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1.
J Nucl Cardiol ; 29(5): 2423-2433, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34476780

RESUMO

BACKGROUND: Dual-gating reduces respiratory and cardiac motion effects but increases noise. With motion correction, motion is minimized and image quality preserved. We applied motion correction to create end-diastolic respiratory motion corrected images from dual-gated images. METHODS: [18F]-fluorodeoxyglucose ([18F]-FDG) PET images of 13 subjects were reconstructed with 4 methods: non-gated, dual-gated, motion corrected, and motion corrected with 4D-CT (MoCo-4D). Image quality was evaluated using standardized uptake values, contrast ratio, signal-to-noise ratio, coefficient of variation, and contrast-to-noise ratio. Motion minimization was evaluated using myocardial wall thickness. RESULTS: MoCo-4D showed improvement for contrast ratio (2.83 vs 2.76), signal-to-noise ratio (27.5 vs 20.3) and contrast-to-noise ratio (14.5 vs 11.1) compared to dual-gating. The uptake difference between MoCo-4D and non-gated images was non-significant (P > .05) for the myocardium (2.06 vs 2.15 g/mL), but significant (P < .05) for the blood pool (.80 vs .86 g/mL). Non-gated images had the lowest coefficient of variation (27.3%), with significant increase for all other methods (31.6-32.5%). MoCo-4D showed smallest myocardial wall thickness (16.6 mm) with significant decrease compared to non-gated images (20.9 mm). CONCLUSIONS: End-diastolic respiratory motion correction and 4D-CT resulted in improved motion minimization and image quality over standard dual-gating.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada Quadridimensional , Humanos , Processamento de Imagem Assistida por Computador/métodos , Movimento (Física) , Tomografia por Emissão de Pósitrons/métodos , Razão Sinal-Ruído
2.
Diabetologia ; 64(8): 1866-1879, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33987714

RESUMO

AIMS/HYPOTHESIS: Chronic low-grade inflammation with local upregulation of proinflammatory molecules plays a role in the progression of obesity-related renal injury. Reduced serum concentration of anti-inflammatory adiponectin may promote chronic inflammation. Here, we investigated the potential anti-inflammatory and renoprotective effects and mechanisms of action of AdipoRon, an adiponectin receptor agonist. METHODS: Wild-type DBA/2J mice were fed with high-fat diet (HFD) supplemented or not with AdipoRon to model obesity-induced metabolic endotoxaemia and chronic low-grade inflammation and we assessed changes in the glomerular morphology and expression of proinflammatory markers. We also treated human glomeruli ex vivo and human podocytes in vitro with AdipoRon and bacterial lipopolysaccharide (LPS), an endotoxin upregulated in obesity and diabetes, and analysed the secretion of inflammatory cytokines, activation of inflammatory signal transduction pathways, apoptosis and migration. RESULTS: In HFD-fed mice, AdipoRon attenuated renal inflammation, as demonstrated by reduced expression of glomerular activated NF-κB p65 subunit (NF-κB-p65) (70%, p < 0.001), TNFα (48%, p < 0.01), IL-1ß (51%, p < 0.001) and TGFß (46%, p < 0.001), renal IL-6 and IL-4 (21% and 20%, p < 0.05), and lowered glomerular F4/80-positive macrophage infiltration (31%, p < 0.001). In addition, AdipoRon ameliorated HFD-induced glomerular hypertrophy (12%, p < 0.001), fibronectin accumulation (50%, p < 0.01) and podocyte loss (12%, p < 0.001), and reduced podocyte foot process effacement (15%, p < 0.001) and thickening of the glomerular basement membrane (18%, p < 0.001). In cultured podocytes, AdipoRon attenuated the LPS-induced activation of the central inflammatory signalling pathways NF-κB-p65, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38-MAPK) (30%, 36% and 22%, respectively, p < 0.001), reduced the secretion of TNFα (32%, p < 0.01), and protected against podocyte apoptosis and migration. In human glomeruli ex vivo, AdipoRon reduced the LPS-induced secretion of inflammatory cytokines IL-1ß, IL-18, IL-6 and IL-10. CONCLUSIONS/INTERPRETATION: AdipoRon attenuated the renal expression of proinflammatory cytokines in HFD-fed mice and LPS-stimulated human glomeruli, which apparently contributed to the amelioration of glomerular inflammation and injury. Mechanistically, based on assays on cultured podocytes, AdipoRon reduced LPS-induced activation of the NF-κB-p65, JNK and p38-MAPK pathways, thereby impelling the decrease in apoptosis, migration and secretion of TNFα. We conclude that the activation of the adiponectin receptor by AdipoRon is a potent strategy to attenuate endotoxaemia-associated renal inflammation.


