Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 320
Filtrar
Más filtros

Intervalo de año de publicación
1.
Cell ; 157(5): 1160-74, 2014 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-24855951

RESUMEN

Developmental signaling is remarkably robust to environmental variation, including temperature. For example, in ectothermic animals such as Drosophila, Notch signaling is maintained within functional limits across a wide temperature range. We combine experimental and computational approaches to show that temperature compensation of Notch signaling is achieved by an unexpected variety of endocytic-dependent routes to Notch activation which, when superimposed on ligand-induced activation, act as a robustness module. Thermal compensation arises through an altered balance of fluxes within competing trafficking routes, coupled with temperature-dependent ubiquitination of Notch. This flexible ensemble of trafficking routes supports Notch signaling at low temperature but can be switched to restrain Notch signaling at high temperature and thus compensates for the inherent temperature sensitivity of ligand-induced activation. The outcome is to extend the physiological range over which normal development can occur. Similar mechanisms may provide thermal robustness for other developmental signals.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Endocitosis , Proteínas de la Membrana/metabolismo , Receptores Notch/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Regulación hacia Abajo , Drosophila melanogaster/citología , Drosophila melanogaster/metabolismo , Transducción de Señal , Temperatura
2.
Cell ; 145(7): 1049-61, 2011 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-21703449

RESUMEN

Atf1, the fission yeast homolog of activation transcription factor-2 (ATF-2), contributes to heterochromatin formation. However, the role of ATF-2 in chromatin assembly in higher organisms remains unknown. This study reveals that Drosophila ATF-2 (dATF-2) is required for heterochromatin assembly, whereas the stress-induced phosphorylation of dATF-2, via Mekk1-p38, disrupts heterochromatin. The dATF-2 protein colocalized with HP1, not only on heterochromatin but also at specific loci in euchromatin. Heat shock or osmotic stress induced phosphorylation of dATF-2 and resulted in its release from heterochromatin. This heterochromatic disruption was an epigenetic event that was transmitted to the next generation in a non-Mendelian fashion. When embryos were exposed to heat stress over multiple generations, the defective chromatin state was maintained over multiple successive generations, though it gradually returned to the normal state. The results suggest a mechanism by which the effects of stress are inherited epigenetically via the regulation of a tight chromatin structure.


Asunto(s)
Factor de Transcripción Activador 2/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/genética , Heterocromatina/metabolismo , Factor de Transcripción Activador 2/análisis , Factor de Transcripción Activador 2/genética , Animales , Proteínas de Drosophila/análisis , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Epigenómica , Eucromatina/metabolismo , Femenino , Heterocromatina/química , Quinasa 1 de Quinasa de Quinasa MAP/metabolismo , Masculino , Mutagénesis , Fosforilación , Transducción de Señal , Estrés Fisiológico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
3.
Proc Natl Acad Sci U S A ; 119(15): e2110256119, 2022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-35394865

RESUMEN

Estrogen receptor α (ERα) is a transcription factor that induces cell proliferation and exhibits increased expression in a large subset of breast cancers. The molecular mechanisms underlying the up-regulation of ERα activity, however, remain poorly understood. We identified FK506-binding protein 52 (FKBP52) as a factor associated with poor prognosis of individuals with ERα-positive breast cancer. We found that FKBP52 interacts with breast cancer susceptibility gene 1 and stabilizes ERα, and is essential for breast cancer cell proliferation. FKBP52 depletion resulted in decreased ERα expression and proliferation in breast cancer cell lines, including MCF7-derived fulvestrant resistance (MFR) cells, suggesting that inhibiting FKBP52 may provide a therapeutic effect for endocrine therapy­resistant breast cancer. In contrast, FKBP51, a closely related molecule to FKBP52, reduced the stability of ERα. Consistent with these findings, FKBP51 was more abundantly expressed in normal tissues than in cancer cells, suggesting that these FKBPs may function in the opposite direction. Collectively, our study shows that FKBP52 and FKBP51 regulate ERα stability in a reciprocal manner and reveals a regulatory mechanism by which the expression of ERα is controlled.


