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Although establishment and maintenance of mitochondria are essential for the production of massive amounts of heme in erythroblasts, mitochondria must be degraded upon terminal differentiation to red blood cells (RBCs), thus creating a biphasic regulatory process. Previously, we reported that iron deficiency in mice promotes mitochondrial retention in RBCs, suggesting that a proper amount of iron and/or heme is necessary for the degradation of mitochondria during erythroblast maturation. Because the transcription factor GATA1 regulates autophagy in erythroid cells, which involves mitochondrial clearance (mitophagy), we investigated the relationship between iron or heme and mitophagy by analyzing the expression of genes related to GATA1 and autophagy and the impact of iron or heme restriction on the amount of mitochondria. We found that heme promotes the expression of GATA1-regulated mitophagy-related genes and the induction of mitophagy. GATA1 might induce the expression of the autophagy-related genes Atg4d and Stk11 for mitophagy through a heme-dependent mechanism in murine erythroleukemia (MEL) cells and a genetic rescue system with G1E-ER-GATA1 erythroblast cells derived from Gata1-null murine embryonic stem cells. These results provide evidence for a biphasic mechanism in which mitochondria are essential for heme generation, and the heme generated during differentiation promotes mitophagy and mitochondrial disposal. This mechanism provides a molecular framework for understanding this fundamentally important cell biological process.

Small cell lung cancer (SCLC) is a highly malignant form of cancer, which originates from primitive neuroendocrine cells in the lung. SCLC cells express several autocrine neurotransmitters/neuropeptides and their respective receptors. Expression of these neuronal markers is frequently regulated by RE1-silencing transcription factor (REST). In SCLC cells, an SCLC-specific isoform of REST (sREST) is highly expressed, whereas REST expression is undetectable, suggesting that the expression of sREST correlates with the pathogenesis of SCLC. Expression of sREST, which is derived through alternative splicing of REST, is abnormally regulated in SCLC cells, but the mechanism is unknown. Most recently, nSR100 (SRRM4) was described as an activator of REST alternative splicing. We now show that nSR100 is highly expressed in SCLC cells correlating with high sREST and low REST expression. Adhesion to the extracellular matrix (ECM) is thought to enhance tumorigenicity and confer resistance to apoptosis. Interestingly, nSR100 expression is enhanced in cells grown with ECM. Overexpression of REST caused repression of sREST and nSR100, the latter containing RE1 element controlled by REST. Culturing the SCLC cell line NCI-N417 cells with ECM also upregulated RE1-containing gene, the voltage-gated calcium channel subunit. Inhibition of the PI3K/Akt/mTOR pathway by LY294002 induced nSR100 expression, whereas the specific MEK/ERK inhibitor U0126 inhibited nSR100 expression. Repressing nSR100 by siRNA effectively repressed sREST, and conversely increased REST in NCI-N417 cells. Taken together, this report clarifies the ECM-dependent signaling pathway that impacts nSR100 expression and its regulation of alternative splicing in SCLC.Implications: The splicing factor nSR100 may be novel SCLC-specific biomarker, as well as a therapeutic target. Mol Cancer Res; 11(10); 1258–68. ©2013 AACR.

PDF - 202KB, Supplementary Figure 1: Growth curve for human SCLC cell lines growing on plastic or ECL extracellular matrix coated plastic dishes. Supplementary Table 1: Primers used for gene expression analysis. Supplementary Table 2: Comprehensive list of SCLC-associated autoantigens and autoantibodies.

A 72-year-old man with type 2 diabetes mellitus with good glucose control for 20 years and maintained on oral hypoglycaemic agents was diagnosed with Hodgkin’s Lymphoma (HL) and started on insulin glargine for glycaemic control. Despite increased doses of insulin, his blood glucose levels went up dramatically. The anti-insulin antibody test proved to be positive, and Scatchard plot analysis showed 2 binding sites with relatively low-affinity constants: K(1) = 0.0032, K(2) = 0.0002 (10(8)/M); and high binding capacities: R(1) = 98.4, R(2) = 372 (10(−8) M), which were compatible with the features of antibody of insulin autoimmune syndrome (IAS). However, hypoglycaemia was not noted throughout the course of treatment. Since the insulin binding ratio of the antibody decreased from 87.3% to 62% after the termination of insulin treatment, it was suggested that the antibody reacted mainly to exogenously injected insulin. Switching insulin preparations or introducing insulin secretagogues did not improve elevated blood glucose levels. The initiation of brentuximab vedotin (BV), a therapeutic agent for relapsed HL, resulted in a remarkable improvement in glycaemic control despite the absence of insulin therapy and partial remission of HL. This case suggested that HL triggered anti-insulin antibody production, which resulted in poor glycaemic control, and that BV could be a new treatment option for autoimmune diseases associated with HL. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00550-1.

