Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
1.
J Am Soc Nephrol ; 31(8): 1883-1904, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32561683

RESUMO

BACKGROUND: The mechanisms leading to extracellular matrix (ECM) replacement of areas of glomerular capillaries in histologic variants of FSGS are unknown. This study used proteomics to test the hypothesis that glomerular ECM composition in collapsing FSGS (cFSGS) differs from that of other variants. METHODS: ECM proteins in glomeruli from biopsy specimens of patients with FSGS not otherwise specified (FSGS-NOS) or cFSGS and from normal controls were distinguished and quantified using mass spectrometry, verified and localized using immunohistochemistry (IHC) and confocal microscopy, and assessed for gene expression. The analysis also quantified urinary excretion of ECM proteins and peptides. RESULTS: Of 58 ECM proteins that differed in abundance between cFSGS and FSGS-NOS, 41 were more abundant in cFSGS and 17 in FSGS-NOS. IHC showed that glomerular tuft staining for cathepsin B, cathepsin C, and annexin A3 in cFSGS was significantly greater than in other FSGS variants, in minimal change disease, or in membranous nephropathy. Annexin A3 colocalized with cathepsin B and C, claudin-1, phosphorylated ERK1/2, and CD44, but not with synaptopodin, in parietal epithelial cells (PECs) infiltrating cFSGS glomeruli. Transcripts for cathepsins B and C were increased in FSGS glomeruli compared with normal controls, and urinary excretion of both cathepsins was significantly greater in cFSGS compared with FSGS-NOS. Urinary excretion of ECM-derived peptides was enhanced in cFSGS, although in silico analysis did not identify enhanced excretion of peptides derived from cathepsin B or C. CONCLUSIONS: ECM differences suggest that glomerular sclerosis in cFSGS differs from that in other FSGS variants. Infiltration of activated PECs may disrupt ECM remodeling in cFSGS. These cells and their cathepsins may be therapeutic targets.


Assuntos
Proteínas da Matriz Extracelular/análise , Glomerulosclerose Segmentar e Focal/metabolismo , Glomérulos Renais/metabolismo , Proteômica/métodos , Catepsinas/fisiologia , Células Epiteliais/fisiologia , Humanos , Imuno-Histoquímica , Glomérulos Renais/química , Microscopia Confocal
2.
Am J Physiol Renal Physiol ; 315(3): F595-F606, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29790391

RESUMO

Acute glomerulonephritis is characterized by rapid glomerular neutrophil recruitment, proteinuria, and glomerular hypercellularity. The current study tested the hypothesis that the release of neutrophil granule contents plays a role in both the loss of filtration barrier leading to proteinuria and the increase in glomerular cells. Inhibition of neutrophil exocytosis with a peptide inhibitor prevented proteinuria and attenuated podocyte and endothelial cell injury but had no effect on glomerular hypercellularity in an experimental acute glomerulonephritis model in mice. Cultivation of podocytes with neutrophil granule contents disrupted cytoskeletal organization, an in vitro model for podocyte effacement and loss of filtration barrier. Activated, cultured podocytes released cytokines that stimulated neutrophil chemotaxis, primed respiratory burst activity, and stimulated neutrophil exocytosis. We conclude that crosstalk between podocytes and neutrophils contributes to disruption of the glomerular filtration barrier in acute glomerulonephritis. Neutrophil granule products induce podocyte injury but do not participate in the proliferative response of intrinsic glomerular cells.


Assuntos
Citoesqueleto de Actina/metabolismo , Doença Antimembrana Basal Glomerular/metabolismo , Comunicação Celular , Exocitose , Taxa de Filtração Glomerular , Neutrófilos/metabolismo , Podócitos/metabolismo , Proteinúria/metabolismo , Citoesqueleto de Actina/patologia , Animais , Doença Antimembrana Basal Glomerular/patologia , Doença Antimembrana Basal Glomerular/fisiopatologia , Doença Antimembrana Basal Glomerular/prevenção & controle , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Exocitose/efeitos dos fármacos , Feminino , Produtos do Gene tat/farmacologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Ativação de Neutrófilo , Infiltração de Neutrófilos , Neutrófilos/efeitos dos fármacos , Podócitos/patologia , Proteinúria/patologia , Proteinúria/fisiopatologia , Proteinúria/prevenção & controle , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Explosão Respiratória , Proteínas SNARE/farmacologia
3.
Ophthalmic Plast Reconstr Surg ; 34(2): e65-e67, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29346169

