RESUMO
We performed a study to investigate the role of ERCC1 (rs11615, rs2298881, and rs3212986) and ERCC2 (rs13181, rs238406, and rs1799793) polymorphisms in the prognosis of gastric cancer. A total of 346 patients with gastric cancer were recruited between May 2009 and May 2012. Single nucleotide polymorphism genotyping was performed using the Sequenom MassARRAY platform. The GA+AA genotype of ERCC2 rs1799793 showed significant and favorable response to chemotherapy than the wide-type GG genotype in multivariate analysis (OR = 1.78, 95%CI = 1.13-2.81). In a Cox proportional hazard model, carriers of ERCC2 rs1799793 GA+AA genotype exhibited longer duration of survival than did those with the GG genotype (hazards ratio = 0.57, 95%CI = 0.35-0.92). In conclusion, our study suggests that ERCC2 rs1799793 polymorphic variation could be used as a predictor for the prognosis of gastric cancer.
Assuntos
Proteínas de Ligação a DNA/genética , Endonucleases/genética , Prognóstico , Neoplasias Gástricas/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Idoso , Biomarcadores Farmacológicos , Reparo do DNA/genética , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
Genetic variations within the paired box gene 6 (PAX6) gene are associated with congenital aniridia. To detect the genetic defects in a Chinese twin family with congenital aniridia and nystagmus, exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Six members from the family of three generations were included in the study. The twins' father presented with congenital aniridia, nystagmus and cataract at birth, while the twins presented with congenital aniridia and nystagmus. A novel mutation c.888 insA in exon 10 of PAX6 was identified in all affected individuals. This study suggests that the novel mutation c.888 insA is likely responsible for the pathogenesis of the congenital aniridia and nystagmus in this pedigree. To the best of our knowledge, this is the first report of this mutation in PAX6 gene in pedigree with aniridia. Furthermore, no PAX6 gene defect was reported in twins with congenital aniridia.
Assuntos
Aniridia/genética , Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Mutação , Nistagmo Congênito/genética , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , Adulto , Aniridia/complicações , Aniridia/diagnóstico , Catarata/complicações , Criança , Éxons , Feminino , Humanos , Masculino , Nistagmo Congênito/complicações , Fator de Transcrição PAX6 , Linhagem , GêmeosRESUMO
We examined a possible relationship -420C>G SNP of the resistin gene with plasma resistin and C-reactive protein concentrations in intracerebral hemorrhage. Three hundred and forty-four Chinese Han patients with intracerebral hemorrhage and 344 age- and gender-matched healthy controls were included in our study. Plasma resistin and C-reactive concentrations were measured and SNP -420C>G was genotyped. The genotype frequencies in controls and patients were not significantly different (P = 0.672). Plasma resistin and C-reactive protein levels were significantly different between the SNP -420C>G genotypes, even after adjustment for age, gender and body mass index. The common homozygote (C-C) had the lowest resistin and C-reactive protein plasma concentrations; the plasma resistin and C-reactive protein concentrations in the heterozygote (C-G) and the rare allele homozygote (G-G) did not differ significantly. Plasma resistin levels were significantly associated with plasma C-reactive protein level. We conclude that SNP -420C>G of the resistin gene could be involved in the inflammatory component of intracerebral hemorrhage through enhanced production of resistin.
Assuntos
Povo Asiático/genética , Hemorragia dos Gânglios da Base/genética , Proteína C-Reativa/metabolismo , Etnicidade/genética , Polimorfismo de Nucleotídeo Único/genética , Resistina/sangue , Resistina/genética , Idoso , Idoso de 80 Anos ou mais , Hemorragia dos Gânglios da Base/sangue , China , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Nitric oxide (NO) plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH). The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP). NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS) in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG).
