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In acute aortic dissection, weekend admissions are reported to be associated with increased mortality compared with weekday admissions.This study aimed to determine whether patients with acute type A aortic dissection (ATAAD) admitted on weekends had higher in-hospital mortality than those admitted on weekdays in the Tokyo metropolitan area, where we developed a patient-transfer system for aortic dissection.Data were collected during the first year after our transfer system began (cohort I) and in the subsequent years from 2013 to 2015 (cohort II).We studied 2,339 patients (500 in cohort I; 1,839 in cohort II) with ATAAD. Patients with weekend admissions had higher in-hospital mortality than those with weekday admissions in cohort I. In association with increased interfacility transfer during weekends and reduced mortality at non-high-volume centers, the in-hospital mortality in the weekend group improved from 37.2% in cohort I to 22.2% in cohort II (We found a significant reduction in in-hospital mortality in patients with weekend admissions for ATAAD. No mortality difference between weekend and weekday admissions was observed in the later years of the study.

OBJECTIVES Preventing loss of life in patients with type A acute aortic dissection (AAD) who present with cardiopulmonary arrest (CPA) can be extremely difficult. Thus, we investigated the early outcomes in these patients. METHODS Patients with type A AAD who were transported to hospitals belonging to the Tokyo Acute Aortic Super-network between January 2015 and December 2019 were considered for this study. We assessed the early mortality of these patients presenting with CPA and also investigated the differences in outcomes between patients with out-of-hospital and in-hospital CPA. RESULTS A total of 3307 patients with type A AAD were transported, 434 (13.1%) of whom presented with CPA. The overall mortality of patients presenting with CPA was 88.2% (383/434), of which 94.5% (240/254) experienced out-of-hospital CPA and 79.4% (143/180) experienced in-hospital CPA (P CONCLUSIONS Patients with type A AAD presenting with CPA exhibited extremely high rates of death. Patient outcomes following in-hospital CPA tended to be better than those following out-of-hospital CPA; however, this difference was not significantly different. To prevent deaths, aortic surgery, when possible, should be considered in patients with type A AAD who sustained CPA.

A 53-year-old male undergoing emergency aortic valve replacement for infective endocarditis developed a hypertensive crisis early during the operation. Suspecting a pheochromocytoma, intravenous phentolamine was immediately administered, after which the procedure was completed as scheduled. Although quite rare, a pheochromocytoma can be encountered during emergency open heart surgery; thus, early recognition of abnormal blood pressure change and appropriate management are important. Here, we present details of blood pressure control mainly by use of phentolamine, in this case, to demonstrate effective management of a hypertensive crisis during emergency cardiac surgery because of a pheochromocytoma.

Although acute type A aortic dissection is relatively rare in young adults, patients with connective tissue diseases are at a higher risk for developing this condition. To the best of our knowledge, type A aortic dissection due to endocrine diseases has been rarely reported. Here, we present a case of acute type A aortic dissection due to primary aldosteronism in a young man with adrenal adenoma. Total arch replacement was successfully performed. Postoperative imaging and endocrine evaluation revealed an adrenal adenoma. This study highlights the importance of considering primary aldosteronism as a potential etiology of acute aortic dissection in young adults. LEARNING OBJECTIVE: Generally, direct or indirect causes of acute type A aortic dissection (ATAAD) are highly diversified. We tend to suspect the familial aortic diseases such as Marfan syndrome when patients with ATAAD are young adults. By contrast, it is useful to know that endocrine diseases such as primary aldosteronism with functional adenoma can be risk factors of ATAAD in young adults.

In patients with multivessel disease (MVD), functional information on lesions improves the prognostic capability of the SYNTAX score. Quantitative flow ratio (QFR®) is an angiography-derived fractional flow reserve (FFR) that does not require a pressure wire or pharmacological hyperemia. We aimed to investigate the feasibility of QFR-based patient information in Heart Teams' discussions to determine the optimal revascularization strategy for patients with MVD. We hypothesized that there is an acceptable agreement between treatment recommendations based on the QFR approach and recommendation based on the FFR approach. The DECISION QFR study is a prospective, multicenter, randomized controlled trial that will include patients with MVD who require revascularization. Two Heart Teams comprising cardiologists and cardiac surgeons will be randomized to select a revascularization strategy (percutaneous coronary intervention or coronary artery bypass graft) according to patient information either based on QFR or on FFR. All 260 patients will be assessed by both teams with reference to the anatomical and functional SYNTAX score/SYNTAX score II 2020 derived from the allocated physiological index (QFR or FFR). The primary endpoint of the trial is the level of agreement between the treatment recommendations of both teams, assessed using Cohen's κ. As of March 2022, the patient enrollment has been completed and 230 patients have been discussed in both Heart Teams. The current trial will indicate the usefulness of QFR, which enables a wireless multivessel physiological interrogation, in the discussions of Heart Teams to determine the optimal revascularization strategy for MVD.