The purpose of this study was to evaluate the initial and long-term outcomes of Percutaneous Transluminal Angioplasty (PTA) for central venous stenosis or occlusion in chronic hemodialysis patients. A total of 363 central venous lesions (277 stenosis and 86 occluded lesions) of 146 patients were enrolled and analyzed retrospectively; these included 130 de novo lesions and 233 restenosis lesions. The procedural success rate in our cohort was 97.0% (352/363 lesions); success rate for stenosis was significantly higher than that for occluded lesions (99.3% vs. 89.5%, P < 0.001). Complications during PTA procedures occurred in nine lesions (2.5%); however, there were no serious complications. A total of 120 stents were implanted for 111 lesions; the rate of stent placement for occluded lesions was significantly higher than that for stenosis lesions (68.8% vs. 18.4%, P < 0.001). The primary patency of de novo lesions was significantly higher than that of restenosis lesions (P = 0.0004); the assisted patency of de novo lesions at 12 and 36 months were 94.4% and 89.0%, respectively. There was no significant difference of primary patency between balloon angioplasty and stent placement for de novo lesions, however, primary patency after stent placement for restenosis lesions was significantly higher than that after balloon angioplasty (P = 0.001). In conclusion, PTA for central venous stenosis or occlusion was safe procedure with low rate of technical failure. The patency of vascular access in long-term was maintained by the repeated intervention. Stent placement could help prolong the patency period for restenosis lesions.

Development of a highly efficient ammonia synthesis process is desirable for achieving a sustainable society. Regarding conventional heterogeneous catalysts, Ru-supported catalyst exhibits higher turn-over frequency (TOF) than Fe-supported or Ni-supported catalysts. However, we found that Fe-supported and Ni-supported catalysts show higher TOF than Ru-supported catalyst in an electric field at the low temperature of 373 K. Density functional theory (DFT) calculations revealed that N2 dissociation through the “associative mechanism” plays a key role in the electric field. The ammonia synthesis activity in the electric field is determined by the N2H formation energy at the metal-support interface.

This study aims to explore the associations between uric acid (UA) and long-term outcomes among patients with acute coronary syndrome (ACS). A total of 1068 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI) were analyzed retrospectively. The patients were divided into 3 groups based on the levels of serum UA upon admission (bottom quintile, middle 3 quintiles, and top quintile). The primary endpoint was all-cause mortality. The patients in the higher UA groups were associated with younger age (71 ± 11 versus 68 ± 12 versus 67 ± 14 years; P0.05) and were more likely to be male (57.6 versus 76.9 versus 84.7%; P0.001). Furthermore, these patients had lower estimated glomerular filtration rates (83 ± 27 versus 74 ± 23 versus 59 ± 24 mL/minute/1.73 m

Although concomitant peripheral artery disease in patients with acute coronary syndrome (ACS) has been considered as a high-risk subgroup with a greater incidence of bleeding after percutaneous coronary intervention (PCI), few data exist regarding the clinical utility of the ankle-brachial index (ABI) for predicting bleeding complications, which affects the subsequent outcome.Eight hundred and twenty-four consecutive patients with ACS who underwent PCI and ABI examination were analyzed retrospectively. Decreased-ABI was defined as ABI0.9. The primary outcome was bleeding complications within 30 days, which was defined according to the Bleeding Academic Research Consortium classification grade ≥3. The secondary endpoint was all-cause death during follow-up.Of the 824 patients with ACS, 137 (16.6%) exhibited decreased-ABI. The incidence of bleeding complications was significantly higher in patients with decreased-ABI, compared with the remaining patients (21.9% vs. 6.0%, p0.001). In multivariate analysis, anemia [odds ratio (OR) 2.14], estimated glomerular filtration rate60mL/min/1.73mAssessment of ABI provides useful information for predicting 30-day bleeding complications and long-term mortality in patients with ACS after PCI.

