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1.
Zhonghua Yi Xue Za Zhi ; 100(1): 47-50, 2020 Jan 07.
Artigo em Chinês | MEDLINE | ID: mdl-31914558

RESUMO

Objective: To evaluate the clinical value of modified computed tomography angiography(CTA) in detecting bronchial artery-pulmonary artery fistula(BPF). Methods: Retrospective analysis was performed on 246 patients with hemoptysis admitted to the First Affiliated Hospital of Wenzhou Medical University from July 2017 to December 2018, who underwent modified CTA and DSA examination at the same time. CT was performed with Toshiba Aquilion one 320 row 640-slice spiral CT scanner. All modified CTA images were read blindly by two radiologists above the attending doctors. The sensitivity, specificity and accuracy of the modified CTA in diagnosing BPF were calculated with the DSA results as the reference,and the consistency of the two tests was analyzed. Results: DSA detected 186 cases of positive and 60 cases of negative, modified CTA detected 160 cases of positive and 86 cases of negative. The sensitivity,specificity and accuracy of modified CTA for BPF diagnosis was 85.5%(159/186),98.3%(59/60), 88.6%(218/246) respectively, and they were with high consistency with DSA examination results (kappa=0.73,P<0.01). Conclusion: Modified CTA has high diagnostic specificity for BPF,which can be used as the preferred method for non-invasive screening of suspected BPF patients.


Assuntos
Angiografia por Tomografia Computadorizada , Fístula , Artérias Brônquicas , Humanos , Artéria Pulmonar , Estudos Retrospectivos
2.
Zhonghua Yi Xue Za Zhi ; 97(37): 2898-2902, 2017 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-29050158

RESUMO

Objective: To discuss the correlation of permeability surface (PS) with hematoma and edema volume in acute spontaneous putaminal and thalamic hematoma using CT perfusion imaging. Methods: A total of 48 acute spontaneous putaminal and thalamic hemorrhage patients were enrolled in this study during October 2015 and December 2016 at the First Affiliated Hospital of Wenzhou Medical University. At the image slice with maximum size of hematoma, PS was measured by drawing various regions of interest (ROI) including"hot spots", perihematomal regions, outward regions, hemisphere regions and contralateral mirror regions. The relative PS (rPS) was calculated as the ratio of ipsilateral to contralateral PS value in each ROI. Hematoma and edema volumes were traced and obtained with commercial software. Results: The"hot spots"PS ((2.8±1.5) ml·100 g(-1)·min(-1)) and perihematomal PS ((2.1±1.4) ml·100 g(-1)·min(-1)) were both significantly higher than the PS of the contralateral mirror regions ((1.1±0.5) ml·100 g(-1)·min(-1)) (P<0.001). There was no significant difference in outward regions PS and contralateral mirror regions PS (P>0.05), nor in hemisphere regions PS and contralateral mirror regions PS (P>0.05). There was no significant difference in"hot spots"rPS and perihematomal rPS (P=0.218). The"hot spots"rPS and Perihematomal rPS were both higher than the rPS of the outward and hemisphere regions (P<0.01). There was no significant difference in the outward and hemisphere regions (P<0.01). The median hematoma volume was 12.63 ml and the median edema volume was 12.36 ml. The edema volume had a positive association with the hematoma volume(r=0.799, P<0.001) and perihematomal PS(r=0.465, P=0.001). Perihematomal PS had a positive association with the hematoma volume (r=0.386, P=0.007). Conclusion: The damage of blood-brain barrier around acute spontaneous hematoma can be measured via CT perfusion imaging. Perihematomal PS was associated with the hematoma and edema volume.


Assuntos
Hematoma , Edema Encefálico , Hemorragia Cerebral , Humanos , Permeabilidade , Tomografia Computadorizada por Raios X
3.
Zhonghua Yan Ke Za Zhi ; 53(4): 260-265, 2017 Apr 11.
Artigo em Chinês | MEDLINE | ID: mdl-28412798

