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Pleural mesothelial cells (PMCs) can become myofibroblasts via mesothelial-mesenchymal transition (MesoMT) and contribute to pleural organization, fibrosis, and rind formation. However, how these transformed mesothelial cells contribute to lung fibrosis remains unclear. Here, we investigated the mechanism of contractile myofibroblast differentiation of PMCs. Transforming growth factor-β (TGF-β) induced marked upregulation of calponin 1 expression, which was correlated with notable cytoskeletal rearrangement in human PMCs (HPMCs) to produce stress fibers. Downregulation of calponin 1 expression reduced stress fiber formation. Interestingly, induced stress fibers predominantly contain α-smooth muscle actin (αSMA) associated with calponin 1 but not β-actin. Calponin 1-associated stress fibers also contained myosin II and α-actinin. Furthermore, focal adhesions were aligned with the produced stress fibers. These results suggest that calponin 1 facilitates formation of stress fibers that resemble contractile myofibrils. Supporting this notion, TGF-β significantly increased the contractile activity of HPMCs, an effect that was abolished by downregulation of calponin 1 expression. We infer that differentiation of HPMCs to contractile myofibroblasts facilitates stiffness of scar tissue in pleura to promote pleural fibrosis (PF) and that upregulation of calponin 1 plays a central role in this process.

High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However, some patients with HAVB/CHB recover with time. The results of electrophysiological studies (EPSs) using permanent pacemaker implantation (PPI) in patients with suspicious HAVB/CHB are considered controversial.This study aimed to evaluate whether HAVB/CHB induction at the bedside using a temporary pacemaker can predict recurrence in patients who had recovered from HAVB/CHB after TAVR.We enrolled a total of 11 patients who had recovered from HAVB/CHB and evaluated their electrophysiology using right ventricular pacing and/or procainamide administration.HAVB/CHB induction was positive. Three patients tested positive for HAVB/CHB, whereas 8 tested negative. The ejection fraction and the interval between HAVB/CHB onset and EPS were found to be significant. HAVB/CHB positive patients underwent PPI. A patient with a balloon-expandable valve tested positive just before recovery of CHB, but tested negative 5 days later and was included in the negative group. The 4 patients who tested negative received a cardiovascular implantable electric device (CIED). We observed HAVB/CHB in 2 patients who had previously tested positive after 3 months. Among those who tested negative, those with CIED had no HAVB/CHB, and others showed neither HAVB/CHB on electrocardiogram nor experienced syncope or sudden death.Our EPS revealed that HAVB/CHB induction may predict HAVB/CHB recurrence after TAVR. Valve type and EPS timing may affect the results.

Pleural mesothelial cells (PMCs) play a central role in the progression of pleural fibrosis. As pleural injury progresses to fibrosis, PMCs transition to mesenchymal myofibroblast via mesothelial mesenchymal transition (MesoMT), and produce extracellular matrix (ECM) proteins including collagen and fibronectin (FN1). FN1 plays an important role in ECM maturation and facilitates ECM-myofibroblast interaction, thus facilitating fibrosis. However, the mechanism of FN1 secretion is poorly understood. We report here that myosin 5b (Myo5b) plays a critical role in the transportation and secretion of FN1 from human pleural mesothelial cells (HPMCs). TGF-β significantly increased the expression and secretion of FN1 from HPMCs and facilitates the close association of Myo5B with FN1 and Rab11b. Moreover, Myo5b directly binds to GTP bound Rab11b (Rab11b-GTP) but not GDP bound Rab11b. Myo5b or Rab11b knockdown via siRNA significantly attenuated the secretion of FN1 without changing FN1 expression. TGF-β also induced Rab11b-GTP formation, and Rab11b-GTP but not Rab11b-GDP significantly activated the actin-activated ATPase activity of Myo5B. Live cell imaging revealed that Myo5b- and FN1-containing vesicles continuously moved together in a single direction. These results support that Myo5b and Rab11b play an important role in FN1 transportation and secretion from HPMCs, and consequently may contribute to the development of pleural fibrosis.