Ammonia is an important chemical feedstock and is produced by Ru or Fe catalyst so far. We investigated Co catalyst for low temperature ammonia synthesis in an electric field. Well-reduced Co/Ce0.5Zr0.5O2 catalyst showed high activity for ammonia synthesis even at 473 K in the electric field. Various characterizations including kinetic tests, operando DRIFTS measurements, TEM observations, and XAFS measurements, revealed that the active site is the interface between supported Co and Ce0.5Zr0.5O2 oxide support, thanks to the surface protonics derived from an electric field.

The transcription repressor BACH1 performs mutually independent dual roles in transcription regulation and chromosome alignment during mitosis by supporting polar ejection force of mitotic spindle. We now found that the mitotic spindles became oblique relative to the adhesion surface following endogenous BACH1 depletion in HeLa cells. This spindle orientation rearrangement was rescued by re-expression of BACH1 depending on its interactions with HMMR and CRM1, both of which are required for the positioning of mitotic spindle, but independently of its DNA-binding activity. A mass spectrometry analysis of BACH1 complexes in interphase and M phase revealed that BACH1 lost during mitosis interactions with proteins involved in chromatin and gene expression but retained interactions with HMMR and its known partners including CHICA. By analyzing BACH1 modification using stable isotope labeling with amino acids in cell culture, mitosis-specific phosphorylations of BACH1 were observed, and mutations of these residues abolished the activity of BACH1 to restore mitotic spindle orientation in knockdown cells and to interact with HMMR. Detailed histological analysis of Bach1-deficient mice revealed lengthening of the epithelial fold structures of the intestine. These observations suggest that BACH1 performs stabilization of mitotic spindle orientation together with HMMR and CRM1 in mitosis, and that the cell cycle-specific phosphorylation switches the transcriptional and mitotic functions of BACH1.

OBJECTIVES To investigate the impact of stent deformity induced by final kissing balloon technique (KBT) for coronary bifurcation lesions on in-stent restenosis (ISR). BACKGROUND In experimental models, the detrimental effects of KBT have been clearly demonstrated, but few data exists regarding the impact of proximal stent deformity induced by KBT on clinical outcomes. METHODS We examined 370 coronary lesions where intravascular ultrasound (IVUS)-guided second-generation drug-eluting stent (DES) implantation for coronary bifurcation lesions was performed. Based on IVUS analysis, the stent symmetry index (minimum/maximum stent diameter) and stent overstretch index (the mean of stent diameter/the mean of reference diameter) were calculated in the proximal main vessel. RESULTS The stent symmetry index was significantly lower (0.75 ± 0.07 vs 0.88 ± 0.06, P

Although statin therapy is beneficial in the setting of acute coronary syndrome (ACS), a substantial proportion of patients with ACS still do not receive the guideline-recommended lipid management in contemporary practice. We hypothesize that the low-density lipoprotein cholesterol (LDL-C) level at the time of admission might affect patient management and the subsequent outcome. Nine-hundred and forty-two consecutive patients with ACS who underwent percutaneous coronary intervention were analyzed retrospectively. The study patients were first divided into two groups based on the LDL-C level on admission: group A (n = 267), with LDL-C

Subclinical peripheral artery disease (PAD) might be associated with pathophysiology of contrast-induced acute kidney injury (CI-AKI). We hypothesized that concomitant PAD in patients with the acute coronary syndrome (ACS) would represent a high-risk subgroup with a greater incidence of CI-AKI, both of which lead to higher mortality after percutaneous coronary intervention (PCI). Six hundred and seventy-five consecutive patients with ACS who underwent PCI and examination of ankle-brachial index (ABI) were analyzed retrospectively. The presence of PAD was defined as an ABI

The organization of the five β-type globin genes on chromosome 11 reflects the timing of expression during erythroid cell development, with the embryonic e-globin gene being located at the 5' end, followed by the two fetal γ-globin genes, and with the adult β- and δ-globin genes being located at the 3' end. Here, we functionally characterized a DNase I-hypersensitive site (HS) located 4 kb upstream of the Gγ-globin gene (HBG-4kb HS). This site is occupied by transcription factors USF1, USF2, EGR1, MafK, and NF-E2 in the human erythroleukemia cell line K562 and exhibits histone modifications typical for enhancers. We generated a synthetic zinc finger (ZF) DNA-binding domain targeting the HBG-4kb HS (HBG-4kb ZF). The HBG-4kb ZF interacted with the target site in vitro and in the context of cells with a high affinity and specificity. Direct delivery of the HBG-4kb ZF to K562 and primary human erythroid cells caused a reduction in γ-globin gene expression which was associated with decreased binding of transcription factors and active histone marks at and downstream of the HS. The data demonstrate that the HBG-4kb HS is important for fetal globin production and suggest that it may act by opening chromatin in a directional manner.

