Luteinizante/fisiología , Masculino , Ovariectomía , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Tiroidectomía , Tiroxina/fisiologíaRESUMEN
When dealing with thousands of genes, all potentially interesting, it is desirable to rank the genes according to their degree of participation in a physiological process. Therefore, genes with the highest Shannon entropy and ERL can be selected as the best toxicity target candidates, permitting preclinical scientists to focus their research and resources on those genes.