RESUMO

Objective: To compare the accuracy of three different formulas for intraocular lens power calculation in high myopic eyes with cataract and analyze their influencial factors. Methods: One hundred and three high myopic patients of cataract (103 eyes), with average age of 60.2±8.8 years old (39.0-77.0), including 45 male and 54 female and with axial length ≥ 26 mm were enrolled in this retrospective case-series study. All of them underwent routine ocular examination and IOLMastermeasurement preoperatively and then underwent phacoemulsification through temporal clear-corneal incision with implantation of HumanOptic posterior chamber Intraocular lens (IOL). All analyses were conducted using SPSS version 19.0. Repeated-measures analysis of variance was applied to compare the refractive results one month postoperatively with the predicted IOL powers calculated by SRK/T, Holladay 1, or Haigis formula before surgery. The differences were further compared based on different grouping of axial length (AXL), corneal curvature (K) and corneal astigmatism (CA). The accuracies of the three formulas were analyzed using Bland-Altman analyses and the possible error sources of each formula were analyzed using multiple regression model. Results: The majority of patients enrolled had hyperopic shift after cataract surgery. The mean errors (ME) of the three formulas were SRK/T: 0.70±0.89D, Holladay 1: (1.20±0.88) D and Haigis: (0.60±0.88) D; the mean absolute errors (MAE) of the three formulas were (0.81±0.79) D, (1.23±0.84) D and (0.76±0.74) D, respectively. Both ME and MAE of Holladay formula were significantly greater than the other two formulas (F=86.31, P<0.01). Besides, the proportion of patients having a prediction error within 0.50 D was lower in those using Holladay formula (20.4%, 21/103) than the other two (SRK/T: 38.8%, 40/103, χ(2)=8.41, P<0.01, Haigis: 45.6%, 47/103, χ(2)=14.84, P<0.01). Bland-Altman analyses showed that the accuracies of all the three formulas were acceptable in patients of cataract with high myopia in clinical practice. ME and MAE tended to be larger with longer axial length, larger corneal curvature and astigmatism of the patients in all three formulas. However, in eyes with axial length> 30 mm or corneal curvature ≤43.00 D, the MAE of Haigis formula was lower than that of SRK/T formula (F=63.26,63.94, both P<0.01). The prediction error of SRK/T formula was positively correlated with axial length and corneal astigmatism (F=33.97, r=0.66, ß=0.48, P<0.01 and ß=0.42, P<0.01), while for Holladay and Haigis formulas, in addition to the previous two factors, the errors were also positively correlated with mean corneal curvature (Holladay 1: F=31.26, r=0.72, AXL: ß=0.52, P<0.01, K: ß=0.20, P<0.05 and CA: ß=0.37, P<0.01; Haigis: F=30.96, r=0.72, AXL: ß=0.33, P<0.01, K: ß=0.40, P<0.01 and CA: ß=0.37, P<0.01). Conclusions: In the selection of IOL formula for high myopic patients with cataract, Haigis or SRK/T would reduce the prediction error and serve as the more accurate formulas than Holladay 1. Haigis formula may be more accurate than SRK/T formula in case of AXL>30 mm or K≤43.00 D. (Chin J Ophthalmol, 2017, 53: 260-265).


Assuntos
Catarata/complicações , Lentes Intraoculares , Miopia/reabilitação , Adulto , Idoso , Astigmatismo , Comprimento Axial do Olho/patologia , Extração de Catarata , Feminino , Humanos , Hiperopia/etiologia , Implante de Lente Intraocular , Cristalino , Masculino , Pessoa de Meia-Idade , Miopia/complicações , Facoemulsificação/métodos , Período Pós-Operatório , Refração Ocular , Estudos Retrospectivos , Testes Visuais
4.
Zhonghua Yi Xue Za Zhi ; 97(5): 359-364, 2017 Feb 07.
Artigo em Chinês | MEDLINE | ID: mdl-28219193