High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However, some patients with HAVB/CHB recover with time. The results of electrophysiological studies (EPSs) using permanent pacemaker implantation (PPI) in patients with suspicious HAVB/CHB are considered controversial.This study aimed to evaluate whether HAVB/CHB induction at the bedside using a temporary pacemaker can predict recurrence in patients who had recovered from HAVB/CHB after TAVR.We enrolled a total of 11 patients who had recovered from HAVB/CHB and evaluated their electrophysiology using right ventricular pacing and/or procainamide administration.HAVB/CHB induction was positive. Three patients tested positive for HAVB/CHB, whereas 8 tested negative. The ejection fraction and the interval between HAVB/CHB onset and EPS were found to be significant. HAVB/CHB positive patients underwent PPI. A patient with a balloon-expandable valve tested positive just before recovery of CHB, but tested negative 5 days later and was included in the negative group. The 4 patients who tested negative received a cardiovascular implantable electric device (CIED). We observed HAVB/CHB in 2 patients who had previously tested positive after 3 months. Among those who tested negative, those with CIED had no HAVB/CHB, and others showed neither HAVB/CHB on electrocardiogram nor experienced syncope or sudden death.Our EPS revealed that HAVB/CHB induction may predict HAVB/CHB recurrence after TAVR. Valve type and EPS timing may affect the results.

Pleural fibrosis is characterized by severe inflammation of the pleural space and pleural reorganization. Subsequent thickening of the visceral pleura contributes to lung stiffness and impaired lung function. Pleural mesothelial cells (PMCs) can become myofibroblasts via mesothelial–mesenchymal transition (MesoMT) and contribute to pleural organization, fibrosis, and rind formation. However, the mechanisms that underlie MesoMT remain unclear. Here, we investigated the role of myocardin in the induction of MesoMT. Transforming growth factor β (TGF-β) and thrombin induced MesoMT and markedly upregulated the expression of myocardin, but not myocardin-related transcription factor A (MRTF-A) or MRTF-B, in human PMCs (HPMCs). TGF-β stimulation notably induced the nuclear translocation of myocardin in HPMCs, whereas nuclear translocation of MRTF-A and MRTF-B was not observed. Several genes under the control of myocardin were upregulated in cells undergoing MesoMT, an effect that was accompanied by a dramatic cytoskeletal reorganization of HPMCs consistent with a migratory phenotype. Myocardin gene silencing blocked TGF-β– and thrombin-induced MesoMT. Although myocardin upregulation was blocked, MRTF-A and MRTF-B were unchanged. Myocardin, α-SMA, calponin, and smooth muscle myosin were notably upregulated in the thickened pleura of carbon black/bleomycin and empyema mouse models of fibrosing pleural injury. Similar results were observed in human nonspecific pleuritis. In a TGF-β mouse model of pleural fibrosis, PMC-specific knockout of myocardin protected against decrements in lung function. Further, TGF-β–induced pleural thickening was abolished by PMC-specific myocardin knockout, which was accompanied by a marked reduction of myocardin, calponin, and α-SMA expression compared with floxed-myocardin controls. These novel results show that myocardin participates in the development of MesoMT in HPMCs and contributes to the pathogenesis of pleural organization and fibrosis.

Background: Little is known about the superiority of balloon angioplasty vs. stent implantation for femoropopliteal (FP) lesions according to subgroup. Methods and Results: This study involved 1,018 de novo (balloon angioplasty, n=462; stent implantation, n=556) and 114 in-stent restenosis (ISR) FP lesions (balloon angioplasty, n=69; stent implantation, n=45) treated with endovascular therapy. For de novo FP lesions, the 3-year primary patency rate was significantly better with stent implantation than with balloon angioplasty (61% vs. 69%, log-rank P=0.001), but it was similar for ISR FP lesions (40% vs. 43%, log-rank P=0.83). For de novo FP lesions, stent implantation was favorable in all subgroups except for female sex (hazard ratio [HR], 0.92; 95% CI: 0.65-1.31, P=0.66), critical limb ischemia (CLI; HR, 0.70; 95% CI: 0.46-1.06, P=0.10), calcified lesion (HR, 0.81; 95% CI: 0.46-1.39, P=0.44), and poor tibial run-off (HR, 0.86; 95% CI: 0.59-1.25, P=0.42) subgroups. No difference was found between the 2 treatment strategies for ISR FP lesions in the majority of subgroups. Stent implantation, however, was favorable in totally occluded ISR FP lesions (HR, 0.45; 95% CI: 0.21-1.01, P=0.05). Conclusions: The primary patency rate in de novo FP lesions for the 2 treatment strategies was similar in the female, calcified lesion, CLI, and poor tibial run-off subgroups. Stent implantation was superior to balloon angioplasty for totally occluded ISR FP lesions.