Asunto(s)
Neoplasias de la Mama , Receptor alfa de Estrógeno , Proteínas de Unión a Tacrolimus , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Estabilidad Proteica , Proteínas de Unión a Tacrolimus/metabolismo
4.
Circ J ; 88(4): 451-459, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-36754386

RESUMEN

BACKGROUND: This study investigated the impact and predictive factors of concomitant significant tricuspid regurgitation (TR) and evaluated the roles of right ventricle (RV) function and the etiology of TR in the clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI).Methods and Results: We assessed grading of TR severity, TR etiology, and RV function in pre- and post-TAVI transthoracic echocardiograms for 678 patients at Keio University School of Medicine. TR etiology was divided into 3 groups: primary TR, ventricular functional TR (FTR), and atrial FTR. The primary outcomes were all-cause and cardiovascular death. At baseline, moderate or greater TR was found in 55 (8%) patients and, after adjustment for comorbidities, was associated with increased all-cause death (hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.19-3.77; P=0.011) and cardiovascular death (HR 2.29; 95% CI 1.06-4.99; P=0.036). RV dysfunction (RVD) also remained an independent predictor of cardiovascular death (HR 2.06; 95% CI 1.03-4.14; P=0.042). Among the TR etiology groups, patients with ventricular FTR had the lowest survival rate (P<0.001). Patients with persistent RVD after TAVI had a higher risk of cardiovascular death than those with a normal or recovered RV function (P<0.001). CONCLUSIONS: The etiology of TR and RV function play an important role in predicting outcomes in concomitant TR patients undergoing TAVI.


Asunto(s)
Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Insuficiencia de la Válvula Tricúspide , Disfunción Ventricular Derecha , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Insuficiencia de la Válvula Tricúspide/cirugía , Resultado del Tratamiento , Disfunción Ventricular Derecha/etiología , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/cirugía , Estudios Retrospectivos , Válvula Aórtica/cirugía
5.
Ann Vasc Surg ; 100: 128-137, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38122978

RESUMEN

BACKGROUND: Although open surgical repair (OSR) is the gold standard for treating arch aneurysms, thoracic endovascular aortic repair (TEVAR) may be a less invasive alternative. However, it remains unclear which of the 2 methods yields better outcomes. In this study, we compared the perioperative outcomes of both procedures for arch aneurysms using a nationwide surgical database. METHODS: Data of patients who underwent elective aortic repair for true arch aneurysms were extracted from the National Clinical Database of Japan. Patients who underwent OSR and Zone 0/1 TEVAR were matched in a 1:1 ratio using propensity scores and their mortality and morbidity rates were compared. RESULTS: A total of 2,815 and 1,125 patients underwent OSR and Zone 0/1 TEVAR, respectively. After propensity score matching, 1,058 patients were included in both groups. Compared with OSR, Zone 0/1 TEVAR was associated with a significantly higher incidence of stroke (5.8 vs. 10.0%, P < 0.001) and paraplegia/paraparesis (1.6 vs. 4.4%, P < 0.001). However, there were no significant differences in the 30-day and operative mortality rates between the 2 groups (2.2 vs. 2.7% and 4.5 vs. 5.4%, respectively). In the Zone 0/1 TEVAR group, postoperative computed tomography was performed in 92.4% of patients, and types I and III endoleaks were identified in 6.4% and 1.1% of patients, respectively. CONCLUSIONS: Zone 0/1 TEVAR has higher incidences of stroke and paraplegia/paraparesis than OSR, with a risk of postoperative endoleaks. Resolving these problems is the key for expanding the application of Zone 0/1 TEVAR and in the meantime OSR remains the gold standard for surgically fit patients.


