Assuntos
Transtornos da Motilidade Ciliar/fisiopatologia , Doenças Raras/fisiopatologia , Adulto , Fatores Etários , Antibacterianos/uso terapêutico , Bronquiectasia/etiologia , Criança , Transtornos da Motilidade Ciliar/diagnóstico por imagem , Transtornos da Motilidade Ciliar/microbiologia , Fibrose Cística/microbiologia , Fibrose Cística/fisiopatologia , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Síndrome de Kartagener/diagnóstico por imagem , Síndrome de Kartagener/microbiologia , Síndrome de Kartagener/fisiopatologia , Pulmão/diagnóstico por imagem , Masculino , Fenótipo , Prognóstico , Doenças Raras/diagnóstico por imagem , Doenças Raras/microbiologia , Análise de Regressão , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/prevenção & controle , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Capacidade VitalRESUMO
Primary ciliary dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM.A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres.The final guideline a) provides agreed terminology and a definition of Class 1 defects which are diagnostic for PCD; b) identifies Class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD; and d) defines adequacy of a diagnostic sample.This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally.
Assuntos
Transtornos da Motilidade Ciliar , Síndrome de Kartagener , Cílios , Ingestão de Alimentos , Humanos , Síndrome de Kartagener/diagnóstico , Microscopia Eletrônica , Microscopia Eletrônica de TransmissãoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfoma de Células B , Proteínas Proto-Oncogênicas c-myc/biossíntese , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/mortalidade , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
Niemann-Pick type C disease (NPC) is a disorder characterized by abnormal intracellular accumulation of unesterified cholesterol and glycolipids. Two distinct disease-causing genes have been isolated, NPC1 and NPC2. The NPC1 protein is involved in the sorting and recycling of cholesterol and glycosphingolipids in the late endosomal/lysosomal system. It has extensive homology with the Patched1 (Ptc1) receptor, a transmembrane protein localized in the primary cilium, and involved in the Hedgehog signaling (Shh) pathway. We assessed the presence of NPC1 and Ptc1 proteins and evaluated the relative distribution and morphology of primary cilia in fibroblasts from five NPC1 patients and controls, and in normal fibroblasts treated with 3-ß-[2-(diethylamino)ethoxy]androst-5-en-17-one (U18666A), a cholesterol transport-inhibiting drug that is widely used to mimic NPC. Immunofluorescence and western blot analyses showed a significant decrease in expression of NPC1 and Ptc1 in NPC1 fibroblasts, while they were normally expressed in U18666A-treated fibroblasts. Moreover, fibroblasts from NPC1 patients and U18666A-treated cells showed a lower percentage distribution of primary cilia and a significant reduction in median cilia length with respect to controls. These are the first results demonstrating altered cytoplasmic expression of Ptc1 and reduced number and length of primary cilia, where Ptc1 is located, in fibroblasts from NPC1 patients. We suggest that the alterations in Ptc1 expression in cells from NPC1 patients are closely related to NPC1 expression deficit, while the primary cilia alterations observed in NPC1 and U18666A-treated fibroblasts may represent a secondary event derived from a defective metabolic pathway.
Assuntos
Fibroblastos/metabolismo , Doença de Niemann-Pick Tipo C/metabolismo , Receptor Patched-1/metabolismo , Acetilação , Adolescente , Adulto , Androstenos/farmacologia , Western Blotting , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Separação Celular , Células Cultivadas , Colesterol/metabolismo , Cílios/efeitos dos fármacos , Cílios/metabolismo , Cílios/patologia , Citoplasma/metabolismo , Regulação para Baixo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Filipina/metabolismo , Imunofluorescência , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Microscopia de Fluorescência , Pessoa de Meia-Idade , Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/patologia , Receptor Patched-1/genética , Cultura Primária de Células , Tubulina (Proteína)/metabolismo , Adulto JovemRESUMO
We report a 6-year-old girl with a subtle form of hypohidrotic ectodermal dysplasia and a phenotype consisting of curly hair, a round face, a stocky build, and obesity, which was associated with intrathoracic neuroblastoma. Although this new association could be a chance occurrence, its description may alert physicians to look for similar combinations and report these, as it may lead to better syndrome delineation, and patient care.
Assuntos
Displasia Ectodérmica/diagnóstico , Neuroblastoma/complicações , Criança , Displasia Ectodérmica/complicações , Feminino , Febre de Causa Desconhecida/complicações , Cabelo/anormalidades , Humanos , Obesidade/complicações , Glândulas Sudoríparas/anormalidades , Neoplasias Torácicas/complicações , Anormalidades DentáriasRESUMO
BACKGROUND: Primary ciliary dyskinesia (PCD) is a congenital, clinically and ultrastructurally heterogeneous disease caused by abnormal structure and/or function of cilia. Kartagener's syndrome is one subgroup of PCD. Acquired ciliary dyskinesia is frequent, generally being associated with or following respiratory tract infections. METHODS: From January 2003 to April 2006, nasal mucociliary transport time was measured in 64 patients and specimens obtained by nasal scraping were examined by transmission electron microscope (TEM). RESULTS: The 64 nasal scrapings led to the diagnosis of 11 (17.2%) cases of PCD and 51 (79.7%) cases of secondary ciliary disorder. In two cases (3.1%) no clear diagnosis was possible. CONCLUSION: Nasal scraping is an easy, cheap, and efficient tool for detecting ciliary abnormalities by TEM and for distinguishing acquired and congenital modifications.
Assuntos
Síndrome de Kartagener/diagnóstico , Mucosa Nasal/ultraestrutura , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cílios/ultraestrutura , Epitélio/ultraestrutura , Feminino , Humanos , Síndrome de Kartagener/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Microtúbulos , Pessoa de Meia-Idade , Depuração MucociliarRESUMO
We report a unique combination of symptoms in a case of Kabuki syndrome (KS), a multiple malformation/mental retardation syndrome that has a prevalence of 1:32,000 to 1:86,000. The patient was a mentally delayed 12-year-old male with trichrome vitiligo, ectodermal defect, and hypogammaglobulinemia A and G. This unique combination of signs, described here for the first time, indicates that KS comprises multiple deficits that affect not only the brain, but ectoderm-derived structures and the immune system as well. Our report may provide important clues for understanding the pathogenesis of the KS.