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1.
JAMA ; 322(14): 1416, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593265

Assuntos
Sepse , Humanos , Fenótipo
2.
JAMA ; 322(14): 1416-1417, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593266

Assuntos
Sepse , Humanos , Fenótipo
3.
JAMA ; 322(14): 1417, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593269

Assuntos
Sepse , Humanos , Fenótipo
4.
Exp Suppl ; 111: 55-84, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588528

RESUMO

Thyroid hormone (TH) action is crucial for the development of several tissues.A number of syndromes are associated with reduced responsiveness to thyroid hormones, expanding the original definition of thyroid hormone resistance, firstly described by Refetoff and collaborators in 1967, which is characterized by elevated circulating levels of T4 and T3 with measurable serum TSH concentrations, as a consequence of mutations of thyroid hormone receptor beta (TRß), recently named as RTHß. More recently, another form of insensitivity to TH has been identified due to mutations in the thyroid hormone receptor alpha (TRα), named RTHα. In this chapter we will focus the discussion on the phenotype of RTHß and RTHα. These diseases share the same pathogenic mechanism caused by dominant negative mutations in TH receptor genes that reduce T3 binding or affect the recruitment of cofactors. As a consequence, thyroid hormone actions are impaired at the tissue level. The phenotypic manifestations of RTHß and RTHα are to some extent correlated with the degree of disruption and the tissue distribution of the TRs being characterized by variable coexistence of hypothyroid or thyrotoxic manifestations in RTHß or by a congenital hypothyroid features in RTHα despite normal TSH and borderline low free T4.


Assuntos
Receptores alfa dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/genética , Hormônios Tireóideos/sangue , Humanos , Fenótipo
5.
Oecologia ; 191(2): 397-409, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494711

RESUMO

Determining the characteristics of non-native plants that can successfully establish and spread is central to pressing questions in invasion ecology. Evidence suggests that some non-native species establish and spread in new environments because they possess characteristics (functional traits) that allow them to either successfully compete with native residents or fill previously unfilled niches. However, the relative importance of out-competing native species vs. filling empty niche space as potential mechanisms of invasion may depend on environmental characteristics. Here, we measured plant functional traits, proxies indicative of competitive and establishment strategies, to determine if these traits vary among native and invasive species and if their prevalence is dependent on environmental conditions. Using a natural environmental gradient in Hawai'i Volcanoes National Park, we evaluated how functional traits differ between native and non-native plant communities and if these differences change along an environmental gradient from hot, dry to cool, wet conditions. Functional trait differences suggested that both competition and open niche space may be important for invasion. Non-native communities tended to have traits associated with faster growth strategies such as higher specific leaf area and lower leaf thickness. However, native and non-native community traits became more dissimilar along the gradient, suggesting that non-native species may be occupying previously unfilled niche space at the hot, dry end of the gradient. We also found that most of the variation in functional trait values amongst plots was due to species turnover rather than intraspecific variation. These results highlight the role of environmental context when considering invasion mechanisms.


Assuntos
Espécies Introduzidas , Plantas , Fenótipo , Folhas de Planta
6.
Anticancer Res ; 39(9): 4957-4963, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519601

RESUMO

BACKGROUND/AIM: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. MATERIALS AND METHODS: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. RESULTS: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. CONCLUSION: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Imunidade Celular/genética , Imunidade Celular/efeitos da radiação , Contagem de Leucócitos , Fenótipo , Polimorfismo de Nucleotídeo Único , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Inata , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Radioterapia Adjuvante , Linfócitos T/imunologia , Linfócitos T/metabolismo
7.
Anticancer Res ; 39(9): 4965-4970, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519602

RESUMO

BACKGROUND/AIM: Colonic crypts with normal epithelium albeit with corrupted shapes (CCS) were previously found beneath nonpolypoid adenomas (NPA). This study aimed to analyze the distribution of proliferating cells (PC) and p53-up-regulated cells in CCS. MATERIALS AND METHODS: Sections from 48 NPA were immunostained with the proliferating-marker Ki67 and against the tumor-suppressor protein p53. RESULTS: Asymmetric-haphazardly distributed PC were found in 87.5% of the NPA, continuous PC-domains in 8.3%, asymmetric-haphazardly distributed single PC in 4.2% and p53-up-regulated cells in 29.2%. In 12 controls, the normal-shaped crypts revealed symmetrically-distributed PC-domains in their lower thirds, and no p53-up-regulated cells. CONCLUSION: The normal epithelium that lines the CCS below NPA, thrives with relocated PC-domains, and with occasional p53-up-regulated cells. These findings strongly suggest that the normal epithelium of CCS beneath NPA might harbor somatic mutations. The accretion of putative mutated CCS might play an important role in the evolution of nonpolypoid adenomas in the human colon.