Assuntos
Dieta Hiperlipídica , Glomérulos Renais/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Nefrite/tratamento farmacológico , Piperidinas/uso terapêutico , Receptores de Adiponectina/agonistas , Idoso , Idoso de 80 Anos ou mais , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Endotoxinas/farmacologia , Feminino , Humanos , Immunoblotting , Imuno-Histoquímica , Glomérulos Renais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos DBA , Camundongos Knockout , Pessoa de Meia-Idade , Nefrite/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Fator de Transcrição RelA/metabolismo
3.
Sensors (Basel) ; 21(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207864

RESUMO

We present a novel method for estimating respiratory motion using inertial measurement units (IMUs) based on microelectromechanical systems (MEMS) technology. As an application of the method we consider the amplitude gating of positron emission tomography (PET) imaging, and compare the method against a clinically used respiration motion estimation technique. The presented method can be used to detect respiratory cycles and estimate their lengths with state-of-the-art accuracy when compared to other IMU-based methods, and is the first based on commercial MEMS devices, which can estimate quantitatively both the magnitude and the phase of respiratory motion from the abdomen and chest regions. For the considered test group consisting of eight subjects with acute myocardial infarction, our method achieved the absolute breathing rate error per minute of 0.44 ± 0.23 1/min, and the absolute amplitude error of 0.24 ± 0.09 cm, when compared to the clinically used respiratory motion estimation technique. The presented method could be used to simplify the logistics related to respiratory motion estimation in PET imaging studies, and also to enable multi-position motion measurements for advanced organ motion estimation.


Assuntos
Tomografia por Emissão de Pósitrons , Respiração , Abdome , Humanos , Processamento de Imagem Assistida por Computador , Movimento (Física) , Tórax
4.
Sensors (Basel) ; 19(19)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554282

RESUMO

Dual cardiac and respiratory gating is a well-known technique for motion compensation in nuclear medicine imaging. In this study, we present a new data fusion framework for dual cardiac and respiratory gating based on multidimensional microelectromechanical (MEMS) motion sensors. Our approach aims at robust estimation of the chest vibrations, that is, high-frequency precordial vibrations and low-frequency respiratory movements for prospective gating in positron emission tomography (PET), computed tomography (CT), and radiotherapy. Our sensing modality in the context of this paper is a single dual sensor unit, including accelerometer and gyroscope sensors to measure chest movements in three different orientations. Since accelerometer- and gyroscope-derived respiration signals represent the inclination of the chest, they are similar in morphology and have the same units. Therefore, we use principal component analysis (PCA) to combine them into a single signal. In contrast to this, the accelerometer- and gyroscope-derived cardiac signals correspond to the translational and rotational motions of the chest, and have different waveform characteristics and units. To combine these signals, we use independent component analysis (ICA) in order to obtain the underlying cardiac motion. From this cardiac motion signal, we obtain the systolic and diastolic phases of cardiac cycles by using an adaptive multi-scale peak detector and a short-time autocorrelation function. Three groups of subjects, including healthy controls (n = 7), healthy volunteers (n = 12), and patients with a history of coronary artery disease (n = 19) were studied to establish a quantitative framework for assessing the performance of the presented work in prospective imaging applications. The results of this investigation showed a fairly strong positive correlation (average r = 0.73 to 0.87) between the MEMS-derived (including corresponding PCA fusion) respiration curves and the reference optical camera and respiration belt sensors. Additionally, the mean time offset of MEMS-driven triggers from camera-driven triggers was 0.23 to 0.3 ± 0.15 to 0.17 s. For each cardiac cycle, the feature of the MEMS signals indicating a systolic time interval was identified, and its relation to the total cardiac cycle length was also reported. The findings of this study suggest that the combination of chest angular velocity and accelerations using ICA and PCA can help to develop a robust dual cardiac and respiratory gating solution using only MEMS sensors. Therefore, the methods presented in this paper should help improve predictions of the cardiac and respiratory quiescent phases, particularly with the clinical patients. This study lays the groundwork for future research into clinical PET/CT imaging based on dual inertial sensors.