We implemented our multidisciplinary heart team (MHT) approach since 2012 for patients with coronary artery disease (CAD) and assessed the effectiveness of it by comparing outcomes in patients treated before and after the introduction of the MHT approach. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for CAD were performed in 802 and 57 patients from 2009 to 2011 in Group NH, and were performed in 867 and 160 patients from 2012 to 2014 in Group H, respectively. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE), defined as the composite of all-cause death, myocardial infarction, stroke, cardiac-related readmission and target vessel repeat revascularisation (TVR) for PCI or revascularisation on grafted vessels for CABG. MACCE occurred significantly more often in Group NH than in Group H at 3 years postoperatively (28.1% vs 21.1%) (log rank P = 0.001). Cox regression analysis showed that the MHT approach [hazard ratio (HR), 0.737; 95% confidence interval (CI), 0.60–0.91; P = 0.004] and ejection fraction (HR 0.976; 95% CI, 0.97–0.98; P

Objectives Although aortic annulus repair has a long history, there are still no ideal devices to control an aortic annulus. We have developed a new method involving the use of an expanded polytetrafluoroethylene graft with the support of a metallic ring holder during implantation from inside an aorta, with no dissection of the surrounding aortic annulus. Methods We used aortic annular rings of 18 to 24 mm made of Gore-Tex tubed grafts (W.L. Gore & Associates, Flagstaff, AZ, USA) and metallic ring holder. After cutting the graft circumferentially to a 5-mm thickness, it was compressed manually to decrease the thickness. Then, a metallic ring holder corresponding to the graft size was inserted into the graft. The metallic ring holder was fixed to the graft with one 4–0 monofilament suture using 6 holes and the side trench on the metallic ring holder. The proper size for the graft was determined, and the appropriate annuloplasty ring was selected. A row of 4–0 double-needle braided sutures with expanded polytetrafluoroethylene spaghettis was sewn from the aortic side into the left ventricular outflow tract with a horizontal mattress stitch. After all sutures around the annulus were placed, they were tied down and the metallic ring holder was removed. The leaflets were repaired if necessary. Results A total of 9 patients with tricuspid aortic valve have undergone this procedure since January 2015. The sizes of the aortic annular rings were 20 mm ( n = 3), 22 mm ( n = 5), and 24 mm ( n = 2). Aortic leaflets were repaired in 6 patients (6 central plications). Concomitant procedures were total aortic arch replacement ( n = 2), mitral valve repair ( n = 2), tricuspid valve repair ( n = 1), and coronary artery bypass grafting ( n = 2). There were no hospital deaths and no major morbidities. All patients were checked for mild or less than mild aortic regurgitation during the mean follow-up period of 13 months. Postoperative echocardiograms showed excellent peak pressure gradients compared with preoperative echocardiograms. Postoperative cardiac computed tomography scans were performed in 6 patients. The discrepancies between the ring size used and postoperative annular size were Conclusions This new flexible ring is easy to use to fix an aortic annulus from the inside. Early results reveal excellent control of aortic regurgitation with the projected annular size. Further investigations are needed to ensure the effectiveness of the ring.

Influenza virus RNA polymerase has cap-dependent endonuclease activity that produces capped RNA fragments for priming viral mRNA synthesis. This enzymatic activity is essential for viral propagation, but it is not present in any host cellular enzyme, making it an attractive target for the development of anti-influenza drugs. Here, we isolated a novel inhibitor of cap-dependent endonuclease, named flupyranochromene, from the fermentation broth of the fungus Penicillium sp. f28743. Structural analysis revealed that this compound bears a putative pharmacophore that chelates divalent metal ion(s) present in the endonuclease active site in the PA subunit of the polymerase. Consistently, in vitro endonuclease assays showed that flupyranochromene exerts its inhibitory effects by blocking endonucleolytic cleavage by the PA subunit of viral RNA polymerase complex.

OBJECTIVES We investigated the various pre- and postoperative complications related to early (30-day) mortality after open surgery for acute type A aortic dissection. METHODS Data from the Tokyo Acute Aortic Super-network database spanning January 2015 to December 2017 were retrospectively reviewed. Pre- and postoperative factors related to early postoperative mortality were assessed in 1504 of 2058 (73.0%) consecutive patients [age: 66.6 (SD: 13.5) years, male: 52.9%] who underwent acute type A aortic dissection repair. RESULTS The early mortality rate following surgical repair was 8.9%. According to multivariable analysis, male sex [odds ratio (OR) 1.670, 95% confidence interval (CI) 1.063–2.624, P = 0.026], use of percutaneous circulatory assist devices (n = 116, 7.7%) including extracorporeal membrane oxygenators or intra-aortic balloon pumps (OR 4.857, 95% CI 2.867–8.228, P CONCLUSIONS Not only critical preoperative conditions but also postoperative cardiac tamponade and vital organ ischaemia are risk factors for early mortality after acute type A aortic dissection repair.

