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Coronary artery spasm (CAS) associated with catheter ablation is an important perioperative complication. Here we describe a case of late-onset CAS with cardiogenic shock that occurred five hours after ablation. A 55-year-old man diagnosed with CAS previously underwent implantable cardioverter-defibrillator (ICD) implantation due to ventricular fibrillation. Inappropriate defibrillation was repeatedly conducted for frequent episodes of paroxysmal atrial fibrillation. Therefore, pulmonary vein isolation and linear ablation, including cava-tricuspid isthmus line, were performed. Five hours after the procedure, the patient experienced chest discomfort and lost his consciousness. Electrocardiogram monitoring of lead II revealed atrioventricular sequential pacing and ST-elevation. Cardiopulmonary resuscitation and inotropic support were immediately started. Meanwhile, coronary angiography revealed diffuse narrowing in the right coronary artery. Intracoronary infusion of nitroglycerin immediately dilated the narrowed lesion; however, the patient required intensive care with percutaneous cardiac pulmonary support and a left ventricular assist device. Pacing thresholds obtained immediately after cardiogenic shock were stable and almost similar to previous results. This showed that the myocardium was electrically responsive to ICD pacing but was unable to contract effectively due to ischemia. LEARNING OBJECTIVE: Coronary artery spasm (CAS) associated with catheter ablation commonly occurs during ablation, but rarely as a late-onset complication. CAS may cause cardiogenic shock despite proper pacing of the dual chamber. Continuous monitoring of the electrocardiogram and arterial blood pressure is crucial for the early detection of late-onset CAS. Continuous infusion of nitroglycerin and admission into the intensive care unit after ablation may prevent fatal outcomes.

Psoriasis is a chronic inflammatory skin disease that involves various systemic organs and tissues and is characterized by scaly erythematous skin. Among the different types of psoriasis, psoriatic arthritis (PsA) is frequently reported, and occasionally develops into severe arthritis leading to joint dysfunction. There are various tools, especially questionnaires, to identify the presence of PsA in European and American populations; however, little is known about the utility of these tools in the Asian population. In this study, we investigated the utility of a representative tool, the psoriasis epidemiology screening tool (PEST) questionnaire, to identify PsA among Japanese patients with psoriasis. A total of 143 patients with psoriasis were enrolled in this study. Among them, 29 patients were diagnosed with PsA. The frequency of PsA was significantly increased in patients with PEST scores > 3, with a sensitivity of 93.1% and a specificity of 78.9%. Among the questions in the PEST questionnaire, “Have you ever had a swollen joint?” showed the highest frequency to answer “Yes” among patients with PsA. Univariate and multivariate analyses revealed that high PEST scores (> 3) was an independent variable in PsA patients. Taken together, our study suggests that the PEST questionnaire is a useful tool to identify PsA among Japanese patients with psoriasis.

This study established a rapid method for the gene expression analysis in potato tubers. The use of microtubers would be useful for primary evaluation of tuber-expressed genes. In the development of transgenic potato or of potato with other genome modifications (e.g., genome editing or RNA-directed DNA methylation (RdDM) and so on) to improve tuber traits, analysis of the target gene is often difficult because of the long cultivation cycle (3–4 months), large areas required, numerous materials for plant cultivation, and considerable efforts needed to obtain transgenic tubers. We demonstrate here rapid and convenient analysis of gene expression in potato microtubers. Enough microtubers for expression analysis can be induced over about 4 weeks in a simple liquid medium in an Erlenmeyer flask. High-quality RNA and protein can be easily prepared from microtubers and used for northern blot, qRT-PCR, and western blot analyses without further purification. We investigated the expression of two tuber-expressed genes (GBSS1 and Vinv) in microtubers derived from the wild-type and from lines derived from RdDM-mediated transcriptional gene silencing. As expected, the expression of both genes was similar between microtubers and normal tubers. Furthermore, we demonstrated that microtubers can be used in western blot and confocal immunofluorescent microscopy analyses. These results suggest that expression analysis using microtubers is a convenient tool for the analysis of tuber-expressed genes such as GBSS1 and Vinv in potato.

AIM Falling is known to be associated with cognitive function. We evaluated the relationship between muscle function and falls in patients with chronic liver disease (CLD). METHODS We enrolled 100 sequential CLD patients without dementia who were admitted to our institution for scheduled treatment from July 2017 to May 2018 (age 71.0 ± 10.2 years; 76 men). All subjects were self-reliant in regard to activities of daily living. On admission, handgrip strength was determined and falls within 1 month of admission were noted. For determining handgrip strength decline (HSD), previously reported values were used (men

Melanoma is a malignant tumor of the melanocytes with an unfavorable clinical behavior. Nivolumab, a representative anti-programmed death 1 (PD-1) antibody, has recently been used for the treatment of metastatic malignant melanoma. However, there have been few appropriate biomarkers predicting the effect of nivolumab before the administration. Furthermore, the detailed characteristics of peripheral blood mononuclear cell (PBMC) profiles during nivolumab treatment remains unclear. In this study, we investigated fluctuations of PBMC profile during nivolumab treatment. PBMC analysis showed T-helper (Th)2-dominant conditions after a first course of nivolumab treatment. In a favorable case treated with nivolumab, a Th1/T-cytotoxic 1 shift was observed after nivolumab was administrated. These results suggest that flow cytometric analysis of PBMC may be helpful for the treatment of nivolumab.

Warfarin is the most widely prescribed oral anticoagulant, but large interindividual variations exist in the dose required to achieve comparable therapeutic effects. Several clinical and genetic variables have been identified that influence warfarin dosing. However, interactions between genotype and nutrition remain uncertain in terms of dietary vitamin K intake. To investigate genotype-nutrient interactions in warfarin anticoagulation therapy, 202 consecutive outpatients (M/F = 142/60, mean age, 69 years) undergoing treatment with warfarin were enrolled. Prevalent single nucleotide polymorphisms in VKORC1 and CYP2C9 were genotyped, and dietary vitamin K intake during the week preceding the blood sampling was quantitatively estimated by a dietitian-assisted questionnaire. Patients were classified according to low, medium, or high vitamin K intake. The mean daily warfarin dose in subjects with a VKORC1-1639 A/A genotype was significantly smaller than that with a -1639A/G genotype (2.74 vs. 3.91 mg/day, respectively, p < 0.0001). Dose requirements did not differ between subjects with a CYP2C9 *1/*3 genotype versus a CYP2C9 *1/*1 genotype. In subjects with a variant VKORC1-1639 G allele, the mean daily warfarin dose was significantly attenuated by low vitamin K intake compared with medium and high intake after adjustment for covariates (3.4 vs. 5.0 vs. 4.0 mg/day, respectively, p = 0.028). No such genotype effects were observed in homozygous patients for the VKORC1-1639 A allele. The results of the present study suggest that the capacity of dietary vitamin K intake to influence warfarin dose requirements during anticoagulation therapy is VKORC1 genotype-dependent, at least in part.

Imatinib and nilotinib are inhibitors that selectively target a set of protein tyrosine kinases, including abelson kinase (Abl), together with the chimeric oncoprotein, breakpoint cluster region-abelson kinase (Bcr-Abl), as well as stem cell factor receptor (KIT), platelet-derived growth factor receptor (PDGFR), discoidin domain receptor (DDR), and colony stimulating factor-1 receptor (CSF-1R). The aim of the present study was to investigate whether imatinib or nilotinib was effective against arthritis in the glucose-6-phosphate isomerase (GPI)-induced arthritis mouse model. Imatinib or nilotinib was administered orally to the arthritic mice at different time points. Efficacy was evaluated by visual scoring and by determining the production of anti-GPI antibody. Splenocytes from the arthritic mice were cultured with GPI in the presence of imatinib or nilotinib in vitro, and cytokine levels in the culture supernatants were analyzed. To investigate the effects of imatinib and nilotinib on T-cell proliferation, lymph node cells from the arthritic mice were cultured with GPI in the presence of imatinib or nilotinib in vitro. Interleukin (IL)-17 mRNA expression in the arthritic ankle joints from the onset of arthritis was analyzed by real-time polymerase chain reaction (PCR). The administration of imatinib from day 0 showed suppression of arthritis (P < 0.05), the administration of nilotinib from day 0 resulted in pronounced suppression of arthritis (P < 0.01), and that from day 7 showed significant inhibition of the progression of arthritis (P < 0.05). A reduction in anti-GPI antibodies was correlated with the therapeutic efficacy of imatinib, but not with that of nilotinib. Imatinib dose-dependently inhibited tumor necrosis factor (TNF)-α, IL-6, interferon (IFN)-γ, and IL-17 production by splenocytes in vitro, while nilotinib inhibited only IL-17 and IFN-γ production in a dose-dependent fashion. Imatinib at 3 μM exerted a mild antiproliferative effect on CD4+ T cells (P < 0.05), whereas imatinib at 10 μM and nilotinib at 3 and 10 μM demonstrated a marked antiproliferative effect (P < 0.01). The IL17 gene expression level on day 7 tended to be higher than that on day 14. These findings suggest that imatinib and nilotinib could prevent autoimmune arthritis, essentially via distinct mechanisms, in that imatinib inhibits both inflammatory and T-cell-derived cytokine production, whereas nilotinib suppresses T-cell-derived cytokine production. Imatinib and nilotinib could have therapeutic potential for rheumatoid arthritis (RA) and other inflammatory diseases.

We describe a case of a 69-year-old woman who developed rapidly progressive hepatocellular carcinoma (HCC) associated with autoimmune hepatitis (AIH) after a 7-year follow-up. Markers for viral hepatitis were negative. Serum tumor markers including alpha-fetoprotein and prothrombin induced by vitamin K absence II rose suddenly, and a large tumor was detected in spite of regular surveillance for HCC. Surgical treatment was performed. The resected liver specimen revealed well to moderately differentiated HCC. Ki67 staining showed rapid proliferation of the HCC. Although the incidence of HCC in patients with AIH has been unclarified, the possible complication by HCC must not be overlooked.

A herd of 28–31 Japanese Black (Bos taurus) cows were allowed to graze an experimental plot comprising monoculture swards of centipedegrass (Eremochloa ophiuroides; CG; preferred grass; 0.30 ha) and bahiagrass (Paspalum notatum; BG; less preferred grass; 0.22 ha) for five consecutive days (09:00–16:00 h) in two seasons (summer and autumn), under a substantial travel cost between the two grasses and a trade-off between the forage preference and some abiotic factors. The two swards were apart from each other and connected by an alley of about 80 m. The CG comprised low (CGL) and high (CGH) availability areas (0.15 ha each). The animals grazed mainly the CGH and CGL, which were in the distance and lacked water and shade, in the morning when the air temperature was relatively low. Then, in the afternoon, they shifted the major grazing area to the BG with water, shade, and close proximity to the barn where they camped. On a daily basis, the animals consistently showed preference for the CGH except one case, switching 6–14 times between the BG and CG. The results demonstrate that animals, even when the preferred species is of lower accessibility and in a less favorable abiotic environment, switch between the preferred and less preferred species and eat mixed diets to show a partial preference. They cope with increased travel costs and trade-offs between forage preference and abiotic environment by reducing switching frequency between the species and shifting target species over the course of the day. Further studies are warranted to test how these mechanisms are successful in maintaining the preference under increased distances and trade-offs.

The aim of this study is to reveal the effect of the balance between operators' processing abilities and the time constraints imposed upon them in simple repetitive work. In the present study, three experimental conditions for the same tasks which are original pattern recognition ones, but with different ways of setting time limits, were prepared: one time limit was adjusted to each subjects' ability, the second was a uniform and relatively strict time limit, and the third was a uniform and relatively lax time limit. For these three experimental conditions, comparisons were made of task performance indices, subjective indices (NASA-TLX: NASA-Task Load Index, SACL: Stress-Arousal Checklist), and physiological indices (frontal midline theta activity at Fz and the fast a activity at Pz in EEG, and heart rate in ECG). The results showed that individual differences were extremely large in terms of time pressure (TP) effects on task performance and operators' psycho-physiological state if a uniform and strict time limit was imposed on operators with different abilities. Meanwhile, the negative effects of TP on operators were small if they were given a uniform time limit but with enough allowance time. In addition, the results from the frontal midline theta activity in EEG suggest that the patterns in changes of concentration of attention on tasks were different according to the way that the time constraints were set.

The aim of this study was to determine the relationship between work and low back pain (LBP) by examining both working postures and the workers' everyday lifestyle. Subjects were 118 male workers in a small-to-medium-sized factory having three kinds of workplaces: the slit line, the packing line, and the crane unit. Working posture analysis with OWAS and interviews were carried out. The result of posture analysis showed that the standing posture with both legs straight and back bent appeared most frequently in all three workplaces. Meanwhile, the prevalence of LBP was almost equal among these groups, with 70% of workers having experienced LBP in each group. But the main cause of LBP differed among the three groups. On the slit line, the result of regression analysis and interview suggested that exercises in the past affected the prevalence of LBP, and that aging and work made LBP worse. On the packing line, many workers were transferred to other positions after a few years, and thus might affect the prevalence of LBP in other workplaces. For the crane unit, it appeared that work in previous positions might affect the occurrence of LBP. Moreover, it seemed that activities in the workplace, rather than lifestyles, contribute to the occurrence of LBP in this factory.

Pontamine sky blue (PSB) is used in brain studies to mark the position of microelectrode and micropipette tips. However, few studies have been made on the effects of PSB on neurons; therefore we examined these effects. When puffed on isolated sensory ganglion cells of rats, PSB increased membrane conductance, depolarized membrane potential, and reduced the amplitude of action potentials. When dripped on frog sympathetic ganglion, much like hexamethonium, PSB decreased the amplitude of compound action potentials of the postganglionic strand. A bath application of PSB to sartorius muscle fibers that had been treated with tetrodotoxin depolarized the membrane potential and increased the frequency and amplitude of miniature end-plate potentials. All these effects were reversible. When injected into the rat's pontine part corresponding to the location of the canine pontine defecation reflex center, PSB produced repetitive colorectal contractions and irreversibly abolished them in response to anal-canal stimulation. The excitatory and blocking effects of PSB and its staining ability make it a useful tool for examining the functions of focal brain parts.

When the natural light waves travel into the interface between water and air a part of the light waves refracts and diffracts at the interface. When these waves travel to the horizontal observation plane located at the bottom of the water these waves make the light intensity profile in this observation plane. It is possible to calculate the wave profile by applying Suzuki-Sumino's method to the light intensity profile observed at the bottom in the shallow water. When it becomes deeper the wave profile can be estimated using the relation between the gradient of the water surface and the intensity gradient of light observed at the bottom.

Carpel margin meristems (CMMs), a pair of meristematic tissues present along the margins of two fused carpel primordia of Arabidopsis thaliana, are essential for the formation of ovules and the septum, two major internal structures of the gynoecium. Although a number of regulatory factors involved in shoot meristem activity are known to be required for the formation of these gynoecial structures, their direct roles in CMM development have yet to be addressed. Here we show that the CUP-SHAPED COTYLEDON genes CUC1 and CUC2, which are essential for shoot meristem initiation, are also required for formation and stable positioning of the CMMs. Early in CMM formation, CUC1 and CUC2 are also required for expression of the SHOOT MERISTEMLESS gene, a central regulator for stem cell maintenance in the shoot meristem. Moreover, plants carrying miR164-resistant forms of CUC1 and CUC2 resulted in extra CMM activity with altered positioning. Our results thus demonstrate that the two regulatory proteins controlling shoot meristem activity also play critical roles in elaboration of the female reproductive organ through the control of meristematic activity.

Human body odour and earwax type are genetically dependent on a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. So far, it still remains to be clear how SNP in the ABCC11 gene is associated with human malodour. In a recent issue of Experimental Dermatology, Baumann et al. propose one of the underlying molecular pathways. Although one of the amino acid conjugated of the odorants, Cys-Gly-3-methyl-3-sulfanylhexanol (3M3SH), was not taken up by the transporter ABCC11, glutathione conjugate of 3MSH (SG-3MSH) was transported by ABCC11. Moreover, SG-3MSH was processed to 3M3SH by γ-glutamyl-transferase 1 (GGT1), which was abundantly expressed in apocrine sweat glands. These findings may pave a way for the pharmacogenetics of human body odour and the development of innovative deodorant products.

Although fentanyl patches (FP) designed to sustain plasma fentanyl concentrations for 3 days are used in many patients for continuous relief of moderate to severe cancer pain, there are some cases in which effective pain relief is sustained less than for 3 days, and in which plasma fentanyl concentrations rapidly decrease at the third day after the application. In this study, we measured the amount of fentanyl remaining in FP after continuous 3-days use to clarify some clinical factors that can influence the remaining amounts in 4 patients. Average estimated fentanyl-dermal transfer rates of the collected 41 patches calculated from their remaining amounts were less than nominal rates (21.2+/-3.4 cf. 25 microg/h (2.5 mg FP); 44.9+/-5.1 cf. 50 microg/h (5 mg FP)). Intra-individual variability was also observed (CV: 6.6-14.3% (2.5 mg FP), 3.9-13.3% (5 mg FP)). The present study suggests that the estimated fentanyl-dermal transfer rates are affected by fever, patients' body mass index and application sites. Although further study is necessary to elucidate factors that can influence the variability in transdermal fentanyl absorption, the approach in this study would contribute to improving appropriate usage of FP.

We describe DNA damage induced by such low concentrations of H 2 O 2 . Plasmid DNA was prepared by the boiling lysis method and the cesium chloride-ethidium bromide method. Samples were withdrawn from the mixture every 2 days, and the transforming activity and single-strand breaks were measured. Transformation of Escherichia coli HB101 by plasmid pUC18 was done by the method of Hanahan. Single-strand breaks of DNA were analyzed by agarose gel electrophoresis as described previously

Introduction Immunosuppressants, including anti-TNFα antibodies, have remarkable effects in rheumatoid arthritis; however, they increase infectious events. The present study was designed to examine the effects and immunological change of action of altered peptide ligands (APLs) on glucose-6-phosphate isomerase (GPI) peptide-induced arthritis. Methods DBA/1 mice were immunized with hGPI325-339, and cells of draining lymph node (DLN) were stimulated with hGPI325-339 to investigate the T-cell receptor (TCR) repertoire of antigen-specific CD4+ T cells by flow cytometry. Twenty types of APLs with one amino acid substitution at a TCR contact site of hGPI325-339 were synthesized. CD4+ T cells primed with human GPI and antigen-presenting cells were co-cultured with each APL and cytokine production was measured by ELISA to identify antagonistic APLs. Antagonistic APLs were co-immunized with hGPI325-339 to investigate whether arthritis could be antigen-specifically inhibited by APL. After co-immunization, DLN cells were stimulated with hGPI325-339 or APL to investigate Th17 and regulatory T-cell population by flow cytometry, and anti-mouse GPI antibodies were measured by ELISA. Results Human GPI325-339-specific Th17 cells showed predominant usage of TCRVβ8.1 8.2. Among the 20 synthesized APLs, four (APL 6; N329S, APL 7; N329T, APL 12; G332A, APL 13; G332V) significantly reduced IL-17 production by CD4+ T cells in the presence of hGPI325-339. Co-immunization with each antagonistic APL markedly prevented the development of arthritis, especially APL 13 (G332V). Although co-immunization with APL did not affect the population of Th17 and regulatory T cells, the titers of anti-mouse GPI antibodies in mice co-immunized with APL were significantly lower than in those without APL. Conclusions We prepared antagonistic APLs that antigen-specifically inhibited the development of experimental arthritis. Understanding the inhibitory mechanisms of APLs may pave the way for the development of novel therapies for arthritis induced by autoimmune responses to ubiquitous antigens.