A 68-year-old man was scheduled to undergo percutaneous coronary intervention for in-stent total occlusion of the severely tortuous right coronary artery. Intravascular ultrasound revealed heavy in-stent calcification. Lesion atherectomy was required; however, severe proximal vessel tortuosity was detected. We introduced a 7-Fr guide-extension catheter beyond the severely tortuous part and performed rotational atherectomy with a 1.5 mm burr. However, the balloon could not expand; therefore, we changed to an orbital atherectomy system. Subsequently, the balloon successfully expanded, and intravascular ultrasound revealed an enlarged lumen. Severe proximal vessel tortuosity limits the use of atherectomy devices; however, a guide-extension catheter delivers the atherectomy device beyond the tortuosity. The delivery of the orbital atherectomy system inside the guide-extension catheter is easy due to its low profile; the debulking effect increases with the number of passes and rotational speed. This strategy is a useful option for treating severe calcified lesions with proximal vessel tortuosity.

A 63 year-old woman with claudication underwent endovascular therapy for diffuse stenosis of the right superficial femoral artery in our hospital. We performed paclitaxel-coated balloon angioplasty using the IN.PACT™ Admiral™ and achieved acceptable results. After 42 days, we performed follow-up optical frequency domain imaging for the right superficial femoral artery lesion treated with paclitaxel-coated balloon and observed several high-intensity regions with attenuation on the lumen surface. Sustained drug availability is a notable characteristic of paclitaxel-coated balloon. To the best of our knowledge, this is the first report on the visualization of sustained drug retention on the lumen surface using follow-up optical frequency domain imaging after paclitaxel-coated balloon angioplasty in a human patient with superficial femoral artery disease.

Objective Angiographic dissection is considered to be associated with restenosis. However, little is known about the impact of the severity of angiographic dissection on future restenosis. Methods A total of 319 consecutive de novo femoropopliteal lesions were treated by balloon angioplasty alone. All of these lesions were divided into three groups: group A, no angiographic dissection; group B, mild dissection, the width of the dissection was less than one-third of the lumen; and group C, severe dissection, the width of the dissection was more than one-third of the lumen. Kaplan-Meier analysis estimated the primary patency rate at 3 years between the groups. Results The primary patency rates at 3 years were 66.0% in group A, 63.8% in group B, and 32.5% in group C (log-rank, P 100 mm (hazard ratio, 1.734; 95% confidence interval, 1.099-2.735; P = .018) and severe angiographic dissection (hazard ratio, 1.956; 95% confidence interval, 1.276-2.997; P = .002) were predictors of primary patency loss at 3 years. When the lesions were divided into two groups according to the lesion length >100 mm or not, angiographic dissection had a larger impact on restenosis in a long lesion >100 mm (≤100 mm: 65.5% in group A, 75.6% in group B, and 48.0% in group C [log-rank, P = .015]; >100 mm: 68.8% in group A, 42.5% in group B, and 24.2% in group C [log-rank, P = .017]). Conclusions Severe angiographic dissection was associated with future restenosis after balloon angioplasty for femoropopliteal lesions, but mild angiographic dissection was not. Angiographic dissection had more impact on future restenosis particularly in treated long lesions. Stents might not be necessary in short lesions with mild dissection.

Fibrosis involves the production of extracellular matrix proteins in tissues and is often preceded by injury or trauma. In pleural fibrosis excess collagen deposition results in pleural thickening, increased stiffness and impaired lung function. Myofibroblasts are responsible for increased collagen deposition, however the molecular mechanism of transportation of procollagen containing vesicles for secretion is unknown. Here, we studied the role of kinesin on collagen-1 (Col-1) containing vesicle transportation in human pleural mesothelial cells (HPMCs). Among a number of cargo transporting kinesins, KIF5A was notably upregulated during TGF-β induced mesothelial-mesenchymal transition (MesoMT). Using superresolution structured illumination microscopy and the DUO-Link technique, we found that KIF5A colocalized with Col-1 containing vesicles. KIF5A knock-down significantly reduced Col-1 secretion and attenuated TGF-β induced increment in Col-1 localization at cell peripheries. Live cell imaging revealed that GFP-KIF5A and mCherry-Col-1 containing vesicles moved together. Kymography showed that these molecules continuously move with a mean velocity of 0.56 μm/sec, suggesting that the movement is directional but not diffusion limited process. Moreover, KIF5A was notably upregulated along with Col-1 and α-smooth muscle actin in pleural thickening in the carbon-black bleomycin mouse model. These results support our hypothesis that KIF5A is responsible for collagen transportation and secretion from HPMCs.

Cardiac resynchronization therapy (CRT) has been increasingly performed in patients having heart failure with dyssynchrony. We report a successful case of total thoracoscopic left ventricular (LV) lead implantation in CRT. A 77-year-old man with marked dyssynchrony of the LV wall motion and a low ejection fraction (EF17%) due to pacemaker-mediated cardiomyopathy was referred to us. CRT was planned, but percutaneous LV lead implantation proved difficult owing to anatomical variations. The LV lead was placed in the post-lateral wall of the LV base using a total thoracoscopic procedure. Preoperative dyspnea and dyssynchrony were clearly improved. In CRT, the LV wall stimulation site is important. The LV lead should be implanted in the latest activation area, which can be detected using speckle tracking echocardiography. Surgical lead implantation can be performed in the ideal area, and this procedure may play a new role as a hybrid CRT.

We aimed to evaluate the additional debulking efficacy of low-speed rotational atherectomy (RA) after high-speed RA by using intravascular imaging. A total of 22 severe calcified coronary lesions in 19 patients (age, 74 ± 10 years; 74% male) were retrospectively analyzed. All of these lesions underwent RA under optical coherence tomography (OCT) or optical frequency domain imaging (OFDI) guidance. At first, we performed high-speed RA with 220,000 rpm until the reduction of rotational speed disappeared; then, low-speed RA with 120,000 rpm using the same burr size was performed. OCT or OFDI was performed after both high-speed and low-speed RAs, and the minimum lumen area were compared. The initial and final burr sizes of high-speed RA were 1.5 (1.5–1.75) and 1.75 (1.5–2.0) mm, respectively. The number of sessions, total duration time, and maximum decreased rotational speed during high-speed RA were 11 ± 5 times, 113 ± 47 s, and 4000 (3000–5000) rpm, respectively. During low-speed RA, the number of sessions, total duration time, and maximum reduction of rotational speed were 3 ± 1 times, 32 ± 11 s, and 1000 (0–2000) rpm, respectively. The minimum lumen area was similar between after high-speed and after low-speed RA [2.61 ± 1.03 mm2 (after high-speed RA) vs. 2.65 ± 1.00 mm2 (after low-speed RA); P = 0.91]. Additional low-speed RA immediately after sufficient debulking by high-speed RA was not associated with increased lumen enlargement. There was no clinical efficacy of low-speed RA after high-speed RA.

Purpose To determine the clinical impact and predictors of slow flow after endovascular treatment (EVT) using the Crosser catheter for debulking infrapopliteal lesions associated with critical limb ischemia. Materials and Methods This retrospective study included 65 patients with critical limb ischemia (70 limbs, 90 infrapopliteal lesions), who underwent EVT using the Crosser catheter between November 2011 and February 2017. The Crosser catheter was used when the balloon catheter could not be passed through the lesion or could not be dilated sufficiently. Slow flow was evaluated after atherectomy using Crosser and was defined as delayed antegrade flow to the foot (total number of cine frames >35). Results Following atherectomy, slow flow developed in 37 infrapopliteal lesions (41.1%). Despite secondary treatment, slow flow persisted in 29 of 37 lesions (78%). After atherectomy using the Crosser catheter, the balloon could be passed through the lesion in all cases. The wound healing rate at 1 year after EVT (overall, 67.8%) was significantly poorer in the presence of slow flow (rate with vs. without slow flow, 45.3% vs. 84.4%, respectively; P = .006), especially among patients with stage ≥3 baseline wound, ischemia, and foot infection. The active length of the Crosser catheter was a predictor of slow flow (odds ratio, 1.05; 95% confidence interval, 1.03–1.08; P Conclusions Slow flow is associated with a poorer wound healing rate at 1 year, especially for patients with severe baseline ischemia. To reduce the risk of slow flow, the active length of the Crosser catheter should be kept at

Purpose: To evaluate the clinical efficacy of poststenting fractional flow reserve (FFR) in terms of predicting restenosis in superficial femoral artery (SFA) disease. Methods: This prospective, single-center, nonrandomized study enrolled 48 patients (mean age 76±9 years; 38 men) with 51 SFA lesions from July 2013 to June 2014. Mean FFR (distal mean pressure/proximal mean pressure) and systolic FFR (distal systolic pressure/proximal systolic pressure) were calculated, and the relationship between these FFR values and restenosis at 12 months was investigated using receiver operating characteristic (ROC) curve analysis. Results: Poststenting FFR was significantly lower in the restenosis group (poststenting mean FFR 0.85±0.07 vs 0.93±0.05, p=0.001; poststenting systolic FFR 0.76±0.14 vs 0.87±0.08, p=0.015). The area under the ROC curve for restenosis in poststenting mean FFR was higher, but not statistically significant, than that in poststenting systolic FFR (0.84 vs 0.74, p=0.08). The best poststenting mean FFR cutoff value for predicting restenosis was 0.92 (sensitivity 0.64, specificity 0.91). The 4.5% restenosis rate at 12 months in the high (>0.92) poststenting mean FFR group was significantly lower (35.7%, p=0.008) than in the low (≤0.92) poststenting mean FFR group. Conclusion: Poststenting mean FFR is useful for predicting restenosis in SFA disease.

The efficacy of second-generation drug-eluting stent (DES) for the treatment of left main disease (LM) and/or three vessel disease (3VD) remains unclear. We compared 2-year outcomes of second- versus first -generation DES implantation among patients with LM and/or 3VD and to assess the differential of risk by complexity of coronary artery disease using synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) scores. Between April 2007 and December 2012, 341 patients with LM and/or 3VD were treated by percutaneous coronary intervention; 154 with first-generation DES and 137 with second-generation DES. After propensity matching, 101 patients remained in each group. The rate of target lesion revascularization (TLR) and major adverse cardiac event (MACE) were compared. TLR and MACE at 2 years were more common in the first- compared with second-generation DES group (TLR 19.8 vs. 8.9 %; p = 0.016, MACE 24.8 vs. 10.9 %; p = 0.008). In patients with low (0-22) and intermediate (23-32) SYNTAX scores, TLR and MACE tended to occur more often with first-generation DES group. In patients with high SYNTAX scores (≧33), TLR and MACE were significantly more common with first-generation DES group (TLR 29.0 vs. 11.1 %; p = 0.035, MACE 35.5 vs. 13.9 %; p = 0.034). Compared with first-generation DES, second-generation DES proved beneficial in reducing risk of TLR and MACE in patients with LM and/or 3VD, particularly among those with high SYNTAX scores (≧33).

A 62-year-old man with effort angina underwent percutaneous coronary intervention in our hospital. The target lesion was severely calcified at the mid part of the right coronary artery. Pre-procedural intravascular imaging and optical frequency domain imaging showed a calcified nodule at the lesion. We performed rotational atherectomy with a 2.0 mm burr and observed an increase in the lumen area; however, a large amount of calcified nodule persisted. We decided to perform rotational atherectomy with a burr size of 2.25 mm; however, distal embolization of the calcified nodule occurred. We failed to retrieve the embolus; hence, we performed balloon dilatation with a 2.0-mm balloon, which was successfully performed. Yet, the lesion with the embolus immediately recoiled. Finally, a drug-eluting stent was implanted in both the distal lesion with the embolus and the lesion with the calcified nodule. Final coronary angiography showed good results. We confirmed good stent expansion and that calcified nodule was compressed outside the stent. Atherectomy of a calcified nodule is effective at achieving sufficient stent expansion and reducing the risk of vessel perforation. However, we experienced distal embolization of the calcified nodule at the time of rotational atherectomy and so distal embolization should be considered at the time of treatment of calcified nodule.