Assuntos
Tomografia por Emissão de Pósitrons/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Análise de Componente Principal
5.
Exp Cell Res ; 350(2): 336-348, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28011197

RESUMO

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Nefropatias Diabéticas/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Miosina não Muscular Tipo IIA/metabolismo , Septinas/metabolismo , Vesículas Transportadoras/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animais , Células Epiteliais/metabolismo , Glucose/metabolismo , Células HEK293 , Humanos , Insulina/metabolismo , Túbulos Renais/metabolismo , Camundongos , Podócitos/metabolismo , Ratos , Septinas/genética
6.
J Cell Sci ; 127(Pt 7): 1476-86, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24496452

RESUMO

The conserved septin family of filamentous small GTPases plays important roles in mitosis, cell migration and cell morphogenesis by forming scaffolds and diffusion barriers. Recent studies in cultured cells in vitro indicate that a septin complex of septin 2, 7 and 9 is required for ciliogenesis and cilia function, but septin function in ciliogenesis in vertebrate organs in vivo is not understood. We show that sept7b is expressed in ciliated cells in different tissues during early zebrafish development. Knockdown of sept7b by using morpholino antisense oligonucleotides caused misorientation of basal bodies and cilia, reduction of apical actin and the shortening of motile cilia in Kupffer's vesicle and pronephric tubules. This resulted in pericardial and yolk sac edema, body axis curvature and hydrocephaly. Notably, in sept7b morphants we detected strong left-right asymmetry defects in the heart and lateral plate mesoderm (situs inversus), reduced fluid flow in the kidney, the formation of kidney cysts and loss of glomerular filtration barrier function. Thus, sept7b is essential during zebrafish development for pronephric function and ciliogenesis, and loss of expression of sept7b results in defects that resemble human ciliopathies.


Assuntos
Pronefro/embriologia , Pronefro/metabolismo , Septinas/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados , Encéfalo/embriologia , Encéfalo/metabolismo , Cílios/metabolismo , Desenvolvimento Embrionário , Técnicas de Silenciamento de Genes , Septinas/biossíntese , Septinas/deficiência , Septinas/genética , Proteínas de Peixe-Zebra/biossíntese
7.
J Pathol ; 235(1): 136-46, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25270124

RESUMO

Germline mutations in RAD51C predispose to breast and ovarian cancers. However, the mechanism of RAD51C-mediated carcinogenesis is poorly understood. We previously reported a first-generation Rad51c-knock-out mouse model, in which a spontaneous loss of both Rad51c and Trp53 together resulted in a high incidence of sebaceous carcinomas, particularly in preputial glands. Here we describe a second-generation mouse model, in which Rad51c is deleted, alone or together with Trp53, in sebaceous glands, using Cre-mediated recombination. We demonstrate that deletion of Rad51c alone is not sufficient to drive tumourigenesis and may only cause keratinization of preputial sebocytes. However, deletion of Rad51c together with Trp53 leads to tumour development at around 6 months of age, compared to 11 months for single Trp53-mutant mice. Preputial glands of double-mutant mice are also characterized by increased levels of cell proliferation and DNA damage and form multiple hyperplasias, detectable as early as 2 months of age. Our results reveal a critical synergy between Rad51c and Trp53 in tumour progression and provide a predictable in vivo model system for studying mechanisms of Rad51c-mediated carcinogenesis.


Assuntos
Carcinogênese/genética , Transformação Celular Neoplásica/genética , Mutação/genética , Rad51 Recombinase/genética , Glândulas Sebáceas/patologia , Proteína Supressora de Tumor p53/genética , Animais , Proteínas de Ligação a DNA , Feminino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Glândulas Sebáceas/metabolismo
8.
Am J Pathol ; 184(6): 1727-39, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24726496

RESUMO

Diabetic nephropathy is a complication of diabetes and a major cause of end-stage renal disease. To characterize the early pathophysiological mechanisms leading to glomerular podocyte injury in diabetic nephropathy, we performed quantitative proteomic profiling of glomeruli isolated from rats with streptozotocin-induced diabetes and controls. Fluorescence-based two-dimensional difference gel electrophoresis, coupled with mass spectrometry, identified 29 differentially expressed spots, including actin-binding protein ezrin and its interaction partner, NHERF2, which were down-regulated in the streptozotocin group. Knockdown of ezrin by siRNA in cultured podocytes increased glucose uptake compared with control siRNA-transfected cells, apparently by increasing translocation of glucose transporter GLUT1 to the plasma membrane. Knockdown of ezrin also induced actin remodeling under basal conditions, but reduced insulin-stimulated actin reorganization. Ezrin-dependent actin remodeling involved cofilin-1 that is essential for the turnover and reorganization of actin filaments. Phosphorylated, inactive cofilin-1 was up-regulated in diabetic glomeruli, suggesting altered actin dynamics. Furthermore, IHC analysis revealed reduced expression of ezrin in the podocytes of patients with diabetes. Our findings suggest that ezrin may play a role in the development of the renal complication in diabetes by regulating transport of glucose and organization of the actin cytoskeleton in podocytes.


Assuntos
Citoesqueleto de Actina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Glucose/metabolismo , Podócitos/metabolismo , Citoesqueleto de Actina/patologia , Actinas/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/patologia , Regulação para Baixo , Técnicas de Silenciamento de Genes , Masculino , Ratos , Ratos Sprague-Dawley
9.
Eur Heart J Cardiovasc Imaging ; 25(2): 285-292, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-37774503

RESUMO

AIMS: To evaluate the incremental value of positron emission tomography (PET) myocardial perfusion imaging (MPI) over coronary computed tomography angiography (CCTA) in predicting short- and long-term outcome using machine learning (ML) approaches. METHODS AND RESULTS: A total of 2411 patients with clinically suspected coronary artery disease (CAD) underwent CCTA, out of whom 891 patients were admitted to downstream PET MPI for haemodynamic evaluation of obstructive coronary stenosis. Two sets of Extreme Gradient Boosting (XGBoost) ML models were trained, one with all the clinical and imaging variables (including PET) and the other with only clinical and CCTA-based variables. Difference in the performance of the two sets was analysed by means of area under the receiver operating characteristic curve (AUC). After the removal of incomplete data entries, 2284 patients remained for further analysis. During the 8-year follow-up, 210 adverse events occurred including 59 myocardial infarctions, 35 unstable angina pectoris, and 116 deaths. The PET MPI data improved the outcome prediction over CCTA during the first 4 years of the observation time and the highest AUC was at the observation time of Year 1 (0.82, 95% confidence interval 0.804-0.827). After that, there was no significant incremental prognostic value by PET MPI. CONCLUSION: PET MPI variables improve the prediction of adverse events beyond CCTA imaging alone for the first 4 years of follow-up. This illustrates the complementary nature of anatomic and functional information in predicting the outcome of patients with suspected CAD.


Assuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Humanos , Angiografia por Tomografia Computadorizada/métodos , Prognóstico , Angiografia Coronária/métodos , Imagem de Perfusão do Miocárdio/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada Multidetectores/métodos , Aprendizado de Máquina , Valor Preditivo dos Testes
10.
Ann Nucl Med ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842629

RESUMO

BACKGROUND: Cardiac positron emission tomography (PET) can visualize and quantify the molecular and physiological pathways of cardiac function. However, cardiac and respiratory motion can introduce blurring that reduces PET image quality and quantitative accuracy. Dual cardiac- and respiratory-gated PET reconstruction can mitigate motion artifacts but increases noise as only a subset of data are used for each time frame of the cardiac cycle. AIM: The objective of this study is to create a zero-shot image denoising framework using a conditional generative adversarial networks (cGANs) for improving image quality and quantitative accuracy in non-gated and dual-gated cardiac PET images. METHODS: Our study included retrospective list-mode data from 40 patients who underwent an 18F-fluorodeoxyglucose (18F-FDG) cardiac PET study. We initially trained and evaluated a 3D cGAN-known as Pix2Pix-on simulated non-gated low-count PET data paired with corresponding full-count target data, and then deployed the model on an unseen test set acquired on the same PET/CT system including both non-gated and dual-gated PET data. RESULTS: Quantitative analysis demonstrated that the 3D Pix2Pix network architecture achieved significantly (p value<0.05) enhanced image quality and accuracy in both non-gated and gated cardiac PET images. At 5%, 10%, and 15% preserved count statistics, the model increased peak signal-to-noise ratio (PSNR) by 33.7%, 21.2%, and 15.5%, structural similarity index (SSIM) by 7.1%, 3.3%, and 2.2%, and reduced mean absolute error (MAE) by 61.4%, 54.3%, and 49.7%, respectively. When tested on dual-gated PET data, the model consistently reduced noise, irrespective of cardiac/respiratory motion phases, while maintaining image resolution and accuracy. Significant improvements were observed across all gates, including a 34.7% increase in PSNR, a 7.8% improvement in SSIM, and a 60.3% reduction in MAE. CONCLUSION: The findings of this study indicate that dual-gated cardiac PET images, which often have post-reconstruction artifacts potentially affecting diagnostic performance, can be effectively improved using a generative pre-trained denoising network.

11.
Am J Pathol ; 176(1): 51-63, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19948823

RESUMO

Mutations leading to nephrin loss result in massive proteinuria both in humans and mice. Early perinatal lethality of conventional nephrin knockout mice makes it impossible to determine the role of nephrin protein in the adult kidney and in extra-renal tissues. Herein, we studied whether podocyte-specific, doxycycline-inducible, rat nephrin expression can rescue nephrin-deficient mice from perinatal lethality. Fourteen littermates out of 72 lacked endogenous nephrin and expressed transgenic rat nephrin. Six of these rescued mice survived until 6 weeks of age, whereas the nephrin-deficient pups died before the age of 5 days. The rescued mice were smaller, developed proteinuria, and showed histological abnormalities in the kidney. Despite foot process effacement, slit diaphragms were observed. Importantly, the expression and localization of several proteins associated with the signaling capacity of nephrin or the regulation of the expression of nephrin were changed in the podocytes. Indeed, all rescued mice showed impaired locomotor activity and distinct histological abnormalities in the cerebellum, and the male mice were also infertile and showed genital malformations. These observations are consistent with normal nephrin expression in the testis and cerebellum. These observations indicate that podocyte-specific expression of rat nephrin can rescue nephrin-deficient mice from perinatal death, but is not sufficient for full complementation.


Assuntos
Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Podócitos/metabolismo , Transgenes/genética , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Doxiciclina/farmacologia , Imunofluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/ultraestrutura , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Especificidade de Órgãos/efeitos dos fármacos , Especificidade de Órgãos/genética , Mortalidade Perinatal , Fenótipo , Podócitos/efeitos dos fármacos , Podócitos/patologia , Podócitos/ultraestrutura , Proteinúria/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos
12.
Nephrol Dial Transplant ; 25(8): 2437-46, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20237062

RESUMO

BACKGROUND: Glomerular slit diaphragm (SD) represents a modified adherens junction composed of molecules belonging to both immunoglobulin and cadherin superfamilies. Cadherins associate with the cytosolic scaffolding protein beta-catenin, but the precise role of beta-catenin in mature or injured podocytes is not known. METHODS: The conditional podocyte-specific beta-catenin-deficient mouse line was generated using the doxycycline-inducible Cre-loxP system. Expression of the beta-catenin-deficient gene was turned off at the age of 8 weeks by doxycycline treatment and the kidney phenotype was analysed. In addition, beta-catenin-deficient and control mice were treated with adriamycin (ADR) and analysed for albuminuria and morphological alterations. RESULTS: Deletion of beta-catenin in mature podocytes did not change the morphology of podocytes nor did it lead to albuminuria. However, lack of beta-catenin attenuated albuminuria after ADR treatment. Electron microscopic examination showed increased podocyte foot process effacement associated with SD abnormalities in ADR-treated control mice compared to beta-catenin-deficient mice. CONCLUSIONS: These results show that beta-catenin in podocytes is dispensable for adult mice, but appears to be important in modulating the SD during ADR-induced perturbation of the filtration barrier.


Assuntos
Albuminúria/induzido quimicamente , Albuminúria/prevenção & controle , Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , Glomérulos Renais/fisiopatologia , beta Catenina/fisiologia , Albuminúria/fisiopatologia , Animais , Antibióticos Antineoplásicos/farmacologia , Caderinas/metabolismo , Modelos Animais de Doenças , Doxorrubicina/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Fenótipo , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , beta Catenina/genética
13.
Differentiation ; 76(5): 506-17, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18177421

RESUMO

CD2-associated protein (CD2AP) is an adapter protein that is involved in various signaling and vesicular trafficking processes and also functions as a linker between plasma membrane proteins and the actin cytoskeleton. The protein is known to have important functions in T cells and glomerular podocytes, but it is also expressed by many other adult-type tissues and cells. Here we analyzed the expression of the protein during early embryonic development and organogenesis of the mouse. The results showed differential tissue-specific regulation of CD2AP in developing and maturing organs. In oocytes and pre-implantation embryos, CD2AP was located diffusely in the cytoplasm, whereas in late blastocysts it was concentrated to the intercellular contacts. During organogenesis, CD2AP was distinctly upregulated upon, e.g., the pretubular aggregation of metanephric mesenchyme cells and the appearance of the osteoblastic rim around cartilages during endochondral ossification. High CD2AP expression was also observed during epithelial-like conversion of some highly specialized secretory cell types such as the odontoblasts, the cells of the choroid plexus and the decidualized cells of the endometrial stroma. In other instances, such as the development of the proximal tubuli of the kidney and the flat alveolar epithelium of the lung, the protein was downregulated upon differentiation and maturation of the cells. Finally, certain cells, e.g., glomerular podocytes, those forming the collecting ducts of the kidney, and the urothelium of the kidney pelvis, expressed CD2AP throughout their differentiation and maturation. Multiple molecules and complex pathways regulate embryogenesis, and scaffolding proteins apparently have pivotal roles in targeting and finetuning, e.g., growth factor- or hormone-induced processes. The cell-type specific spatio-temporal regulation of CD2AP during development suggests that this adapter protein is a key regulatory partner in many signaling pathways and cellular processes governing differentiation and morphogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas do Citoesqueleto/fisiologia , Desenvolvimento Embrionário/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Organogênese/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Transporte Biológico/genética , Transporte Biológico/fisiologia , Blastocisto/metabolismo , Diferenciação Celular , Proteínas do Citoesqueleto/biossíntese , Proteínas do Citoesqueleto/genética , Citoesqueleto/ultraestrutura , Desenvolvimento Embrionário/genética , Feminino , Camadas Germinativas/metabolismo , Idade Gestacional , Masculino , Camundongos , Oócitos/metabolismo , Especificidade de Órgãos , Organogênese/genética , Ovário/metabolismo , Placenta/metabolismo , Gravidez , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Testículo/metabolismo
15.
Front Neurosci ; 12: 373, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29946231

RESUMO

This paper introduces an event-based methodology to perform arbitrary linear basis transformations that encompass a broad range of practically important signal transforms, such as the discrete Fourier transform (DFT) and the discrete wavelet transform (DWT). We present a complexity analysis of the proposed method, and show that the amount of required multiply-and-accumulate operations is reduced in comparison to frame-based method in natural video sequences, when the required temporal resolution is high enough. Experimental results on natural video sequences acquired by the asynchronous time-based neuromorphic image sensor (ATIS) are provided to support the feasibility of the method, and to illustrate the gain in computation resources.

