TNF Receptor-Associated Factor 5 Limits IL-27 Receptor Signaling in CD4+ T Lymphocytes.

TNF receptor-associated factor 5 (TRAF5) restrains early signaling activity of the IL-6 receptor in naive CD4+ T cells by interacting with the shared gp130 chain, although TRAF5 was initially discovered as a cytoplasmic adaptor protein to activate signaling mediated by TNF receptor family molecules. This leads to the question of whether TRAF5 limits signaling via the receptor for IL-27, which is composed of gp130 and WSX-1. The aim of this study is to clarify the role of TRAF5 in IL-27 receptor signaling and to understand the differential role of TRAF5 on cytokine receptor signaling. We found that Traf5 -/- CD4+ T cells displayed significantly higher levels of phosphorylated STAT1 and STAT-regulated genes Socs3 and Tbx21, as early as 1 h after IL-27 exposure when compared with Traf5 +/+ CD4+ T cells. Upon IL-27 and TCR signals, the Traf5 deficiency significantly increased the induction of IL-10 and promoted the proliferation of CD4+ T cells. Traf5 -/- mice injected with IL-27 displayed significantly enhanced delayed-type hypersensitivity responses, demonstrating that TRAF5 works as a negative regulator for IL-27 receptor signaling. In contrast, IL-2 and proliferation mediated by glucocorticoid-induced TNF receptor-related protein (GITR) and TCR signals were significantly decreased in Traf5 -/- CD4+ T cells, confirming that TRAF5 works as a positive regulator for cosignaling via GITR. Collectively, our results demonstrate that TRAF5 reciprocally controls signals mediated by the IL-27 receptor and GITR in CD4+ T cells and suggest that the regulatory activity of TRAF5 in gp130 is distinct from that in TNF receptor family molecules in a T cell.

Outcomes of pulmonary valve replacement using a bioprosthetic valve and polytetrafluoroethylene bicuspid valve for pulmonary valve regurgitation after intracardiac repair of tetralogy of Fallot.

BACKGROUND: Excellent results have been reported regarding pulmonary valve replacement (PVR) for pulmonary valve regurgitation (PR) after intracardiac repair (ICR) in patients with tetralogy of Fallot (TOF). However, there are apparently no reports comparing the following procedures: PVR using a bioprosthetic valve and PVR using a polytetrafluoroethylene (PTFE) bicuspid valve. Herein, we retrospectively analyzed the outcomes of PVR for PR after ICR of TOF in our institution and assessed which of the two PVR procedures was better. METHODS: From June 2008 to December 2017, we performed PVR for PR after ICR of TOF in 34 patients. Patients with the right ventricle to the pulmonary artery conduits were excluded. Preoperative and postoperative cardiac magnetic resonance imagings (cMRIs) were performed in all patients. The patients were divided into the bioprosthetic valve group (BV group, n = 17) and the PTFE bicuspid valve group (PTFE group, n = 17). RESULTS: There were no significant differences in the preoperative cMRI data and perioperative factors between the two groups. There were no deaths in either group. Postoperative cMRI showed that the PR fraction and the right ventricular end-diastolic volume index (RVEDVI)/left ventricular end-diastolic volume index ratio were significantly improved in both groups. However, RVEDVI was significantly improved only in the BV group. Re-PVR was required in four patients in the PTFE group. CONCLUSION: PVR using a bioprosthetic valve was more effective for PR treatment after ICR of TOF than PVR using a PTFE bicuspid valve.

Midterm outcome of aortic valve neocuspidization for aortic valve stenosis with small annulus.

OBJECTIVE: At our institution, we actively perform aortic valve neocuspidization (AVNeo) for aortic valve stenosis (AS) with a small annulus. In this report, we aimed to evaluate the midterm outcome of AVNeo for AS with a small annulus. METHODS: From February 2011 to May 2017, we performed AVNeo for AS with a small annulus in 34 patients. Their mean age was 77.0 ± 9.1 years. Preoperative transthoracic echocardiography (TTE) revealed a mean peak pressure gradient average of 84.2 ± 31.1 mmHg. The effective orifice area index (EOAi) was 0.45 ± 0.14 cm2/m2. The mean annulus diameter was 18.4 ± 1.1 mm. Our procedure complies with the three cuspid suturing to the aortic annulus with glutaraldehyde-treated autologous pericardium. RESULTS: There were no conversion to aortic valve replacement and no concomitant annulus enlargement. There were two inhospital mortalities resulting from a noncardiac cause. Three patients underwent reoperation owing to aortic regurgitation (n = 2) and infective endocarditis (n = 1). One patient underwent a pacemaker implantation for complete atrioventricular block. The mean follow-up period was 28.0 ± 22.7 months. Postoperative TTE showed a mean peak pressure gradient average of 18.3 ± 9.4 mmHg and a calculated mean EOAi of 1.18 ± 0.35 cm2/m2. The freedom from reoperation rates were 94.1% and 90.8% at 1 year and 5 years of follow-up, respectively. The overall survival rates were 91.2% and 76.8% at 1 and 5 years of follow-up, respectively. CONCLUSIONS: The midterm outcome of AVNeo for AS with a small annulus was excellent. The long-term outcome and reliability of this procedure must be fully clarified.

