RESUMO
Our aim was to investigate the ability of an artificial intelligence (AI)-based algorithm to differentiate innocent murmurs from pathologic ones. An AI-based algorithm was developed using heart sound recordings collected from 1413 patients at the five university hospitals in Finland. The corresponding heart condition was verified using echocardiography. In the second phase of the study, patients referred to Helsinki New Children's Hospital due to a heart murmur were prospectively assessed with the algorithm, and then the results were compared with echocardiography findings. Ninety-eight children were included in this prospective study. The algorithm classified 72 (73%) of the heart sounds as normal and 26 (27%) as abnormal. Echocardiography was normal in 63 (64%) children and abnormal in 35 (36%). The algorithm recognized abnormal heart sounds in 24 of 35 children with abnormal echocardiography and normal heart sounds with normal echocardiography in 61 of 63 children. When the murmur was audible, the sensitivity and specificity of the algorithm were 83% (24/29) (confidence interval (CI) 64-94%) and 97% (59/61) (CI 89-100%), respectively. CONCLUSION: The algorithm was able to distinguish murmurs associated with structural cardiac anomalies from innocent murmurs with good sensitivity and specificity. The algorithm was unable to identify heart defects that did not cause a murmur. Further research is needed on the use of the algorithm in screening for heart murmurs in primary health care. WHAT IS KNOWN: ⢠Innocent murmurs are common in children, while the incidence of moderate or severe congenital heart defects is low. Auscultation plays a significant role in assessing the need for further examinations of the murmur. The ability to differentiate innocent murmurs from those related to congenital heart defects requires clinical experience on the part of general practitioners. No AI-based auscultation algorithms have been systematically implemented in primary health care. WHAT IS NEW: ⢠We developed an AI-based algorithm using a large dataset of sound samples validated by echocardiography. The algorithm performed well in recognizing pathological and innocent murmurs in children from different age groups.
Assuntos
Algoritmos , Ecocardiografia , Cardiopatias Congênitas , Sopros Cardíacos , Ruídos Cardíacos , Humanos , Pré-Escolar , Estudos Prospectivos , Feminino , Masculino , Criança , Sopros Cardíacos/diagnóstico , Lactente , Ecocardiografia/métodos , Cardiopatias Congênitas/diagnóstico , Sensibilidade e Especificidade , Inteligência Artificial , Adolescente , Auscultação Cardíaca/métodos , Finlândia , Recém-Nascido , Programas de Rastreamento/métodosRESUMO
Immune responses are best initiated in the environment of lymphoid tissues wherein circulating lymphocytes enter by interacting with endothelial adhesion molecules. In type 1 diabetes, immune responses against pancreatic islets develop, but the environment in which this occurs remains unidentified. To determine whether lymphocyte homing to lymphoid organs is involved in the pathogenesis of diabetes in nonobese diabetic (NOD) mice, we blocked the function of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is a vascular addressin-mediating lymphocyte homing into mucosal lymphoid tissues, in these mice. While ineffective if started later, a blockade started at 3 wk of age reduced the incidence of diabetes from 50% to 9% (p < 0.01). This finding is associated with Peyer's patch atrophy, a marked decrease of naive (CD44(low) CD45RB(high)) T lymphocytes, and a reduction in the relative numbers of memory (CD44(high)) T lymphocytes in the spleen. The potential of these spleen cells to cause diabetes was diminished. Anti-MAdCAM-1 treatment also inhibited both lymphocyte entry into the pancreas and diabetes development in NOD/SCID recipients after the transfer of lymphocytes derived from the mesenteric lymph nodes of young, but not of diabetic, NOD donors. Therefore, MAdCAM-1 may be required during two distinct steps in an early phase of diabetes development: for the entry of naive lymphocytes into the lymphoid tissues in which diabetes-causing lymphocytes are originally primed, and for the subsequent homing of these lymphocytes into the pancreas. The role of MAdCAM-1 as a mucosal vascular addressin suggests that mucosal lymphoid tissues are involved in the initiation of pathologic immune responses in NOD mice.
Assuntos
Diabetes Mellitus Experimental/imunologia , Imunoglobulinas/fisiologia , Mucoproteínas/fisiologia , Receptores de Retorno de Linfócitos/fisiologia , Transferência Adotiva , Animais , Moléculas de Adesão Celular , Diabetes Mellitus Tipo 1/imunologia , Feminino , Receptores de Hialuronatos/análise , Ilhotas Pancreáticas/imunologia , Antígenos Comuns de Leucócito/análise , Camundongos , Camundongos Endogâmicos NOD , Pâncreas/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Baço/imunologiaRESUMO
Ly-6C belongs to the Ly-6 family of glycosyl phosphatidylinositol-anchored surface glycoproteins and is expressed on a subset of mature CD8(+) T cells. Ly-6C ligation can mediate T cell activation and causes interleukin 2 secretion in cytolytic T cell clones. We characterize herein a new mAb 1G7.G10 against Ly-6C that recognizes an epitope involved in lymphocyte adhesion and in lymphocyte homing. Pretreatment of lymph node lymphocytes and of purified CD8(+) T cells (but not of lymphocytes depleted of CD8(+) T cells) with 1G7.G10 reduced their in vitro binding to lymph node high endothelial venules by 28% and 34%, respectively. This effect was bypassed by cross-linking Ly-6C molecules with 1G7.G10 and a second-step antibody. The in vivo homing of (donor) CD8(+) T lymphocytes to lymph nodes was reduced by Ly-6C blocking with 1G7. G10 (whole antibody) or with its fragments [F(ab) or F(ab)2] by 20% or by 32% and 48%, respectively. Cross-linking of Ly-6C in vitro induced very late antigen-4 and lymphocyte function-associated antigen 1-mediated aggregation of CD8(+) T cells, suggesting that ligand binding to Ly-6C leads to activation of integrins. This activation may facilitate homing of Ly-6C+ CD8(+) T cells in vivo.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos Ly/imunologia , Linfócitos T CD8-Positivos/citologia , Endotélio Vascular/citologia , Integrinas/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Linfócitos T CD8-Positivos/imunologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Células Cultivadas , Endotélio Vascular/imunologia , Linfonodos/citologia , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologiaRESUMO
AIMS/HYPOTHESIS: The NPHS1 gene product, nephrin, is a crucial component of the glomerular filtration barrier preventing proteinuria and previously assumed to be kidney-specific. The aim of this study was to describe the expression of nephrin mRNA and protein in human pancreas as well as identify the nephrin-expressing cell types. METHODS: RNA dot blot, reverse transcriptase-polymerase chain reaction, sequencing, immunoblotting and dual immunofluorescence were used for the characterisation of nephrin in the pancreas. RESULTS: Except for the kidney, the pancreas was found to be the only tissue expressing nephrin as screened with a human tissue RNA dot blot. The expression was verified with reverse transcriptase-polymerase chain reaction and by sequencing nephrin from a human pancreatic complementary DNA library. Nephrin antibody in immunoblot detected a 165,000 M(r) protein in the pancreas. Dual immunofluorescence showed that nephrin was specifically localised in the beta cells of the islets of Langerhans. There was no overlap with glucagon, somatostatin, or the ductal cell marker cytokeratin 19. CONCLUSION/INTERPRETATION: These data show that nephrin is a novel molecule of pancreatic beta cells.
Assuntos
Expressão Gênica , Ilhotas Pancreáticas/metabolismo , Proteínas/genética , Cadáver , Fluoresceína-5-Isotiocianato , Imunofluorescência , Corantes Fluorescentes , Glucagon/análise , Humanos , Immunoblotting , Queratinas/análise , Rim/química , Rim/embriologia , Córtex Renal/química , Proteínas de Membrana , Peso Molecular , Pâncreas/química , Proteínas/análise , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Somatostatina/análiseRESUMO
Diabetic nephropathy is a major complication of diabetes leading to thickening of the glomerular basement membrane, glomerular hypertrophy, mesangial expansion, and overt renal disease. The pathophysiologic mechanisms of diabetic nephropathy remain poorly understood. Nephrin is a recently found podocyte protein crucial for the interpodocyte slit membrane structure and maintenance of an intact filtration barrier. Here we have assessed the role of nephrin in two widely used animal models of diabetes, the streptozotocin model of the rat and the nonobese diabetic mouse. In both models, the expression levels of nephrin-specific mRNA as determined by real-time quantitative polymerase chain reaction increased up to two-fold during several weeks of follow-up. Immunohistochemical stainings revealed nephrin also more centrally within the glomerular tuft along with its preferential site in podocytes. Interestingly, as detected by immunoblotting, nephrin protein was also found in the urine of streptozotocin-induced rats. We conclude that nephrin is connected to the early changes of diabetic nephropathy and thus may contribute to the loss of glomerular filtration function.