Background This study aimed to elucidate the prognostic value of objective nutritional status after transcatheter aortic valve replacement (TAVR). Methods This study enrolled 150 consecutive patients who underwent TAVR between February 2014 and March 2017. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score before TAVR. Patients were divided into a high CONUT score (malnutrition status >4 points, n = 30) or low CONUT score (normal nutritional status 1–4 points, n = 120) group. The primary endpoint was mortality within 1-year post-TAVR. Results Patients in the high CONUT group were characterized by low body mass index (kg/m2) (20.3 ± 2.4 vs. 22.8 ± 3.5, p Conclusions Objective malnutrition status was predictive of mortality post-TAVR and provided complementary prognostic information to the CFS. Thus, objective nutritional status may refine the clinical risk stratification of patients who undergo TAVR.

A 78-year-old woman had paroxysmal atrial fibrillation and effort angina. Two months before she was admitted for a coronary angiography, she had been feeling dizzy. A Holter 24-hour electrocardiography monitor exhibited an asymptomatic episode of 2.9 seconds of RR interval. She underwent a coronary angiography, which showed intermediate stenosis in the left descending artery. Fractional flow reserve (FFR) measurement using intracoronary papaverine administration was performed. After intracoronary papaverine (12 mg) administration, pause of 4 seconds led to polymorphic ventricular tachycardia (VT), although the VT terminated spontaneously. Premature ventricular beat occurred and led to sustained polymorphic VT. In cardiac electrophysiology study, pacing from the right atrium showed that the maximum sinus node recovery time (SRT) was 910 ms. After procainamide (10 mg/kg) administration, the maximum SRT was 16.3 seconds with some junctional escapes. After intravenous papaverine administration, there was a slight change. Intracoronary papaverine administration induced about 9-seconds pause with some junctional escapes. We conclude that intracoronary papaverine administration reveals potential sinus node dysfunction. The patient has been asymptomatic since the implantation of the pacemaker. Patients with suspicious sinus dysfunction should be careful.

We compared first-generation and second-generation drug-eluting stent (DES) with respect to neoatherosclerosis using optical coherence tomography or optical frequency domain imaging. In-stent restenoses in 102 first-generation and 114 second-generation DES were retrospectively assessed. Neoatherosclerosis, which was defined as the presence of lipid-laden neointima or calcification inside a stent, was observed in 33 (27.2%) and 31 (32.4%) lesions in the first-generation and second-generation DES respectively. In the first-generation DES group, the lipid length was significantly longer (5.5 ± 3.8 vs. 3.1 ± 2.1 mm, P = 0.0007), the lipid arc was significantly larger (324 ± 70° vs. 250 ± 94°, P = 0.002), the prevalence of a 360° lipid arc was significantly greater (58 vs. 31%, P = 0.03), and the fibrous cap was significantly thinner (153 ± 85 vs. 211 ± 95 µm, P = 0.02) compared with those in the second-generation DES group. These differences remained significant after adjusting for the age of the stent (lipid length: P