RESUMO

The authors report a case of isolated congenital orbital myofibroma causing sphenoid dysplasia and presenting as global restriction of extraocular motility and ptosis in a neonate. Sphenoid wing dysplasia is most commonly associated neurofibromatosis 1 but this patient had no evidence of neurofibromatosis on clinical examination and genetic testing. Congenital orbital myofibroma can have secondary effects on bone and likely the lesion was present early in development leading to aplasia of the sphenoid bone. To the best of the authors' knowledge, this is the first reported case of sphenoid wing aplasia secondary to congenital orbital myofibroma independent of neurofibromatosis 1.


Assuntos
Miofibroma/patologia , Neoplasias Orbitárias/patologia , Osso Esfenoide/anormalidades , Assimetria Facial/etiologia , Humanos , Recém-Nascido , Masculino
4.
J Clin Rheumatol ; 18(7): 363-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23047537

RESUMO

Chloroquine and hydroxychloroquine are used to chronically treat certain rheumatologic diseases and are generally considered safe. We describe 2 patients with skeletal myopathy and fatal cardiomyopathy-uncommon and underrecognized adverse effects of these agents. Both patients developed arrhythmias and heart failure, and 1 patient had documented diaphragmatic involvement. Muscle specimens showed typical vacuolar myopathy (indicative of impaired autophagy) with myeloid bodies in both patients and curvilinear bodies in 1 patient. Antimalarial-induced cardiomyopathy should be considered in patients receiving these medications with otherwise unexplained muscle weakness or cardiac symptoms. Whether autophagy enhancers can be used to manage such myopathies merits investigation.


Assuntos
Antimaláricos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico , Adulto , Antimaláricos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Evolução Fatal , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pessoa de Meia-Idade
7.
Arch Pathol Lab Med ; 139(4): 543-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25822764

RESUMO

CONTEXT: Neuroblastoma (NB) is the most common extracranial tumor of childhood. Although most cases have a distinctive histology, a subset of primitive cases require immunohistochemical studies to distinguish them from other small round blue cell tumors of childhood. Immunohistochemistry is also used to detect small amounts of tumor metastatic to the bone marrow and in posttreatment samples with obscuring fibrosis, calcification, or inflammation. The transcription factor PHOX2B is essential for the differentiation and survival of sympathetic neurons and chromaffin cells, and therefore is highly specific for the peripheral autonomic nervous system. OBJECTIVE: To determine the diagnostic utility of PHOX2B immunohistochemistry as a marker of primary, treated, and metastatic NB. DESIGN: Neuroblastoma tissue microarrays were stained with PHOX2B, CD57, and synaptophysin. Arrays containing rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor were stained with PHOX2B, and negative bone marrow samples were stained with PHOX2B and CD57. RESULTS: PHOX2B and CD57 were similar to synaptophysin in their ability to detect NB. PHOX2B and CD57 similarly showed robust staining in posttreatment NB and NB metastatic to the bone marrow. In contrast to the cytoplasmic staining pattern seen with synaptophysin and CD57, clear and strong nuclear PHOX2B permitted identification of individual tumor cells. PHOX2B staining was absent in all cases of rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor, and in the negative bone marrow. CONCLUSIONS: PHOX2B and CD57 are useful markers of NB. PHOX2B is specific for NB in its differential diagnosis with other small round cell tumors, and its nuclear staining may be helpful for accurate bone marrow tumor quantification.


Assuntos
Neoplasias da Medula Óssea/metabolismo , Proteínas de Homeodomínio/biossíntese , Neuroblastoma/metabolismo , Fatores de Transcrição/biossíntese , Neoplasias da Medula Óssea/secundário , Antígenos CD57/biossíntese , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica/métodos , Neuroblastoma/diagnóstico , Neuroblastoma/cirurgia , Reprodutibilidade dos Testes , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/metabolismo , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/metabolismo , Sensibilidade e Especificidade , Sinaptofisina/biossíntese , Análise Serial de Tecidos , Tumor de Wilms/diagnóstico , Tumor de Wilms/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA