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1.
Ann Nutr Metab ; 76 Suppl 1: 43-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33774611

RESUMO

Adults consuming sugar-sweetened beverages (SSBs) are at increased risk of becoming overweight/obese and developing lifestyle-related diseases. Furthermore, a low water intake is associated with increased health risks, such as CKD. These issues are especially pressing in Mexico where SSB intake is high. The present research aimed to describe the attitudes of Mexican adults who are considered high sugar-low water drinkers (HS-LWDs). HS-LWDs were defined as adults aged 18-45 years, drinking at least 2 servings (500 mL) of SSB/day and maximum 3 servings (750 mL) of water/day. The study included 2.858 HS-LWD (58% males) living in the urban area of Mexico City. Data were collected using an online, self-administered questionnaire. Bayesian approach was applied to analyze attitudes in life and towards drinking. Results showed that social aspects, such as sharing with friends and family and self-image, were the dominant attitudes in life. The main reason to choose a beverage was to get sensations, resulting in 2 axes, one was pleasure oriented and one was health oriented. Getting sensations was also a main driver to drink linked to a moment, together with self-image. The Bayesian network analysis demonstrated 5 attitude profiles, based on the most important attitudes defining each profile: mood and pleasure, self-image and body image, sharing and restoring, pleasure and energy, and health and success. This study allowed describing HS-LWD attitudes, in life and towards drinking. It constitutes a first step in understanding this target group's attitudes and behavior, offering potential recommendations for tailored interventions to promote the adoption of healthier drinking habits.


Assuntos
Dieta Saudável/psicologia , Comportamento de Ingestão de Líquido , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Bebidas Adoçadas com Açúcar , Adolescente , Adulto , Afeto , Teorema de Bayes , Ingestão de Líquidos , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Prazer , Autoimagem , Inquéritos e Questionários , População Urbana , Adulto Jovem
2.
Dev Growth Differ ; 61(1): 124-138, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30569461

RESUMO

Many animals can change the size, shape, texture and color of their regenerated coats in response to different ages, sexes, or seasonal environmental changes. Here, we propose that the feather core branching morphogenesis module can be regulated by sex hormones or other environmental factors to change feather forms, textures or colors, thus generating a large spectrum of complexity for adaptation. We use sexual dimorphisms of the chicken to explore the role of hormones. A long-standing question is whether the sex-dependent feather morphologies are autonomously controlled by the male or female cell types, or extrinsically controlled and reversible. We have recently identified core feather branching molecular modules which control the anterior-posterior (bone morphogenetic orotein [BMP], Wnt gradient), medio-lateral (Retinoic signaling, Gremlin), and proximo-distal (Sprouty, BMP) patterning of feathers. We hypothesize that morpho-regulation, through quantitative modulation of existing parameters, can act on core branching modules to topologically tune the dimension of each parameter during morphogenesis and regeneration. Here, we explore the involvement of hormones in generating sexual dimorphisms using exogenously delivered hormones. Our strategy is to mimic male androgen levels by applying exogenous dihydrotestosterone and aromatase inhibitors to adult females and to mimic female estradiol levels by injecting exogenous estradiol to adult males. We also examine differentially expressed genes in the feathers of wildtype male and female chickens to identify potential downstream modifiers of feather morphogenesis. The data show male and female feather morphology and their color patterns can be modified extrinsically through molting and resetting the stem cell niche during regeneration.


Assuntos
Plumas/crescimento & desenvolvimento , Plumas/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Morfogênese/genética , Animais , Galinhas , Feminino , Masculino , Caracteres Sexuais
3.
J Vasc Interv Radiol ; 29(3): 425-431, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29402612

RESUMO

PURPOSE: To evaluate the performance of automated feeder detection (AFD) software (EmboGuide; Philips Healthcare, Best, The Netherlands) on hepatocellular carcinoma (HCC) tumors during transarterial chemoembolization. MATERIALS AND METHODS: Forty-four first-time transarterial chemoembolization patients (37 men; mean age, 62 ± 11 years) were enrolled between May 2012 and July 2013. A total of 86 HCC lesions were treated (2.0 ± 1.4 lesions per patient; 27.6 ± 15.9 mm maximum diameter). One hundred forty-seven feeding arteries were found with digital subtraction angiography (DSA), cone-beam computed tomography (CT), and AFD software with the option of manual adjustment (MA). Three independent interventional radiologists analyzed the cone-beam CT images retrospectively with and without AFD and MA. Compared with the number of treated vessels, the number of true positives, false positives, false negatives, sensitivity, and interreader agreement were determined using clustered binary data analysis. RESULTS: Cone-beam CT enabled detection of 100 ± 3.5 feeding arteries (70% sensitivity) with 68.6% agreement among readers. AFD software significantly improved detection to 127±0.6 feeding arteries (86% sensitivity, P = .008) with 99.7% reader agreement and reduced the number of false negatives from an average of 47 ± 3.5 to 20 ± 0.6 (P = .008). MA of the AFD results produced similar feeding artery detection rates (127 ± 5.1, 86% sensitivity, P = .8), with lower interreader agreement (91.6%) and slightly fewer false positives (16 ± 0.0 to 14 ± 2.5, P = .4). CONCLUSIONS: AFD software significantly improved feeding artery detection rates during transarterial chemoembolization of HCC lesions with better user reproducibility compared with cone-beam CT alone. In conjunction with DSA, AFD enables maximum feeding artery detection in this setting.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Radiografia Intervencionista/métodos , Software , Angiografia Digital , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
Eur Radiol ; 25(8): 2291-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25693664

RESUMO

OBJECTIVES: To evaluate myocardial enhancement of patients with cardiac amyloidosis (CA) using computed tomography (CT). METHODS: Thirteen patients with CA and 11 control patients were examined with first-pass and delayed CT acquisition. A qualitative and quantitative analysis of images was performed. Myocardial attenuation, myocardial signal-to-noise ratio (SNRmyoc), blood pool SNR (SNRblood), contrast-to-noise ratio between blood pool and myocardium (CNRblood-myoc) and relative attenuation index (RAI) defined as variation of myocardial attenuation between delayed and first-pass acquisitions were calculated. RESULTS: Two false negative cases (15 %) and three false positive cases (27 %) were detected on qualitative analysis. SNRmyoc of patients with CA was significantly (p < 0.05) lower on first-pass (4.08 ± 1.9) and higher on delayed acquisition (7.10 ± 2.7) than control patients (6.1 ± 2.2 and 5.03 ± 1.8, respectively). Myocardial attenuation was higher in CA (121 ± 39 HU) than control patients (81 ± 17 HU) on delayed acquisition. CNRblood-myoc was significantly (p < 0.05) lower in CA (1.51 ± 0.7) than control patients (2.85 ± 1.2) on delayed acquisition. The RAI was significantly (p < 0.05) higher in CA (0.12 ± 0.25) than in control patients (-0.56 ± 0.21). CONCLUSION: Dual phase MDCT can detect abnormal myocardial enhancement in patients with CA. KEY POINTS: • CT can detect abnormal first-pass and delayed enhancement in cardiac amyloidosis. • Measurement of relative myocardial enhancement between acquisitions helps to detect cardiac amyloidosis. • CT may provide useful data to diagnose cardiac amyloidosis.


Assuntos
Amiloidose/diagnóstico por imagem , Meios de Contraste , Cardiopatias/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada Multidetectores/métodos , Intensificação de Imagem Radiográfica/métodos , Idoso , Feminino , Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Razão Sinal-Ruído
5.
Nature ; 451(7176): 340-4, 2008 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-18202659

RESUMO

In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge are regulated by the surrounding microenvironment, or niche. The activation of such stem cells is cyclic, involving periodic beta-catenin activity. In the adult mouse, regeneration occurs in waves in a follicle population, implying coordination among adjacent follicles and the extrafollicular environment. Here we show that unexpected periodic expression of bone morphogenetic protein 2 (Bmp2) and Bmp4 in the dermis regulates this process. This BMP cycle is out of phase with the WNT/beta-catenin cycle, thus dividing the conventional telogen into new functional phases: one refractory and the other competent for hair regeneration, characterized by high and low BMP signalling, respectively. Overexpression of noggin, a BMP antagonist, in mouse skin resulted in a markedly shortened refractory phase and faster propagation of the regenerative wave. Transplantation of skin from this mutant onto a wild-type host showed that follicles in donor and host can affect their cycling behaviours mutually, with the outcome depending on the equilibrium of BMP activity in the dermis. Administration of BMP4 protein caused the competent region to become refractory. These results show that BMPs may be the long-sought 'chalone' inhibitors of hair growth postulated by classical experiments. Taken together, results presented in this study provide an example of hierarchical regulation of local organ stem cell homeostasis by the inter-organ macroenvironment. The expression of Bmp2 in subcutaneous adipocytes indicates physiological integration between these two thermo-regulatory organs. Our findings have practical importance for studies using mouse skin as a model for carcinogenesis, intra-cutaneous drug delivery and stem cell engineering studies, because they highlight the acute need to differentiate supportive versus inhibitory regions in the host skin.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Derme/metabolismo , Cabelo/crescimento & desenvolvimento , Regeneração/fisiologia , Transdução de Sinais , Células-Tronco/citologia , Fator de Crescimento Transformador beta/metabolismo , Tecido Adiposo/metabolismo , Animais , Proteína Morfogenética Óssea 2 , Proteína Morfogenética Óssea 4 , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Derme/citologia , Derme/transplante , Cabelo/citologia , Folículo Piloso/citologia , Folículo Piloso/metabolismo , Camundongos , Camundongos Endogâmicos , Células-Tronco/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
6.
Arch Pathol Lab Med ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38797516

RESUMO

CONTEXT.­: Leptomeningeal disease (LMD) is a clinical sequela of central nervous system metastasis involving the cerebrospinal fluid (CSF), often seen in late-stage solid tumors. It has a grave prognosis without urgent treatment. Standard of care methodologies to diagnose LMD include CSF cytology, magnetic resonance imaging, and clinical evaluation. These methods offer limited sensitivity and specificity for the evaluation of LMD. Here, we describe the analytic performance characteristics of a microfluidic-based tumor cell enrichment and detection assay optimized to detect epithelial cells in CSF using both contrived samples as well as CSF from patients having suspected or confirmed LMD from carcinomas. OBJECTIVE.­: To demonstrate the feasibility of using a microfluidic, multi-antibody cell capture assay to identify and quantify tumor cells in CSF. DESIGN.­: An artificial CSF solution was spiked with 34 different human carcinoma cell lines at different concentrations and assayed for the ability to detect tumor cells to assess analytic accuracy. Two cell lines were selected to assess linearity, intra-assay precision, interinstrument precision, and sample stability. Clinical verification was performed on 65 CSF specimens from patients. Parameters assessed included the number of tumor cells, coefficient of variation percentage, and percentage of tumor cell capture (TCC). RESULTS.­: Among contrived samples, average tumor cell capture ranged from 50% to 82% (261 of 522; 436 of 531), and coefficients of variation ranged from 7% to 67%. The cell capture assay demonstrated a sensitivity of 92% and a specificity of 95% among clinical samples. CONCLUSIONS.­: This assay demonstrated the ability to detect and enumerate epithelial cells in contrived and clinical specimens in an accurate and reproducible fashion. The use of cell capture assays in CSF may be useful as a sensitive test for the diagnosis and longitudinal monitoring of LMD from solid tumors.

7.
Radiology ; 269(2): 362-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23696680

RESUMO

PURPOSE: To evaluate the performance of a low-b-value diffusion-weighted (DW) echo-planar (EP) imaging sequence for detection of regional and diffuse myocardial edema in patients with acute myocarditis. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained from all subjects. Thirteen patients with acute myocarditis and a control group of seven healthy adults underwent low-b-value (50 sec/mm(2)) DW cardiac magnetic resonance imaging. DW EP images were acquired in the four-chamber long-axis section and analyzed qualitatively and quantitatively. Short inversion time inversion-recovery (STIR) T2-weighted and late gadolinium chelate enhancement images were acquired in the same plane and analyzed. Late gadolinium chelate enhancement was used as the reference standard. Statistical analyses were performed with a receiver operating characteristic analysis and a nonparametric Wilcoxon test. RESULTS: Qualitative analysis showed myocardial high-signal-intensity areas in 100% (13 of 13) of patients on DW EP, 38% (five of 13) on STIR T2-weighted, and 100% (13 of 13) on late gadolinium chelate enhancement images. In eight patients (61%), high-signal-intensity areas were exhibited on DW EP images that were not detected on STIR T2-weighted images, but were colocalized with lesions detected on late gadolinium chelate enhancement images. Similar results were obtained by using an automatic analysis with dedicated cardiac software. The global myocardial signal intensity ratio was significantly higher (P = .03) in patients than in controls for DW EP (2.2 ± 0.4 [standard deviation] vs 1.1 ± 0.4, respectively), and exhibited no significant difference (P = .14) for STIR T2-weighted (1.7 ± 0.6 vs 1.4 ± 0.1, respectively) images. Sensitivity and diagnostic accuracy were higher for DW EP images than for STIR T2-weighted images (92% vs 54%, and 95% vs 70%, respectively), and specificity was the same (100% vs 100%). CONCLUSION: A low-b-value DW EP imaging sequence is a feasible alternative to the standard STIR T2-weighted sequence for detection of regional and global myocardium edema in patients with acute myocarditis. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13121811/-/DC1.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Edema/diagnóstico , Miocardite/patologia , Doença Aguda , Adulto , Meios de Contraste , Eletrocardiografia , Feminino , Humanos , Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Masculino , Meglumina , Compostos Organometálicos
8.
Breast Cancer Res Treat ; 133(2): 487-500, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21947652

RESUMO

The rearranged during transfection/papillary thyroid carcinoma (RET/PTC) tyrosine kinase is an oncogene implicated in the tumorigenesis of thyroid cancer. Recent studies by us and others have shown that RET/PTC kinase expression is induced by estrogen in breast cancer cells. Due to the critical involvement of estrogen-regulated genes in the pathogenesis of breast cancer, we investigated the expression, regulation, and function of RET/PTC kinase in breast cancer cells. We found that RET/PTC kinase expression correlates with estrogen receptor (ER) expression in breast cancer cells and tumor specimens, and that RET/PTC kinase expression is associated with a poor prognosis in ER-positive breast cancer patients. We found that estrogen rapidly induces RET/PTC kinase expression in an ER-dependent manner in breast cancer cells and that this induction is through a transcriptional regulatory mechanism. Using reporter assays, small interfering RNA (siRNA) assays, and chromatin immunoprecipitation (ChIP) assays, we demonstrated the necessity of crosstalk between ER and the forkhead box A1 (FOXA1) transcription factor in regulating RET/PTC kinase expression. In functional studies, increased expression of RET/PTC kinase induced by estrogen stimulation resulted in elevated phosphorylation of multiple downstream kinase signaling pathways. Conversely, knockdown of RET/PTC expression was associated with the inhibition of these same kinase signaling pathways, and, in fact, decreased the stimulatory effect of estrogen on the proliferation of ER-positive breast cancer cells. These results demonstrate a novel pathway of ER and FOXA1 transcription factor crosstalk in regulating RET/PTC kinase expression, and demonstrate that RET/PTC kinase is a critical regulator for the proliferation of ER-positive breast cancer cells. Taken together, our study suggests that RET/PTC kinase may serve as a novel prognostic biomarker and therapeutic target for prevention and treatment of ER-positive breast cancer.


Assuntos
Neoplasias da Mama/genética , Proteínas Proto-Oncogênicas c-ret/genética , Receptores de Estrogênio/genética , Sequência de Bases , Sítios de Ligação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Elementos Facilitadores Genéticos , Estrogênios/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ordem dos Genes , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Ligação Proteica , Proteínas Proto-Oncogênicas c-ret/metabolismo , Receptores de Estrogênio/metabolismo , Transdução de Sinais
9.
Breast Cancer Res Treat ; 134(1): 101-15, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22212555

RESUMO

Estrogen signaling is a critical pathway that plays a key role in the pathogenesis of breast cancer. In a previous transcriptional profiling study, we identified a novel panel of estrogen-induced genes in breast cancer. One of these genes is solute carrier family 22 member 5 (SLC22A5), which encodes a polyspecific organic cation transporter (also called OCTN2). In this study, we found that estrogen stimulates SLC22A5 expression robustly in an estrogen receptor (ER)-dependent manner and that SLC22A5 expression is associated with ER status in breast cancer cell lines and tissue specimens. Although the SLC22A5 proximal promoter is not responsive to estrogen, a downstream intronic enhancer confers estrogen inducibility. This intronic enhancer contains a newly identified estrogen-responsive element (ERE) (GGTCA-CTG-TGACT) and other transcription factor binding sites, such as a half ERE and a nuclear receptor related 1 (NR4A2/Nurr1) site. Estrogen induction of the luciferase reporter was dependent upon both the ERE and the NR4A2 site within the intronic enhancer. Small interfering RNA against either ER or Nurr1 inhibited estrogen induction of SLC22A5 expression, and chromatin immunoprecipitation assays confirmed the recruitment of both ER and Nurr1 to this enhancer. In functional assays, knockdown of SLC22A5 inhibited L: -carnitine intake, resulted in lipid droplet accumulation, and suppressed the proliferation of breast cancer cells. These results demonstrate that SLC22A5 is an estrogen-dependent gene regulated via a newly identified intronic ERE. Since SLC22A5 is a critical regulator of carnitine homeostasis, lipid metabolism, and cell proliferation, SLC22A5 may serve as a potential therapeutic target for breast cancer in the future.


Assuntos
Neoplasias da Mama/metabolismo , Estrogênios/fisiologia , Expressão Gênica , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Elementos de Resposta , Sequência de Bases , Sítios de Ligação , Neoplasias da Mama/genética , Carnitina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Humanos , Íntrons , Metabolismo dos Lipídeos , Luciferases/biossíntese , Luciferases/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Ligação Proteica , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Membro 5 da Família 22 de Carreadores de Soluto
10.
Ann Vasc Surg ; 26(2): 175-84, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22078306

RESUMO

BACKGROUND: Evolution of stentgraft and vascular imaging technologies allows endovascular treatment (ET) of juxta-renal aneurysms (JRA). However, endoleaks rates and implants stability are not well documented. The aim of this study was to report the incidence and the perioperative treatment of the endoleaks occurring during ET for JRA. MATERIAL AND METHODS: Between January 2000 and April 2010, a total of 957 treated aneurysms were prospectively collected in a database. ET cases for JRA were selected from this database. Pre- and postoperative imaging was retrospectively analyzed to determine the incidence, localization, and treatment of the endoleaks detected following this technique. RESULTS: The series included 50 patients (5%; age, 73 ± 12 years; 44 men). Mean diameter was 60 ± 12 mm. The ET included 38 fenestrated and/or branched endografts and 12 endografts implanted according to the chimney technique. One hundred and forty-three target vessels were perfused. Immediately after endograft deployment, angiography showed endoleaks in 15 patients (30%): 11 type Ia, 1 type II, and 3 type III endoleaks. These endoleaks were treated by aortic endograft modeling and/or stenting in 11 patients, and by placing an aortic extension in two patients. Despite modeling, two patients had a persistent type Ia endoleak and were respectively treated by placing a Palmaz stent and by performing proximal embolization. Despite these procedures, completion angiography showed five residual endoleaks (10%): two type Ia, two type II, and one type III. Immediate postoperative computed tomography (CT) angiography showed endoleaks in 13 patients (28%): six type I, six type II, and one mixed type II/III. Among these 13 patients, on the initial angiography, nine presented with an endoleak, three with a type II and one with a type Ib. Early mortality (<30 days) was 8% (four patients). With a mean follow-up of 12 months, (range, 1-42), six patients presented with a persisting endoleak (four type II, one type Ia, and one multiple type). Aneurysm growth (≥5 mm) was reported in two patients (4%), and nine secondary endovascular procedures were performed to treat these endoleaks. CONCLUSION: Endoleaks are frequent during ET of JRA. They are treated not only according to their type but also according to the implant characteristics (fenestrated or chimney). Although most endoleaks can be perioperatively treated with simple endovascular means, treatment of persisting type Ia endoleaks remains challenging.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Embolização Terapêutica , Endoleak/terapia , Procedimentos Endovasculares/instrumentação , Falha de Prótese , Stents , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Endoleak/mortalidade , Endoleak/cirurgia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Clin Breast Cancer ; 22(4): e457-e462, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34920954

RESUMO

INTRODUCTION: Diagnosis of LM is limited by low sensitivity of cerebrospinal fluid (CSF) cytopathology. Detecting tumor cells in CSF (CSF-TCs) might be more sensitive. We evaluated if CNSide (CNSide), a novel assay for tumor cell detection in CSF, can detect CSF-TCs better than conventional CSF cytology. METHODS: We enrolled adults with metastatic breast cancer and clinical suspicion for LM to undergo lumbar puncture (LP) for CSF cytopathology and CNSide. CNSide captured CSF-TCs using a primary 10-antibody mixture, streptavidin-coated microfluidic channel, and biotinylated secondary antibodies. CSF-TCs were assessed for estrogen receptor (ER) expression by fluorescent antibody and HER2 amplification by fluorescent in situ hybridization (FISH). CSF cell-free DNA (cfDNA) was extracted for next-generation sequencing (NGS). Leptomeningeal disease was defined as positive CSF cytology and/or unequivocal MRI findings. We calculated sensitivity and specificity of CSF cytology and CNSide for the diagnosis of LM. RESULTS: Ten patients, median age 51 years (range, 37-64), underwent diagnostic LP with CSF evaluation by cytology and CNSide. CNSide had sensitivity of 100% (95% Confidence Interval [CI], 40%-100%) and specificity of 83% (95% CI, 36%-100%) for LM. Among these patients, concordance of ER and HER2 status between CSF-TCs and metastatic biopsy were 60% and 75%, respectively. NGS of CSF cfDNA identified somatic mutations in three patients, including one with PIK3CA p.H1047L in blood and CSF. CONCLUSIONS: CNSide may be a viable platform to detect CSF-TCs, with potential use as a diagnostic tool for LM in patients with metastatic breast cancer. Additional, larger studies are warranted.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , Carcinomatose Meníngea , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Carcinomatose Meníngea/secundário
12.
Eur Radiol ; 21(1): 46-53, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20680287

RESUMO

OBJECTIVE: To evaluate a diffusion-weighted (DW) black blood MR sequence for the detection of myocardium signal abnormalities in patients with recent myocardial infarction (MI). METHODS: A DW black blood EPI sequence was acquired at 1.5 T in 12 patients with recent MI. One slice per patient was acquired with b=0 and b=50 s/mm2. A standard short tau inversion recovery (STIR) T2-weighted sequence was acquired at the same level. Viability was assessed with delayed-enhancement sequences. Images were analyzed qualitatively and quantitatively. A non parametric Wilcoxon test was used for statistical analysis, with a significance level of P<.05. RESULTS: The mean quality of blood suppression was higher on DW EPI images than on STIR T2-weighted images (3.9±0.3 and 3.0±0.7, respectively; P=0.01). Myocardial high signal areas were detected in respectively 100% (12/12) and 67% (8/12) of the patients on DW EPI and STIR T2-weighted images. The four patients (33%) with false-negative STIR T2 findings all had high signal areas on DW EPI images corresponding to the location of the MI on the delayed-enhanced images. CONCLUSION: DW EPI sequences are a feasible alternative to standard STIR T2-weighted sequences for detecting myocardium high signal areas in patients with recent MI.


Assuntos
Imagem de Difusão por Ressonância Magnética , Imagem Ecoplanar/métodos , Infarto do Miocárdio/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia
13.
AJR Am J Roentgenol ; 197(5): 1081-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22021499

RESUMO

OBJECTIVE: MRI has become the primary tool for assessment of myocardial inflammation in patients with suspected acute myocarditis. Optimal diagnostic performance is achieved with late gadolinium-enhanced sequences, but cine balanced steady-state free precession (SSFP) MRI sequences are routinely used to evaluate cardiac function. Our aim was to prospectively assess the diagnostic value of unenhanced and contrast-enhanced cine SSFP MRI sequences in comparison with late gadolinium-enhanced sequences for imaging of patients with strong evidence of acute myocarditis. SUBJECTS AND METHODS: Eighteen patients with strong evidence of acute myocarditis underwent 1.5-T cardiac MRI. Unenhanced and contrast-enhanced cine SSFP images and late gadolinium-enhanced images were obtained. The images were analyzed both qualitatively and quantitatively. Data were analyzed with analysis of variance and the Bonferroni test or paired Student t test. RESULTS: Areas of high signal intensity were detected in 28% (5/18), 94% (17/18), and 89% (16/18) of patients on unenhanced cine, contrast-enhanced cine, and late gadolinium-enhanced images. In one patient, contrast-enhanced cine images revealed subepicardial areas of high signal intensity that were not visible on late gadolinium-enhanced images. The location and transmural nature of involved segments matched on contrast-enhanced cine and late gadolinium-enhanced images (both, r = 0.91, p < 0.0001). The contrast-to-noise ratio was significantly higher on contrast-enhanced cine images than on late gadolinium-enhanced images (p < 0.05). CONCLUSION: Contrast-enhanced cine MRI is a valuable tool for detection of lesions of acute myocarditis and should be recommended for routine clinical MRI.


Assuntos
Imagem Cinética por Ressonância Magnética/métodos , Miocardite/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Análise de Variância , Meios de Contraste , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos , Estudos Prospectivos , Estatísticas não Paramétricas
14.
Am J Pathol ; 173(5): 1339-48, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18832580

RESUMO

Epithelial appendages, such as mammary glands and hair, arise as a result of epithelial-mesenchymal interactions. Bone morphogenetic proteins (BMPs) are important for hair follicle morphogenesis and cycling and are known to regulate a wide variety of developmental processes. For example, overexpression of BMPs inhibits hair follicle formation. We hypothesized that the down-regulation of the BMP signaling pathway in the basal epidermis expands regions that are competent to form hair follicles and could alter the fate of the epithelium in the mouse nipple to a hair-covered epidermal phenotype. To test our hypothesis, we used a transgenic mouse model in which keratin 14 (KRT14) promoter-mediated overexpression of Noggin, a BMP antagonist, modulates BMP activity. We observed the conversion of nipple epithelium into pilosebaceous units. During normal mammary gland organogenesis, BMPs are likely used by the nipple epithelium to suppress keratinocyte differentiation, thus preventing the formation of pilosebaceous units. In this report, we characterize the morphology and processes that influence the development of hairs within the nipple of the KRT14-Noggin mouse. We demonstrate that Noggin acts, in part, by reducing the BMP signal in the epithelium. Reduction of the BMP signal in turn leads to a reduction in the levels of parathyroid hormone-related protein. We propose that during evolution of the nipple, the BMP pathway was co-opted to suppress hair follicle formation and create a more functional milk delivery apparatus.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Derme/citologia , Células Epidérmicas , Células Epiteliais/citologia , Cabelo/citologia , Mamilos/citologia , Animais , Apoptose , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Derme/metabolismo , Epiderme/metabolismo , Células Epiteliais/metabolismo , Feminino , Cabelo/metabolismo , Cabelo/ultraestrutura , Folículo Piloso/citologia , Folículo Piloso/ultraestrutura , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Mamilos/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/genética , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Regiões Promotoras Genéticas/genética , Proteínas Smad/metabolismo
16.
Int J Dev Biol ; 48(2-3): 181-91, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15272383

RESUMO

The feather is a complex epidermal organ with hierarchical branches and represents a multi-layered topological transformation of keratinocyte sheets. Feathers are made in feather follicles. The basics of feather morphogenesis were previously described (Lucas and Stettenheim, 1972). Here we review new molecular and cellular data. After feather buds form (Jiang et al., this issue), they invaginate into the dermis to form feather follicles. Above the dermal papilla is the proliferating epidermal collar. Distal to it is the ramogenic zone where the epidermal cylinder starts to differentiate into barb ridges or rachidial ridge. These neoptile feathers tend to be downy and radially symmetrical. They are replaced by teleoptile feathers which tend to be bilateral symmetrical and more diverse in shapes. We have recently developed a "transgenic feather" protocol that allows molecular analyses: BMPs enhance the size of the rachis, Noggin increases branching, while anti- SHH causes webbed branches. Different feather types formed during evolution (Wu et al., this issue). Pigment patterns along the body axis or intra-feather add more colorful distinctions. These patterns help facilitate the analysis of melanocyte behavior. Feather follicles have to be connected with muscles and nerve fibers, so they can be integrated into the physiology of the whole organism. Feathers, similarly to hairs, have the extraordinary ability to go through molting cycles and regenerate. Some work has been done and feather follicles might serve as a model for stem cell research. Feather phenotypes can be modulated by sex hormones and can help elucidate mechanisms of sex hormone-dependent growth control. Thus, the developmental biology of feather follicles provides a multi-dimension research paradigm that links molecular activities and cellular behaviors to functional morphology at the organismal level.


Assuntos
Plumas/anatomia & histologia , Plumas/embriologia , Morfogênese , Animais , Evolução Biológica , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Transporte , Diferenciação Celular , Divisão Celular , Embrião de Galinha , Derme/citologia , Derme/embriologia , Células Epidérmicas , Epiderme/embriologia , Plumas/citologia , Hormônios Esteroides Gonadais/metabolismo , Proteínas Hedgehog , Queratinócitos , Melanócitos/fisiologia , Modelos Biológicos , Pigmentos Biológicos/metabolismo , Proteínas/metabolismo , Fatores Sexuais , Transativadores/metabolismo
17.
J Vasc Surg Cases ; 1(2): 102-104, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31724644

RESUMO

Abdominal aortic aneurysm rupture remains a cardiovascular catastrophe with strikingly high morbidity and mortality rates. Endovascular aneurysm repair management has recently emerged as a valuable treatment modality for ruptured abdominal aortic aneurysm, but better outcomes have to be reached. Image fusion may potentially improve perioperative outcomes in selected patients, guiding navigation and device implantation and limiting contrast dosage during interventions. We report an 83-year-old man presenting with an 80-mm infrarenal aortic aneurysm rupture suitable for endovascular aneurysm repair. Endovascular navigation and stent graft deployment were achieved using computed tomography image fusion for the first reported case in English.

18.
Amyloid ; 21(4): 246-55, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25211144

RESUMO

BACKGROUND: Most of the studies that described cardiac amyloidosis using cardiac magnetic resonance (CMR) imaging refer to patients with primary light chain (AL) amyloidosis. The goal of this study was to evaluate cardiac involvement in patients with hereditary transthyretin associated (ATTR) amyloidosis and asymptomatic carriers and its relationships with clinical symptoms and genotype, using CMR imaging. METHODS AND RESULTS: Fifty-three patients with hereditary ATTR amyloidosis and 14 asymptomatic carriers were included in this study. Morphological, functional and late gadolinium enhancement (LGE) findings were noted on CMR images. A positive LGE suggesting cardiac amyloidosis was detected in 60% of patients. The pattern of LGE was diffuse, focal and circumferential in 32, 26 and 2% of patients, respectively. The inferior basal segment was the most frequently involved (93%) in case of focal involvement. Diffuse pattern was exclusively encountered in patients with cardiac symptoms. Nineteen percent of patients with isolated neurological symptoms and 20% of subjects without left ventricular wall thickening exhibited cardiac abnormalities on CMR. CONCLUSION: Cardiac involvement can be detected in patients with hereditary ATTR amyloidosis with isolated neurological symptoms and without left ventricular wall thickening, suggesting that CMR could be useful in detecting preclinical cardiac amyloidosis.


Assuntos
Neuropatias Amiloides Familiares/fisiopatologia , Coração/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Neuropatias Amiloides Familiares/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Cancer Cell ; 26(1): 77-91, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-25026212

RESUMO

Ovarian cancer has a clear predilection for metastasis to the omentum, but the underlying mechanisms involved in ovarian cancer spread are not well understood. Here, we used a parabiosis model that demonstrates preferential hematogenous metastasis of ovarian cancer to the omentum. Our studies revealed that the ErbB3-neuregulin 1 (NRG1) axis is a dominant pathway responsible for hematogenous omental metastasis. Elevated levels of ErbB3 in ovarian cancer cells and NRG1 in the omentum allowed for tumor cell localization and growth in the omentum. Depletion of ErbB3 in ovarian cancer impaired omental metastasis. Our results highlight hematogenous metastasis as an important mode of ovarian cancer metastasis. These findings have implications for designing alternative strategies aimed at preventing and treating ovarian cancer metastasis.


Assuntos
Neoplasias Epiteliais e Glandulares/secundário , Células Neoplásicas Circulantes/patologia , Omento/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Animais , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Invasividade Neoplásica , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/prevenção & controle , Células Neoplásicas Circulantes/metabolismo , Neuregulina-1/genética , Neuregulina-1/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/terapia , Parabiose , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/prevenção & controle , Interferência de RNA , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo , Transdução de Sinais , Fatores de Tempo , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Int J Cardiol ; 164(3): 306-11, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21794940

RESUMO

BACKGROUND: To compare magnetic resonance (MR) imaging and multidetector computed tomography (MDCT) for the assessment of myocardial infarction (MI) after alcohol septal ablation (ASA). METHODS: Ten patients (mean age, 60 years ± 16) were examined with both MDCT and 1.5-T MR imaging performed 10 minutes after injection, within 3 days after ASA. Half of them had a temporary pacemaker (PM) during MDCT examination. Global image quality (IQ) and localization of MI were noticed on both MDCT and MR images. Volumes of MI, contrast-to-noise ratios (CNR) and signal-to-noise ratios (SNR) were also calculated. ASA effectiveness was evaluated by echocardiography immediately and 3 months after procedure. RESULTS: Global IQ was considered adequate for both procedures. In 8 patients, MI reached the basal part of the septum on both MDCT and MR images. The 2 remaining patients exhibited sparing of the basal septum on MDCT and MR images. Volumes of MI were within the same range with the 2 techniques (MDCT: 22.1 ± 8.8 mL; MR imaging: 23.8 ± 9.4 mL) and correlated well each other (R(2)=0.85, p<0.002). The 2 patients with sparing of the basal interventricular septum had persistent gradient on echocardiography 3 months after ASA, suggesting failure of the procedure. The volumes of MI didn't correlate with the reduction of pressure gradient on echocardiography 3 months after ASA (R(2)=0.02, p<0.05). CONCLUSIONS: Evaluation of post ASA MI is feasible with MDCT by comparison with MR imaging. MDCT might serve as an alternative imaging method in case of PM implantation.


Assuntos
Técnicas de Ablação , Cardiomiopatia Hipertrófica/cirurgia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada Multidetectores/métodos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatia Hipertrófica/diagnóstico , Etanol/uso terapêutico , Estudos de Viabilidade , Feminino , Septos Cardíacos/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Miocárdio/patologia , Necrose , Estudos Prospectivos
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