RESUMO
An MRI of the brain and spine of an 11-year-old male revealed the following abnormality which is consistent with his chronic condition.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Globo Pálido/diagnóstico por imagem , Anormalidades Múltiplas , Criança , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Planar cell polarity (PCP) describes the polarized orientation of cells within the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP signaling in migrating cells remain undefined. Here, the establishment of PCP must be coordinated with dynamic changes in cell adhesion and extracellular matrix (ECM) organization. During gastrulation, the membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) is required for PCP and convergence and extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell-surface availability of MMP14 in manner that is dependent on focal adhesion kinase. We demonstrate that zebrafish trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss-of-function convergence and extension phenotype. This study identifies a mechanism linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in migrating gastrula cells requires regulated proteolytic degradation or remodeling of the ECM. Our findings implicate matrix metalloproteinases as downstream effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2 affects diverse morphogenetic processes.
Assuntos
Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Gástrula/metabolismo , Gastrulação/genética , Metaloproteinase 14 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Adesão Celular/fisiologia , Membrana Celular/metabolismo , Movimento Celular/fisiologia , Polaridade Celular/fisiologia , Embrião não Mamífero , Endocitose/fisiologia , Matriz Extracelular/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/genética , Gástrula/embriologia , Técnicas de Silenciamento de Genes , Metaloproteinase 14 da Matriz/genética , Proteínas de Membrana/genética , Mutação , Transporte Proteico/fisiologia , Proteólise , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaAssuntos
Ascaríase/complicações , Ascaris/isolamento & purificação , Doenças Biliares/complicações , Sistema Biliar/parasitologia , Endossonografia/métodos , Pâncreas/parasitologia , Pancreatite Necrosante Aguda/diagnóstico por imagem , Adolescente , Adulto , Animais , Ascaríase/diagnóstico por imagem , Sistema Biliar/diagnóstico por imagem , Doenças Biliares/diagnóstico por imagem , Doenças Biliares/parasitologia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pâncreas/diagnóstico por imagem , Pancreatite Necrosante Aguda/etiologia , Adulto JovemRESUMO
Gender-related alcohol and drug abuse problems are related not only to biologic differences but also to social and environment factors, all of which can influence the clinical presentation, consequences of use, and treatment approaches. The number of women becoming addicted to alcohol or drugs of abuse has significantly increased with women becoming the fastest-growing group of substance abusers in the United States. Given that women experience a more rapid progression of their addiction than men, it is important that we understand and address the differences to help develop prevention and treatment programs that are tailored for women, incorporating trauma assessment and management, comorbidities, financial independence, pregnancy, and child care.
Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Criança , Comorbidade , Feminino , Humanos , Masculino , Grupos Minoritários , Gravidez , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados UnidosRESUMO
OBJECTIVES: Screening in selected high risk populations for Barrett's oesophagus (BO) and oesophageal varices (OVs) has been proposed, but there are obstacles with conventional oesophagogastroduodenoscopy (C-OGD), including patient acceptability. Portable and disposable office-based transnasal endoscopy (TNE) is a feasible and accurate alternative to C-OGD that may have use in primary and secondary care. This article outlines a qualitative analysis of patient experiences of TNE and C-OGD in order to gain an insight into an acceptable delivery of an endoscopic screening service. DESIGN: Purposeful sampling identified 23 participants who then underwent semi-structured interviews to determine their experiences of both procedures. Thematic analysis was conducted to derive meaning from their lived experiences. SETTING: A secondary care endoscopy unit, clinic room and interview room. PARTICIPANTS: Patients referred for BO or OV surveillance and for endoscopy to investigate dyspepsia underwent unsedated TNE using the EG Scan II device followed by C-OGD with or without sedation (patient choice), as part of a clinical trial. RESULTS: The themes that arose from our analysis were: inclusivity in one's own healthcare, comfort level and convenience, validity of the procedure and application to a screening population and a sense of altruism and reciprocity. Positive aspects of TNE included participant empowerment, reduced discomfort and avoidance of conscious sedation. Participants felt that if TNE screening was of proven efficacy it would be welcomed, though views on use in a community setting were mixed. CONCLUSIONS: Most patients preferred TNE to unsedated C-OGD and the reasons they gave featured strongly in the emerging themes. Preferences between TNE and sedated C-OGD were more subtle, with equivalent comfort scores but merits and drawbacks of both being discussed. This information identifies opportunities and challenges in establishing an endoscopic screening service. Trial registration number ISRCTNregistry identifier: 70595405; Pre-results.
Assuntos
Esôfago de Barrett/diagnóstico , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/diagnóstico , Programas de Rastreamento/métodos , Cirurgia Endoscópica por Orifício Natural , Aceitação pelo Paciente de Cuidados de Saúde , Idoso , Idoso de 80 Anos ou mais , Equipamentos Descartáveis , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/instrumentação , Nariz , Pesquisa QualitativaRESUMO
Pediatric central nervous system (CNS) tumor survivors are at risk for experiencing cognitive late effects (CLEs). Caregivers of survivors may be unaware of these changes or receive untimely information regarding CLEs. Conversely, health care providers (HCPs) may face barriers to providing education. This study aims to (a) understand the knowledge and resource gap for caregivers regarding CLEs and (b) explore how HCPs currently provide education. Caregivers and HCPs were both interviewed. Qualitative analysis was performed using emergent coding. Fifteen caregivers and eight HCPs participated. Caregivers generally felt confident in assisting their survivor but experienced "information overload" during initial diagnosis and treatment. HCPs reported difficulties in determining appropriate timing for education and perceived that caregivers typically lack understanding of CLEs. Caregivers should be aware of and understand a survivor's risk for CLEs to help survivors manage changes. With increasing survival rates of pediatric CNS tumor patients, HCPs must be prepared to provide appropriate education and referrals regarding CLEs for long-term care.
Assuntos
Sobreviventes de Câncer , Cuidadores , Neoplasias do Sistema Nervoso Central/reabilitação , Educação de Pacientes como Assunto , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Ocupacional , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVES: To analyze the demand for services from the nation's medical laboratories, which is predicted to dramatically increase as our citizens age and millions receive insurance coverage through the Affordable Care Act. METHODS: A systematic review of relevant publications and databases was conducted to assess the current state of the nation's medical laboratory workforce and to examine the impact of population demographics and health reform on workforce development to address the future demand for laboratory services. RESULTS: Building a Laboratory Workforce to Meet the Future, a new report from the American Society for Clinical Pathology (ASCP), provides a comprehensive strategy to address the future workforce needs of the nation's medical laboratories to meet this demand to provide timely, accurate, and safe patient care and to fully realize the benefits of personalized medicine. CONCLUSIONS: The report, from the ASCP Task Force on the Laboratory Professionals Workforce, is a comprehensive review of the myriad of factors affecting recruitment and retention of qualified laboratory professionals and provides a set of thoughtful recommendations outlining a multifaceted approach to bolster the pipeline of potential candidates for the profession as well as leadership in health care.
Assuntos
Laboratórios , Patologia Clínica , Necessidades e Demandas de Serviços de Saúde , Humanos , Laboratórios/organização & administração , Patologia Clínica/organização & administração , Sociedades Médicas , Estados Unidos , Recursos HumanosRESUMO
Mycobacterium bovis bacille Calmette Guerin vaccination protects against pulmonary tuberculosis in the United Kingdom but not in Malawi. We investigated whether a difference in the clonal T-cell response to BCG vaccination might account for this. The results of clonal analysis were compared to those obtained by skin testing and in a whole blood interferon gamma assay. Pre-vaccination antigen specific T-cell clones were detected, but the majority of clones present 12 months after vaccination were not present earlier. The magnitude of the clonal response did not correlate well with results of the other assays. These data indicate that single assays may not be reliable and that a stable memory T-cell repertoire is slow to develop.