Dissection of the splanchnic artery unrelated to an aortic lesion is extremely rare. We describe a patient with dissection of the celiac and splenic arteries causing splenic circulatory impairment. A 55-year-old Japanese man was referred to our hospital for left back pain that suddenly occurred 3 days previously and spread to the left flank. He had complicated sleep apnea syndrome well controlled with continuous positive airway pressure, and had been prophylactically taking aspirin (100 mg/day) because of asymptomatic cerebral lacunar infarcts. Contrast-enhanced computed tomography (CT) in the arterial phase revealed dissection from the celiac root extending to the entire splenic artery, the caliber of which was irregularly narrowed, causing malperfusion in the spleen. Because of hemodynamic stability and lack of impending sequelae, the patient was carefully observed with rest, strict blood pressure control, and aspirin administration. One month later, CT revealed restoration of the caliber of the dissected arteries and regression of the organizing false lumen, which confirmed the patient's recovery. Despite the extreme rarity or nonspecific symptoms, splanchnic artery dissection should be considered a potentially life-threatening emergency. This case supports the possible benefit of starting antithrombotic treatment early to prevent thrombotic sequelae such as organ infarction and aneurysmal formation.

Background: A number of previous studies have shown that myocardial viability can be assessed by positron emission tomography (PET) using 18 F-fluorodeoxyglucose ( 18 F-FDG). However, there has been no multicenter study that verified the ability of this modality for diagnosing myocardial viability in Japan. We therefore conducted a prospective one arm's unrandomized multicenter clinical trial in order to confirm the diagnostic ability of 18 F-FDG (95% two-sided confidence interval) in the 30 patients of the efficacy-analysis set was 63.9 %( 54.6-72.5%). Moreover, the proportion of patients with improved wall motion, on a per-patient basis, was 86.7 %( 26 of 30 cases). As for the safety, no serious adverse events occurred and the agent was well-tolerated. Conclusions: The identification of myocardial viability by 18 F-FDG will be widely beneficial in predicting improvement in myocardial wall motion after coronary revascularization. No serious safety concerns associated with the use of 18 F-FDG were observed.

Elucidation of how the differentiation of hematopoietic stem and progenitor cells (HSPCs) is reconfigured in response to the environment is critical for understanding the biology and disorder of hematopoiesis. Here we found that the transcription factors (TFs) Bach2 and Bach1 promoted erythropoiesis by regulating heme metabolism in committed erythroid cells to sustain erythroblast maturation and by reinforcing erythroid commitment at the erythro-myeloid bifurcation step. Bach TFs repressed expression of the gene encoding the transcription factor C/EBPβ, as well as that of its target genes encoding molecules important for myelopoiesis and inflammation; they achieved the latter by binding to their regulatory regions also bound by C/EBPβ. Lipopolysaccharide diminished the expression of Bach TFs in progenitor cells and promoted myeloid differentiation. Overexpression of Bach2 in HSPCs promoted erythroid development and inhibited myelopoiesis. Knockdown of BACH1 or BACH2 in human CD34+ HSPCs impaired erythroid differentiation in vitro. Thus, Bach TFs accelerate erythroid commitment by suppressing the myeloid program at steady state. Anemia of inflammation and myelodysplastic syndrome might involve reduced activity of Bach TFs.

Background (18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) is assumed to be the most useful method for evaluating the viability of the myocardium. However, there are few reports regarding serial changes in (18)F-FDG-PET images of acute myocardial infarction (AMI). We evaluated serial changes in glucose-loaded (18)F-FDG-PET, (123)I-β-methyl-p-iodophenyl-penta-decanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and (99m)Tc-Tetrofosmin (TF) gated SPECT images in patients with AMI. Methods and results We enrolled 7 consecutive patients with first anterior AMI who successfully underwent percutaneous coronary intervention (PCI). (18)F-FDG-PET images were obtained in the acute, subacute, chronic, mid-term and long-term phases. (123)I-BMIPP and (99m)Tc-TF SPECT images were obtained in the subacute, chronic, mid-term and long-term phases. We determined the total defect score (TDS) for each image. The TDS of the glucose-loaded (18)F-FDG-PET, (123)I-BMIPP and( 99m)Tc-TF SPECT images indicated significant serial decrease (P (123)I-BMIPP>(99m)Tc-TF in all phases. Conclusions The defect areas of glucose-loaded (18)F-FDG-PET images were significantly larger than those of (123)I-BMIPP and( 99m)Tc-TF SPECT images during 9 months follow-up of patients with successful PCI for anterior AMI. Additionally, the impairment of glucose metabolism was prolonged.