RESUMO

Objective: To investigate the change of cerebral microcirculation of chronic cerebral circulation insufficiency(CCCI) patients and the relationship between CCCI and crossed cerebellar diaschisis(CCD)by using 320-detector row of low-dose volume CT perfusion imaging. Methods: A total of 158 patients (103 males, 55 females, from 45 to 82 years old, the mean age was 62.9) with symptoms of CCCI were admitted to the First Affiliated Hospital of Wenzhou Medical University from June 2013 to January 2016. Low-dose CTP imaging of whole brain was performed to them using 320-detector row volume CT scanner. The perfusion parameters such as cerebral blood flow(CBF), cerebral blood volume(CBV), mean transit time(MTT), time to peak(TTP) and DLY in both cerebral blood supply areas and cerebellum were got, so were the 4-dimensional CTA images, and rCBF, rCBV, rMTT and rTTP were calculated by ipsilateral/contralateral value. Comparative t-test and independent t-test were applied to analyzing these parameters quantitatively.Chi-square test and Logistic regression model were applied to analyzing the related clinical risk factors. Results: (1) All 108 patients in CCCI group showed asymmetric perfusion within two cerebral hemispheres in CTP images. The CBF, CBV of diseased side were lower than the contralateral mirror area (t(CBF)=-12.89, t(CBV)=-7.031, P(CBF, CBV)<0.001); the MTT of the diseased side was shorter than the contralateral mirror area (t(MTT) =13.310, P(MTT)<0.001); the TTP of the diseased side was longer than the contralateral mirror area (t(TTP)=-4.012, P(TTP)<0.001). The rCBF and rCBV of CCCI group were lower than that in non-CCCI group (t(rCBF)=3.079, t(rCBV)=2.760, P(rCBF, rCBV)<0.01), while the rTTP of CCCI group was longer than that in non-CCCI group (t(rTTP)=4.846, P(rTTP)<0.001). (2)The results of Chi-square test showed that the differences of gender (χ(2)=4.036, P=0.045), hyperlipidemia (χ(2)=7.687, P=0.006), as well as smoking (χ(2)=11.868, P=0.001) had statistical significance between CCCI group and non-CCCI group.Multi-factor Logistic regression analysis showed that hyperlipidemia (OR value=3.736, P=0.016) and smoking (OR value=4.641, P=0.01) were the risk factors of CCCI, while gender had no relationship with it.(3)The incidence of CCD was 18.5% in the CCCI group, and at the same time, the supratentorial corresponding blood supply areas were classified.A total of 10(34.5%) cases were in blood supply area of posterior cerebral artery, 6(20.7%) cases were in blood supply area of middle cerebral artery, 12(41.4%) cases were of anterior cerebral artery, while only 1(3.5%) case was of basal ganglia, in which 4 cases were in blood supply area of posterior cerebral artery, another 4 cases were middle cerebral artery, 7 cases were of anterior cerebral artery and no case of basal ganglia respectively leading CCD alone. Conclusions: CTP could display the microcirculation situation of abnormal brain tissue perfusion area intuitively and quantitatively. Additionally, it could reflect the degree of relationship between cerebral several blood supply areas and cerebellum.


Assuntos
Circulação Cerebrovascular , Imagem de Perfusão , Idoso , Idoso de 80 Anos ou mais , Cerebelo , Transtornos Cerebrovasculares , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média , Perfusão , Tomografia Computadorizada por Raios X
5.
Zhonghua Yi Xue Za Zhi ; 96(33): 2644-2647, 2016 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-27666885

RESUMO

Objective: To investigate the clinical efficacy and safety of temporary heart pacemaker for emergency treatment of patients with acute and severe cardiovascular diseases. Methods: The clinical data of 147 patients with cardiac arrest or bradyarrhythmia from August 2007 to December 2015, was analyzed retrospectively in Department of internal and Emergency Medicine, People's Hospital of Henan. Based on the rescue methods, all patients were divided into two groups: observation group (80 cases, among whom, 49 cases with cardiac arrest and 31 cases with bradyarrhythmia) and control group (67 cases, among whom 39 cases with cardiac arrest and 28 cases with bradyarrhythmia). Patients in observation group received temporary heart pacemaker, and patients in control group received traditional cardio-pulmonary resuscitation and drug treatment. The rate of rescue and complications were analyzed and compared in two groups. Results: The total rescue rate in observation group was 96.3%, which was significantly higher than that in control group (44.8 %) (P<0.05). Further analysis showed that the rescue rate of patients with cardiac arrest in observation group was significantly higher than that in control group (95.1% vs 45.1%) (P<0.05), and the rescue rate of patients with bradyarrhythmia in observation group was significantly higher than that in control group (97.4% vs 44.4%) (P<0.05). Complications were observed in 4 patients: pericardial effusion (1 case ), ventricular fibrillation (1 cases) and catheter dislocation (2 cases). Conclusion: Temporary heart pacemaker was safe and effective in the treatment of patients with acute and severe cardiovascular diseases with improved rescue rate.


Assuntos
Doenças Cardiovasculares , Humanos , Marca-Passo Artificial , Derrame Pericárdico , Estudos Retrospectivos , Fibrilação Ventricular
6.
Genet Mol Res ; 15(3)2016 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-27525942

RESUMO

Rice blast caused by Magnaporthe oryzae is one of the most devastating rice diseases worldwide. To understand the genetic diversity of indica landrace accessions and identify simple sequence repeat (SSR) markers that are associated with blast resistance, a population of 276 indica landraces from across the world was constructed. This population was then used to evaluate the blast-resistance phenotype through artificial inoculation under controlled conditions in 2012 and 2013. The genetic diversity and association of the population with resistance were analyzed by examining the phenotype for 160 SSR markers distributed on 12 rice chromosomes. The 276 accessions were classified into seven groups using model- and distance-based cluster analyses. Associations between SSR markers and blast resistance showed that 26 SSR markers were significantly associated with blast resistance in 2012 and 2013 (P < 0.01) and that the phenotypic variation ranged from 2.68 to 13.11%. Nineteen of the markers associated with blast resistance were located in regions where genes or quantitative trait loci (QTLs) have been previously reported, and seven were newly identified in this study. These results indicate that marker-trait association has potential advantages over classical linkage analysis and QTL mapping, and that these markers could be used for marker-assisted selection in rice blast-resistance-breeding programs.