Assuntos
Adenoma/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Mucosa Intestinal/metabolismo , Proteína Supressora de Tumor p53/genética , Adenoma/metabolismo , Adenoma/patologia , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Humanos , Fenótipo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 886-889, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515782

RESUMO

OBJECTIVE: To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS). METHODS: Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c.3779+1G>A and c.5052_c.5053insT, were respectively identified in the 2 patients. Among these, c.3779+1G>A was a previously known pathological mutation, while c.5052_c.5053insT was unreported previously. Both variants were predicted to be pathological. CONCLUSION: Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.


Assuntos
Proteína de Ligação a CREB/genética , Síndrome de Rubinstein-Taybi/genética , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fenótipo
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 901-904, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515786

RESUMO

OBJECTIVE: To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. METHODS: Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. RESULTS: The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c.92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. CONCLUSION: The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.


Assuntos
Afibrinogenemia/genética , Fibrinogênio/genética , Afibrinogenemia/congênito , Análise Mutacional de DNA , Feminino , Humanos , Mutação , Linhagem , Fenótipo
11.
Adv Exp Med Biol ; 1167: 237-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520359

RESUMO

In recent years, there has been growing interest in using Drosophila for drug discovery as it provides a unique opportunity to screen small molecules against complex disease phenotypes in a whole animal setting. Furthermore, gene-compound interaction experiments that combine compound feeding with complex genetic manipulations enable exploration of compound mechanisms of response and resistance to an extent that is difficult to achieve in other experimental models. Here, I discuss how compound screening and testing approaches reported in Drosophila fit into the current cancer drug discovery pipeline. I then propose a framework for a Drosophila-based cancer drug discovery strategy which would allow the Drosophila research community to effectively leverage the power of Drosophila to identify candidate therapeutics and push our discoveries into the clinic.


Assuntos
Antineoplásicos/farmacologia , Drosophila , Descoberta de Drogas , Neoplasias/tratamento farmacológico , Animais , Modelos Animais de Doenças , Técnicas Genéticas , Fenótipo
12.
Adv Exp Med Biol ; 1178: 25-38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493220

RESUMO

Schizophrenia is a severe and debilitating psychiatric disorder believed to have neurodevelopmental origins. Several studies have associated energy metabolism dysfunction with the disorder, mostly related to glycolysis alterations. Glucose is the obligatory energy substrate of the brain and glycolysis is the first step for its metabolism. This takes place predominantly in glial cells, astrocytes and oligodendrocytes, whereas neurons present a predominant oxidative profile. Thus, glial cells generate either lactate or pyruvate to neurons for ATP production. In addition, some aspects of schizophrenia may reflect an advanced aging phenotype with effects on various neural cell types at different stages of the disease. Given the role of glial cells in brain energy metabolism, the association of glycolysis dysfunction and the accelerated aging of neuronal cells in schizophrenia, studies focusing on those aspects can yield important insights into the causes and implications of the disorder. In turn, this may lead to novel therapeutic strategies for improved treatment of individuals suffering with this disorder.


Assuntos
Envelhecimento , Glicólise , Neuroglia , Esquizofrenia , Metabolismo Energético , Glucose/metabolismo , Humanos , Neuroglia/metabolismo , Fenótipo , Esquizofrenia/fisiopatologia
13.
Adv Exp Med Biol ; 1200: 71-89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31471795

RESUMO

The ability to adapt to changing environmental conditions is critical for any species to survive. Many environmental changes occur too rapidly for an organism's genome to adapt in time. Accordingly, being able to modify either its own phenotype, or the phenotype of its offspring to better suit future anticipated environmental conditions could afford an organism a significant advantage. However, a range of animal models and human epidemiological data sets are now showing that environmental factors such as changes in the quality or quantity of an individual's diet, temperature, stress or exposure to pollutants can all adversely affect the quality of parental gametes, the development of the preimplantation embryo and the health and wellbeing of offspring over multiple generations. This chapter will examine transgenerational effects of both maternal and paternal environmental factors on offspring development and wellbeing in both human and animal model studies. Changes in the epigenetic status of either parental or grand-parental gametes provide one candidate mechanism through which the impacts of environmental experience can be passed from one generation to another. This chapter will therefore also focus on the impact of parental and grand-parental diet on epigenetic transgenerational inheritance and offspring phenotype.