16.
Phys Med Biol ; 62(20): 8080-8101, 2017 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-28880843

RESUMO

Positron emission tomography (PET) is a non-invasive imaging technique which may be considered as the state of art for the examination of cardiac inflammation due to atherosclerosis. A fundamental limitation of PET is that cardiac and respiratory motions reduce the quality of the achieved images. Current approaches for motion compensation involve gating the PET data based on the timing of quiescent periods of cardiac and respiratory cycles. In this study, we present a novel gating method called microelectromechanical (MEMS) dual gating which relies on joint non-electrical sensors, i.e. tri-axial accelerometer and gyroscope. This approach can be used for optimized selection of quiescent phases of cardiac and respiratory cycles. Cardiomechanical activity according to echocardiography observations was investigated to confirm whether this dual sensor solution can provide accurate trigger timings for cardiac gating. Additionally, longitudinal chest motions originating from breathing were measured by accelerometric- and gyroscopic-derived respiratory (ADR and GDR) tracking. The ADR and GDR signals were evaluated against Varian real-time position management (RPM) signals in terms of amplitude and phase. Accordingly, high linear correlation and agreement were achieved between the reference electrocardiography, RPM, and measured MEMS signals. We also performed a Ge-68 phantom study to evaluate possible metal artifacts caused by the integrated read-out electronics including mechanical sensors and semiconductors. The reconstructed phantom images did not reveal any image artifacts. Thus, it was concluded that MEMS-driven dual gating can be used in PET studies without an effect on the quantitative or visual accuracy of the PET images. Finally, the applicability of MEMS dual gating for cardiac PET imaging was investigated with two atherosclerosis patients. Dual gated PET images were successfully reconstructed using only MEMS signals and both qualitative and quantitative assessments revealed encouraging results that warrant further investigation of this method.


Assuntos
Coração/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Movimento/fisiologia , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodos , Técnicas de Imagem de Sincronização Respiratória/métodos , Artefatos , Eletrocardiografia/métodos , Coração/fisiologia , Humanos , Respiração
17.
Sci Rep ; 7(1): 10731, 2017 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-28878342

RESUMO

Lack of CD2-associated protein (CD2AP) in mice increases podocyte apoptosis and leads to glomerulosclerosis and renal failure. We showed previously that SHIP2, a negative regulator of the PI3K/AKT signalling pathway, interacts with CD2AP. Here, we found that the expression level and activity of SHIP2 and production of reactive oxygen species (ROS) are increased in cultured CD2AP knockout (CD2AP-/-) mouse podocytes. Oxidative stress was also increased in CD2AP-/- mouse glomeruli in vivo. We found that puromycin aminonucleoside (PA), known to increase ROS production and apoptosis, increases SHIP2 activity and reduces CD2AP expression in cultured human podocytes. PDK1 and CDK2, central regulators of AKT, were downregulated in CD2AP-/- or PA-treated podocytes. Downregulation of PDK1 and CDK2, ROS generation and apoptosis were prevented by CD2AP overexpression in both models. Notably, inhibition of SHIP2 activity with a small molecule inhibitor AS1949490 ameliorated ROS production in CD2AP-/- podocytes, but, surprisingly, further reduced PDK1 expression and aggravated apoptosis. AKT- and ERK-mediated signalling was diminished and remained reduced after AS1949490 treatment in the absence of CD2AP. The data suggest that inhibition of the catalytic activity of SHIP2 is beneficial in reducing oxidative stress, but leads to deleterious increase in apoptosis in podocytes with reduced expression of CD2AP.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/deficiência , Apoptose/genética , Proteínas do Citoesqueleto/deficiência , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/antagonistas & inibidores , Podócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Biomarcadores , Células Cultivadas , Imunofluorescência , Regulação da Expressão Gênica , Humanos , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
18.
Sci Rep ; 7(1): 6823, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28754888