Hepatitis B virus (HBV) is the causative agent of chronic liver disease and is correlated with the development of subsequent hepatic cirrhosis and hepatocellular carcinoma. Current antiviral therapy using nucleos(t)ide analogs is effective in suppressing viral replication and interrupting disease progression, but HBV is rarely cured completely. Thus, there remains an unmet need for the development of novel anti-HBV drugs. Here, we report the identification of N-(4-Nitrophenyl)-1-phenylethanone hydrazone (ANPH) as a novel structural class of selective inhibitors targeting the replication of the HBV genome using adenovirus vector-mediated HBV genome transduction. ANPH inhibited viral genome replication in HepG2.2.15 cells by inducing the formation of empty capsids devoid of pregenomic RNA without affecting its transcription and translation. Biochemical assays using a truncated core protein consisting of the assembly domain showed that ANPH accelerates the formation of morphologically intact capsids. Taken together, we propose that ANPH might provide a new structural scaffold to design a new anti-HBV drug in medicinal chemistry as well as chemical probes for HBV core protein functions in the future.

A 53-year-old male undergoing emergency aortic valve replacement for infective endocarditis developed a hypertensive crisis early during the operation. Suspecting a pheochromocytoma, intravenous phentolamine was immediately administered, after which the procedure was completed as scheduled. Although quite rare, a pheochromocytoma can be encountered during emergency open heart surgery, thus early recognition of abnormal blood pressure change and appropriate management are important. Here, we present details of blood pressure control mainly by phentolamine use in this case to demonstrate effective management of a hypertensive crisis during emergency cardiac surgery because of a pheochromocytoma.

Myxomas account for a majority of the reported primary cardiac tumors that are relatively rare, and biatrial myxomas in an atrial septal defect are extremely rare. Here, we present the case of a healthy 79-year-old woman who was referred to our hospital after a giant mass in the left atrium was incidentally detected by transthoracic echocardiography. Although she was asymptomatic, we surgically resected the mass soon after admission, considering the risk of embolism. During the surgery, we observed the giant bilateral tumor in an atrial septal defect, which was, on pathological evaluation, found to be a myxoma.

Background Helicobacter cinaedi is rarely identified as a cause of infected aneurysms; however, the number of reported cases has been increasing over several decades, especially in Japan. We report three cases of aortic aneurysm infected by H. cinaedi that were successfully treated using meropenem plus surgical stent graft replacement or intravascular stenting. Furthermore, we performed a systematic review of the literature regarding aortic aneurysm infected by H. cinaedi. Case presentation We present three rare cases of infected aneurysm caused by H. cinaedi in adults. Blood and tissue cultures and 16S rRNA gene sequencing were used for diagnosis. Two patients underwent urgent surgical stent graft replacement, and the other patient underwent intravascular stenting. All three cases were treated successfully with intravenous meropenem for 4 to 6 weeks. Conclusions These cases suggest that although aneurysms infected by H. cinaedi are rare, clinicians should be aware of H. cinaedi as a potential causative pathogen, even in immunocompetent patients. Prolonged incubation periods for blood cultures are necessary for the accurate detection of H. cinaedi.

The no-touch saphenous vein harvesting technique is considered to be the ideal procedure to achieve the best quality of vein, whereas the endoscopic vein harvesting (EVH) technique is considered to be ideal for decreasing wound complications. We developed a new technique of EVH with perivascular tissue preservation. This procedure was performed by dissecting the immediate anterior and posterior perivascular connective tissues of the saphenous vein followed by cutting approximately 1 cm laterally from the saphenous vein with the use of a harvester (MAQUET Getinge Group, Getinge AB, Göteborg, Sweden). Histopathological examination revealed preserved perivascular tissue and intimal folding.

Congenital left ventricular diverticulum (CLVD) is a rare congenital anomaly and may be associated with fatal adverse events. A previously healthy 20-year-old man collapsed as a result of sudden ventricular fibrillation (VF). Despite intractable VF, he had return of spontaneous circulation with cardiopulmonary resuscitation and subsequent introduction of venoarterial extracorporeal membrane oxygenation (ECMO). After ECMO was discontinued, cardiac magnetic resonance imaging revealed CLVD at the posterolateral wall of the left ventricle. Given the risk of recurrent VF and left ventricular rupture, he underwent surgical repair for CLVD and implantation of a subcutaneous implantable cardioverter defibrillator.

