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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Background Some adults suffer sudden cardiac death after previous surgical repair of tetralogy of Fallot (TOF), and in such cases, ventricular tachycardia is believed to be the most frequent cause of death. However, we report a case of cardiac arrest due to paroxysmal complete atrioventricular block in an adult with dextrocardia and repaired TOF. Case summary A 49-year-old woman with dextrocardia and a history of surgical treatment for TOF lost consciousness three times. A previously implanted loop recorder showed a 60-second cardiac arrest, and complete atrioventricular block was diagnosed. An electrophysiological study showed prolongation of the His-ventricular interval but no ventricular tachycardia. A dual chamber pacemaker was implanted, and there has been no recurrence of syncope in the 23 months since implantation. Discussion There is little evidence for paroxysmal complete atrioventricular block in patients with repaired TOF. This case suggests that paroxysmal complete atrioventricular block can occur late after surgical repair of TOF, and research needs to elucidate whether it is the cause of sudden cardiac death in some patients with TOF.

Background An association between uric acid (UA) and cardiovascular diseases, including heart failure (HF), has been reported. However, whether UA is a causal risk factor for HF is controversial. In particular, the prognostic value of lowering UA in patients with HF with preserved ejection fraction (HFpEF) is unclear. Methods and Results We enrolled patients with HFpEF from the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry. We investigated whether UA was correlated with the composite events, including all‐cause mortality and HF rehospitalization, in patients with hyperuricemia and HFpEF (UA >7.0 mg/dL). Additionally, we evaluated whether lowering UA for 1 year (≥1.0 mg/dL) in them reduced mortality or HF rehospitalization. We finally analyzed 464 patients with hyperuricemia. In multivariable Cox regression analysis, UA was an independent determinant of composite death and rehospitalization (hazard ratio [HR], 1.15 [95% CI, 1.03–1.27], P =0.015). We divided them into groups with severe and mild hyperuricemia according to median estimated value of serum UA (8.3 mg/dL). Cox proportional hazards models revealed the incidence of all‐cause mortality was significantly higher in the group with severe hyperuricemia than in the group with mild hyperuricemia (HR, 1.73 [95% CI, 1.19–2.25], P =0.004). The incidence of all‐cause mortality was significantly decreased in the group with lowering UA compared with the group with nonlowering UA (HR, 1.71 [95% CI, 1.02–2.86], P =0.041). The incidence of urate‐lowering therapy tended to be higher in the group with lowering UA than in the group with nonlowering UA (34.9% versus 24.6%, P =0.06). Conclusions UA is a predictor for the composite of all‐cause death and HF rehospitalization in patients with hyperuricemia and HFpEF. In these patients, lowering UA, including the use of urate‐lowering therapy, may improve prognosis.

Purpose: The purpose of this study is to elucidate the impact of out-stent plaque characteristics on vascular response after implantation of second generation drug-eluting stent (G2-DES). Methods: Enrolled were 37 patients with 39 coronary artery lesions into which three types of G2-DES were successfully implanted (9 Nobori biolimus-, BES; 15 Xience everolimus-, EES; 15 Resolute zotarolimus-eluting stents; R-ZES). Immediately after (baseline) and one year after the implantation (follow-up), iMAP-intravascular ultrasound (IVUS) was performed to measure out-stent plaque volume (OSPV) and its components. Percent OSPV and vulnerable plaque index (VPI) were defined as percentile of OSPV to vessel volume and as percentile of lipidic plus necrotic volume to OSPV. Coronary angioscopy at follow-up rated the degree of arterial repair by neointimal stent coverage (NSC). Results: Poor NSC was found in approximately 60% of each G2-DES. In BES, % OSPV at baseline was significantly greater in poor NSC than in good NSC (36.2 ± 3.9 vs. 27.3 ± 4.0%, P = 0.01). In EES, %OSPV was significantly greater in poor NSC than in good NSC (41.0 ± 4.1 vs. 32.6 ± 2.7%, P