Aim The optimal fractional flow reserve (FFR) measurement method for superficial femoral artery (SFA) lesions remains to be established. We clarified the optimal measuring procedure for FFR for SFA lesions and investigated the necessary dose of papaverine for inducing maximal hyperemia in SFA lesions. Methods Forty-eight patients with SFA lesions who underwent measurement of peripheral FFR (pFFR: distal mean pressure divided by proximal mean pressure) after endovascular treatment by the contralateral femoral crossover approach were prospectively enrolled. In the pFFR measurement, a guide sheath was placed on top of the common iliac bifurcation and pressure equalization was performed. After advancing the pressure wire distal to the SFA lesion, sequential papaverine administration selectively to the affected common iliac artery was performed. Results There were no symptoms, electrocardiogram changes, and significant pressure drops at the guide sheath tip with increasing papaverine dose. pFFR changes following 20, 30, and 40 mg of papaverine were 0.87±0.10, 0.84±0.10, and 0.84±0.10, respectively (P＜0.001). Although not significantly different, pFFR decreased more in several patients at 30 mg of papaverine than at 20 mg. The pFFR at 40 mg of papaverine was almost similar to that at 30 mg of papaverine. The necessary papaverine dose was not changed according to sex and number of run-off vessels. Conclusions The contralateral femoral crossover approach is useful in FFR measurement for SFA lesions, and maximal hyperemia is induced by 30 mg of papaverine.

Human myosin VIIA (HM7A) is responsible for human Usher syndrome type 1B, which causes hearing and visual loss in humans. Here we studied the regulation of HM7A. The actin-activated ATPase activity of full-length HM7A (HM7AFull) was lower than that of tail-truncated HM7A (HM7AΔTail). Deletion of the C-terminal 40 amino acids and mutation of the basic residues in this region (R2176A or K2179A) abolished the inhibition. Electron microscopy revealed that HM7AFull is a monomer in which the tail domain bends back toward the head-neck domain to form a compact structure. This compact structure is extended at high ionic strength or in the presence of Ca2+. Although myosin VIIA has five isoleucine-glutamine (IQ) motifs, the neck length seems to be shorter than the expected length of five bound calmodulins. Supporting this observation, the IQ domain bound only three calmodulins in Ca2+, and the first IQ motif failed to bind calmodulin in EGTA. These results suggest that the unique IQ domain of HM7A is important for the tail-neck interaction and, therefore, regulation. Cellular studies revealed that dimer formation of HM7A is critical for its translocation to filopodial tips and that the tail domain (HM7ATail) markedly reduced the filopodial tip localization of the HM7AΔTail dimer, suggesting that the tail-inhibition mechanism is operating in vivo. The translocation of the HM7AFull dimer was significantly less than that of the HM7AΔTail dimer, and R2176A/R2179A mutation rescued the filopodial tip translocation. These results suggest that HM7A can transport its cargo molecules, such as USH1 proteins, upon release of the tail-dependent inhibition. Background: Regulation of myosin VIIA (HM7A) has been studied in Drosophila but not in humans. Results: The tail domain inhibits HM7A ATPase activity and translocation to filopodial tips. Conclusion: The tail domain inhibition mechanism of HM7A is operating both in vitro and in vivo. Significance: The results provide a clue to understand the mechanism of human Usher syndrome.

For a knot K with Δ K ( t ) ≐ t 2 − 3 t + 1 in a homology 3-sphere, let M be the result of 2 / q -surgery on K. We show that appropriate assumptions on the Reidemeister torsion and the Casson–Walker–Lescop invariant of the universal abelian covering of M imply q = ± 1 , if M is a Seifert fibered space.

Objectives This study investigated the safety and prognosis of ultra-long second DES (UL-2nd DES) implantation in real-world practice. Background Long stenting is a widely known predictor of stent thrombosis (ST) or target lesion revascularization (TLR) in first-generation drug-eluting stents (DES). Methods Participants were 1,669 patients (2,763 lesions) who had undergone successful second DES implantation; they were assigned to one of three groups: ultra-long 2nd DES (UL-DES; >50 mm, 166 patients, 259 lesions), long second DES (L-DES; 20–50 mm, 758 patients, 1,212 lesions), or short second DES (S-DES

Streptococcal toxic shock syndrome (STSS) is a life-threatening disease caused by infection of beta-hemolytic streptococci. Here, we report an uncommon case of STSS with both diffuse peritonitis and necrotizing fasciitis and summarize previous cases. The patient was diagnosed with STSS due to an infection of the soft tissue of the lower extremity after surgery for diffuse peritonitis. The general condition had rapidly deteriorated with multiple organ dysfunction. Immediate intensive care, including mechanical ventilation, hemodiafiltration, and repeated debridement, is indispensable for a favorable outcome.

We aimed to evaluate the optical frequency-domain imaging (OFDI) findings after rotational atherectomy (RA) that predict good stent expansion for severely calcified coronary lesions. Fifty consecutive calcified lesions were subjected to RA under OFDI guidance. We performed OFDI just after RA and stenting. We measured the morphology of calcium after RA, and assessed how these factors influence stent expansion. The stent expansion index was defined as the minimum stent area divided by the average of the proximal and distal reference lumen areas. Minimum thickness of calcification in the intima after RA showed a significant negative correlation with stent expansion (r = − 0.53, P

Polymeric component is associated with the increased risk of delayed vessel healing and stent endothelialization. We aimed to clarify neointimal coverage within 1 month after implantation of the new-generation abluminal biodegradable polymer (BP) drug-eluting stent (DES) compared with the second-generation durable polymer (DP) everolimus-eluting stent (EES). Between November 2015 and October 2016, 32 BP-DES and 25 DP-EES were evaluated by optical frequency domain imaging (OFDI) within 1 month after the procedure. The average interval to follow-up OFDI was not significantly different between the groups (16.3 ± 7.7 days in BP-DES vs. 15.4 ± 7.4 days in DP-EES, P = 0.75). Neointimal coverage was significantly superior in BP-DES in both apposed and malapposed strut (apposed: 53.9% in BP-DES vs. 28.0% in DP-EES, P 0.001; malapposed: 22.9% in BP-DES vs. 7.5% in DP-EES, P = 0.001). When the follow-up period was divided into 2 and 2 weeks, neointimal coverage was also significantly superior in BP-DES ( 2 weeks: 47.7% in BP-DES vs. 19.2% in DP-EES, P 0.001; 2 weeks: 60.1% in BP-DES vs. 37.4% in DP-EES, P = 0.001). The new-generation BP-DES showed excellent early neointimal coverage compared with the second-generation DP-EES in both apposed and malapposed struts.

OBJECTIVES We clarified characteristics and clinical outcomes of critical limb ischemia (CLI) patients who underwent repeat endovascular therapy (EVT) for infrapopliteal lesions. BACKGROUND High restenosis rate after infrapopliteal EVT remains a major concern. METHODS Patients with CLI who underwent EVT between April 2007 and February 2014, were divided into the following three groups according to how often EVT was repeated: Group A, no repeat of EVT; Group B, EVT repeated once/twice; and Group C, EVT repeated ≥3 times. RESULTS Wound healing rates at 1 year were 93.9% in Group A, 77.1% in Group B, and 27.3% in Group C (P

Motor activity of myosin III is regulated by autophosphorylation. To investigate the role of the kinase activity on the transporter function of myosin IIIA (Myo3A), we identified the phosphorylation sites of kinase domain (KD), which is responsible for the regulation of kinase activity and thus motor function. Using mass spectrometry, we identified six phosphorylation sites in the KD, which are highly conserved among class III myosins and Ste20-related misshapen (Msn) kinases. Two predominant sites, Thr¹⁸⁴ and Thr¹⁸⁸, in KD are important for phosphorylation of the KD as well as the motor domain, which regulates the affinity for actin. In the Caco2 cells, the full-length human Myo3A (hMyo3AFull) markedly enlarged the microvilli, although it did not show discrete localization within the microvilli. On the other hand, hMyo3AFull(T184A) and hMyo3AFull(T188A) both showed clear localization at the microvilli tips. Our results suggest that Myo3A induces large actin bundle formation to form microvilli, and phosphorylation of KD at Thr¹⁸⁴ and Thr¹⁸⁸ is critical for the kinase activity of Myo3A, and regulation of Myo3A translocation to the tip of microvilli. Retinal extracts potently dephosphorylate both KD and motor domain without IQ motifs (MDIQo), which was inhibited by okadaic acid (OA) with nanomolar range and by tautomycetin (TMC) with micromolar range. The results suggest that Myo3A phosphatase is protein phosphatase type 2A (PP2A). Supporting this result, recombinant PP2Ac potently dephosphorylates both KD and MDIQo. We propose that the phosphorylation-dephosphorylation mechanism plays an essential role in mediating the transport and actin bundle formation and stability functions of hMyo3A.