While the incidence of endograft infection is very low, the treatment is difficult when it occurs. We herein present the case of a 52-year-old male who had undergone a graft replacement in the proximal descending thoracic aorta for dissected aortic aneurysm (DA) 6 years previously and hybrid surgery 2 years previously, which consisted of an abdominal graft replacement, visceral and renal debranching surgery and endovascular surgery for a ruptured abdominal DA and residual thoracoabdominal DA. Following collapse from septic shock due to an endograft infection, we performed an in situ reconstruction of the entire thoracoabdominal aorta following intensive antibiotic therapy and 2 preoperative CT-guided percutaneous interventions. He was discharged 4 weeks after the surgery without any complications.

Viral infections are a major global health threat. Over the last 50 years, significant efforts have been devoted to the development of antiviral drugs and great success has been achieved for some viruses. However, other virus infections, such as epidemic influenza, still spread globally and new threats continue to arise from emerging and re-emerging viruses and drug-resistant viruses. In this review, the contributions of microbial products isolated in Institute of Microbial Chemistry for antiviral research are summarized. In addition, the current state of development of antiviral drugs that target influenza virus and hepatitis B virus, and the future prospects for antivirals from natural products are described and discussed.The Journal of Antibiotics advance online publication, 11 October 2017; doi:10.1038/ja.2017.115.

There are no previous reports of intraabdominal sarcoma with metastasis to the thoraco-abdominal aorta causing rupture. Here we present the case of a previously healthy 50-year old male who presented to our institution with sudden, sharp back pain. Chest and abdominal computed tomography revealed aortic rupture at the twelfth thoracic level as well as a giant mass in the left upper abdomen. We performed thoracic endovascular aortic aneurysm repair. Histopathology of a biopsy taken from a rib metastasis was thought to be either differentiated liposarcoma or malignant fibrous histocytoma. The patient is currently undergoing chemotherapy. .

The complicated replication mechanisms of hepatitis B virus (HBV) have impeded HBV studies and anti-HBV therapy development as well. Herein we report efficient genome replication of HBV applying adenovirus vectors (AdVs) showing high transduction efficiency. Even in primary hepatocytes derived from humanized mice the transduction efficiencies using AdVs were 450-fold higher compared than those using plasmids. By using an expression unit consisting of the CMV promoter, 1.03-copy HBV genome and foreign poly(A) signal, we successfully generated an improved AdV (HBV103-AdV) that efficiently provided 58 times more pregenomic RNA than previously reported AdVs. The HBV103-AdV-mediated HBV replication was easily and precisely detected using quantitative real-time PCR in primary hepatocytes as well as in HepG2 cells. Notably, when the AdV containing replication-defective HBV genome of 1.14 copy was transduced, we observed that HBV DNA-containing circular molecules (pseudo-ccc DNA) were produced, which were probably generated through homologous recombination. However, the replication-defective HBV103-AdV hardly yielded the pseudo-ccc, probably because the repeated sequences are vey short. Additionally, the efficacies of entecavir and lamivudine were quantitatively evaluated using this system at only 4 days postinfection with HBV103-AdVs. Therefore, this system offers high production of HBV genome replication and thus could become used widely.

Yeast capping enzymes differ greatly from those of mammalian, both structurally and mechanistically. Yeast-type capping enzyme repressors are therefore candidate antifungal drugs. The 5′-guanine-N7 cap structure of mRNAs are an essential feature of all eukaryotic organisms examined to date and is the first co-transcriptional modification of cellular pre-messenger RNA. Inhibitors of the RNA 5′-triphosphatase in yeast are likely to show fungicidal effects against pathogenic yeast such as Candida. We discovered a new RNA 5′-triphosphatase inhibitor, designated as the kribellosides, by screening metabolites from actinomycetes. Kribellosides belong to the alkyl glyceryl ethers. These novel compounds inhibit the activity of Cet1p (RNA 5′-triphosphatase) from Saccharomyces cerevisiae in vitro with IC50s of 5–8 μM and show antifungal activity with MICs ranging from 3.12 to 100 μg ml−1 against S. cerevisiae.

Double-orifice mitral valve (DOMV) is a relatively rare cardiac anomaly. Although usually associated with various cardiac anomalies, co-presence of DOMV and noncompaction of left ventricular myocardium (NCLVM) is extremely rare. Here, we present a 24-year-old male who underwent mitral valve repair using artificial chordae and annuloplasty at the posterior commissure for severe mitral regurgitation (MR), resulting from flail anterior leaflet of the larger postero-medial orifice and dilatation of left ventricle with NCLVM. One year later, he underwent second mitral valve repair for recurrence of MR. Further endoscopic evaluation of the left ventricle, and reinforcement via artificial ring, enabled us to achieve repair.

ATG7 is an autophagy-related E1-like enzyme that is essential for two ubiquitination-like reactions, ATG12-conjugation and LC3-lipidation. The existence of functional sequences at the amino-terminal region of human ATG7 remains uncertain. Mutational analyses of ATG7 revealed that both mutant ATG7ΔFAP lacking the FAP motif and ATG7FAPtoDDD, in which the Phe15-Ala16-Pro17 sequence was changed to Asp-Asp-Asp, could not complement defects in endogenous ATG12-conjugation and LC3-lipidation when expressed in Atg7-deficient mouse embryonic fibroblasts (MEFs). However, wild-type ATG7 complemented the defects in these cells. Overexpression of GFP-ATG10 and GFP-ATG12 rescued a defect in ATG12-conjugation in Atg7-deficient MEFs expressing mutant ATG7ΔFAP and ATG7FAPtoDDD, whereas overexpression of all ATG proteins related to ATG12-conjugation and LC3-lipidation could not rescue a defect in LC3-lipidation in Atg7-deficient MEFs expressing these ATG7 mutants. Both ATG7ΔFAP and ATG7FAPtoDDD mutants showed severe defects in the formation of an E2-substrate intermediate of ATG3 with LC3 in LC3-lipidation, but were able to form an E1-substrate intermediate of ATG7 with LC3 and the E1- and E2-substrate intermediates in ATG12-conjugation with reduced efficiency. These ATG7 mutants could also form the ATG12-ATG3 conjugate. Co-immunoprecipitation experiments revealed that the FAP motif of ATG7 is essential for the interaction of ATG7 with ATG3, but not for ATG7-homodimerization. These results indicated that the FAP motif of ATG7 is indispensable for formation of the ATG3-LC3 E2-substrate intermediate through the interaction of ATG7 with ATG3.

We report two cases of non-obstructive mesenteric ischemia (NOMI), a rare but potentially lethal complication after cardiovascular surgery, which was successfully managed. In both cases (a 74-year-old chronic hemodialysis patient who underwent emergency aortic valve replacement and coronary artery bypass graft (CABG), and a 74-year-old patient who underwent emergency abdominal aortic aneurysm operation), NOMI occurred early postoperatively (on day 8 and 22, respectively). They suffered from severe abdominal pain, confusion, and metabolic acidosis. Contrast-enhanced multi-detector CT (MDCT) scan and subsequent selective mesenteric angiography revealed characteristic signs of NOMI, for which selective papaverine infusion through the angiography catheter was performed. It was effective in both cases to halt progressive bowel ischemia and bided our time to perform a hemicolectomy of the necrotic segment. Contrast-enhanced MDCT scan and subsequent selective angiography are vital for diagnosis. If the condition does not improve after selective papaverine infusion, exploratory laparotomy and resection of necrotic intestinal segment should be performed immediately.

For a 75 year-old man with extensive aortic aneurysm, who had undergone a previous infra-renal abdominal Y-graft, a staged replacement of remaining segments was performed. A hybrid procedure of open-laparotomy debranching of visceral branches and endovascular stentgraft insertion in the thoracoabdominal aorta was performed first, followed by subsequent direct replacement between the proximal ascending and distal arch using cardiopulmonary bypass. Three months thereafter dissection of enlarged proximal descending aorta occurred, for which we performed an emergent endovascular stentgraft deployment which bridged “elephant trunk” of the arch graft and the previous stentgraft. Consequently total aortic replacement was successfully accomplished without any neurological sequela.

A 62-year-old man with past history of chronic atrial fibrillation, congestive heart failure, and pneumonia was referred to our hospital for further workup of pulmonary sequestration. Enhanced computed tomography revealed intralobar pulmonary sequestration (IPS) of the lower left lobe, as well as aortic aneurysmal dilation at the origin of the aberrant feeding artery. We performed a hybrid operation consisting of thoracic endovascular aortic repair and excision of the IPS and left lower lobe by video-assisted thoracic surgery. The patient was discharged 5 days later without complications.

The proper management of a patient with active infective endocarditis (IE) remains to be determined, especially when his or her condition is complicated with intracranial mycotic aneurysm. Here we present a 46-year-old company employee hospitalized with a subarachnoid hemorrhage caused by a ruptured mycotic aneurysm. Cardiac echography showed a verruca on the posterior mitral cusp and leaflet destruction, resulting in severe valvular regurgitation (determined pathogen was α-streptococcus). High-dose antibiotic infusion and restriction of physical activity to prevent heart failure were combined with emergency craniotomy drainage and coiling of the necks of two cerebral mycotic aneurysms. After 2 months of conservative therapy for IE, he suddenly collapsed with hypotension and bradycardia because of embolic occlusion of the proximal right coronary artery (RCA). An emergent operation was carried out to remove the emboli in the RCA and to replace the mitral valve with a mechanical prosthesis. The postoperative course was uneventful. Although disturbances of spatial recognition and manual dexterity remained, he was able to walk and talk. After postoperative sufficient-duration antibiotic therapy, which lasted 20 days, he was transferred to a rehabilitation center.

Environmental isolates of Salmonella enterica serover Enteritidis (S. Enteritidis) clones were grown to the logarithmic phase, washed and re-suspended in saline or Luria-Bertani (LB) medium, and then 10-µL aliquots of the suspensions were dried overnight at room temperature. The dried bacteria were mixed with 1 mL of ice-cold PBS, suspended and examined for colony-forming activity. All of the pathogenic clones with high levels of SEp22, identical to Salmonella Dps, maintained good viability if suspended in LB medium prior to drying. However, none of the non-virulent strains, exhibiting low levels of SEp22, survived. Similar results were obtained with sep22-knocked out mutants, suggesting that SEp22 is important for the acquisition of dry-resistance. Nutritional factors, such as LB medium, cabbage extracts, and egg yolk but not egg white, were shown to be necessary for the acquisition of dry-resistance, because none of the clones remained viable irrespective of SEp22 expression if suspended in saline. Scanning electron micrograms also supported the importance of nutrition, showing re-growth of the bacteria after drying in LB but not in saline. These results suggest the importance of both SEp22 expression and nutrients for the acquisition of dry-resistance by S. Enteritidis.

Background Graft stenosis may be associated with future graft failure. The purpose of this investigation was to compare graft stenosis between radial artery (RA) grafts and saphenous vein grafts (SVGs) at least 5 years postoperatively using the multicenter Radial Artery Patency Study (RAPS) data. Methods Two hundred thirty-four patients underwent late invasive angiography after coronary artery bypass operations. The study population consists of 163 patients with thrombolysis in myocardial infarction (TIMI) 3 flow of both the RA graft and study SVGs. Angiograms were reviewed centrally and in a blinded fashion. Graft stenosis was recorded for the proximal anastomosis, graft body, and distal anastomosis; significant stenosis was defined as greater than or equal to 50%. Major adverse cardiac events (MACE) were reported in patients with and those without significant graft stenosis. Results There was no difference in significant graft stenosis of the patent RA grafts and SVGs (14 of 163 [8.6%] versus 19 of 163 [11.7%]) or in the proximal anastomosis (5 of 163 [3.1%] versus 5 of 163 [3.1%]), graft body (6 of 163 [3.7%] versus 13 of 163 [8.0%]), or distal anastomosis (4 of 163 [2.5%] versus 5 of 163 [3.1%]) considered separately. However, the overall burden of graft body disease was higher in SVGs ( p = 0.03). MACE was higher in patients with significant graft stenosis than in patients without stenosis (10 of 28 [35.7%] versus 7 of 135 [5.2%]; p Conclusions There was no significant difference in the rates of significant stenosis of patent RA grafts and SVGs more than 5 years postoperatively. However, the burden of graft body stenosis was less in RA grafts compared with SVGs, suggesting that the RA grafts will continue to outperform the SVGs late after operation.

Fibroblast-like stromal cells modulate cancer cells through secreted factors and adhesion, but those factors are not fully understood. Here, we have identified critical stromal factors that modulate cancer growth positively and negatively. Using a cell co-culture system, we found that gastric stromal cells secreted IL-6 as a growth and survival factor for gastric cancer cells. Moreover, gastric cancer cells secreted PGE2 and TNFα that stimulated IL-6 secretion by the stromal cells. Furthermore, we found that stromal cells secreted glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Extracellular GAPDH, or its N-terminal domain, inhibited gastric cancer cell growth, a finding confirmed in other cell systems. GAPDH bound to E-cadherin and downregulated the mTOR-p70S6 kinase pathway. These results demonstrate that stromal cells could regulate cancer cell growth through the balance of these secreted factors. We propose that negative regulation of cancer growth using GAPDH could be a new anti-cancer strategy.

We isolated and characterized a pathogenicity-related protein in Salmonella enterica serovar Enteritidis (SE) from poultry farms, and designated it as SEp22, which has recently been identified with Salmonella Dps, a DNA-binding protein (12, 13, Amano et al., manuscript in preparation). Expression of SEp22 was shown to be transcriptionally regulated, because another SE strain without virulence was found to possess a full-length non-mutated gene of sep22, but had little expression of SEp22 mRNA and much lower levels of SEp22 protein compared to the virulent standard strain SE Cl#15-1. Besides, expression of SEp22 was connected with bacterial growth, showing reduced expression in the logarithmic phase but increased expression from the late logarithmic to stationary phases. These changes were slightly later than those in σ 3 8 levels as well as SEp22 mRNA, suggesting that expression of SEp22 is under transcriptional control through RNA polymerase activity by σ 3 8 . In addition, high levels of SEp22 in the stationary phase were rapidly reduced upon incubation of the bacteria in fresh medium. This reduction was dependent on bacterial concentration in the culture, temperature, and time of incubation, suggesting proteolytic degradation of SEp22 in growing bacteria.

A 20-year-old man with fever and chest pain was referred to our hospital, where purulent pericarditis was confirmed by various examinations. Hemodynamic collapse and acute pulmonary edema occurred 1 week later, caused by acute severe aortic valvular regurgitation (AR). Emergency surgery revealed that the AR had been caused by avulsion of the aortic valvular commissure, which seemed to have resulted from penetration of the pericardial inflammatory process to the aortic root. We report this case because purulent pericarditis is now relatively uncommon and resultant aortic commissure avulsion is even rarer.

We describe the case of a 17-year-old boy with bicuspid aortic valve with two raphae, for whom subvalvular circular annuloplasty and adjustable cusp suspension procedures successfully terminated severe regurgitation.

Unicuspid aortic valve is a rare anomaly. We report 2 cases of successfully treated unicuspid valves with aortic dilatations by using a tricuspidization and reimplantation procedure. Two men, 35 and 39 years old, with severe aortic regurgitation and stenosis received this procedure. The sclerotic portion of a unicuspid valve, including 2 rudimentary commissures, was resected and reconstructed with autologous pericardium to create a tricuspid valve. An aortic root was replaced with a prosthetic graft. Postoperative echocardiogram showed trivial aortic regurgitation and minimal pressure gradient. Follow-up was 32 and 34 months, respectively. These valves remained stable in these periods. Tricuspidization and reimplantation is a promising procedure.

A 34-year-old man was admitted to our hospital because of sudden respiratory failure caused by massive pulmonary embolism. After arrival in the hospital, the patient experienced cardiopulmonary arrest, and we promptly initiated percutaneous cardiopulmonary support, in addition to sternal compressions for cardiopulmonary resuscitation. Computed tomography revealed massive pulmonary embolisms and intraperitoneal bleeding due to liver injury. After interventional hemostasis of the hepatic arteries, we performed emergent pulmonary embolectomy and hemostasis of the liver with gauze packing. Absence of further intraperitoneal bleeding was confirmed 2 days later on a second look. The patient was discharged 2 month later without neurologic sequelae.

We describe here an initial successful case of valve-sparing surgery using reimplantation technique in a 24-year-old male with aortic root dilatation with truncal valve insufficiency after common arterial trunk repair. Concomitant right ventricular outflow tract reconstruction with expanded polytetrafluoroethylene was also successfully performed. He was discharged home on postoperative day 10 without stenosis or regurgitation of repaired valves. He is in New York Heart Association class I condition without any anticoagulant agents 6 months after operation. Of course, careful follow-up will be needed though our early result is acceptable.

mRNA capping is the first cotranscriptional modification of mRNA in the nucleus. In Saccharomyces cerevisiae, the first two steps of mRNA capping are catalyzed by the RNA triphosphatase Cet1p and the RNA guanylyltransferase Ceg1p. Cet1p and Ceg1p interact to form a mRNA capping enzyme complex and the guanylyltransferase activity of Ceg1p is stimulated by binding with Cet1p. The Cet1p-Ceg1p complex needs to be transported into the nucleus, where mRNA capping occurs. However, the molecular mechanism of nuclear transport of the Cet1p-Ceg1p complex is not known. Here, we show that Cet1p is responsible and that the Cet1p-Ceg1p interaction is essential for the nuclear localization of the Cet1p-Ceg1p complex. The results indicate that the Cet1p-Ceg1p interaction is important not only for the activation of Ceg1p, but also for nuclear import of the complex.