Background Arterial repair delays after intracoronary implantation of Cypher sirolimus-eluting stents (SES), a representative first-generation drug-eluting stent. It remains unclear whether this delay would catch up with bare metal stents (BMS) during extremely long observation. The aim of this study was angioscopic observation of extremely late arterial repair after Cypher SES implantation. Methods Thirty-seven SES and 17 BMS were implanted into 22 and 9 patients with angina pectoris, respectively. Duration after implantation (DAI) ranged from 3 to 10.5years in both stents. Coronary angioscopy revealed neointimal stent coverage (NSC), presence of in-stent yellow plaque (YP), and mural thrombi (MT). NSC was semi-quantified into 4 grades (grade 0, no coverage; grade 1, thin coverage; grade 2, thick coverage; grade 3, fully embedded into neointima). Results In the BMS-implanted lesions (BMSL), NSC was either grade 1 (24%) or grade 3 (74%), with rare YP and no MT. In the SES-implanted lesions (SESL), NSC was various, i.e. grade 0 (5%), grade 1 (59%), grade 2 (22%), and grade 3 (14%). YP and MT were observed in 27 and 24% of in SESL, respectively. In SESL with DAI>8years ( n =5), NSC was either grade 1 (40%) or grade 3 (60%), although YP and MT were more frequently observed (60 and 40%, respectively). Conclusions Arterial repair after SES implantation caught up with BMS at around 8years with regards to NSC, although prevalence of YP and MT remained still greater in SESL than BMSL at extremely late phase.

Sirolimus, a bio-suppressive drug, delays coronary arterial repair after implantation of Cypher sirolimus-eluting stents (SES), a representative first generation drug-eluting stent. It remains unclear, however, whether this delayed repair would catch up with bare metal stents (BMS) along extremely long observation. The aim of this study was angioscopic comparison of coronary arterial repair through a decade after implantation of SES and BMS. Enrolled were 31 patients with previous implantation of SES (n = 22) or BMS (n = 9). Duration after stent implantation (DSI) ranged from 3 to 10.5 years in both groups. Thirty-seven SES were implanted into the SES group and 17 BMS into the BMS group. The 54 stented segments were analyzed by quantitative coronary angiography (QCA) and non-obstructive coronary angioscopy (CAS). Under continuous flush of low-molecular-weight dextran, CAS visualized in-stent appearance, i.e. endothelial stent coverage (ESC), presence of yellow plaque (YP), and in-stent mural thrombi (ISMT). ESC was semi-quantified into 4 grades (grade 0, no coverage; grade 1, thin coverage; grade 2, decent coverage; grade 3, full coverage). QCA showed in-stent restenosis neither in SES- nor BMS-implanted segments (% diameter stenosis 14.8 ± 7.9 vs. 16.2 ± 8.2, respectively). Incidence of YP was 27% in SES and 6% in BMS (P < 0.03). Incidence of ISMT was 24% in SES, whereas never in BMS. ESC grade of BMS was either grade 1 (24%) or grade 3 (76%). SES-implanted segments were divided into two groups, i.e. DSI > 8 years (n = 5) and DSI < 8 years (n = 32). In the former (10.5 > DSI > 8 years), ESC grade of SES was either grade 1 (40%) or grade 3 (60%), being similar to ESC after BMS implantation. In the latter (8 > DSI > 3 years), however, ESC grade varied from grade 0 (6%), grade 1 (63%), grade 2 (25%), and grade 3 (6%). Incidence of YP or ISMT was 60% in the former, suggesting progression of neoatherosclerosis at extremely late phase. In conclusion, from the viewpoint of ESC, coronary arterial repair at SES implantation appeared to catch up with BMS at around 8 years later, although incidence of YP or ISMT remained still greater in SES than BMS at extremely late phase.

Background Arterial repair after intracoronary stenting depends on stent types and plaque vulnerability. The aim of this study was angioscopic comparison of arterial repair after implantation of the second-generation drug-eluting stents (G2-DES) between the stable and vulnerable plaques. Methods Four types of G2-DES were successfully implanted into stable plaques (n=41) and vulnerable plaques (n=34): 13 and 9 Xience-everolimus-, 7 and 6 Endeavor-zotarolimus-, 15 and 9 Resolute-zotarolimus-, and 6 and 10 Nobori-biolimus-eluting stents (EES, E-ZES, R-ZES, and BES), respectively. Coronary angioscopy at 1-year follow-up revealed in-stent appearance, such as neointimal stent coverage (NSC), presence of yellow plaques (YP), and in-stent mural thrombus (MT). NSC was graded into poor and good coverage. Results Yellow plaques and mural thrombi were found more frequently in the vulnerable plaques than in the stable plaques (29% vs. 12%, P=0.06; 12 vs. 0%, P=0.02; respectively). In EES, poor NSC was observed more frequently in the vulnerable plaques than in the stable plaques (54% vs. 11%, P=0.04). In BES, YP was observed more frequently in the vulnerable plaques than in the stable plaques (80% vs. 17%, P=0.01). In E-ZES and R-ZES, there were no significant differences with regards to angioscopic parameters between the stable and vulnerable plaques. Conclusions Arterial repair after EES and BES implantation into the vulnerable plaques remained vulnerable even at 1-year follow-up.

Nowadays, PC is normally used in companies and information which contains secrets is often managed on PCs. Protection of the information is one of the important things in nowadays society. Virtual machine is one of the solutions of the problem since guest OS can be observed by hypervisor. However, in this case, sending secrets to outside cannot be prevented. Moreover, the observation sometimes decreases usability since many actions of users such as using USB drive are prohibited. Therefore, in this paper, we propose a method that encrypts messages between a server and a client with a key which is provided from a server. In our method, secret information is encrypted so that any application software program cannot open files without correct keys. When application software programs which are registered on the list access files with secrets, Virtual machine decrypts the files and it pass through them to the application software programs. That is, only registered application software programs can open and edit specific files without any special custom to the programs. Of course, the method does not prevent other software programs from accessing files without secrets. In our proposed method, secrets can be kept without customizing application software programs and usability of computers does not decrease since there is no limitation in using computers.

SummaryA 62-year-old man presented to hospital with chest oppression. Coronary angiography revealed total occlusion of the right coronary artery and inferior myocardial infarction was diagnosed. He was treated by percutaneous coronary intervention with stenting for myocardial infarction. After four months, echocardiography revealed a huge aneurysm protruding below the inferior surface of the left ventricle. It was considered to be a pseudoaneurysm from the echocardiographic findings. The patient had no symptoms and he refused surgery, so progression of the aneurysm was monitored carefully. At seven months after revascularization, the aneurysm showed a marked increase in size, with a maximal diameter of 48mm and orifice diameter of 22mm. Accordingly, the patient agreed to undergo surgical excision. The aneurysm was resected and the defect was closed with a pericardial patch. Pathological examination revealed all of the myocardial elements in the aneurysm wall and thrombus in its lumen. In conclusion, this was a rare case of venricular subepicardial aneurysm.

Very late stent thrombosis (VLST), a rare complication of stenting, has been reported to develop more frequently at later than 1 year after the deployment of the drug-eluting stent (DES) compared with the bare-metal stent (BMS). However, the causes for the difference in the incidence remain unknown. Serial angioscopy on 1,591 and 1,952 days after BMS deployment in a Japanese male patient with acute myocardial infarction revealed incomplete neointimal coverage (INC) without the development of cardiovascular event. Therefore, the potential development of VLST remains undeniable in BMS-deployed patients who had INC.

A 49-year-old woman was referred to hospital because of chest discomfort. Coronary angiography revealed subtotal occlusion of the left coronary artery and the right coronary artery, but subsequent hemodynamic collapse occurred. Based on the results of intravascular ultrasound the occlusion was suspected to be caused by coronary vasospasm, which was not relieved by intracoronary injection of isosorbide dinitrate (1 mg), but was alleviated by nicorandil (2 mg), a potassium-channel opener. After discharge from hospital, the patient stopped taking her medication and returned complaining of chest discomfort again. Intravenous verapamil (5 mg) did not improve it, but direct intracoronary administration of nicorandil (2 mg) did bring relief. This case suggests that nicorandil is effective for coronary vasospasm. (Circ J 2008; 72: 327 - 330)

Background. There have only been a few studies that visualized the human coronary tree continuously from coronary arteries to capillaries in the clinical setting. The purpose of this study was to visualize the human coronary tree non-invasively with myocardial contrast echocardiography (MCE) by changing frame rates.Methods. MCE was performed intravenously using TMLevovist. Study population consisted of 20 patients with ischemic heart disease. We performed 3 kinds of MCE: intermittent, semi-real, and real-time harmonic imaging.Results. 1. Myocardial blood flow velocity and volume were obtained from the time-intensity replenishment curve with intermittent imaging. Curve fitting was possible in 75% of the targeted region of interest. 2. Semi-real-time perfusion image was obtained with a frame rate of 5/sec. We observed a cyclic variation of echo-intensity in one cardiac cycle in only viable region (Peak subtracted signal intensity: 53±29 in end-diastole and 33±27 in end-systole, pConclusions. Thus, coronary tree following major epicardial coronary arteries was visualized non-invasively from the small artery to the capillary bed with 3-staged intravenous-MCE in the clinical setting.