RESUMO

Gyrocardiography (GCG) is a new non-invasive technique for assessing heart motions by using a sensor of angular motion - gyroscope - attached to the skin of the chest. In this study, we conducted simultaneous recordings of electrocardiography (ECG), GCG, and echocardiography in a group of subjects consisting of nine healthy volunteer men. Annotation of underlying fiducial points in GCG is presented and compared to opening and closing points of heart valves measured by a pulse wave Doppler. Comparison between GCG and synchronized tissue Doppler imaging (TDI) data shows that the GCG signal is also capable of providing temporal information on the systolic and early diastolic peak velocities of the myocardium. Furthermore, time intervals from the ECG Q-wave to the maximum of the integrated GCG (angular displacement) signal and maximal myocardial strain curves obtained by 3D speckle tracking are correlated. We see GCG as a promising mechanical cardiac monitoring tool that enables quantification of beat-by-beat dynamics of systolic time intervals (STI) related to hemodynamic variables and myocardial contractility.


Assuntos
Determinação da Frequência Cardíaca/métodos , Hemodinâmica , Contração Miocárdica , Rotação , Adulto , Determinação da Frequência Cardíaca/normas , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Referência
19.
IEEE J Biomed Health Inform ; 21(5): 1233-1241, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27834656

RESUMO

In this paper, a novel method to detect atrial fibrillation (AFib) from a seismocardiogram (SCG) is presented. The proposed method is based on linear classification of the spectral entropy and a heart rate variability index computed from the SCG. The performance of the developed algorithm is demonstrated on data gathered from 13 patients in clinical setting. After motion artifact removal, in total 119 min of AFib data and 126 min of sinus rhythm data were considered for automated AFib detection. No other arrhythmias were considered in this study. The proposed algorithm requires no direct heartbeat peak detection from the SCG data, which makes it tolerant against interpersonal variations in the SCG morphology, and noise. Furthermore, the proposed method relies solely on the SCG and needs no complementary electrocardiography to be functional. For the considered data, the detection method performs well even on relatively low quality SCG signals. Using a majority voting scheme that takes five randomly selected segments from a signal and classifies these segments using the proposed algorithm, we obtained an average true positive rate of [Formula: see text] and an average true negative rate of [Formula: see text] for detecting AFib in leave-one-out cross-validation. This paper facilitates adoption of microelectromechanical sensor based heart monitoring devices for arrhythmia detection.


Assuntos
Fibrilação Atrial/diagnóstico , Cinetocardiografia/métodos , Processamento de Sinais Assistido por Computador , Algoritmos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino
20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 2370-2373, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28268801

RESUMO

This study presents a new technique which allows identification of individual heartbeats from seismocardiograms (SCG) with high accuracy. Our method is electrocardiogram (ECG) independent and designed based upon S-transform and Shannon energy. The S-transform which is a time-frequency (TF) representation first provides frequency-dependent resolution while preserving a direct relationship with Fourier spectrum. Subsequently, individual heartbeats are detected in the time domain by calculating the Shannon energy (SSE) of each obtained local spectrum and employing other techniques such as successive mean quantization transform (SMQT) and adaptive thresholding. A total of 30 recordings were analysed in this study by measuring SCG and simultaneous electrocardiogram (ECG) in supine position. The performance of the algorithm was tested using the standard ECGs obtained from each test subject. The obtained results were as follows (sensitivity, precision, and detection error rate): (98.0%, 98.4% and 0.2%). In conclusion, the results confirmed that combination of S-transform, Shannon energy, and other techniques considerably enhanced the efficiency for the heartbeat detection in seismocardiograms.


Assuntos
Eletrocardiografia , Frequência Cardíaca , Processamento de Sinais Assistido por Computador , Algoritmos , Humanos
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