Although Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score based on angiographic scoring system was developed in patients with previous coronary artery bypass grafting (CABG), few data exist regarding its prognostic utility in patients undergoing percutaneous coronary intervention (PCI). We examined 272 patients with previous CABG (217 men; mean age, 70.4 ± 9.7 years) undergoing PCI. Severity of the coronary anatomy was evaluated using CABG-SYNTAX score. The primary end point of this study was cardiovascular death. The baseline CABG-SYNTAX score ranged from 2 to 53.5, with an average of 26.0 ± 10.2. In the index procedures, PCI for the native coronary accounted for nearly all patients (88%). During follow-up (median 4.1 years), 40 cardiovascular deaths had occurred. In multivariate analysis, age75 years (hazard ratio [HR] 2.82, 95% CI 1.45 to 5.52), left ventricular ejection fraction40% (HR 2.99, 95% CI 1.39 to 6.07), end-stage renal disease (HR 2.90, 95% CI 1.15 to 6.75), peripheral artery disease (HR 2.20, 95% CI 1.10 to 4.64), and CABG-SYNTAX score25 (HR 2.37, 95% CI 1.19 to 5.05) were independent predictors of cardiovascular death. After creating a composite risk score in consideration of identified predictors, the freedom from cardiovascular death at 5 years was 98%, 86%, and 58% in the low (0 to 1), medium (2), and high (3 to 5) scores, respectively (p0.001). The area under the receiver-operating characteristic curve for cardiovascular death for the CABG-SYNTAX and composite risk scores were 0.66 and 0.77, respectively (p0.05). In conclusion, the combination of angiographic and clinical characteristics is useful for risk stratification in patients with previous CABG undergoing PCI.

症例54歳，男性．50歳時に肝機能障害を指摘されたが，膵炎発作の既往なし．嗜好歴は，缶ビール2本/日，焼酎水割5～6杯/日． 心窩部痛を主訴に近医受診．血液検査，腹部CTにて急性膵炎と診断され当院へ救急搬送となった．当院で施行した腹部CT所見で，膵管癒合不全，十二指腸副乳頭部での膵石嵌頓が疑われたため，同日緊急内視鏡検査を施行した．副乳頭からの造影にて尾部膵管までの背側膵管が独立して認められ，背側膵管は拡張し，内部に陰影欠損を認めた．内視鏡的副乳頭切開術後，経鼻膵管ドレナージを施行した．保存的治療で膵炎，背側膵管拡張は軽快し，陰影欠損は消失した．経過良好にて第36病日に退院し，16ヵ月後の現在まで膵炎の再発を認めていない． 膵管癒合不全において，膵石が副乳頭に嵌頓し慢性背側膵炎が増悪する例は稀であり，内視鏡的副乳頭切開術が膵炎の重症化を予防するうえで有効であったので報告する．

A number of structures in industrial facilities are installed on supports, and there have been cases in which damage to such structures has been caused by coupled vibration. In seismic design procedure, the response magnification is obtained from the natural frequency and the modal damping ratio of the coupled system between the structure and the supportive structure. Therefore, the simplified estimation method for calculating the natural frequency and the modal damping ratio of the coupled system is required in the seismic design. In the past study, an equation to calculate the modal damping ratio of a coupled system was presented. The proposed equation was useful for obtaining the modal damping ratio without performing an eigenvalue analysis or a shaking test. In current seismic design procedure, for simplicity, the design response spectrum is used to estimate the acceleration response magnification of a system having one degree of freedom (1-DOF). Though the response magnification of a coupled system can be calculated based on the response magnifications of the 1st mode and the 2nd mode, the participation factor and modal matrix of the coupled system are required. In order to obtain the response magnification, a simpler method that does not involve the participation factor or the modal matrix is proposed, and the characteristics of the proposed method are examined.