Asunto(s)
Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Reparación Endovascular de Aneurismas , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Puntaje de Propensión , Endofuga/etiología , Japón , Resultado del Tratamiento , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Paraplejía/etiología , Paraparesia/complicaciones , Paraparesia/cirugía , Estudios Retrospectivos
6.
BMC Ophthalmol ; 24(1): 219, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38783230

RESUMEN

PURPOSE: Vitreous humor (VH) is used for postmortem biochemical studies because it is well protected in an uncontaminated state even after death. The goal of this research was to investigate electrolyte concentrations in the VH from human eyes with and without a history of vitrectomy surgery. METHODS: We analyzed the sodium (Na), potassium (K), chloride (Cl) and magnesium (Mg) concentrations from 34 VH samples from 34 patients. Eleven samples were from eyes with a history of vitrectomy, and the remaining 23 eyes had no history of vitrectomy. The correlations of Na, K, Cl and Mg concentrations with patient age, interval between first and second vitrectomy, and lens status (history of cataract surgery) were also evaluated. RESULTS: The Na, K, Cl and Mg concentrations in VH from vitrectomized eyes were 134.1 ± 7.9 mmol/L, 3.7 ± 0.2 mmol/L, 99.7 ± 6.7 mmol/L and 0.59 ± 0.09 mmol/L, respectively; all were significantly lower than the corresponding concentrations in VH from control eyes (lower by 5.0%, 11.0%, 11.7%, and 22.6%, respectively). Na, K, Cl and Mg concentrations in VH from vitrectomized eyes did not show significant correlations with patient ages or the interval between their first and second vitrectomies. There were no significant differences in Na, K, Cl and Mg concentrations in VH between phakic eyes and intraocular lens-implanted eyes. CONCLUSIONS: With the increasing number of vitrectomies being performed, it is necessary to consider the history of vitrectomy when using a subject's VH in forensic examination.


Asunto(s)
Vitrectomía , Cuerpo Vítreo , Humanos , Cuerpo Vítreo/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto , Electrólitos/análisis , Medicina Legal/métodos , Sodio/análisis , Potasio/análisis , Magnesio/análisis
7.
Circulation ; 145(14): 1056-1066, 2022 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-35209732

RESUMEN

BACKGROUND: We reviewed the results of endovascular aneurysm repair in patients from the Japanese Committee for Stentgraft Management registry to determine the significance of persistent type II endoleak (p-T2EL) and the risk of late adverse events, including aneurysm sac enlargement. METHODS: The prospectively captured medical records of 17 099 patients <75 years of age who underwent endovascular aneurysm repair for abdominal aortic aneurysm from 2006 to 2015 were reviewed. Patients were divided into 2 groups (with or without p-T2EL) and compared to examine the correlation between p-T2EL and the occurrence of aneurysm sac enlargement after endovascular aneurysm repair. RESULTS: Of the patients, 4957 (29.0%) had p-T2EL and 12 142 (71.0%) had no p-T2EL (non-T2EL). Mean age was significantly higher (P<0.001), and there were fewer men (P<0.001) in the p-T2EL group. Among comorbidities, hypertension (P=0.019) and chronic kidney disease (P=0.040) were more prevalent and respiratory disorders were less prevalent (P<0.001) in the p-T2EL group. From each group, 4957 patients were matched according to propensity score to adjust for differences in patient characteristics. The cumulative incidence rates of abdominal aortic aneurysm-related mortality (p-T2EL: 52 of 4957 [1.0%] versus non-T2EL: 21 of 12 142 [0.2%]), rupture (p-T2EL: 38 of 4957 [0.8%] versus non-T2EL: 13 of 12 142 [0.1%]), sac enlargement (≥5 mm; p-T2EL: 1359 of 4957 [27.4%] versus non-T2EL: 332 of 12 142 [2.7%]), and reintervention (p-T2EL: 739 of 4957 [14.9%] versus non-T2EL: 91 of 12 142 [0.7%]) were significantly higher in the p-T2EL than the nonpT2EL group (P<0.001). Propensity score matching yielded higher estimated incremental risk, including abdominal aortic aneurysm-related mortality, rupture, sac enlargement (≥5 mm), and reintervention for p-T2EL (P<0.001). Cox regression analysis revealed older age (P=0.010), proximal neck diameter (P=0.003), and chronic kidney disease (P<0.001) as independent positive predictors and male sex as an independent negative predictor (P=0.015) of sac enlargement. CONCLUSIONS: The Japanese Committee for Stentgraft Management registry data show a correlation between p-T2EL and late adverse events, including aneurysm sac enlargement, reintervention, rupture, and abdominal aortic aneurysm-related mortality after endovascular aneurysm repair. Besides p-T2EL, older age, female sex, chronic kidney disease, and dilated proximal neck were associated with sac enlargement.