Assuntos
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Óxido Nítrico/fisiologia , Reprodução , Animais , Tronco Encefálico/fisiologia , Feminino , Hormônio Foliculoestimulante/farmacocinética , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/farmacocinética , Hormônio Liberador de Gonadotropina/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Leptina/farmacologia , Hormônio Luteinizante/farmacocinética , Masculino , Ratos , Comportamento Sexual AnimalRESUMO
Nitric oxide (NO) plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH). The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP). NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS) in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG).
Assuntos
Animais , Masculino , Feminino , Ratos , Óxido Nítrico/fisiologia , Reprodução , Encéfalo , Hormônio Foliculoestimulante/farmacocinética , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/farmacocinética , Hipotálamo/fisiologia , Leptina/fisiologia , Hormônio Luteinizante/farmacocinética , Adeno-Hipófise/fisiologia , Comportamento Sexual AnimalRESUMO
The effects of hypothalamic lesions designed to destroy either the anterior median eminence (ME) or the posterior and mid-ME on pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined in castrated male rats. In sham-operated animals, mean plasma FSH concentrations rose to peak at 10 min after the onset of sampling, whereas LH declined to a nadir during this time. In the final sample at 120 min, the mean FSH concentrations peaked as LH decreased to its minimal value. In rats with anterior ME lesions, there was suppression of LH pulses with continuing FSH pulses in 12 of 21 rats. On the other hand, in animals with posterior to mid-ME lesions, 3 out of 21 rats had elimination of FSH pulses, whereas LH pulses were maintained. Fifteen of 42 operated rats had complete ME lesions, and pulses of both hormones were abolished. The remaining 12 rats had partial ME lesions that produced a partial block of the release of both hormones. The results support the concept of separate hypothalamic control of FSH and LH release with the axons of the putative FSH-releasing factor (FSHRF) neuronal system terminating primarily in the mid- to caudal ME, whereas those of the LHRH neuronal system terminate in the anterior and mid-median eminence. We hypothesize that pulses of FSH alone are mediated by release of the FSHRF into the hypophyseal portal vessels, whereas those of LH alone are mediated by LHRH. Pulses of both gonadotropins simultaneously may be mediated by pulses of both releasing hormones simultaneously. Alternatively, relatively large pulses of LHRH alone may account for simultaneous pulses of both gonadotropins since LHRH has intrinsic FSH-releasing activity.
Assuntos
Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Eminência Mediana/fisiologia , Animais , Peso Corporal , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/fisiologia , Gonadotropinas Hipofisárias/metabolismo , Hormônio Luteinizante/sangue , Masculino , Eminência Mediana/anatomia & histologia , Eminência Mediana/lesões , Neurônios/metabolismo , Orquiectomia , Tamanho do Órgão , Hipófise/anatomia & histologia , Hipófise/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Neurons containing neural nitric oxide synthase (nNOS) are found in various locations in the hypothalamus and, in particular, in the paraventricular and supraoptic nuclei with axons which project to the median eminence and extend into the neural lobe where the highest concentrations of NOS are found in the rat. Furthermore, nNOS is also located in folliculostellate cells and LH gonadotropes in the anterior pituitary gland. To define the role of NO in the release of hypothalamic peptides and pituitary hormones, we injected an inhibitor of NOS, Ng-monomethyl-L-arginine (NMMA) or a releasor of NO, nitroprusside (NP) into the third ventricle (3V) of conscious castrate rats and determined the effect on the release of various pituitary hormones. In vitro, we incubated medial basal hypothalamic (MBH) fragments and studied inhibitors of NO synthase and also releasors of NO. The results indicate that NOergic neurons play an important role in stimulating the release of corticotrophin-releasing hormone (CRH), luteinizing hormone releasing-hormone (LHRH), prolactin-RH's, particularly oxytocin, growth hormone-RH (GHRH) and somatostatin, but not FSH-releasing factor from the hypothalamus. NO stimulates the release of LHRH, which induces sexual behavior, and causes release of LH from the pituitary gland. The intrahypothalamic pathway by which NO controls LHRH release is as follows: glutamergic neurons synapse with noradrenergic terminals in the MBH which release nonepinephrine (NE) that acts on alpha 1 receptors on the NOergic neuron to increase intracellular free Ca++ which combines with calmodulin to activate NOS. The NOS diffuses to the LHRH terminal and activates guanylate cyclase (GC), cyclooxygenase and lipoxygenase causing release of LHRH via release of cyclic GMP, PGE2 and leukotrienes, respectively. Alcohol and cytokines can block LHRH release by blocking the activation of cyclooxygenase and lipoxygenase without interfering with the activation of GC. GABA also blocks the response of the LHRH neurons to NO and recent experiments indicate that granulocyte macrophage colony-stimulating factor (GMCSF) blocks the response of the LHRH neuron to NP by activation of GABA neurons since the blockade can be reversed by the competitive inhibitor of GABAa receptors, bicuculine.