Early and mid-term results of isolated aortic valve neocuspidization in patients with aortic stenosis.

OBJECTIVES: This study aimed to elucidate the surgical outcome of aortic valve neocuspidization (AVNeo) in patients with aortic stenosis (AS). METHODS: From December 2010 to June 2017, we performed AVNeo for aortic valve pathologies in 144 patients. Of them, we evaluated 57 patients with AS who underwent AVNeo. Their mean age was 77.5 ± 8.8 years. Fifty-five patients had AS from degenerative changes, 1 from pericardium endocarditis, and 1 from prosthetic valve endocarditis. Forty patients had a tricuspid aortic valve, 1 had a unicuspid valve, 14 had a bicuspid valve, 1 had a quadricuspid valve, and 1 had postoperative aortic valve replacement (AVR). Preoperative echocardiography revealed an average peak pressure gradient of 89 ± 32.9 mmHg and a mean pressure gradient of 52 ± 18.8 mmHg. The surgical procedure complies with the 3 cuspid suturing to the aortic annulus with the glutaraldehyde-treated pericardium. RESULTS: There were no conversions to AVR. There were 2 noncardiac-related deaths owing to liver failure and sepsis. Postoperative echocardiography showed an average peak pressure gradient of 22 ± 10.7 mmHg 1 week after the procedure and 19.2 ± 9.7 mmHg 20 months after the procedure. Two patients underwent reoperation owing to infective endocarditis and recurrent aortic regurgitation. The mean follow-up period was 30.4 ± 20.8 months. The freedom from reoperation rates was 98.1 and 95.3% at 12 and 81 months of follow-up, respectively. CONCLUSIONS: AVNeo is suitable for patients with AS considering its early and mid-term outcomes. Verification of long-term outcomes and reliability is necessary.

Comparison of aortic annulus dimensions after aortic valve neocuspidization with those of normal aortic valve using transthoracic echocardiography.

OBJECTIVES: This study aimed to elucidate the physiological feasibility of aortic valve neocuspidization (AVNeo) by comparing the aortic annulus dimensions between patients after AVNeo and patients with normal aortic valves. METHODS: From December 2010 to October 2017, we performed AVNeo for various aortic valve pathologies in 147 patients. Of these patients, the aortic annulus dimensions were measured in 25 patients who underwent AVNeo for aortic valve disease as follow-up examination and compared with those measured in 15 patients who had normal aortic valves. Measurements were recorded using electrocardiography-gated transthoracic echocardiography. RESULTS: No significant differences in the aortic annulus dimensions were observed between the patients who had undergone AVNeo and those who had normal aortic valves. In a cardiac cycle, the annulus area in the systolic phase was consistently larger than that in the diastolic phase, which was a physiological condition. CONCLUSIONS: The movement of the aortic annulus after AVNeo is comparable with that of the aortic annulus of a normal aortic valve. Thus, AVNeo can be regarded as a more physiological operation in that it maintains the characteristics of the aortic valve similar to those of a normal aortic valve.

Treatment of prosthetic valve endocarditis by aortic valve neocuspidization using bovine pericardium.

A 78-year-old man who had undergone aortic valve and ascending aorta replacements presented with fever and was referred to our hospital. Blood culture revealed Gram-positive cocci, thus antibiotic therapy was started. Brain magnetic resonance imaging showed fresh cerebral infarction without cerebral haemorrhage or mycotic aneurysm. Transoesophageal echocardiogram revealed a vegetation that was attached to the right coronary cusp. The patient underwent successful aortic valve neocuspidization using glutaraldehyde-treated bovine pericardium. The postoperative course was uneventful with intravenous antibiotics administered for 6 weeks after confirming a negative blood culture, and no cardiac events occurred on follow-up by transthoracic echocardiogram 14 months postoperatively.

Towards single cell heat shock response by accurate control on thermal confinement with an on-chip microwire electrode.

Metal electrodes with micron scale width enable the heating of less than a dozen cells in a confluent layer at predictable temperatures up to 85 °C with an accuracy of ±2 °C. Those performances were obtained by a preliminary robust temperature calibration based on biotin-rhodamine fluorescence and by controlling the temperature map on the substrate through thermal modeling. The temperature accuracy was proved by inducing the expression of heat shock proteins (HSP) in a few NIH-3T3 cells through a confined and precise temperature rise. Our device is therefore effective to locally induce a heat shock response with almost single-cell resolution. Furthermore, we show that cells heated at a higher temperature than the one of heat shock remain alive without producing HSP. Electrode deposition being one of the most common engineering processes, the fabrication of electrode arrays with a simple control circuit is clearly within reach for parallel testing. This should enable the study of several key mechanisms such as cell heat shock, death or signaling. In nanomedicine, controlled drug release by external stimuli such as for example temperature has attracted much attention. Our device could allow fast and efficient testing of thermoactivable drug delivery systems.