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1.
Cell ; 157(5): 1160-74, 2014 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-24855951

RESUMO

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.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Endocitose , Proteínas de Membrana/metabolismo , Receptores Notch/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Regulação para Baixo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Transdução de Sinais , Temperatura
2.
Cell ; 145(7): 1049-61, 2011 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-21703449

RESUMO

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.


Assuntos
Fator 2 Ativador da Transcrição/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/genética , Heterocromatina/metabolismo , Fator 2 Ativador da Transcrição/análise , Fator 2 Ativador da Transcrição/genética , Animais , Proteínas de Drosophila/análise , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Epigenômica , Eucromatina/metabolismo , Feminino , Heterocromatina/química , MAP Quinase Quinase Quinase 1/metabolismo , Masculino , Mutagênese , Fosforilação , Transdução de Sinais , Estresse Fisiológico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
3.
Proc Natl Acad Sci U S A ; 119(15): e2110256119, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35394865

RESUMO

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.


Assuntos
Neoplasias da Mama , Receptor alfa de Estrogênio , Proteínas de Ligação a Tacrolimo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Estabilidade Proteica , Proteínas de Ligação a Tacrolimo/metabolismo
4.
Circ J ; 88(4): 451-459, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36754386

RESUMO

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.


Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Insuficiência da Valva Tricúspide , Disfunção Ventricular Direita , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Insuficiência da Valva Tricúspide/cirurgia , Resultado do Tratamento , Disfunção Ventricular Direita/etiologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Estudos Retrospectivos , Valva Aórtica/cirurgia
5.
Ann Vasc Surg ; 100: 128-137, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38122978

RESUMO

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.


Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Correção Endovascular de Aneurisma , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações , Pontuação de Propensão , Endoleak/etiologia , Japão , Resultado do Tratamento , Fatores de Risco , Acidente Vascular Cerebral/complicações , Paraplegia/etiologia , Paraparesia/complicações , Paraparesia/cirurgia , Estudos Retrospectivos
6.
BMC Ophthalmol ; 24(1): 219, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783230

RESUMO

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.


Assuntos
Vitrectomia , Corpo Vítreo , Humanos , Corpo Vítreo/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto , Eletrólitos/análise , Medicina Legal/métodos , Sódio/análise , Potássio/análise , Magnésio/análise
7.
Kyobu Geka ; 77(7): 491-495, 2024 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-39009546

RESUMO

OBJECTIVE: This study aimed to review the results of the bio-Bentall procedure in patients over 65 years of age at our hospital. MATERIALS AND METHODS: Of the 65 aortic root replacement procedures performed at our hospital from October 2015 to January 2024, we reviewed 45 bio-Bentall procedures performed on patients 65 years of age or older. These patients consisted of 39 men and 6 women, with a mean age of 72 years. There were 5 patients with aortic dissection and 40 patients with non-dissection, and 6 patients had reoperation. There were 19 concomitant surgeries, including coronary artery bypass grafting, valve surgery, and aortic procedure. The bioprosthetic valves used were Magna EASE in 17 patients, Inspiris in 25 patients, Trifecta in 2 patients, and Avalus in 1 patient. All Valsalva grafts used were J Graft Valsalva. RESULTS: The mean intubation time was 19 hours, and the mean intensive care unit( ICU) stay was 6 days. The number of in-hospital deaths was 3 patients, and the mean length of hospital stay was 18 days. The remote mortality rate was 4( 1 heart failure, 2 lung cancer, and 1 pancreatic cancer). There have been no case of reoperation, structural valve deterioration (SVD), or thromboembolism to date, and the rates of freedom of reoperation, SVD, and thromboembolism were all 100%. The 1-, 3-, 5-, and 7-year survival rates were 91.1%, 86.4%, 83.6%, and 83.6%, respectively. CONCLUSION: The surgical and long-term outcomes of the bio-Bentall procedure in patients over 65 years of age were stable. In patients who may outlive the bioprosthetic valve life, it is important to perform an appropriate and durable Bentall procedure, including valve-in-valve, prioritizing the future of each patient.


Assuntos
Valva Aórtica , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Resultado do Tratamento , Próteses Valvulares Cardíacas , Bioprótese
8.
Circulation ; 145(14): 1056-1066, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35209732

RESUMO

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.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Embolização Terapêutica/efeitos adversos , Endoleak/epidemiologia , Endoleak/etiologia , Endoleak/cirurgia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
Nucleic Acids Res ; 49(13): 7298-7317, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34226921

RESUMO

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.


Assuntos
Códon de Iniciação , Fator de Iniciação 2 em Eucariotos/metabolismo , Iniciação Traducional da Cadeia Peptídica , Biologia Computacional/métodos , Fator de Iniciação 3 em Eucariotos/metabolismo , Células HEK293 , Humanos , Fases de Leitura Aberta , Pegadas de Proteínas , Proteômica , Análise de Sequência de RNA
10.
J Artif Organs ; 26(2): 151-155, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35906510

RESUMO

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.


Assuntos
Displasia Arritmogênica Ventricular Direita , Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Esquerda , Disfunção Ventricular Direita , Masculino , Humanos , Adulto , Displasia Arritmogênica Ventricular Direita/cirurgia , Displasia Arritmogênica Ventricular Direita/complicações , Coração Auxiliar/efeitos adversos , Insuficiência Cardíaca/cirurgia , Disfunção Ventricular Esquerda/complicações , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Disfunção Ventricular Direita/etiologia , Função Ventricular Direita
11.
BMC Biol ; 20(1): 65, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35264151

RESUMO

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.


Assuntos
Proteínas de Drosophila , Receptores Notch , Proteínas de Drosophila/metabolismo , Endocitose/fisiologia , Ligantes , Receptores Notch/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
12.
Cardiol Young ; 33(9): 1763-1764, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36997311

RESUMO

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.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Comunicação Interatrial , Edema Pulmonar , Cirurgia Torácica , Humanos , Criança , Edema Pulmonar/diagnóstico , Edema Pulmonar/etiologia , Edema Pulmonar/terapia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Comunicação Interatrial/cirurgia , Comunicação Interatrial/complicações , Toracotomia/efeitos adversos
13.
J Artif Organs ; 25(2): 174-177, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34056668

RESUMO

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.


Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Idoso de 80 Anos ou mais , Feminino , Átrios do Coração , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Complicações Pós-Operatórias/etiologia , Reoperação , Resultado do Tratamento
14.
J Card Surg ; 37(12): 5073-5080, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36378886

RESUMO

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.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Estudos Retrospectivos , Duração da Cirurgia , Dissecção Aórtica/cirurgia , Aorta/cirurgia , Transfusão de Sangue , Complicações Pós-Operatórias/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Doença Aguda , Aorta Torácica/cirurgia
15.
Genes Cells ; 25(6): 427-438, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32267063

RESUMO

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.


Assuntos
Ciclo Celular/genética , Embrião de Mamíferos/metabolismo , Placenta/metabolismo , Placentação/genética , Proteínas Quinases Associadas a Fase S/metabolismo , Células-Tronco/metabolismo , Trofoblastos/metabolismo , Animais , Diferenciação Celular/genética , Proliferação de Células/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Embrião de Mamíferos/embriologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placenta/embriologia , Gravidez , Ratos , Proteínas Quinases Associadas a Fase S/genética
16.
J Vasc Surg ; 74(1): 45-52.e1, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33340702

RESUMO

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.


Assuntos
Aorta Abdominal/fisiopatologia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Remodelação Vascular , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/fisiopatologia , Aorta Abdominal/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Aortografia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento
17.
Catheter Cardiovasc Interv ; 97(6): E875-E886, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926552

RESUMO

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.


Assuntos
Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Hemodinâmica , Humanos , Japão , Desenho de Prótese , Sistema de Registros , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
18.
Circ J ; 85(7): 967-976, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33642425

RESUMO

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.


Assuntos
Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Humanos , Japão/epidemiologia , Tomografia Computadorizada Multidetectores , Desenho de Prótese , Sistema de Registros , Resultado do Tratamento
19.
Ann Vasc Surg ; 71: 535.e7-535.e10, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32946998

RESUMO

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.


Assuntos
Aorta Torácica/anormalidades , Transtornos de Deglutição/etiologia , Deglutição , Malformações Vasculares/complicações , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Implante de Prótese Vascular , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/cirurgia
20.
Retina ; 41(5): 921-930, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33079787

RESUMO

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.


Assuntos
Monitorização Intraoperatória/métodos , Miopia Degenerativa/complicações , Retina/transplante , Perfurações Retinianas/cirurgia , Retalhos Cirúrgicos , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Retina/diagnóstico por imagem , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Transplante Autólogo
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