Assuntos
Vacina BCG/imunologia , Memória Imunológica/imunologia , Mycobacterium tuberculosis/química , Linfócitos T/metabolismo , Tuberculose/imunologia , Formação de Anticorpos , Antígenos de Bactérias/imunologia , Vacina BCG/administração & dosagem , Humanos , Interferon gama/metabolismo , Malaui , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Tuberculina/imunologia , Teste Tuberculínico , Tuberculose/prevenção & controle , Reino Unido , VacinaçãoRESUMO
T cell differentiation and repertoire selection depend critically on several distinct thymic epithelial cell types, whose lineage relationships are unclear. We have investigated these relationships via functional analysis of the epithelial populations within the thymic primordium. Here, we show that mAbs MTS20 and MTS24 identify a population of cells that, when purified and grafted ectopically, can differentiate into all known thymic epithelial cell types, attract lymphoid progenitors, and support CD4(+) and CD8(+) T cell development in nude mice. In contrast, other epithelial populations in the thymic primordium can fulfill none of these functions. These data establish that the MTS20(+)24(+) population is sufficient to generate a functional thymus in vivo and thus argue strongly that all thymic epithelial cell types derive from a common progenitor cell.
Assuntos
Células-Tronco/citologia , Linfócitos T/citologia , Timo/citologia , Animais , Anticorpos Monoclonais , Biomarcadores , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Diferenciação Celular , Células Epiteliais/citologia , Feminino , Citometria de Fluxo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Nus , FenótipoRESUMO
The age-associated decline in immunocompetence is paralleled by changes in the proportions of PBL subpopulations. In turn, the size and composition of the peripheral lymphocyte pool is determined by input from the thymus and bone marrow and by the balance of proliferation and death in each lymphocyte subpopulation. We compared the kinetics of lymphocyte subtypes in young (seven of eight CMV seronegative) and healthy elderly human subjects (six of seven CMV seropositive), using deuterated glucose DNA labeling in vivo to measure rates of T cell proliferation and disappearance. For CD45RO(+) cells of both CD4(+) and CD8(+) subtypes and for CD4(+)CD45RA(+) cells the kinetics of proliferation and disappearance were remarkably similar between elderly and young subjects. In the young, the kinetics of CD8(+)CD45RA(+) cells with a naive phenotype resembled those of CD4(+)CD45RA(+) cells. However, CD8(+)CD45RA(+) T cells from the elderly exhibited a predominantly primed phenotype, and for this subset, although the proliferation rate was similar to that of other CD45RA(+) cells, the disappearance rate of labeled cells was greatly decreased compared with that of all other T cell subsets. Our data provide a direct demonstration that there are no substantial changes in in vivo kinetics for most T cell populations in healthy elderly compared with young subjects. However, primed CD8(+)CD45RA(+) cells show unusual kinetic properties, indicating the persistence of these cells in the blood and dissociation of proliferation from disappearance.
Assuntos
Envelhecimento/imunologia , Subpopulações de Linfócitos T/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Divisão Celular , Células Clonais/citologia , Deutério/farmacocinética , Feminino , Glucose/farmacocinética , Humanos , Imunocompetência , Antígenos Comuns de Leucócito/análise , Contagem de Linfócitos , Masculino , Fenótipo , Receptores de Antígenos de Linfócitos T alfa-beta/análiseRESUMO
The CD45 (leucocyte common) antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor signalling in lymphocytes, and expression of different CD45 isoforms is associated with distinct functions. Here we describe a novel polymorphism in exon 4 (A54G) of the gene encoding CD45 (PTPRC) that results in an amino acid substitution of Thr-19 to Ala in exon 4. The 54G allele was identified in African Ugandan populations and was found with a suggestive but not statistically significant increase in frequency amongst HIV-seropositive Ugandans. This suggests that the 54G variant and CD45 splicing abnormalities might be associated with HIV infection.