Asunto(s)
Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Embolización Terapéutica/efectos adversos , Endofuga/epidemiología , Endofuga/etiología , Endofuga/cirugía , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Japón/epidemiología , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
8.
Nucleic Acids Res ; 49(13): 7298-7317, 2021 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-34226921

RESUMEN

Although ribosome-profiling and translation initiation sequencing (TI-seq) analyses have identified many noncanonical initiation codons, the precise detection of translation initiation sites (TISs) remains a challenge, mainly because of experimental artifacts of such analyses. Here, we describe a new method, TISCA (TIS detection by translation Complex Analysis), for the accurate identification of TISs. TISCA proved to be more reliable for TIS detection compared with existing tools, and it identified a substantial number of near-cognate codons in Kozak-like sequence contexts. Analysis of proteomics data revealed the presence of methionine at the NH2-terminus of most proteins derived from near-cognate initiation codons. Although eukaryotic initiation factor 2 (eIF2), eIF2A and eIF2D have previously been shown to contribute to translation initiation at near-cognate codons, we found that most noncanonical initiation events are most probably dependent on eIF2, consistent with the initial amino acid being methionine. Comprehensive identification of TISs by TISCA should facilitate characterization of the mechanism of noncanonical initiation.


Asunto(s)
Codón Iniciador , Factor 2 Eucariótico de Iniciación/metabolismo , Iniciación de la Cadena Peptídica Traduccional , Biología Computacional/métodos , Factor 3 de Iniciación Eucariótica/metabolismo , Células HEK293 , Humanos , Sistemas de Lectura Abierta , Huella de Proteína , Proteómica , Análisis de Secuencia de ARN
9.
J Artif Organs ; 26(2): 151-155, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35906510

RESUMEN

Implantation of left ventricular assist device (LVAD) for arrhythmogenic right ventricular (RV) cardiomyopathy is challenging associated with small LV cavity, laterally dislocated LV apex, thin and fragile RV free wall. A 43-year-old male with more than 10 years of medical treatment developed congestive heart failure related to biventricular failure. Durable LVAD was indicated to prevent further deterioration of the RV function, which would be exacerbated by progression of LV dysfunction. To simulate surgery, we printed-out a 3D heart model based on enhanced CT scanning study to identify the optimal coring position in the LV apex, by which the inflow directs the mitral valve. We then found that the mini-cuff of the HeartMate3 should be fixed in the paper-thin RV free wall by the usual cuff-sewing method. In the surgery, after the coring as planned, 5 pairs of interrupted sutures on the medial side were passed from the luminal side of the LV and then to the mini-cuff, and the lateral side of the mini-cuff was fixed with a continuous sutures, not to sew into the RV wall. The surgery was completed without complications with a good hemodynamics. The 3D heart model facilitated this unique method, indicating a usefulness of printed-out heart model for cases with unusual cardiac anatomy, which needs implantation of durable LVAD.


Asunto(s)
Displasia Ventricular Derecha Arritmogénica , Insuficiencia Cardíaca , Corazón Auxiliar , Disfunción Ventricular Izquierda , Disfunción Ventricular Derecha , Masculino , Humanos , Adulto , Displasia Ventricular Derecha Arritmogénica/cirugía , Displasia Ventricular Derecha Arritmogénica/complicaciones , Corazón Auxiliar/efectos adversos , Insuficiencia Cardíaca/cirugía , Disfunción Ventricular Izquierda/complicaciones , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Disfunción Ventricular Derecha/etiología , Función Ventricular Derecha
10.
BMC Biol ; 20(1): 65, 2022 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-35264151

RESUMEN

BACKGROUND: Ubiquitylation of the ligands and the receptor plays an important part in the regulation of the activity of the evolutionary conserved Notch signalling pathway. However, its function for activation of Notch is not completely understood, despite the identification of several E3 ligases devoted to the receptor. RESULTS: Here we analysed a variant of the Notch receptor where all lysines in its intracellular domain are replaced by arginines. Our analysis of this variant revealed that ubiquitylation of Notch is not essential for its endocytosis. We identified two functions for ubiquitylation of lysines in the Notch receptor. First, it is required for the degradation of free Notch intracellular domain (NICD) in the nucleus, which prevents a prolonged activation of the pathway. More importantly, it is also required for the incorporation of Notch into intraluminal vesicles of maturing endosomes to prevent ligand-independent activation of the pathway from late endosomal compartments. CONCLUSIONS: The findings clarify the role of lysine-dependent ubiquitylation of the Notch receptor and indicate that Notch is endocytosed by several independent operating mechanisms.