BACKGROUND The loss-of-function genotype of cytochrome P450 2C19 (CYP2C19) has been proposed as a risk factor for stent thrombosis in patients with drug-eluting stent implantation. The aim of this study was to clarify the clinical features of patients with angioscopically-detected in-stent mural thrombi (ISMT). METHODS AND RESULTS Enrolled were 100 stented segments in 55 patients with stable angina (20 bare-metal stents; 39 Cypher sirolimus-eluting stents [SES]; 26 Endeavor zotarolimus-eluting stents [ZES]; 13 Xience V everolimus-eluting stents; and 2 Nobori biolimus-eluting stents). Dual antiplatelet therapy (100 mg aspirin+75 mg clopidogrel once daily) had been continued since stenting. A poor metabolizer (PM) of clopidogrel was defined as a homozygote of CYP2C19 loss-of-function alleles. Coronary angioscopy revealed ISMT in 6 patients (5 SES, 1 ZES). Between the ISMT group and control group (n=49), there were no significant differences with regards to the VerifyNow P2Y12platelet function assay or in-stent endothelial coverage grade. Exact logistic regression analyses with stepwise forward selection at a significance level of 0.10 were performed to reveal predictive variables for ISMT (respectively: odds ratio, 95% confidence interval, P value: CYP2C19 PM genotype (3.28, 0.88-24.80, 0.09), SES implantation (3.37, 0.90-28.09, 0.08), and presence of yellow plaque (3.69, 1.14-25.70, 0.02). CONCLUSIONS Patients with ISMT were characterized by SES implantation, poor clopidogrel metabolism, and in-stent yellow plaque.

Background:The loss-of-function genotype of cytochrome P450 2C19 (CYP2C19) has been proposed as a risk factor for stent thrombosis in patients with drug-eluting stent implantation. The aim of this study was to clarify the clinical features of patients with angioscopically-detected in-stent mural thrombi (ISMT).Methods and Results:Enrolled were 100 stented segments in 55 patients with stable angina (20 bare-metal stents; 39 Cypher sirolimus-eluting stents [SES]; 26 Endeavor zotarolimus-eluting stents [ZES]; 13 Xience V everolimus-eluting stents; and 2 Nobori biolimus-eluting stents). Dual antiplatelet therapy (100 mg aspirin+75 mg clopidogrel once daily) had been continued since stenting. A poor metabolizer (PM) of clopidogrel was defined as a homozygote of CYP2C19 loss-of-function alleles. Coronary angioscopy revealed ISMT in 6 patients (5 SES, 1 ZES). Between the ISMT group and control group (n=49), there were no significant differences with regards to the VerifyNow P2Y

The second generation drug-eluting stents (G2-DES) have been implanted safely at culprit lesions not only of stable angina pectoris but also of acute coronary syndrome. The aim of this study was to angioscopically characterize vascular response after implantation of various G2-DES and to compare

Very late stent thrombosis (VLST) is one of the most serious issues in the era of drug-eluting stents (DES). VLST has been attributed to delayed neointimal stent coverage (NSC) due to bio-suppressive drugs and vulnerability of in-stent neoatherosclerosis. The latter was recently proposed by pathologists as in-stent atherosclerotic lesions at chronic phase of coronary stenting. The aim of this study was angioscopic observation of in-stent vessel wall at 3 years after implantation of various generations of DES. Enrolled were 37 stented segments in 26 patients with stable angina (25 Cypher sirolimus-eluting stents, SES; 5 Endeavor zotarolimus-eluting stents, ZES; and 7 Xience V everolimus eluting stents, EES). Dual anti-platelet therapy, aspirin plus clopidogrel, had been continued since the stenting procedure. Coronary angiography showed no in-stent restenosis at chronic phase. Coronary angioscopy revealed the in-stent appearance; that is, grades of NSC [between score 0 (no coverage) and score 3 (full coverage)], presence of yellow plaque (YP), and subclinical stent thrombosis (ST). There was no significant difference in grades of NSC among SES, ZES, and EES (1.40±0.57, 1.71±0.77, and 1.80±0.75, respectively). YP and ST were not found in EES. YP was 24% and 20% in SES and ZES, respectively. ST was 20% both in SES and ZES. In conclusion, in-stent neoatherosclerosis appears not to progress at least for 3 years in EES-stented coronary segments, a representative of the second generation of DES.

Coronary pseudoaneurysm is a rare complication of percutaneous coronary intervention with a drug-eluting stent. Neither precise incidence of the complication has been known, nor there has been any established therapeutic approach for it. A 69-years-old male with effort angina underwent percutaneous coronary intervention to his left main coronary artery (LMCA). After pre-dilatation with a balloon, Endeavor zotarolimus-eluting stent (E-ZES) was successfully implanted into the lesion that extended from his LMCA to left anterior descending artery. At 6 months after stenting, coronary angiography (CAG) and intravascular ultrasound (IVUS) revealed coronary pseudoaneurysm at the stented segment. Follow-up CAG at 13 months after stenting showed the spontaneous and complete resolution of the pseudoaneurysm. Subsequent IVUS, optical coherence tomography, and coronary angioscopy visualized complete neointimal coverage of stent struts. This is the first case report of E-ZES-related pseudoaneurysm with relatively rapid resolution. Our patient suggests that E-ZES might incidentally contribute to this favorable outcome.

New tumor formation was suppressed by retinoic acid (RA) administration in xeroderma pigmentosum (XP) patients who have a defect in nuclear excision repair. However, the inhibition is not due to enhanced removal of UV-damaged DNA. These results prompted us to investigate whether or not RA metabolism is abnormal in XP fibroblasts and what the underlying mechanism is. Compared with wild type fibroblasts, low activities of RA synthesis were determined on HPLC in mouse fibroblasts lacking XP group A (XPA) gene and UV-induced XPA deficient cancer cells. Moreover, we observed an impaired expression of cytochrome P450 1a1 in XPA deficient fibroblasts by RT-PCR and a decreased expression of retinoic acid receptor γ in XPA deficient cancer cells by Western blotting. Finally, pre-treatment of RA isoforms significantly protected the XPA deficient fibroblasts from UV-induced death. These results suggest that decreased structure activity of RA synthesis, resulting from impaired mRNA expression of cytochrome P450 1a1 may, at least together with UV irradiation, involve in skin carcinogenesis in XP patients.

Mammalian NADPH-ferredoxin reductase (EC 1.18.1.2) functions in the mitochondrial electron transport chain for cytochrome P-450-dependent steroid hydroxylation. Significant homology of three-dimensional structure exists in the surroundings of FAD between NADPH-ferredoxin reductase and NADH-cytochrome b5 reductase. The latter is involved in the bioreduction of mitomycin C (MC), a prototype antitumor agent. In this study, we assessed the capacity of NADPH-ferredoxin reductase to activate MC. Mitomycin C increased the NADPH oxidase activity of NADPH-ferredoxin reductase. In the absence of ferredoxin, the Km value of NADPH-ferredoxin reductase for MC was 73.5 +/- 2.3 microM. While in the presence of 500 nM ferredoxin, a Lineweaver-Burk plot exhibited a biphasic curve. NADPH-ferredoxin reductase-mediated reduction of MC resulted in the formation of an alkylated complex of 4-(p-nitrobenzyl) pyridine and an increase in plasmide DNA single-strand breaks under hypoxic conditions. With the addition of 500 nM ferredoxin, the amount of the alkylated complex of 4-(p-nitrobenzyl) pyridine and the plasmide DNA single-strand breaks increased by 40% and 37%, respectively. However, neither alkylated complex of 4-(p-nitrobenzyl) pyridine nor DNA strand breaks was observed in the presence of SOD and catalase under aerobic conditions. These findings demonstrate that NADPH-ferredoxin reductase is capable of catalyzing the bioactivation of mitomycin C under hypoxic conditions in vitro.

We have established xeroderma pigmentosum group A ( XPA ) gene-knockout mice with nucleotide excision repair (NER) deficiency, which rapidly developed skin tumors when exposed to a low dose of chronic UV like XP-A patients, confirming that the NER process plays an important role in preventing UVB-induced skin cancer. To examine the in vivo mutation in the UVB-irradiated epidermis, we established XPA (−/−), (+/−) and (+/+) mice carrying the Escherichia coli rpsL transgene with which the mutation frequencies and spectra in the UVB-irradiated epidermal tissue can be examined conveniently. The XPA (−/−) mice showed a higher frequency of UVB-induced mutation in the rpsL transgene with a low dose (150 J/m 2 ) of UVB-irradiation than the XPA (+/−) and (+/+) mice, while, at a high dose (900 J/m 2 ) they showed almost the same frequency of mutation as the XPA (+/−) and (+/+) mice, probably because of cell death in the epidermis of the XPA (−/−) mice. However, CC→TT tandem transition, a hallmark of UV-induced mutation, was detected at higher frequency in the XPA (−/−) mice than the XPA (+/−) and (+/+) mice at both doses of UVB. This rpsL/XPA mouse system will be useful for further analyzing the role of NER in the mutagenesis and carcinogenesis induced by various carcinogens.