Assuntos
Resistência à Doença/genética , Oryza/genética , Doenças das Plantas/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Análise por Conglomerados , Genes de Plantas , Estudos de Associação Genética , Ligação Genética , Variação Genética , Interações Hospedeiro-Patógeno , Magnaporthe/fisiologia , Repetições de Microssatélites , Oryza/microbiologia , Melhoramento Vegetal , Doenças das Plantas/microbiologia , Locos de Características Quantitativas
7.
Genet Mol Res ; 13(4): 9756-65, 2014 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-25501185

RESUMO

Bodao, a japonica landrace from the Taihu Lake region of China, is highly resistant to most Chinese isolates of Magnaporthe oryzea, a form of rice blast. To effectively dissect the influence of genetics on this blast resistance, a population of 155 recombinant inbred lines (F2:8) derived from a cross of Bodao x Suyunuo was inoculated with 12 blast isolates. Using a quantitative trait locus (QTL) mapping approach, 13 QTL on chromosomes 1, 2, 9, 11, and 12 were detected from Bodao. Five QTL, including qtl11-1-1, qtl11-3-7, qtl11-4-9, qtl12-1-1, and qtl12-2-3, have not been previously reported. The qtl11-3-7 and qtl11-4-9 may be the two main effective QTL and resistant to 7 and 9 isolates, respectively. The results of the present study will be valuable for the fine mapping and cloning of these two new resistance genes.


Assuntos
Cromossomos de Plantas/imunologia , Oryza/genética , Doenças das Plantas/imunologia , Imunidade Vegetal/genética , Locos de Características Quantitativas/imunologia , China , Mapeamento Cromossômico , Cromossomos de Plantas/química , Cruzamentos Genéticos , Magnaporthe/imunologia , Oryza/imunologia , Oryza/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia
8.
Genet Mol Res ; 13(1): 649-59, 2014 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-24615030

RESUMO

Microsomal epoxide hydrolase 1 (EPHX1) is an important biological phase II metabolic enzyme that is extensively involved in the metabolism of diverse environmental carcinogens such as polycyclic aromatic hydrocarbons and heterocyclic amines. Many articles have reported the association between EPHX1 (Tyr113His and His139Arg) polymorphisms and esophageal cancer risk, but the results are controversial. This study aimed to identify the association between EPHX1 (Tyr113His and His139Arg) polymorphisms and esophageal cancer risk by meta-analysis. The odds ratio (OR) with 95% confidence interval (95%CI) was used to evaluate the strength of the associations. Heterogeneity was estimated by the chi-square-based Q-statistic test and the P value. Meanwhile, the random-effect or fixed-effect model was used according to the between-study heterogeneity. Begg's funnel plot and the Egger test were performed to assess the publication bias of articles. Finally, 8 case-control studies involving 1158 cases and 1868 controls for the Tyr113His polymorphism and 7 case-control studies involving 901 cases and 1615 controls for the His139Arg polymorphism were included in this meta-analysis. Meta-analysis showed that the Tyr113His polymorphism was a stronger power trend towards risk for esophageal cancer using a recessive model (CC versus CT+TT, OR = 1.204, 95%CI = 1.001-1.450, P = 0.049). However, no significant associated risk was found between the His139Arg polymorphism and esophageal cancer. These findings suggest that the Tyr113His polymorphism might be a stronger power trend towards risk for esophageal cancer. However, no evidence was found for the association between the EPHX1 His139Arg polymorphism and esophageal cancer risk.


Assuntos
Epóxido Hidrolases/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença , Feminino , Estudos de Associação Genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco
9.
Sci Rep ; 4: 3715, 2014 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-24430057

RESUMO

Silicon nanoarray hybrid solar cells benefit from the ease of fabrication and the cost-effectiveness of the hybrid structure, and represent a new research focus towards the utilization of solar energy. However, hybrid solar cells composed of both inorganic and organic components suffer from the notorious stability issue, which has to be tackled before the hybrid solar cells could become a viable alternative for harvesting solar energy. Here we show that Si nanoarray/PEDOT:PSS hybrid solar cells with improved stability can be fabricated via eliminating the water inclusion in the initial formation of the heterojunction between Si nanoarray and PEDOT:PSS. The Si nanoarray hybrid solar cells are stable against rapid degradation in the atmosphere environment for several months without encapsulation. This finding paves the way towards the real-world applications of Si nanoarray hybrid solar cells.

