Assuntos
Placenta Acreta , Aorta Abdominal/cirurgia , Cesárea , Constrição , Feminino , Humanos , Histerectomia , Placenta Acreta/cirurgia , GravidezAssuntos
Placenta Acreta , Placenta Prévia , Cesárea , Constrição , Feminino , Humanos , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/cirurgia , GravidezRESUMO
We describe a novel surgical technique in 31 women with histopathologically confirmed placenta accreta spectrum (PAS) disorders managed by a multidisciplinary team using a prophylactic infrarenal abdominal aortic cross-clamping technique during caesarean hysterectomy. We conclude that this new surgical procedure is a relatively safe technique to potentially control operative blood loss. Our work may stimulate others to develop protocols assessing this innovative technique to improve the surgical outcome of PAS disorders.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Cesárea/métodos , Hemostasia Cirúrgica/métodos , Histerectomia/métodos , Placenta Acreta , Hemorragia Pós-Parto , Adulto , Aorta Abdominal , Cesárea/efeitos adversos , Constrição , Duração da Terapia , Feminino , Humanos , Histerectomia/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde , Equipe de Assistência ao Paciente , Placenta Acreta/diagnóstico , Placenta Acreta/cirurgia , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Taiwan , Ultrassonografia Doppler em Cores/métodosRESUMO
The temperature-dependent polarized photoluminescence spectra of nonpolar ZnO samples were investigated by 263â nm laser. The degree of polarization (DOP) of m-plane quantum wells changes from 76% at 10â K to 40% at 300â K, which is much higher than that of epilayer. The strong anisotropy was presumably attributed to the enhanced confinement effect of a one-dimension confinement structure formed by the intersection of quantum well and basal stacking fault. The polarization of laser beam also has an influence on the DOP. It is assumed that the luminescence polarization should be affected not only by the in-plane strains but also the microstructural defects, which do modify the electronic band structure.
RESUMO
The NF-κB transcription factor has a central role in diverse processes, including inflammation, proliferation and cell survival, and its activity is dysregulated in diseases such as autoimmunity and cancer. We recently identified the TRE17/ubiquitin-specific protease 6 (USP6) oncogene as the first de-ubiquitinating enzyme to activate NF-κB. TRE17/USP6 is translocated and overexpressed in aneurysmal bone cyst (ABC), a pediatric tumor characterized by extensive bone degradation and inflammatory recruitment. In the current study, we explore the mechanism by which TRE17 induces activation of NF-κB, and find that it activates the classical NF-κB pathway through an atypical mechanism that does not involve IκB degradation. TRE17 co-precipitates with IκB kinase (IKK), and IKK activity is augmented in stable cell lines overexpressing TRE17, in a USP-dependent manner. Optimal activation of NF-κB by TRE17 requires both catalytic subunits of IKK, distinguishing its mechanism from the classical and non-canonical pathways, which require either IKKß or IKKα, respectively. TRE17 stimulates phosphorylation of p65 at serine 536, a modification that has been associated with enhanced transcriptional activity and nuclear retention. Induction of S536 phosphorylation by TRE17 requires both IKKα and IKKß, as well as the IKKγ/NEMO regulatory subunit of IKK. We further demonstrate that TRE17(long) is highly tumorigenic when overexpressed in NIH3T3 fibroblasts, and that inhibition of NF-κB significantly attenuates tumor formation. In summary, these studies uncover an unexpected signaling mechanism for activation of classical NF-κB by TRE17. They further reveal a critical role for NF-κB in TRE17-mediated tumorigenesis, and suggest that NF-κB inhibitors may function as effective therapeutic agents in the treatment of ABC.
Assuntos
Transformação Celular Neoplásica/metabolismo , NF-kappa B/metabolismo , Fragmentos de Peptídeos/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina Tiolesterase/metabolismo , Animais , Células HeLa , Humanos , Quinase I-kappa B/metabolismo , Camundongos , Camundongos Nus , Células NIH 3T3 , Serina/metabolismoRESUMO
Aneurysmal bone cyst (ABC) is an aggressive, pediatric bone tumor characterized by extensive destruction of the surrounding bone. Although first described over 60 years ago, its molecular etiology remains poorly understood. Recent work revealed that ABCs harbor translocation of TRE17/USP6, leading to its transcriptional upregulation. TRE17 encodes a ubiquitin-specific protease (USP), and a TBC domain that mediates binding to the Arf6 GTPase. However, the mechanisms by which TRE17 overexpression contributes to tumor pathogenesis, and the role of its USP and TBC domains, are unknown. ABCs are characterized by osteolysis, inflammatory recruitment and extensive vascularization, the processes in which matrix proteases have a prominent role. This led us to explore whether TRE17 regulates the production of matrix metalloproteinases (MMPs). In this study we show that TRE17 is sufficient to induce expression of MMP-9 and MMP-10, in a manner requiring its USP activity, but not its ability to bind Arf6. TRE17 induces transcription of MMP-9 through activation of nuclear factor-kappaB (NF-kappaB), mediated in part by the GTPase RhoA and its effector kinase, ROCK. Furthermore, xenograft studies show that TRE17 induces formation of tumors that reproduce multiple features of ABC, including a high degree of vascularization, with an essential role for the USP domain. In sum, these studies reveal that TRE17 is sufficient to initiate tumorigenesis, identify MMPs as novel TRE17 effectors that likely contribute to ABC pathogenesis and define the underlying signaling mechanism of their induction.
Assuntos
Cistos Ósseos Aneurismáticos/metabolismo , Metaloproteinases da Matriz/biossíntese , NF-kappa B/metabolismo , Oncogenes , Proteínas Proto-Oncogênicas/metabolismo , Ubiquitina Tiolesterase/metabolismo , Animais , Cistos Ósseos Aneurismáticos/enzimologia , Cistos Ósseos Aneurismáticos/genética , Cistos Ósseos Aneurismáticos/patologia , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Camundongos , Estrutura Terciária de Proteína , Transporte Proteico , Proteínas Proto-Oncogênicas/química , Transdução de Sinais , Transcrição Gênica , Ubiquitina Tiolesterase/química , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Visfatin is an adipokine that is highly expressed in visceral fat. Plasma levels of visfatin have been reported to be higher in subjects with obesity and/or type 2 diabetes mellitus. However, the role of visfatin in endothelial dysfunction has been largely unexplored. OBJECTIVES: We investigated the possible pathogenic role of visfatin in endothelial dysfunction, particularly focusing on its effect on inflammatory mediators. DESIGN: Primary human umbilical vein endothelial cells (HUVECs) pretreated with visfatin (1, 10 and 50 ng ml(-1)) were used to study the relationship between visfatin and endothelium dysfunction. Expressions of adhesion molecules (ICAM-1, VCAM-1 and E-selectin) and cytokines (interleukin (IL)-6 and IL-8) affected by visfatin were investigated by enzyme-linked immunosorbent assay, flow cytometry and real-time PCR. Activity of nuclear factor (NF)-kappaB was examined by electrophoretic mobility shift assay. RESULTS: At a visfatin concentration of 50 ng ml(-1), significant increases in IL-6, IL-8, ICAM-1, VCAM-1 and E-selectin gene expression along with increased IL-6, IL-8 and sE-selectin protein levels in the conditioned medium were detected. Flow cytometry showed that the addition of visfatin significantly increased ICAM-1 expression and VCAM-1 expression (10 and 50 ng ml(-1), respectively). Electrophoretic mobility shift assay confirmed that visfatin increased the DNA-binding activity of NF-kappaB. In addition, pretreatment with visfatin (10 and 50 ng ml(-1)) increased human monocyte cell line THP-1 adhesion to HUVECs. CONCLUSIONS: Our findings suggest that visfatin causes endothelial dysfunction by increasing inflammatory and adhesion molecule expression at least partly through the upregulation of NF-kappaB activity.
Assuntos
Moléculas de Adesão Celular/metabolismo , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Nicotinamida Fosforribosiltransferase/farmacologia , Células Cultivadas , Selectina E/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , NF-kappa B/metabolismo , Veias Umbilicais/citologia , Regulação para Cima/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismoAssuntos
Complicações na Gravidez/diagnóstico , Gravidez Múltipla , Ruptura Uterina/diagnóstico , Adulto , Feminino , Humanos , Leiomioma/cirurgia , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias , Gravidez , Complicações na Gravidez/diagnóstico por imagem , Gêmeos , Ultrassonografia Pré-Natal , Neoplasias Uterinas/cirurgia , Ruptura Uterina/diagnóstico por imagemRESUMO
Placenta accreta is a pregnancy complication characterized by the presence of life-threatening uteroplacental neovascularization. The factors involving its development are unknown. Vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and their receptors (VEGFR) have important roles in vascular remodeling. We have investigated the differential expression of these proteins in placentae from placenta accreta (cases) and normal placentation (controls). Immunohistochemically, the expression of VEGFR-2 in the syncytiotrophoblast was significantly lower in cases than in controls during both the second and third trimesters (P = 0.005 and 0.002, respectively). However, VEGFR-2 expression in the cytotrophoblastic and extravillous trophoblastic cells and VEGFR-1, -3 and Ki-67 in the trophoblast populations were not significantly different between controls and cases (P > 0.05). Ki-67 immunostaining also showed that endothelial cells of the larger vessels were stained weaker in normal placenta than in placenta accreta. The majority of VEGFR-2 expression, as demonstrated by Western blot or reverse transcription polymerase chain reaction, was consistent with the immunohistochemical findings in the syncytiotrophoblast. Furthermore, enzyme-linked immunosorbent assay in the placental lysates showed that the women with placenta accreta demonstrated significantly higher VEGF (P = 0.001) and lower soluble VEGFR-2 (P = 0.015) concentrations than did women with normal pregnancy. PlGF and soluble VEGFR-1 levels did not show any significance in study groups (P > 0.05). These observations suggest that the participation of up-regulated VEGF and down-regulated VEGFR-2 (both membrane-bound and soluble forms) may be associated with the development of placenta accreta.
Assuntos
Regulação da Expressão Gênica , Placenta Acreta/metabolismo , Proteínas da Gravidez/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Fator de Crescimento Placentário , Gravidez , Proteínas da Gravidez/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/genéticaAssuntos
Doenças Fetais/diagnóstico por imagem , Fibrossarcoma/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias Torácicas/diagnóstico por imagem , Ultrassonografia Pré-Natal , Axila , Diagnóstico Diferencial , Feminino , Fibrossarcoma/congênito , Humanos , Gravidez , Neoplasias Torácicas/congênito , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler de PulsoRESUMO
A case of fetal axillary hemangiolymphangioma coexisting with intralesional hemorrhage is presented. At 27 weeks' gestation, the fetus was found to have a 52 x 43-mm left axillary multilocular cystic mass which showed no signals on color Doppler. The mass was composed mostly of sonolucent spaces. At 29 weeks' gestation, an arterial flow signal (15 cm/s) was detected within the mass. In addition, two low-density echogenic cystic spaces with bidirectional flow waveforms were found, which raised the suspicion of intratumoral bleeding. Two weeks later, a fine-needle aspiration of the mass revealed both straw-colored and chocolate-colored fluid. The tumor size increased from 52 x 43 mm at 27 weeks to 100 x 79 mm at 37 weeks. Blood clots developed gradually in the hemorrhagic spaces. The pregnancy proceeded smoothly to term and at 38 weeks an elective Cesarean section was performed. After a surgical excision of the mass at the age of 4 days, a mixed cavernous hemangioma and cystic lymphangioma with secondary intralesional hemorrhage was confirmed histopathologically.
Assuntos
Doenças Fetais/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Hemorragia/etiologia , Linfangioma/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Braço/diagnóstico por imagem , Braço/patologia , Axila/diagnóstico por imagem , Axila/patologia , Feminino , Doenças Fetais/patologia , Hemangioma/complicações , Hemangioma/patologia , Hemorragia/diagnóstico por imagem , Humanos , Linfangioma/complicações , Linfangioma/patologia , Gravidez , Neoplasias Torácicas/diagnóstico por imagem , Neoplasias Torácicas/patologiaRESUMO
Rho family GTPases Rac and Cdc42 are pivotal regulators of apoptosis in multiple cell types. However, little is known about the mechanism by which these GTPases are regulated in response to apoptotic stimuli. Here, we demonstrate that TIAM1, a Rac-specific guanine nucleotide exchange factor, is cleaved by caspases during apoptosis. TIAM1 cleavage occurs in multiple cell lines in response to diverse apoptotic stimuli such as ceramide, Fas, and serum deprivation. Processing occurs at residue 993 of TIAM1 and removes the NH(2)-terminal of TIAM's two pleckstrin homology domains, leaving a stable fragment containing the Dbl homology and COOH-terminal pleckstrin homology domains. This leads to functional inactivation of TIAM1, as determined by failure of the cleavage product to stimulate GTP loading of Rac in vivo. Furthermore, this product is defective in signaling to two independent Rac effectors, c-Jun NH(2)-terminal kinase and serum response factor. Finally, we demonstrate that in cells treated with ceramide, cleavage of TIAM1 coincided with the inactivation of endogenous Rac. These results reveal a novel mechanism for regulating guanine nucleotide exchange factor activity and GTPase-mediated signaling pathways.
Assuntos
Apoptose , Caspases/metabolismo , Proteínas/metabolismo , Células 3T3 , Animais , Sítios de Ligação , Proteínas Sanguíneas/química , Células COS , Linhagem Celular , Membrana Celular/metabolismo , Ceramidas/metabolismo , Ceramidas/farmacologia , Ativação Enzimática , GTP Fosfo-Hidrolases/metabolismo , Fatores de Troca do Nucleotídeo Guanina , Humanos , Immunoblotting , Proteínas Quinases JNK Ativadas por Mitógeno , Células Jurkat , Luciferases/metabolismo , Camundongos , Microscopia de Fluorescência , Proteína Quinase 8 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas de Neoplasias , Células PC12 , Fosfoproteínas/química , Testes de Precipitina , Estrutura Terciária de Proteína , Ratos , Fator de Resposta Sérica/metabolismo , Transdução de Sinais , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , Fatores de Tempo , Células Tumorais Cultivadas , Proteínas rac de Ligação ao GTP/metabolismoRESUMO
A case of placenta previa increta/percreta was diagnosed at 18 weeks' gestation with the 3-dimensional color power Doppler imaging technique. Unusually extensive uteroplacental vascular network architecture was seen on the 3-dimensional angiohistogram. After appropriate counseling, the patient chose to terminate the pregnancy. A hysterectomy was performed with prophylactic preoperative embolization of internal iliac arteries at 21 weeks' gestation, and histopathologic examination revealed placenta previa increta/percreta. This new 3-dimensional angiohistogram technique allowed us to visualize all 3 orthogonal planes of the angioarchitectural information. It appears to be a useful complementary tool and is likely to play a more defining and clarifying role in assessing the quantification of abnormal uteroplacental neovascularization for patients with placenta previa increta/percreta.
Assuntos
Imageamento Tridimensional , Neovascularização Patológica/diagnóstico por imagem , Placenta Prévia/diagnóstico por imagem , Placenta Prévia/fisiopatologia , Placenta/irrigação sanguínea , Ultrassonografia Doppler em Cores , Útero/irrigação sanguínea , Adulto , Angiografia Digital , Feminino , Humanos , Placenta/diagnóstico por imagem , Gravidez , Útero/diagnóstico por imagemRESUMO
Enteric duplications are rare lesions, and relatively few cases have been diagnosed prenatally. We present, to our knowledge, the first case of an associated communicating ileal duplication cyst in a huge omphalocele diagnosed prenatally. The prenatal ultrasound findings revealed four features of the cystic lesion including peristaltic movements of the cystic wall, communication between the cyst and normal bowel lumen, intra-cystic echogenic contents, and echogenic mesenteric tissue (fat) close to the cyst. These distinct characteristics helped us to make a firm in utero diagnosis.
Assuntos
Doenças Fetais/diagnóstico por imagem , Hérnia Umbilical/diagnóstico por imagem , Doenças do Íleo/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Cistos/diagnóstico por imagem , Cistos/cirurgia , Diagnóstico Diferencial , Feminino , Doenças Fetais/cirurgia , Hérnia Umbilical/cirurgia , Humanos , Doenças do Íleo/cirurgia , Recém-Nascido , Masculino , GravidezAssuntos
Regulação Enzimológica da Expressão Gênica , Proteínas Quinases/genética , Proteínas Quinases S6 Ribossômicas/genética , Transdução de Sinais , Animais , Anticorpos , Células Cultivadas , Immunoblotting , Oócitos , Fosforilação , Testes de Precipitina , Proteínas Quinases/imunologia , Proteínas Quinases/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Quinases S6 Ribossômicas/imunologia , Proteínas Quinases S6 Ribossômicas/metabolismo , Xenopus laevis , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: The perinatal management of congenital complete heart block (CCHB) remains controversial. The purpose of this study was to present a therapeutic modality for CCHB. METHODS: We collected retrospective cases of all pregnant women admitted to our hospital between January 1992 and June 1999 whose babies developed CCHB antenatally. After a series of examinations, maternal, fetal and neonatal data were analyzed. RESULTS: Nine fetuses from six mothers (cases 1-6) in nine different pregnancies were studied. In case 1, both consecutive fetuses had CCHB and in case 2, all three consecutive fetuses had CCHB. The other mothers (cases 3-6) had only one fetus each with CCHB. Of the seven fetuses with isolated CCHB, four underwent observation only due to late-onset, or nonimmunologic CCHB, two received dexamethasone and/or intravenous immunoglobulin therapy because of the presence of hydropic signs, and one received dexamethasone at 23 weeks' gestation due to early-onset CCHB. Shortening fractions of the right ventricle had good compensation in four fetuses, without any treatment, and improving compensation in two of three fetuses receiving dexamethasone therapy. All seven fetuses were delivered smoothly and pacemakers were implanted shortly after birth. Two other fetuses had a poor outcome due to associated ventricular septal defect or hemoglobin Bart's disease. Furthermore, we gave dexamethasone (2 mg/day) instead of prednisolone (10 mg/day) for the next pregnancies of patients 3 to 5, beginning at 12 weeks of gestation. No fetal CCHB developed again. CONCLUSIONS: For pregnant women with previous fetal immunologic CCHB, early initiation of dexamethasone instead of prednisolone might be effective to cross the placenta and avoid recurrences. Dexamethasone is also effective for fetal CCHB of early onset, fetal hydrops or heart failure. Observation only is suggested for nonimmunologic CCHB and remote or late-onset immunologic CCHB. Other modalities were tried for very sick fetuses, but their effectiveness was not predictable.
Assuntos
Bloqueio Cardíaco/congênito , Adulto , Dexametasona/uso terapêutico , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/terapia , Humanos , Recém-Nascido , Gravidez , Estudos RetrospectivosRESUMO
A case of mixed intrahepatic arteriovenous shunts in a fetus diagnosed at 35 weeks' gestation is presented. Color Doppler ultrasonography in the fetal liver demonstrated complicated vascular connections fed by the hepatic arterial branches and drained into the portal and middle hepatic veins. Pulsed Doppler ultrasonography identified a high cardiac output state by the detection of increased flow velocities of the great vessels. The contribution of Doppler ultrasonography to hemodynamic changes is highlighted. The management is briefly discussed.
Assuntos
Malformações Arteriovenosas/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Artéria Hepática/anormalidades , Veias Hepáticas/anormalidades , Ultrassonografia Doppler de Pulso , Ultrassonografia Pré-Natal , Velocidade do Fluxo Sanguíneo , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/etiologia , Ecocardiografia , Feminino , Artéria Hepática/diagnóstico por imagem , Veias Hepáticas/diagnóstico por imagem , Humanos , Recém-Nascido , Veia Porta/anormalidades , Veia Porta/diagnóstico por imagem , Gravidez , Ultrassonografia Doppler em CoresRESUMO
OBJECTIVE: The aim of this study was to evaluate the efficacy of transabdominal color Doppler ultrasound in diagnosing placenta previa accreta. DESIGN: Eighty patients with persistent placenta previa underwent transabdominal B-mode and color Doppler ultrasound evaluation in the second and third trimesters because they had a high risk of placenta accreta. Color Doppler imaging criteria used included diffuse intraparenchymal placental lacunar flow; focal intraparenchymal placental lacunar flow; bladder-uterine serosa interphase hypervascularity; prominent subplacental venous complex; and loss of subplacental Doppler vascular signals. The color Doppler images were interpreted prospectively for signs of placenta previa accreta according to the exhibited color Doppler sonographic features. RESULTS: Sixteen of the 80 patients exhibited characteristic color Doppler imaging patterns highly specific for placenta accreta according to the preceding criteria, and 14 of these had histopathological proof of placenta accreta. Two patients had false-positive color Doppler imaging evidence mistaken for interphase hypervascularity caused by bladder varices. Thirteen patients underwent hysterectomy in the group suspicious for accreta. Of the 64 patients with negative color Doppler imaging results, three had placenta accreta, while two required cesarean hysterectomy; the remaining patient underwent uterine artery ligation for bleeding from the lower uterine segment. The sensitivity of color Doppler imaging in the diagnosis of placenta previa accreta was 82.4% (14/17) and the specificity was 96.8% (61/63). The positive and negative predictive values were 87.5% (14/16) and 95.3% (61/64), respectively. CONCLUSIONS: Variable vascular morphological patterns of placenta previa accreta were exhibited and categorized by transabdominal color Doppler sonography in the antenatal period. The identification of these specific vascular patterns had a positive impact on the peripartum clinical management of the affected patients.