The cancer tissue contains lots of stromal cells. Among them, fibroblast-like stromal cells regulate the growth of cancer cells positively and negatively through secreted factors and adhesion. We have been studying the interactions between cancer cells and stromal cells using small molecules that can modulate the interactions. We previously reported that gastric stromal cells enhance the growth of gastric cancer cells through secretion of IL-6, which is stimulated by gastric cancer cells through PGE2 and TNF-alpha reciprocally. Here we report that GAPDH, a house keeping protein, is a negative regulator of the interactions. By purifying the growth inhibitory activity against gastric cancer cells from secreted factors of gastric stromal cell we unexpectedly identified GAPDH as an active substance. While GAPDH is known to be secreted extracellularly, its growth inhibitory activity has not yet. As a result, GAPDH is found to be secreted from various organ-derived stromal cells and to inhibit the growth of various cancer cell lines. We have found that this growth inhibitory activity of GAPDH doesn't need its original enzymatic activity and GAPDH inhibits mTOR-p70S6 kinase pathway by binding to E-cadherin on cancer cell membranes. We propose that negative regulation of cancer growth using GAPDH could be a new anti-cancer strategy. Citation Format: Kawada Manabu, Junjiro Yoshida, Hiroyuki Inoue, Shun-ichi Ohba, Manabu Yamasaki, Ihomi Usami, Shuichi Sakamoto, Hikaru Abe, Takumi Watanabe, Akio Nomoto, Masakatsu Shibasaki. Stromal cells suppress cancer development by secreted GAPDH-E-cadherin interaction. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A196.

Septal hyper-contractility is thought to be the principal cause of significant left ventricular outflow tract obstruction (LVOT) and systolic anterior motion (SAM) of the mitral valve by making the distance between the mitral valve and papillary muscle shorter. A seven-year-old patient with severe hypertrophic obstructive cardiomyopathy underwent direct interventricular septal myectomy/myotomy using the resection/crush method to modify hyper-contractility. The procedure successfully reduced the pressure gradient from 180 mmHg to 7.6 mmHg, and systolic anterior movement of the mitral leaflet disappeared. Mitral regurgitation improved from grade 2 to grade 0. Postoperative echocardiographic vector velocity imaging (VVI) study revealed a reduced twist angle, depicting attenuated ventricular contraction power from a maximum twist 17.9° to 7.9°. Perioperative VVI revealed that interventricular septal myectomy/myotomy is useful, not only in reducing LVOT obstruction, but also in reducing hyper-contractility, which increases the distance from the mitral valve to the papillary muscle and relieves SAM.

Recently, several new anticoagulants have been used instead of warfarin for preventing thromboembolism. In the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, the direct thrombin inhibitor dabigatran etexilate was as an effective and safe as dose-adjusted warfarin for prevention of stroke in high-risk patients with atrial fibrillation. However, the safety and efficacy of thromboprophylaxis after mechanical valve replacement is uncertain. We report a 57-year-old man with a mechanical heart valve who experienced acute upper limb thromboembolism during dabigatran intake. Dabigatran might be inadequate for thromboprophylaxis after mechanical valve replacement.

Campylobacter jejuni is a microaerophilic bacterium that causes diarrhea in humans. The first step in establishing an infection is adherence to a host cell, which involves two major cell-binding proteins, Peb1A (CBF1) and Peb4 (CBF2). Because the functional role of Peb4 on the cell adhesion remains unclear compared with that of Peb1A, a C. jejuni peb4 deletion mutant was constructed and cell adherence and ability to colonize mouse intestine were studied. The result showed that adherence of the peb4 mutant strain to INT407 cells was 1-2% that of the wild-type strain. Mouse challenge experiments showed a reduced level and duration of intestinal colonization by the mutant compared with the wild-type strain. In addition, fewer peb4 mutant cells than wild-type cells responded to stress by forming a biofilm. Proteomic analysis revealed that the expression levels of proteins involved in various adhesion, transport, and motility functions, which are required for biofilm formation by the pathogen, were lower in the peb4 mutant than in the wild-type strain. A Peb4 homolog has prolyl cis/trans-isomerase activity, suggesting that the loss of this activity in the mutant strain may be responsible for the repression of these proteins.

An oxidative stress-sensitive protein was found in the microaerophile Campylobacter jejuni. A novel 27-kDa protein was found to decrease concomitantly with a decrease in viability from either exogenous H(2)O(2) stress or endogenous oxidative stresses in aerobic conditions. Sequence analyses revealed that the 27-kDa protein was identical to Cj0012c in C. jejuni NCTC11168 and its deduced 215 amino acid sequence has similarity to two non-heme iron proteins found in other bacteria, rubredoxin oxidoreductase (Rbo) and rubrerythrin (Rbr). Thus, we designated the protein as Rrc (Rbo/Rbr-like protein of C. jejuni). In H(2)O(2)-treated cells, Western blot analysis showed some bands smaller than Rrc, and RT-PCR showed similar expression of Rrc mRNA to the control without treatment, suggesting that the sensitive response of Rrc to oxidative stress is due to degradation of the protein.