10.
Toxicol Lett ; 209(3): 282-90, 2012 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-22265867

RESUMO

Fetuses with intrauterine growth retardation (IUGR) induced by prenatal nicotine exposure are susceptible to adult metabolic syndrome. Our goals for this study were to investigate the effects of prenatal nicotine exposure on the fetal hypothalamic-pituitary-adrenal (HPA) axis and glucose and lipid metabolism and to explain the susceptibility to adult metabolic syndrome for fetuses with nicotine induced-IUGR. Pregnant Wistar rats were administered 0.25, 0.5, and 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 11 to 20. Nicotine exposure significantly increased the levels of fetal blood corticosterone and decreased the expression of placental 11ß-hydroxysteroid dehydrogenase-2 (11ß-HSD-2). Moreover, nicotine exposure significantly increased the expressions of fetal hippocampal 11ß-HSD-1 and glucocorticoid receptor (GR) and decreased the expressions of fetal hypothalamus corticotropin-releasing hormone, adrenal steroid acute regulatory protein, and cholesterol side-chain cleavage enzyme. Additionally, increased expressions of 11ß-HSD-1 and GR were observed in fetal liver and gastrocnemius muscle, and these tissues also expressed lower levels of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, and insulin receptor, while expressing increased levels of adiponectin receptor, leptin receptors, and AMP-activated protein kinase α2. Prenatal nicotine exposure causes HPA axis-associated neuroendocrine metabolic alterations in fetal rats. The underlying mechanism may involve activated glucocorticoid metabolism in various fetal tissues.


Assuntos
Desenvolvimento Fetal/efeitos dos fármacos , Glucocorticoides/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Exposição Materna/efeitos adversos , Neurossecreção/efeitos dos fármacos , Nicotina/toxicidade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Animais , Glicemia/metabolismo , Western Blotting , Relação Dose-Resposta a Droga , Feminino , Sangue Fetal/química , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/metabolismo , Idade Gestacional , Glucocorticoides/sangue , Sistema Hipotálamo-Hipofisário/embriologia , Sistema Hipotálamo-Hipofisário/metabolismo , Injeções Subcutâneas , Troca Materno-Fetal , Sistema Hipófise-Suprarrenal/embriologia , Sistema Hipófise-Suprarrenal/metabolismo , Placenta/enzimologia , Placenta/metabolismo , Gravidez , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real
11.
Oncogene ; 31(1): 116-27, 2012 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-21666725

RESUMO

Expression of the breast cancer-associated gene 1 (BRCA1) in sporadic breast cancers is usually reduced, yet the underlying mechanisms remains elusive. To identify factors that are responsible for reduced BRCA1 expression, we screened 92 known transcription factors for their ability to regulate expression of BRCA1. Among several potential regulators, the Gli-Krueppel-related transcription factor Yin Yang 1 (YY1) showed the most dramatic transactivation of the BRCA1 promoter. YY1 binds to the promoter of BRCA1, and its overexpression resulted in increased expression of BRCA1 and a number of BRCA1 downstream genes. We further showed that overexpression of YY1 in cancer cells inhibited cell proliferation, foci formation and tumor growth in nude mice. To assess the clinical relevance between YY1 and BRCA1, we studied expression of YY1 and BRCA1 from human breast cancer samples and tissue arrays, and detected a significant positive correlation between the level of YY1 and BRCA1 expression in these cancers. Taken together, these findings suggest that YY1 is a key regulator of BRCA1 expression and may be causally linked to the molecular etiology of human breast cancer.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , Genes BRCA1 , Proteínas Supressoras de Tumor/fisiologia , Fator de Transcrição YY1/fisiologia , Animais , Proteína BRCA1/análise , Mama/embriologia , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Ciclo Celular , Linhagem Celular Tumoral , Transformação Celular Neoplásica/patologia , Feminino , Humanos , Camundongos , Regiões Promotoras Genéticas , Fator de Transcrição YY1/análise
12.
J Biol Chem ; 276(10): 7602-8, 2001 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-11106668

RESUMO

Although human c-IAP1 and c-IAP2 have been reported to possess antiapoptotic activity against a variety of stimuli in several mammalian cell types, we observed that full-length c-IAP1 and c-IAP2 failed to protect cells from apoptosis induced by Bax overexpression, tumor necrosis factor alpha treatment or Sindbis virus infection. However, deletion of the C-terminal RING domains of c-IAP1 and c-IAP2 restored antiapoptotic activity, indicating that this region negatively regulates the antiapoptotic function of the N-terminal BIR domain. This finding is consistent with the observation by others that the spacer region and RING domain of c-IAP1 functions as an E3 ligase, promoting autoubiquitination and degradation of c-IAP1. In addition, we found that c-IAP1 is cleaved during apoptosis to 52- and 35-kDa fragments. Both fragments contain the C-terminal end of c-IAP1 including the RING finger. In vitro cleavage of c-IAP1 with apoptotic cell extracts or with purified recombinant caspase-3 produced similar fragments. Furthermore, transfection of cells with the spacer-RING domain alone suppressed the antiapoptotic function of the N-terminal BIR domain of c-IAP1 and induced apoptosis. Optimal death-inducing activity of the spacer-RING required both the spacer region and the zinc-binding RING domain of c-IAP1 but did not require the caspase recruitment domain located within the spacer region. To the contrary, deletion of the caspase recruitment domain increased proapoptotic activity, apparently by stabilizing the C-terminal fragment.


Assuntos
Apoptose , Caspases/metabolismo , Proteínas Virais/química , Proteínas Virais/metabolismo , Animais , Sítios de Ligação , Células CHO , Caspase 3 , Linhagem Celular , Cricetinae , Deleção de Genes , Humanos , Immunoblotting , Proteínas Inibidoras de Apoptose , Modelos Genéticos , Mutagênese Sítio-Dirigida , Plasmídeos/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Vírus Sindbis/genética , Transfecção , Zinco/metabolismo
13.
Gene ; 236(1): 87-95, 1999 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-10433969

RESUMO

DNA methylation plays an important role in animal development and gene regulation. In mammals, several genes encoding DNA cytosine methyltransferases have been identified. DNMT1 is constitutively expressed and is required for the maintenance of global methylation after DNA replication. In contrast, the murine Dnmt3 family genes appear to be developmentally regulated and behave like de novo DNA methyltransferases in vitro. In this study, we have cloned human DNMT3A and DNMT3B that encode full-length DNMT3A and DNMT3B proteins with 98% and 94% amino acid sequence identity to their murine homologues. The DNMT3A and DNMT3B show high homology in the carboxy terminal catalytic domain and contain a conserved cysteine-rich region, which shares homology with the X-linked ATRX gene of the SNF2/SWI family. We have mapped human DNMT3A and DNMT3B to chromosomes 2p23 and 20q11.2 respectively, and determined the DNMT3B genomic structure. We further show that DNMT3A expression is ubiquitous and can be readily detected in most adult tissues, whereas DNMT3B is expressed at very low levels in most tissues except testis, thyroid and bone marrow. Significantly, both DNMT3A and DNMT3B expression is elevated in several tumor cell lines to levels comparable to DNMT1. The cloning of the human DNMT3 genes will facilitate further biochemical and genetic studies of their functions in establishment of DNA methylation patterns, regulation of gene expression and tumorigenesis.


Assuntos
DNA-Citosina Metilases/genética , Sequência de Aminoácidos , Mapeamento Cromossômico , Clonagem Molecular , Ilhas de CpG , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , DNA Complementar/análise , Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Modelos Genéticos , Dados de Sequência Molecular , Família Multigênica , RNA Mensageiro/análise , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Células Tumorais Cultivadas
14.
Blood ; 94(2): 411-6, 1999 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-10397707

RESUMO

The malignant Reed-Sternberg cell of Hodgkin's disease, first described a century ago, has resisted in-depth analysis due to its extreme rarity in lymphomatous tissue. To directly study its genome-wide gene expression, approximately 11,000,000 bases (27,518 cDNA sequences) of expressed gene sequence was determined from living single Reed-Sternberg cells, Hodgkin's tissue, and cell lines. This approach increased the number of genes known to be expressed in Hodgkin's disease by 20-fold to 2,666 named genes. The data here indicate that Reed-Sternberg cells from both nodular sclerosing and lymphocyte predominant Hodgkin's disease were derived from an unusual B-cell lineage based on a comparison of their gene expression to approximately 40,000,000 bases (10(5) sequences) of expressed gene sequence from germinal center B cells (GCB) and dendritic cells. The data set of expressed genes, reported here and on the World Wide Web, forms a basis to understand the genes responsible for Hodgkin's disease and develop novel diagnostic markers and therapies. This study of the rare Reed-Sternberg cell, concealed in its heterogenous cellular context, also provides a formidable test case to advance the limit of analysis of differential gene expression to the single disease cell.


Assuntos
Linfócitos B/patologia , Regulação Neoplásica da Expressão Gênica , Doença de Hodgkin/patologia , Proteínas de Neoplasias/análise , Células de Reed-Sternberg/classificação , Diferenciação Celular , Linhagem da Célula , DNA Complementar/genética , Células Dendríticas/metabolismo , Etiquetas de Sequências Expressas , Biblioteca Gênica , Centro Germinativo/citologia , Doença de Hodgkin/genética , Humanos , Proteínas de Neoplasias/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Células de Reed-Sternberg/metabolismo , Células de Reed-Sternberg/patologia , Homologia de Sequência do Ácido Nucleico , Células Tumorais Cultivadas
15.
Genomics ; 43(1): 69-77, 1997 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-9226374

RESUMO

We have isolated a prostate-specific gene (NKX3.1) in humans that is homologous to the Drosophila NK homeobox gene family. Northern blot analyses indicate that this gene is expressed at high levels in adult prostate and at a much lower level in testis, but is expressed little or not at all in several other tissues. In an androgen-dependent prostate carcinoma line, LNCaP, NKX3.1 mRNA is expressed at a basal level that was increased markedly upon androgen stimulation; the NKX3.1 mRNA was undetectable in several other human tumor cell lines including two androgen-independent prostate carcinoma lines. The NKX3.1 gene maps to chromosome band 8p21, a region frequently reported to undergo a loss of heterozygosity associated with tissue dedifferentiation and loss of androgen responsiveness during the progression of prostate cancer. Based on these data we propose that NKX3.1 is a candidate gene for playing a role in the opposing processes of androgen-driven differentiation of prostatic tissue and loss of that differentiation during the progression of prostate cancer.


Assuntos
Cromossomos Humanos Par 8/genética , Genes Homeobox , Proteínas de Homeodomínio/genética , Próstata/metabolismo , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Adulto , Sequência de Aminoácidos , Androgênios/metabolismo , Androgênios/farmacologia , Animais , Sequência de Bases , Deleção Cromossômica , Mapeamento Cromossômico , Clonagem Molecular , DNA/genética , Drosophila/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Genes de Insetos , Humanos , Hibridização in Situ Fluorescente , Masculino , Camundongos , Dados de Sequência Molecular , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/metabolismo , Próstata/crescimento & desenvolvimento , Neoplasias da Próstata/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Tecidual , Células Tumorais Cultivadas
16.
J Biol Chem ; 271(50): 31779-82, 1996 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-8943214

RESUMO

A new member of the mouse NK family of homeobox genes that is related to Drosophila NK-3 has been identified. Expression of this gene, termed Nkx-3.1, is largely restricted to the prostate gland in adult animals. The level of Nkx-3.1 mRNA decreases markedly in response to castration, suggesting that its expression is androgen-dependent. In situ hybridization analyses demonstrated that expression of Nkx-3.1 in the prostate is confined to epithelial cells. In newborns, Nkx-3.1 mRNA is detected in the urethral epithelium that is being induced by the surrounding mesenchyme to invaginate to form prostatic buds. Together, these observations suggest that the Nkx-3.1 protein, which likely functions as a transcription factor, plays a prominent role both in the initiation of prostate development and in the maintenance of the differentiated state of prostatic epithelial cells.


Assuntos
Androgênios/metabolismo , Genes Homeobox , Proteínas de Homeodomínio/genética , Próstata/metabolismo , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Northern Blotting , Proteínas de Drosophila , Regulação da Expressão Gênica no Desenvolvimento , Hibridização In Situ , Masculino , Camundongos , Dados de Sequência Molecular , RNA Mensageiro/metabolismo
17.
J Biol Chem ; 271(28): 16720-4, 1996 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-8663294

RESUMO

Members of the ICE/Ced-3 gene family are likely effector components of the cell death machinery. Here, we characterize a novel member of this family designated ICE-LAP6. By phylogenetic analysis, ICE-LAP6 is classified into the Ced-3 subfamily which includes Ced-3, Yama/CPP32/apopain, Mch2, and ICE-LAP3/Mch3/CMH-1. Interestingly, ICE-LAP6 contains an active site QACGG pentapeptide, rather than the QACRG pentapeptide shared by other family members. Overexpression of ICE-LAP6 induces apoptosis in MCF7 breast carcinoma cells. More importantly, ICE-LAP6 is proteolytically processed into an active cysteine protease by granzyme B, an important component of cytotoxic T cell-mediated apoptosis. Once activated, ICE-LAP6 is able to cleave the death substrate poly(ADP-ribose) polymerase into signature apoptotic fragments.


Assuntos
Caspases , Cisteína Endopeptidases/genética , Proteínas de Helminto/genética , Serina Endopeptidases/metabolismo , Linfócitos T Citotóxicos/enzimologia , Sequência de Aminoácidos , Apoptose/genética , Sítios de Ligação , Proteínas de Caenorhabditis elegans , Caspase 1 , Caspase 9 , Cisteína Endopeptidases/metabolismo , DNA Complementar , Granzimas , Humanos , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Células Tumorais Cultivadas
18.
Cell ; 85(6): 829-39, 1996 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-8681378

RESUMO

The gene cul-1 (formerly lin-19) is a negative regulator of the cell cycle in C. elegans. Null mutations cause hyperplasia of all tissues. cul-1 is required for developmentally programmed transitions from the G1 phase of the cell cycle to the GO phase or the apoptotic pathway. Moreover, the mutant phenotype suggests that G1-to-S phase progression is accelerated, overriding mechanisms for mitotic arrest and producing abnormally small cells. Significantly, diverse aspects of cell fate and differentiation are unaffected in cul-1 mutants. cul-1 represents a conserved family of genes, designated cullins, with at least five members in nematodes, six in humans, and three in budding yeast.