Assuntos
Hormônios Hipotalâmicos/fisiologia , Hipotálamo/fisiologia , Óxido Nítrico/fisiologia , Hipófise/fisiologia , Hormônio Adrenocorticotrópico/fisiologia , Animais , Hormônio Liberador de Gonadotropina/fisiologia , Ocitocina/fisiologia , Ratos , Ácido gama-Aminobutírico/fisiologiaRESUMO
Previous experiments in this and other laboratories have revealed that nitric oxids (NO) plays a role in controlling the release of corticotropin-releasing hormone (CRH) and luteinizing-hormone-releasing hormone (LHRH). Therefore, we have investigated its role in control of growth hormone (GH) release in conscious rats by microinjecting NG-monomethyl-L-arginine (NMMA), an inhibitor of NO synthase (NOS), into the third ventricle (3V) of conscious, freely moving castrate male rats. An initial blood sample (0.3 ml) was drawn from an indwelling intra-atrial catheter just prior to injection of NMMA [1 mg in 5 microliters of 0.9% NaCl (saline)] into the 3V. To maintain the inhibitory action on NOS, a second injection of NMMA was administered into the 3V 60 min after the first. Additional blood samples (0.3 ml) were removed at 10 min intervals for 120 min. Other animals received injections of the diluent at the same times and volumes as NMMA. Interleukin (IL)-1 alpha (0.06 pmol in 2 microliters saline) was injected into the 3V immediately after the first injection of NMMA, whereas other animals received the NMMA diluent followed by IL-1 alpha. The effects of IL-1 alpha were almost identical to those of NMMA in that there was a dramatic lowering of plasma GH achieved primarily by a reduction in height of the GH pulses without a significant reduction in their number.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hormônio do Crescimento/metabolismo , Óxido Nítrico/fisiologia , Animais , Arginina/administração & dosagem , Arginina/análogos & derivados , Arginina/farmacologia , Interações Medicamentosas , Injeções Intraventriculares , Interleucina-1/farmacologia , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Taxa Secretória/efeitos dos fármacos , ômega-N-MetilargininaRESUMO
The common denominator of a unique disseminated multi-focal miliary myocardial hyaline necrosis and fibrosis in Keshan disease (KSD) and cystic fibrosis (CF) and a commonality of the affected age groups of fetuses and preschool children led to the review of existing KSD autopsy material to search for pancreatic and hepatic lesions considered pathognomonic for CF. Pancreatic lesions considered pathognomonic for CF were found in 595, or 35% of 1700 documented cases of KSD. The pancreatic lesions were limited to tissues of fetuses and preschool children. Adults dying of KSD had diagnostic lesions limited to the cardiovascular system, liver, and skeletal muscle. Varying degrees of focal biliary cirrhosis were identified in 850, or 50% of the KSD autopsies, and 85, or 5% developed severe lobular cirrhosis. The common denominator in CF and KSD appears to be a primary or induced secondary selenium deficiency in age-susceptible humans, prenatally at or around 22 wk of fetal life, during early postnatal life, or during the rapid-growth preschool years. The basic difference between the natural history of CF and KSD is that the selenium deficiency is totally environmental in KSD and appears to be the result of a maternal malabsorptive syndrome or an abnormality of selenium transfer in CF.