The lateral distribution of Ru(4,4′-dicarboxy-2,2′-bipyridine)2(NCS)2 (N3) dye molecules on a titanium dioxide (TiO2) surface was examined by using a scanning tunneling microscope. Pivalate ((CH3)3CCOO−) -covered rutile TiO2(1 1 0) surfaces were immersed in acetonitrile containing the N3 dye. The N3 molecules which replaced the pivalates were observed as protrusions embedded in the pivalate monolayer. A two-dimensional radial distribution function indicated that the adsorbed N3 molecules tended to be aggregated. Trapping of an N3 molecule in the solution by a preadsorbed N3 molecule was proposed as a driving force for the aggregation. The hydrogen bonds between the carboxyl groups of two N3 molecules contribute to the trapping.

症例 16歳男性 潰瘍性大腸炎にて全結腸切除・回腸瘻造設術の既往あり。癒着性イレウスの診断で入院。２日間にわたりＸ線透視下にイレウス管挿入を約１時間ずつかけて試みるもトライツ靭帯よりチューブが進まなかった。そのためダブルバルーン内視鏡下でのイレウス管挿入を施行した。ダブルバルーン内視鏡を十二指腸から空腸へ貯留した腸液とガスを吸引しながら挿入した。トライツ靭帯付近は癒着のため屈曲が強く内視鏡の挿入がやや困難であった。内視鏡を空腸内に十分深く挿入後，ガイドワイヤーを留置してスコープを抜去，ガイドワイヤーを胃管を使用し鼻から出したあと，ガイドワイヤーガイド下にイレウス管を空腸内に留置した。その後腸管減圧が成功し27日後退院した。本法はトライツ靭帯や空腸の癒着などのため通常の方法でイレウス管挿入が困難な場合にチューブを深部挿入できる点で大変有用である。

Trithiocyanato(4,4',4''-tricarboxy-2,2':6',2''-terpyridine)ruthenium(II), "black dye", was adsorbed on a rutile TiO(2)(110) surface and imaged by an ultrahigh vacuum scanning tunneling microscope. The TiO(2)(110)-(1 x 1) surface was prepared in a vacuum, covered with pivalate monolayer, and immersed in acetonitrile containing black dye. Black dyes exchanging preadsorbed pivalates were observed on the surface as protrusions with lateral dimensions from 2 to 10 nm. Protrusions with a minimum lateral dimension of 2 nm were assigned to single, isolated black dyes, and larger protrusions were attributed to aggregated dyes. When deoxycholic acid was added to the dye solution, the number ratio of the single dyes to the aggregated dyes increased, while adsorbed deoxycholic acid was not observed.

Reaction of steric encumbered trichlorostannane with disodium sulfide or dilithium selenide gave 2,4-dimercapto-1,3,2,4-dithiadistannetane or tetraselenadistannabicyclo[2.1.1]hexane, respectively. Reactions of steric encumbered trihydrostannane with elemental chalcogens gave pentachalcogenadistannabicyclo[k.1.1]heptanes (k = 2 and 3). The two bridgehead tin atoms of the first polychalcogenadistannabicyclo[k.l.m]alkanes are concluded to have no significant bonding interaction, judging from the longer bond distances than those of the normal tin–tin single bonds.

The objective of the present investigation was to determine the feasibility of assessing left ventricular systolic ejection and diastolic filling via the automatic edge detection method employing ECG-gated blood pool single-photon emission tomography (SPET GBP) data. Methods: Thirtyfive patients, who had undergone both SPET GBP and ECG-gated equilibrium blood pool scintigraphy by the planar method (planar GBP), were enrolled in this study. Planar GBP was performed with a single-headed gamma camera. From the left anterior oblique projection, data were acquired at 24 frames/cardiac cycle with ECG-gating during the equilibrium state. SPET GBP was conducted utilizing a triple-headed gamma camera, with 60 projection views over 360 degrees by 60 sec per view, in 16 frames/cardiac cycle. In each frame, left ventricular volume was determined by automatic edge detection employing a quantitative gated SPET program. Additionally, the timevolume curve was fitted by the 4th harmonics of Fourier transform. Ejection fraction (EF, %), peak ejection rate (PER, /sec), peak filling rate (PFR, /sec) and mean filling rate during the initial onethird of diastolic time (1/3 FRm) were calculated from the fitted curve. These parameters were also calculated with planar GBP data. Result: Left ventricular ejection and filling parameters were calculated by SPET GBP with the automatic edge detection program for all patient data. Correlation coefficients of EF, PER, PFR and 1/3 FRm between SPET and planar GBP were 0.91 (p < 0.001), 0.82 (p < 0.001), 0.78 (p < 0.001) and 0.74 (p < 0.001), respectively. Conclusion: Ejection and filling rates can be calculated using SPET GBP with the edge-detection software. These parameters displayed significant correlations with those values obtained via planar GBP. Additional studies are warranted to determine the reliability of parameters with SPET GBP.

Miscibility in statistical AB/AB copolymers was investigated from the viewpoint of the copolymer sequence effect based on the Balazs theory. The AB copolymers used were poly[(p-chlorostyrene)-co-(hexyl methacrylate)], poly(styrene-co-HMA) and poly[(methyl methacrylate)-co-HMA]. Miscibility in the former two systems displayed deviation from the Flory–Huggins theory extended to statistical copolymers, and such behavior was interpreted as the sequence effect based on the Balazs theory. From calculations of the probabilities, Z, of interactions between triads, changes in Z for AAA/BBB, AAA/BBA, AAA/ABA, AAB/BBB and BAB/BBB were remarkable around the miscibility boundaries. In order to obtain insight into the miscibility behavior, we related the interaction parameters for the triads, i.e. χAAA/BBA = χAAA/ABA, χAAB/BBB = χBAB/BBB, and χAAB/BBA = χBAB/BBA = χAAB/ABA = χBAB/ABA. Using the above treatment, the χ parameters were estimated from the experimental miscibility data. Reproducibility in miscibility was good for all of the systems. In addition, the parameters were comparable to those obtained by using the Cantow–Schulz assumption. Copyright © 2004 Society of Chemical Industry

The Seismic Design Code for High Pressure Gas Facilities was established in 1982 in advance of those in other industrial fields, the only exception being that for nuclear power plants. In 1995, Hyogoken Nanbu earthquake caused approximately 6000 deaths and more than $1 billion (US) loss of property in the Kobe area, Japan. This unexpected disaster underlined the idea that industrial facilities should pay special consideration to damages including ground failure due to the liquefaction. Strong ground motions caused serious damage to urban structures in the area. Thus, the Seismic Design Code of the High Pressure Gas Facilities were improved to include two-step design assessments, that is, for Level 1 earthquakes (operating basis earthquake: a probable strong earthquake during the service life of the facilities), and Level 2 earthquakes (safety shutdown earthquake: a possible strongest earthquake with extremely low probability of occurrence). For Level 2 earthquakes, ground failure by possible liquefaction will be taken into account. For a Level 1 earthquake, the required seismic performance is that the system must remain safe without critical damage after the earthquake, including no gas leakage. For a Level 2 earthquake, the required seismic performance is that the system must remain safe without gas leakage. This means a certain non-elastic deformation without gas leakage may be allowed. The High Pressure Gas Safety Institute of Japan set up the Seismic Safety Promotion Committee to modify their code, in advance of other industries, and has continued to investigate more effective seismic design practices for more than 5 years. The final version of the guidelines has established design practices for the both Level 1 and Level 2 earthquakes. In this paper, the activities of the committee, their new design concepts and scope of applications are explained.

After the Great Hyogoken-nanbu Earthquake (1995), the Seismic Design Code for High-Pressure Gas Facilities of Japan was amended. This amended code requires two-step seismic assessments, that is, the evaluation of the Level 1 Required Seismic Performance for Level 1 earthquakes and that of the Level 2 Required Seismic Performance for Level 2 earthquakes. Seismic design of piping systems is newly included within the scope of the code. For Level 2 earthquakes, possible ground displacement due to liquefaction is taken into account. The evaluation method of the Level 1 Required Seismic Performance is specified in the amended code and that of the Level 2 Required Seismic Performance is proposed in the guideline. The evaluation of the former is based on elastic design and that of the latter on elastoplastic design. The propriety of the design criteria of piping systems with respect to ground displacement was confirmed by large deformation tests. In this paper, seismic design criteria of piping systems in the amended code and the evaluation method of the Level 2 Required Seismic Performance proposed in the guideline are introduced, and the results of the large deformation tests are reported.