Assuntos
Caenorhabditis elegans/genética , Proteínas de Ciclo Celular , Ciclo Celular/fisiologia , Proteínas Culina , Genes de Helmintos/genética , Proteínas de Helminto/genética , Sequência de Aminoácidos , Animais , Apoptose/fisiologia , Sequência de Bases , Caenorhabditis elegans/química , Caenorhabditis elegans/embriologia , Mapeamento Cromossômico , Clonagem Molecular , DNA Complementar/genética , Camadas Germinativas , Proteínas de Helminto/química , Proteínas de Helminto/fisiologia , Humanos , Larva , Dados de Sequência Molecular , Mutação , RNA de Helmintos/genética , RNA Mensageiro/genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Leveduras
19.
J Biol Chem ; 271(3): 1621-5, 1996 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-8576161

RESUMO

Members of the ICE/ced-3 gene family have been implicated as components of the cell death pathway. Based on similarities with the structural prototype interleukin-1 beta-converting enzyme (ICE), family members are synthesized as proenzymes that are proteolytically processed to form active heterodimeric enzymes. In this report, we describe a novel member of this growing gene family, ICE-LAP3, which is closely related to the death effector Yama/CPP32/Apopain. Pro-ICE-LAP3 is a 35-kDa protein localized to the cytoplasm and expressed in a variety of tissues and cell lines. Overexpression of a truncated version of ICE-LAP3 (missing the pro-domain) induces apoptosis in MCF7 breast carcinoma cells. Importantly, upon receipt of a death stimulus, endogenous ICE-LAP3 is processed to its subunit forms, suggesting a physiological role in cell death. This is the first report to demonstrate processing of a native ICE/ced-3 family member during execution of the death program and the first description of the subcellular localization of an ICE/ced-3 family member.


Assuntos
Apoptose/fisiologia , Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/metabolismo , Caspases , Cisteína Endopeptidases , Proteínas de Helminto/química , Proteínas/química , Proteínas/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Receptor fas/farmacologia , Adulto , Sequência de Aminoácidos , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Neoplasias da Mama , Caspase 7 , Linhagem Celular , Primers do DNA , Feminino , Feto , Expressão Gênica , Proteínas de Helminto/metabolismo , Humanos , Dados de Sequência Molecular , Família Multigênica , Reação em Cadeia da Polimerase , Biossíntese de Proteínas , Precursores de Proteínas/biossíntese , Precursores de Proteínas/metabolismo , Ratos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Células Tumorais Cultivadas
20.
Endocrinology ; 137(1): 160-5, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8536608

RESUMO

We have isolated a candidate Müllerian inhibiting substance (MIS) type II receptor complementary DNA from an embryonic rat urogenital ridge library and have studied its binding to MIS, its developmental pattern of expression and tissue distribution. By in situ hybridization with a full-length riboprobe, the receptor is expressed in the mesenchymal cells surrounding the Müllerian duct at embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat fetal gonads. Expression of the messenger RNA was also seen in the granules cells and seminiferous tubules of pubertal gonads. Northern analysis revealed that the MIS type II receptor messenger RNA is highly expressed in embryonic, pubertal, and adult testes and ovaries, as well as in the gravid uterus. The timing of expression in the gonads of both sexes was also analyzed by Northern analyses that showed high levels of expression at the time of Müllerian duct regression, much lower levels neonatally and prepubertally and then increased expression again with sexual maturation. The tissue and developmental specificity of expression of this receptor, which make it likely that this is the functional MIS type II receptor, can be used to advantage in therapeutic targeting strategies and to decipher the function of MIS in the gonads.


Assuntos
Envelhecimento/metabolismo , Animais Recém-Nascidos/metabolismo , Desenvolvimento Embrionário e Fetal , Feto/metabolismo , Receptores de Peptídeos/metabolismo , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Sequência de Bases , Northern Blotting , Feminino , Hibridização In Situ , Masculino , Sondas Moleculares/genética , Dados de Sequência Molecular , Ratos/embriologia , Receptores de Peptídeos/genética , Receptores de Fatores de Crescimento Transformadores beta
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