Asunto(s)
Proteínas de Drosophila , Receptores Notch , Proteínas de Drosophila/metabolismo , Endocitosis/fisiología , Ligandos , Receptores Notch/metabolismo , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
11.
Cardiol Young ; 33(9): 1763-1764, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36997311

RESUMEN

Re-expansion pulmonary edema is a serious complication that can occur after minimally invasive cardiac surgery through a right mini-thoracotomy. Herein, we describe two paediatric cases where re-expansion pulmonary edema was observed after simple atrial septal defect closure through a right mini-thoracotomy. This is the first case report of re-expansion pulmonary edema after a paediatric cardiac surgery.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Defectos del Tabique Interatrial , Edema Pulmonar , Cirugía Torácica , Humanos , Niño , Edema Pulmonar/diagnóstico , Edema Pulmonar/etiología , Edema Pulmonar/terapia , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/complicaciones , Toracotomía/efectos adversos
12.
J Artif Organs ; 25(2): 174-177, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34056668

RESUMEN

The MitraClip system is used for patients with severe mitral regurgitation (MR) who are at high risk for open surgery. However, some patients need surgical revision for various complications. The acute outcome of MitraClip treatment for atrial functional MR (aFMR) is scarcely reported. Herein, we describe a rare case of an 80-year-old woman treated with a MitraClip for aFMR with mitral annular dilatation and failed leaflet adaptation. The patient suffered from single leaflet device attachment (SLDA) and posterior leaflet injury 3 days posttreatment. The patient successfully underwent mitral valve replacement. The postoperative pulmonary hypertension was markedly improved and the left atrial volume was reduced. A MitraClip should be carefully used for aFMR with mitral annular dilatation and failed leaflet adaptation as it may cause SLDA.


Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Anciano de 80 o más Años , Femenino , Atrios Cardíacos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/etiología , Insuficiencia de la Válvula Mitral/cirugía , Complicaciones Posoperatorias/etiología , Reoperación , Resultado del Tratamiento
13.
J Card Surg ; 37(12): 5073-5080, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36378886

RESUMEN

BACKGROUND: The effect of the surgical sealant AQUABRID on outcomes after acute aortic dissection repair has not been evaluated. The objective of this study was to examine whether the use of AQUABRID affects the volume of intraoperative blood transfusion or operative time in patients undergoing emergency surgery to repair acute aortic dissection. METHODS: A multicenter retrospective cohort study from January 2007 to December 2021. A total of 399 patients underwent emergency acute aortic dissection repair. Propensity score matching was used to adjust for the type of surgery and other patient characteristics. RESULTS: A total of 387 of the eligible 399 patients were included in this study and propensity score matching yielded 94 patients for whom characteristics were not significantly different between the two groups. The type of surgery was exactly matched (ascending aorta replacement: 19 [40%]; partial arch replacement: 13 [28%]; total arch replacement: 15 [32%] in each group). Within the matched cohort, there was a statistically significant difference in the volume of intraoperative blood transfusion. (AQUABRID vs. control: 34 [26-38] vs. 50 [38-60] U in Japan, p = .03). Operating time was significantly shorter in the AQUABRID group (total operation: mean ± SD, 343 ± 92 vs. 402 ± 161 min, p = .03; reconstruction for arch vessels: 29 ± 17 vs. 56 ± 22, p < .01). The rate of postoperative complications was comparable in the two groups. Failure to use AQUABRID was a significant predictor of the need for massive transfusion (>40 U) (odds ratio: 7.20; 95% confidence interval: 2.56-20.23; p < .01). CONCLUSIONS: The use of AQUABRID during emergency acute aortic dissection repair significantly decreased the volume of intraoperative blood transfusion and the duration of surgery.


Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Humanos , Estudios Retrospectivos , Tempo Operativo , Disección Aórtica/cirugía , Aorta/cirugía , Transfusión Sanguínea , Complicaciones Posoperatorias/cirugía , Aneurisma de la Aorta Torácica/cirugía , Enfermedad Aguda , Aorta Torácica/cirugía
14.
Genes Cells ; 25(6): 427-438, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32267063

RESUMEN

All trophoblast subtypes of the placenta are derived from trophoblast stem cells (TSCs). TSCs have the capacity to self-renew, but how the proliferation of these cells is regulated in the undifferentiated state has been largely unclear. We now show that the F-box protein Skp2 regulates the proliferation of TSCs and thereby plays a pivotal role in placental development in mice on the C57BL/6 background. The placenta of Skp2-/- mouse embryos on the C57BL/6 background was smaller than that of their Skp2+/+ littermates, with the mutant embryos also manifesting intrauterine growth retardation. Although the Skp2-/- mice were born alive, most of them died before postnatal day 21, presumably as a result of placental defects. Depletion of Skp2 in TSCs cultured in the undifferentiated state resulted in a reduced rate of proliferation and arrest of the cell cycle in G1 phase, indicative of a defect in self-renewal capacity. The cell cycle arrest apparent in Skp2-deficient TSCs was reversed by additional ablation of the cyclin-dependent kinase inhibitor (CKI) p57 but not by that of the CKI p27. Our results thus suggest that Skp2-mediated degradation of p57 is an important determinant of the self-renewal capacity of TSCs during placental development, at least in mice of certain genetic backgrounds.


Asunto(s)
Ciclo Celular/genética , Embrión de Mamíferos/metabolismo , Placenta/metabolismo , Placentación/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Células Madre/metabolismo , Trofoblastos/metabolismo , Animales , Diferenciación Celular/genética , Proliferación Celular/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/metabolismo , Embrión de Mamíferos/embriología , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Placenta/embriología , Embarazo , Ratas , Proteínas Quinasas Asociadas a Fase-S/genética
15.
J Vasc Surg ; 74(1): 45-52.e1, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33340702

RESUMEN

OBJECTIVE: This study evaluated the efficacy of the provisional extension to induce complete attachment (PETTICOAT) technique for type B and postoperative residual type B aortic dissections compared with the conventional thoracic endovascular aortic repair (TEVAR) technique. METHODS: In this retrospective study, we compared sequential aortic morphologic changes in consecutive patients with type B and postoperative residual type B aortic dissections treated with the PETTICOAT technique between January 2016 and December 2017 with patients treated with the conventional TEVAR between January 2013 and December 2015. Outcomes included aortic remodeling and aorta-related adverse events for 2 years postoperatively. RESULTS: Forty-eight patients were included in this study (24 in the PETTICOAT group, 24 patients in the conventional TEVAR group). Although both groups showed aortic remodeling in the descending thoracic aorta, the PETTICOAT group developed significantly better aortic remodeling in the abdominal aorta compared with the conventional TEVAR group during the observation period. The PETTICOAT group had significantly fewer aorta-related adverse events compared with the conventional TEVAR group (8% vs 54%; P < .001). Aorta-related adverse events more commonly occurred in the poor remodeling group compared with in the good remodeling group (P = .001; hazard ratio, 8.32; 95% confidence interval, 2.26-30.64). CONCLUSIONS: This study suggests that the PETTICOAT technique for aortic dissection may promote aortic remodeling and decrease the incidence of aorta-related adverse events. Additional studies are required to confirm these preliminary findings.