Background: Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes that encode sarcomeric proteins. Although some patients with HCM have shown dilated cardiomyopathy (DCM)-like features, the relationship between genotype and histologic findings is not well known. Hypothesis: Family members with the same gene mutation may show the same histopathologic changes and clinical manifestations. Methods: Siblings with HCM caused by an Arg92Trp mutation in the cardiac troponin T gene, showing DCM-like features, were examined. Results: The patients were a 69-year-old woman and her 57-year-old brother who both died from congestive heart failure. Their autopsies revealed the same histopathologic findings in the heart. The anterior walls and interventricular septa of their hearts were replaced with extensive fibrosis and showed thinning. Myocyte hypertrophy, disarray, and thickened medial walls of the intramural coronary arteries were found. On electron microscopy, the number of mitochondria was seen to be increased and they formed many clusters. Conclusions: Patients with HCM caused by an Arg92Trp mutation in the cardiac troponin T gene may have the same histopathologic findings, whichmay result in DCM-like features.

The first stable stannanetriol and germanetriol bearing sterically congested aryl groups were synthesized by hydrolysis of the corresponding trichloro-stannane and -germane. The stannanetriol is monomeric in solution as well as in the crystalline state, as evidenced by X-ray diffraction analysis and CP-MAS NMR spectroscopy. The stannanetriol reacted with silicone grease to afford a cagelike compound having three Sn–O–Si–O–Sn linkages in the molecule. All the group 14 triols can be converted to the corresponding trihalo compounds in good yields.

A 78-year-old man with unstable angina showed 90 % stenosis in the proximal left anterior descending artery. Pre-procedural intravascular ultrasound revealed ruptured plaque and attenuated plaque in the lesion. Under these conditions, two overlapping sirolimus-eluting stent (SES) implantation in this lesion resulted in slow flow which was recovered by intracoronary nitrates, nicorandil, and nitroprusside without further complications. When the patient showed up again 5 years later with recurrence of angina pectoris, angiography revealed a hazy ulcerated in-stent restenosis (ISR) at the site of the SES. Pre-procedural optical coherence tomography (OCT) imaging revealed multiple intimal ruptures, cavity formation behind the stent struts, a thin-cap fibroatheroma containing neointima surrounded by signal-poor, lipid-rich area in the proximal SES, suggesting the progression of neoatherosclerosis within SES. Importantly, there occurred slow flow again after balloon angioplasty for this lesion. We would suggest careful OCT examination is warranted to confirm development of neoatherosclerosis within the stent, and distal protection device should be considered to prevent slow flow phenomenon even in a patient with very late ISR.

Small cell lung cancer (SCLC) is a highly malignant form of cancer, which originates from primitive neuroendocrine cells in the lung. SCLC cells express several autocrine neurotransmitters/neuropeptides and their respective receptors. Expression of these neuronal markers is frequently regulated by RE1-silencing transcription factor (REST). In SCLC cells, an SCLC-specific isoform of REST (sREST) is highly expressed, whereas REST expression is undetectable, suggesting that the expression of sREST correlates with the pathogenesis of SCLC. Expression of sREST, which is derived through alternative splicing of REST, is abnormally regulated in SCLC cells, but the mechanism is unknown. Most recently, nSR100 (SRRM4) was described as an activator of REST alternative splicing. We now show that nSR100 is highly expressed in SCLC cells correlating with high sREST and low REST expression. Adhesion to the extracellular matrix (ECM) is thought to enhance tumorigenicity and confer resistance to apoptosis. Interestingly, nSR100 expression is enhanced in cells grown with ECM. Overexpression of REST caused repression of sREST and nSR100, the latter containing RE1 element controlled by REST. Culturing the SCLC cell line NCI-N417 cells with ECM also upregulated RE1-containing gene, the voltage-gated calcium channel subunit. Inhibition of the PI3K/Akt/mTOR pathway by LY294002 induced nSR100 expression, whereas the specific MEK/ERK inhibitor U0126 inhibited nSR100 expression. Repressing nSR100 by siRNA effectively repressed sREST, and conversely increased REST in NCI-N417 cells. Taken together, this report clarifies the ECM-dependent signaling pathway that impacts nSR100 expression and its regulation of alternative splicing in SCLC. Implications: The splicing factor nSR100 may be novel SCLC-specific biomarker, as well as a therapeutic target. Mol Cancer Res; 11(10); 1258–68. ©2013 AACR.