Assuntos
Adaptação Biológica/genética , Dieta , Meio Ambiente , Epigênese Genética , Animais , Humanos , Modelos Animais , Fenótipo
14.
Zhonghua Yi Xue Za Zhi ; 99(32): 2502-2506, 2019 Aug 27.
Artigo em Chinês | MEDLINE | ID: mdl-31484276

RESUMO

Objective: To investigate the characteristics of different phenotypes of refractory non-erosive gastroesophageal reflux disease (NERD), the types of esophageal motility and the related factors of symptoms. Methods: A retrospective analysis was made of the patients with refractory NERD of Beijing Tongren Hospital affiliated to Capital Medical University from September 2015 to August 2017. All patients underwent electronic gastroscopy, esophageal manometry and 24-hour dynamic esophageal pH impedance monitoring. They were divided into four phenotype groups according to the results. Results: A total of 231 patients were enrolled in the study. There were 111(48.1%)cases in phenotype 1 group, 9 (3.9%)cases in phenotype 2 group, 100 (43.3%)cases in phenotype 3 group and 11 (4.8%) cases in phenotype 4 group. Compared with the other three groups, the number of weak acid reflux [(86±55) vs (37±8), (70±52), (31±9) times] and the number of gas reflux [(86±76) vs (38±13), (58±57), (26±10)] in phenotype 1 group increased significantly (allP<0.005). Dynamics disorders were common in refractory NERD patients (139/231, 60.2%). Mild esophageal dynamics disorder was the main type of dynamics disorder (118/139, 84.9%). There was no significant difference among the phenotype groups. Multivariate unconditional Logistic regression analysis showed that the risk factors for reflux-related symptoms were female ratio, Chicago power classification, gas reflux and weak acid reflux (OR=3.731, 2.452, 1.036 and 1.037, P<0.05). Conclusions: The characteristics of gastroesophageal reflux and the types of motility disorders are different in different phenotype groups of refractory NERD patients. The risk factors of reflux-related symptoms are female ratio, Chicago motility classification, gas reflux and the frequency of weak acid reflux.


Assuntos
Esofagite Péptica , Refluxo Gastroesofágico , Monitoramento do pH Esofágico , Feminino , Humanos , Masculino , Fenótipo , Estudos Retrospectivos
15.
Stud Health Technol Inform ; 267: 164-172, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31483269

RESUMO

Phenotyping means the determination of clinical relevant phenotypes, e.g. by classification or calculation based on EHR data. Within the German Medical Informatics Initiative, the SMITH consortium is working on the implementation of a phenotyping pipeline. to extract, structure and normalize information from the EHR data of the hospital information systems of the participating sites; to automatically apply complex algorithms and models and to enrich the data within the research data warehouses of the distributed data integration centers with the computed results. Here we present the overall picture and essential building blocks and workflows of this concept.


Assuntos
Registros Eletrônicos de Saúde , Informática Médica , Algoritmos , Fenótipo
16.
Hum Genet ; 138(10): 1183-1200, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471722

RESUMO

The glutamate pyruvate transaminase 2 (GPT2) gene produces a nuclear-encoded mitochondrial enzyme that catalyzes the reversible transfer of an amino group from glutamate to pyruvate, generating alanine and alpha-ketoglutarate. Recessive mutations in GPT2 have been recently identified in a new syndrome involving intellectual and developmental disability (IDD), postnatal microcephaly, and spastic paraplegia. We have identified additional families with recessive GPT2 mutations and expanded the phenotype to include small stature. GPT2 loss-of-function mutations were identified in four families, nine patients total, including: a homozygous mutation in one child [c.775T>C (p.C259R)]; compound heterozygous mutations in two siblings [c.812A>C (p.N271T)/c.1432_1433delGT (p.V478Rfs*73)]; a novel homozygous, putative splicing mutation [c.1035C>T (p.G345=)]; and finally, a recurrent mutation, previously identified in a distinct family [c.1210C>T (p.R404*)]. All patients were diagnosed with IDD. A majority of patients had remarkably small stature throughout development, many < 1st percentile for height and weight. Given the potential biological function of GPT2 in cellular growth, this phenotype is strongly suggestive of a newly identified clinical susceptibility. Further, homozygous GPT2 mutations manifested in at least 2 of 176 families with IDD (approximately 1.1%) in a Pakistani cohort, thereby representing a relatively common cause of recessive IDD in this population, with recurrence of the p.R404* mutation in this population. Based on variants in the ExAC database, we estimated that approximately 1 in 248 individuals are carriers of moderately or severely deleterious variants in GPT2.