Asunto(s)
Aorta Abdominal/fisiopatología , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Remodelación Vascular , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/fisiopatología , Aorta Abdominal/diagnóstico por imagen , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/fisiopatología , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/fisiopatología , Aortografía , Prótesis Vascular , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Angiografía por Tomografía Computarizada , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Stents , Factores de Tiempo , Resultado del Tratamiento
16.
Catheter Cardiovasc Interv ; 97(6): E875-E886, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32926552

RESUMEN

OBJECTIVES: To compare safety, efficacy, and hemodynamics of transfemoral transcatheter aortic valve replacement (TAVR) using self-expanding and balloon-expandable transcatheter heart valves (THVs) in patients with a small aortic annulus. BACKGROUND: Few studies have directly compared TAVR outcomes using third-generation THVs, focusing on patients with small aortic annuli. METHODS: In a multicenter TAVR registry, we analyzed data from 576 patients with a small annulus and who underwent transfemoral TAVR using third-generation THVs. Propensity score matching was used to adjust baseline clinical characteristics. RESULTS: The device success rate in the overall cohort was 92.0% (Evolut R: 92.1% vs. Sapien 3:92.0%, p = 0.96). One year after TAVR, patients treated with Evolut R maintained a lower mean pressure gradient (mPG) and a higher indexed effective orifice area (iEOA) in the matched cohort {mPG: 9.0 [interquartile range (IQR): 6.0-11.9] vs. 12.0 [IQR: 9.9-16.3] mmHg, p < .001; iEOA: 1.20 [IQR: 1.01-1.46] vs. 1.08 [IQR: 0.90-1.28] cm2 /m2 , p < .001}. However, no significant differences were reported in the incidence of severe prosthesis-patient mismatch and aortic regurgitation at 1 year. Furthermore, both groups showed comparable outcomes with no differences in terms of all-cause mortality (log-lank test, p = .81). CONCLUSIONS: TAVR for patients with a small annulus using third-generation THVs was associated with high device success. Evolut R seems to be superior to Sapien 3 in hemodynamic performance for patients with a small annulus and body surface area up to 1 year after TAVR. Nevertheless, all-cause mortality at 1 year was similar between both groups.


Asunto(s)
Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Hemodinámica , Humanos , Japón , Diseño de Prótesis , Sistema de Registros , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento
17.
Circ J ; 85(7): 967-976, 2021 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-33642425

RESUMEN

BACKGROUND: The details and consequences of a small aortic annulus among transcatheter aortic valve replacement (TAVR) patients remain uncertain. This study investigated the short-term outcomes in patients with small annular size and compared the 30-day outcome between intra- and supra-annular devices, with similar outer casing diameter in this subgroup.Methods and Results:Cases registered in the Japanese national TAVR registry between August 2013 and December 2017 were analyzed. Among a total of 5,870 registered patients, 647 (11.0%) had small annulus (area ≤314 mm2) measured by multi-detector computed tomography. Patients with a small annulus had a significantly smaller indexed effective orifice area (iEOA, 1.10 cm2/m2[0.92-1.35] vs. 1.16 cm2/m2[0.96-1.39], P<0.001) and higher mean pressure gradient (mPG, 10.0 mmHg [6.9-14.2] vs. 8.5 mmHg [6.0-11.5], P<0.001) compared with a normal-sized annulus. Among patients with a small annulus, those receiving a 20 mm intra-annular device had a smaller iEOA (0.94 cm2/m2[0.78-1.06] vs. 1.07 cm2/m2[0.8-1.24], P=0.001) and higher mPG (14.0 mmHg [10.0-18.5] vs. 11.0 [7.0-14.0], P<0.001) compared with those receiving a 23-mm supra-annular device, although the incidence of paravalvular leakage (≥moderate) was similar (14.4% vs. 16.5%, P=0.69). CONCLUSIONS: Patients with a small annulus were associated with less hemodynamic improvement. A supra-annular device is associated with better echocardiographic improvement in patients with a small annulus, without increasing paravalvular leakage.


Asunto(s)
Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Humanos , Japón/epidemiología , Tomografía Computarizada Multidetector , Diseño de Prótesis , Sistema de Registros , Resultado del Tratamiento
18.
Ann Vasc Surg ; 71: 535.e7-535.e10, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32946998

RESUMEN

Dysphagia aortica is a rare pathology primarily caused by an aortic aneurysm or Kommerrell's diverticulum. Herein, we describe an extremely rare case of dysphagia aortica due to a congenitally angulated descending aorta in a 50-year-old woman successfully treated by open surgery. The woman underwent David procedure for aortic regurgitation 5 years previously, with the same anatomy of an angulated descending aorta without symptoms. She has difficulty in swallowing solid food from 1 month. Total aortic arch replacement using the elephant trunk technique and secondary descending aortic replacement released the esophageal compression by the abnormal aorta and completely improved her symptom.