Xeroderma pigmentosum group A gene (XPA)-deficient mice are defective in nucleotide excision repair (NER) and are therefore highly sensitive to ultraviolet (UV)-induced skin carcinogenesis. We established cell lines from skin cancers of UVB-irradiated XPA-deficient mice to investigate the phenotypic changes occurring during skin carcinogenesis. As anticipated, the skin cancer cell lines were devoid of NER activity but were less sensitive to killing by UV-irradiation than the XPA(-/-) fibroblast cell line. The lines were also more resistant to 6-thioguanine (6-TG) than XPA(-/-) and XPA(+/+) fibroblasts, which was suggestive of a mismatch repair (MMR) defect. Indeed, in vitro mismatch binding and MMR activity were impaired in several of these cell lines. Moreover, these cell lines displayed cell cycle checkpoint derangements following UV-irradiation and 6-TG exposure. The above findings suggest that MMR downregulation may help cells escape killing by UVB, as was seen previously for methylating agents and cisplatin, and thus that MMR deficient clones are selected for during the tumorigenic transformation of XPA(-/-) cells.

A 62-year-old man was performed stent implantation for right subclavian artery stenosis two years ago. For the evaluation of stent patency, multislice computed tomography (MSCT) was performed. Volume rendering image demonstrated that the stent was patent, but curved multiplanar reformation revealed a relatively low- density area inside the stent, suggesting intimal hyperplasia. Cross-sectional images were converted into Plaque Map display, which color-codes CT densities. Plaque was eccentrically distributed from ten o'clock to four o'clock. The attenuation of the plaque was 250--350 HU, which was less than the attenuation of contrast media (350--500 HU). Invasive aortography demonstrated the stent to be mildly stenosed in the corresponding position. Gray-scale and VH (virtual histology)-intravascular ultrasound demonstrated that eccentric intimal thickening consisted with predominant fibrous plaque. MSCT combined with Plaque Map effectively detected intimal thickening of subclavian artery stent.

We aimed to determine the effects of the oral direct renin inhibitor aliskiren on in vivo oxidative stress in atrial fibrillation (AF) patients. In this study, 150mg oral direct renin inhibitor aliskiren was administered once daily to 12 permanent AF patients. Aliskiren significantly reduced urinary excretion of the oxidative stress biomarker 8-iso-prostglandin F2α and serum levels of matrix metalloproteinase-2(MMP-2). We concluded that aliskiren reduces in vivo oxidative stress and serum MMP-2 levels in patients with permanent AF.

We report the case of a 69-year-old male whose left circumflex coronary artery was perforated immediately after implantation of an Endeavor zotarolimus-eluting stent (E-ZES). Despite successful hemostasis by long balloon inflation, a coronary pseudoaneurysm remained at the E-ZES-implanted segment. Coronary angiography performed one year after the coronary perforation showed the pseudoaneurysm had disappeared. Simultaneous optical coherence tomography and coronary angioscopy revealed that stent struts of the E-ZES were fully covered with thick neointima. This is the first case report of a relatively rapid healing process for an E-ZES-related coronary pseudoaneurysm.

In the era of the drug-eluting stent, very late stent thrombosis has been the most serious issue in the field of interventional cardiology. A sirolimus-eluting stent (SES) was implanted in an in-stent restenotic lesion in the left circumflex artery of a 69-year-old man. Repetitive coronary angiography and angioscopy revealed that stent struts were covered with yellow neointima at 2 years after the SES deployment. At 4 years after the deployment, coronary angiography revealed the total occlusion of the SES. Angioscopy showed massive mural thrombi and yellow atherosclerotic plaques. Dual anti-platelet therapy (DAPT), ticlopidine and aspirin, had been continued since the SES deployment. Interventional cardiologists should heed the risk of silent chronic thrombotic occlusion even if struts of SES are fully covered with neointima under continued DAPT.

SummaryBackgroundClinical features of diastolic heart failure (DHF) have not been well characterized, leading to an inaccuracy in the diagnosis of DHF. Recently, the ratio of transmitral E velocity to early diastolic mitral annular velocity (E/E′) has been shown to be useful to assess LV filling pressure.PurposeWe tested the hypothesis that persistent elevation of E/E′ ratio is one of the characteristics of patients with DHF.MethodsCandidates of this study were 89 patients who presented to the emergency department because of acute pulmonary congestion. Those with an ejection fraction of >45% on admission comprised the DHF group (n=18). A control group consisted of consecutive 30 hypertensive patients with an ejection fraction of >45%. Doppler echocardiographic data were obtained with plasma BNP measure in the chronic stage >6 months after the emergent admission.ResultsThe E/E′ ratio was higher in the DHF group than in the control group (16.7±2.8 vs. 9.4±3.3, p

Anomalous coronary arteries are usually identified incidentally by angiography or autopsy, but some "malignant" coronary anomalies are associated with a high incidence of syncope, arrhythmia, myocardial infarction, and sudden death. So far, the pathogenesis of the coronary events in such cases has only been revealed by autopsy. In the present case report, a patient with anomalous origin of the right coronary artery from the left sinus of Valsalva developed acute myocardial infarction, and visualization of the anomaly and assessment of the culprit plaque in the artery were done by multidetector row computed tomography and intravascular ultrasound.

Bulky DNA lesions are mainly repaired by nucleotide excision repair (NER), in which the interaction of ERCC1 with XPA protein recruits the ERCC1–XPF complex, which acts as a structure-specific endonuclease in the repair process. However, additional functions besides NER have been suggested for the ERCC1–XPF complex, because ERCC1- or XPF-deficient rodent cells are significantly more sensitive to DNA interstrand cross-linking (ICL) agents such as cis-diamminedichloroplatinum(II) (CDDP) than any other NER-deficient cells and because ERCC1-deficient mice suffer a more severe phenotype than XPA-deficient mice. By using RNA interference we show here that suppression of ERCC1 expression increases the sensitivity of xeroderma pigmentosum group A (XPA)-deficient human cells to CDDP but not to UV. This increased sensitivity to CDDP is observed in mouse cells defective in Xpa as well but not in cells defective both in Xpa and the mismatch repair gene Msh2. These data suggest that ERCC1 and MSH2 are involved co-operatively in CDDP resistance in mammalian cells. As a possible molecular basis, we show further a physical interaction between endogenous ERCC1 and MSH2 complexes in HeLa cell extracts. Using tagged ERCC1 in COS7 cells, the minimum region in ERCC1 necessary for the immuno-precipitation of MSH2 is turned out to be the carboxyl-terminal domain between the 184th and 260th amino acid, which is partly overlapping with the XPF-binding domain of ERCC1. This interaction may be important in additional functions of ERCC1–XPF including the repair of CDDP-induced DNA damage.

Cardiac involvement in progressive systemic sclerosis (PSS) is common and has a strong negative impact on the prognosis, especially when autoantibodies are present. To determine whether ultrasonic tissue characterization can detect early ultrastructural changes in the sclerodermal myocardium, we analyzed the transmural heterogeneity in myocardial integrated backscatter (THIB). "A-THIB" was defined as the absolute difference in integrated backscatter between the left (subendocardial) and right (subepicardial) ventricular halves of the myocardium in the septum and posterior wall, and was measured in 11 patients with PSS and 10 age- and sex-matched healthy participants. A-THIB in patients with PSS was higher than that in healthy participants (1.3 +/- 1.3 vs 4.0 +/- 1.4 dB for the septum and 1.1 +/- 0.7 dB vs 2.8 +/- 0.4 dB for the posterior wall; mean +/- SD, respectively, P.0005). Septal A-THIB was higher in patients with PSS with than without anti-Scl70 or antinucleolar antibodies (3.2 +/- 1.1 vs 5.0 +/- 1.0 dB, P =.0165). Early changes in the myocardium of patients with PSS, possibly related to increased interstitial collagen deposition, can be detected by quantitative analysis of THIB.

DLG, the mammalian homolog of the Drosophila Discs Large suppressor protein, functions as a scaffolding protein that facilitates the transmission of diverse downstream signals. In the present study, we attempted to identify partner proteins for DLG, and found that DLG interacts through its PDZ domains with the ribosome receptor. The ribosome receptor is an integral endoplasmic reticulum protein that has been suggested to be involved in secretion. Our finding raises the possibility that DLG plays a role in the regulation of secretion by interacting with the ribosome receptor.

Nucleotide excision repair (NER) removes a wide variety of lesions from the genome and is deficient in the genetic disorder, xeroderma pigmentosum (XP). In this paper, an in vitro analysis of the XP group A gene product (XPA protein) is reported. Results of an analysis on the pathogenesis of ultraviolet (UV)-B-induced skin cancer in the XPA gene-knockout mouse are also described: (1) contrary to wild type mice, significant bias of p53 mutations to the transcribed strand and no evident p53 mutational hot spots were detected in the skin tumors of XPA-knockout mice. (2) Skin cancer cell lines from UVB-irradiated XPA-knockout mice had a decreased mismatch repair activity and an abnormal cell cycle checkpoint, suggesting that the downregulation of mismatch repair helps cells escape killing by UVB and that mismatch repair-deficient clones are selected for during the tumorigenic transformation of XPA (-/-) cells. (3) The XPA-knockout mice showed a higher frequency of UVB-induced mutation in the rpsL transgene at a low dose of UVB-irradiation than the wild type mice. CC-->TT tandem transition, a hallmark of UV-induced mutation, was detected at higher frequency in the rpsL transgene in the XPA-knockout mice than the wild type mice. This rpsL/XPA mouse system will be useful for further analysing the role of NER in the mutagenesis induced by various carcinogens. (4) The UVB-induced immunosuppression was greatly enhanced in the XPA-knockout mice. It is possible that an enhanced impairment of the immune system by UVB irradiation is involved in the high incidence of skin cancer in XP.

We investigated whether or not neuronal nitric oxide synthase (nNOS) (EC 1.14.13.39) was converted to the P-420 form on exposure to sodium cholate, mercury chloride or urea, and the reconversion of the P-420 to the P-450 form. Sodium cholate and mercury chloride induced the conversion of nNOS from the P-450 to the P-420 form in concentration- and incubation time-dependent manners, and the nNOS activity decreased. In the presence of glycerol, l -arginine and/or tetrahydrobiopterin, the sodium cholate-treated P-420 form could be reconverted to the P-450 form under constant experimental conditions, and the nNOS activity could also be restored. The mercury chloride-treated P-420 form of nNOS could be reconverted to the P-450 form on incubation with reduced glutathione (GSH) or l -cysteine, and the nNOS activity was recovered. However, no reconversion of the mercury chloride-treated P-420 form to the P-450 form was observed in the presence of glycerol, l -arginine, or tetrahydrobiopterin. Urea (4.0 M) dissociated nNOS into its subunits, but nNOS remained in the P-450 form. The nNOS monomer was more susceptible to sodium cholate. After removing the urea by dialysis, and supplementation of the nNOS solution with glycerol, l -arginine or BH 4 , the P-420 was reconverted to the P-450 form, and the reassociation of nNOS monomers was also observed. These results suggested that nNOS was more stable as to exposure to sodium cholate, mercury chloride or urea in comparison to microsomal cytochrome P-450, which may be due to the different heme environment and protein structure.

Treatment of de novo coronary stenosis with sirolimus-eluting stents is associated with very low rates of target lesion revascularization and other major adverse cardiac events in the short-term after implantation, but a definite frequency of late-stent thrombosis (LST) over a long-term follow-up has become evident. One of the predictors of LST is stent overlap. We reported the angioscopic findings of very delayed healing at sites of sirolimus-eluting stent overlap 21 months post-implantation.

Background: Low pressure baroreflex reflex senses the pressure of atriums and delivers its input to the central vasomotor center via vagal nerve (VN). However, its quantitative effect against sympathetic nerve activity (SNA) remains unclear. In this study, we investigated whether volume loading could change SNA through the low pressure baroreflex with or without VN. Methods and Materials: In 5 anesthetized and ventilated Sprague-Dawley rats, we isolated carotid sinus and controlled carotid sinus pressure (CSP) at 90mmHg. Arterial pressure (AP), central venous pressure (CVP) and sympathetic nerve activity (SNA) of splanchnic nerve were recorded simultaneously. We infused 5% of estimated blood volume plasma expander every 1 minute and observed the response of SNAwith or without VN. Results: Volume loading increased CVP from 3.160.4mmHg to 7.560.4 mmHg. SNA increased in low CVP range as volume loading, meanwhile, SNA decreased in high CVP range. After bilateral VN denervation, the increase in CVP didn’t change SNA at all. Conclusions: These results suggest that the increase CVP by volume loading evokes biphasic (acceleratory in low CVP and inhibitory in high CVP) changes in SNA through the low pressure baroreflex with VN.