Assuntos
Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Genes Recessivos , Predisposição Genética para Doença , Mutação , Fenótipo , Transaminases/genética , Adolescente , Alelos , Substituição de Aminoácidos , Deficiências do Desenvolvimento/metabolismo , Ativação Enzimática , Éxons , Feminino , Frequência do Gene , Estudos de Associação Genética , Genética Populacional , Genótipo , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Imagem por Ressonância Magnética , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Modelos Moleculares , Linhagem , Conformação Proteica , Sítios de Splice de RNA , Análise de Sequência de DNA , Relação Estrutura-Atividade , Transaminases/química , Transaminases/metabolismo
18.
Pol J Pathol ; 70(2): 100-108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556560

RESUMO

The most recent classification of the lung cancer expanded the diagnostic criteria of its histological subtypes and included its immunophenotypic profile. We performed the study to compare the reliability of selected markers in high-grade non-small cell lung carcinoma (NSCLC) in the oligobiopsies with the matched postoperative samples. We evaluated expression of p40, p63, TTF1, cytokeratin 5/6, cytokeratin 7, napsin A, desmoglein 3, desmocollin 3 and mucin secretion as detected by mucicarmine staining. The study cohort included 123 cases of poorly-differentiated NSCLC. The tissue oligobiopsy material was available in 38 cases. Tissue microarrays (TMAs) from all postoperative cases were constructed. Comparing the immunophenotype between postsurgical samples and oligobiopsies we found an almost perfect agreement for most of performed IHC reactions. The highest concordance of results was found for desmoglein 3, CK7, and p40, whereas the lowest - for desmocollin 3. Immunoprofile of the oligobiopsies corresponded well to that in the resection specimens. The most useful markers in poorly differentiated ADs are: TTF1 and napsin A, and for non-keratinizing SCCs: p40, p63, CK5/6 and desmoglein 3.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Biópsia , Humanos , Gradação de Tumores , Fenótipo , Reprodutibilidade dos Testes
19.
An Acad Bras Cienc ; 91(3): e20180036, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553363

RESUMO

This work aimed to determine variance components and genetic parameters, as well as phenotypic, genetic and environmental correlations among black oat (Avena strigosa) families grown in different crop season. Seventy-six black oat families and three controls (BRS Madrugada, BRS Centauro, BRS 139 Neblina) were evaluated in two crop seasons (2016 and 2017), using families with intercalary controls experimental design. The results reveled high potential of black oat families to compose a breeding program, due to families and controls variance were similar, variance components expressed greater genetic variance origin for crop season. Panicle weight and panicle grain weight presented high heritability and, these are correlated with panicle length. Thus, these traits can be used to select superior genotypes. Divergent meteorological conditions between crop seasons expressed few variations among phenotypic, genetic and environmental correlations, and it did not alter magnitude and sense of phenotypic and genetic correlations.


Assuntos
Avena/crescimento & desenvolvimento , Avena/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/genética , Variação Genética , Genótipo , Fenótipo , Estações do Ano
20.
Lancet ; 394(10197): 533-540, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31395441

RESUMO

One of the primary goals of genomic medicine is to improve diagnosis through identification of genomic conditions, which could improve clinical management, prevent complications, and promote health. We explore how genomic medicine is being used to obtain molecular diagnoses for patients with previously undiagnosed diseases in prenatal, paediatric, and adult clinical settings. We focus on the role of clinical genomic sequencing (exome and genome) in aiding patients with conditions that are undiagnosed even after extensive clinical evaluation and testing. In particular, we explore the impact of combining genomic and phenotypic data and integrating multiple data types to improve diagnoses for patients with undiagnosed diseases, and we discuss how these genomic sequencing diagnoses could change clinical management.


Assuntos
Doenças Raras/diagnóstico , Análise de Sequência de DNA/métodos , Adulto , Criança , Diagnóstico Precoce , Genômica , Humanos , Fenótipo , Diagnóstico Pré-Natal/métodos , Doenças Raras/genética , Sequenciamento Completo do Exoma , Sequenciamento Completo do Genoma
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