Asunto(s)
Aorta Torácica/anomalías , Trastornos de Deglución/etiología , Deglución , Malformaciones Vasculares/complicaciones , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Implantación de Prótesis Vascular , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/fisiopatología , Trastornos de Deglución/cirugía , Femenino , Humanos , Persona de Mediana Edad , Recuperación de la Función , Resultado del Tratamiento , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/cirugía
19.
Retina ; 41(5): 921-930, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33079787

RESUMEN

PURPOSE: To describe the intraoperative and postoperative morphological and functional outcomes after autologous neurosensory retinal flap transplantation (ART) for a high myopia-related refractory macular hole (MH). METHODS: This prospective interventional study enrolled five eyes of five patients (age range 54-84 years) with highly myopic refractory MHs who underwent ART. All cases were evaluated with intraoperative optical coherence tomography and postoperative optical coherence tomography, optical coherence tomography angiography, and microperimetry for at least 6 months postoperatively. RESULTS: Intraoperatively, the MH was covered by an ART flap with a persistent small subretinal space that was filled with the ART flap after 4 days to 6 days. Optical coherence tomography discriminated the original from the transplanted retina. The mean basal diameter of the original MH decreased from 1,504 ± 684 µm preoperatively to 1,111 ± 356 µm postoperatively. The best-corrected visual acuity improved in two cases, was stable in two cases, and deteriorated in one case. Microperimetry demonstrated no obvious postoperative changes in the fixation points and the absolute scotoma corresponding to the base of MHs with chorioretinal atrophy. In two eyes, choroidal neovascularization developed beneath the transplanted retinas. CONCLUSION: Transplanted tissue was in a fixed position by 1 week postoperatively with a decreased diameter of the original MH. Postoperative fixation points were on the original retina at the MH edge. Because choroidal neovascularization may develop, detailed monitoring is required.


Asunto(s)
Monitoreo Intraoperatorio/métodos , Miopía Degenerativa/complicaciones , Retina/trasplante , Perforaciones de la Retina/cirugía , Colgajos Quirúrgicos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Retina/diagnóstico por imagen , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/etiología , Trasplante Autólogo
20.
Vascular ; 29(6): 826-831, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33478338

RESUMEN

OBJECTIVE: We investigated the outcomes of extended coverage of the descending thoracic aorta by thoracic endovascular aortic repair (TEVAR) for residual chronic type B aortic dissection after type A aortic dissection (TAAD) repair. METHODS: From November 2015 to August 2020, 36 patients underwent extended TEVAR for residual intimal tear after TAAD repair. We specifically investigated the methods and outcomes of this procedure. RESULTS: TEVAR consisted of isolated TEVARs (n = 29), single-vessel debranching TEVAR (6), and two-vessel debranching TEVAR (1). The mean time from TAAD repair to TEVAR was 27 ± 33 months (2-86 months). The TEVAR devices used were Valiant (28 cases), GORETAG (4), Relay plus (2), and TX2 (2). Technical success of TEVAR was 100%. The distal ends of the stent grafts were T 8 (1 case), T 9 (5), T 10 (6), T 11 (9), and T 12 (15), with an average of T 11 ± 1. The average length of hospital stay after TEVAR was 9 ± 3 days (5-17 days). There were no surgical/hospital deaths or complications. The average postoperative follow-up period was 21 ± 15 months without death or reintervention. CONCLUSIONS: The short-term outcomes of extended TEVAR for residual chronic type B aortic dissection after TAAD repair were acceptable without perioperative SCI. Aggressive descending thoracic aorta coverage may prevent aortic events, and extended TEVAR may be a preemptive treatment for the downstream aorta. Mid- to long-term results should be clarified.


Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Adulto , Anciano , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Prótesis Vascular , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Enfermedad Crónica , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Factores de Tiempo , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA