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Insulin-like growth factors are polypeptides, with arrays similar to insulin, and insulin-like growth factor 1 (IGF-1) is secreted via stimulation by growth hormone (GH) in the liver. The lack of both GH and IGF-1 leads to physiological age-related changes in the cardiovascular system; however, the role of IGF-1 and GH in hypertension has not been fully elucidated. Thus, we examined the association between plasma IGF-1 and GH levels and hypertension. Among 1368 health check-up examination participants in the town of Tanushimaru, 1094 subjects were analyzed after excluding subjects with diabetes mellitus or impaired liver function. Multiple linear and logistic regression analyses were performed for factors related to systolic and diastolic blood pressures (BPs). Characteristics of participants stratified by IGF-1 and GH quartiles were compared using analysis of covariance. We calculated odds ratios associated with each standard deviation increase in IGF-1 and GH levels for hypertension, which was defined as BP ≥ 140/90 mmHg and/or the use of antihypertensive medication. Multivariable analysis showed that FPG, insulin, HOMA-IR, eGFR, total cholesterol, triglycerides, and the use of medication for hypertension were associated with the Z-score of IGF-1 measurement quartiles. Next, we found that BMI, systolic and diastolic BPs, insulin, HOMA-IR, total cholesterol, HDL-cholesterol, triglycerides, smoking, and alcohol intake were associated with GH quartiles, indicating that hypertension was inversely associated with GH but not IGF-1. A significant and inverse relationship between serum GH and hypertension was found after adjustment for confounders. In conclusion, decreased GH but not IGF-1, was associated with hypertension in a general population.

Background Remote ischemic preconditioning (RIPC) induced by transient limb ischemia is a powerful innate mechanism of cardioprotection against ischemia. Several described mechanisms explain how RIPC may act through neural pathways or humoral factors; however, the mechanistic pathway linking the remote organ to the heart has not yet been fully elucidated. This study aimed to investigate the mechanisms underlying the RIPC-induced production of Janus kinase (JAK)-signal transducer and activator of the transcription (STAT)-activating cytokines and cardioprotection by using mouse and human models of RIPC. Methods and results Screened circulating cardioprotective JAK-STAT-activating cytokines in mice unexpectedly revealed increased serum erythropoietin (EPO) levels after RIP induced by transient ischemia. In mice, RIPC rapidly upregulated EPO mRNA and its main transcriptional factor, hypoxia-inducible factor-1α (HIF1α), in the kidney. Laser Doppler blood flowmetry revealed a prompt reduction of renal blood flow (RBF) after RIPC. RIPC activated cardioprotective signaling pathways and the anti-apoptotic Bcl-xL pathway in the heart, and reduced infarct size. In mice, these effects were abolished by administration of an EPO-neutralizing antibody. Renal nerve denervation also abolished RIPC-induced RBF reduction, EPO production, and cardioprotection. In humans, transient limb ischemia of the upper arm reduced RBF and increased serum EPO levels. Conclusions Based on the present data, we propose a novel RIPC mechanism in which inhibition of infarct size by RIPC is produced through the renal nerve-mediated reduction of RBF associated with activation of the HIF1α-EPO pathway.

Because of the protective effect of estrogen for atherosclerosis, the prevalence of acute coronary syndrome in women before menopause is low. We report a rare case of unstable angina in a young Japanese female who had a history of cigarette smoking and contraceptive use. Her coronary stenosis was successfully treated by percutaneous coronary intervention.

Objectives The study investigated the role of myocardial suppressor of cytokine signaling-3 (SOCS3), an intrinsic negative feedback regulator of the janus kinase and signal transducer and activator of transcription (JAK-STAT) signaling pathway, in the development of left ventricular (LV) remodeling after acute myocardial infarction (AMI). Background LV remodeling after AMI results in poor cardiac performance leading to heart failure. Although it has been shown that JAK-STAT–activating cytokines prevent LV remodeling after AMI in animals, little is known about the role of SOCS3 in this process. Methods Cardiac-specific SOCS3 knockout mice (SOCS3-CKO) were generated and subjected to AMI induced by permanent ligation of the left anterior descending coronary artery. Results Although the initial infarct size after coronary occlusion measured by triphenyltetrazolium chloride staining was comparable between SOCS3-CKO and control mice, the infarct size 14 days after AMI was remarkably inhibited in SOCS3-CKO, indicating that progression of LV remodeling after AMI was prevented in SOCS3-CKO hearts. Prompt and marked up-regulations of multiple JAK-STAT–activating cytokines including leukemia inhibitory factor and granulocyte colony-stimulating factor (G-CSF) were observed within the heart following AMI. Cardiac-specific SOCS3 deletion enhanced multiple cardioprotective signaling pathways including STAT3, AKT, and extracellular signal-regulated kinase (ERK)-1/2, while inhibiting myocardial apoptosis and fibrosis as well as augmenting antioxidant expression. Conclusions Enhanced activation of cardioprotective signaling pathways by inhibiting myocardial SOCS3 expression prevented LV remodeling after AMI. Our data suggest that myocardial SOCS3 may be a key molecule in the development of LV remodeling after AMI.

Sannai-Maruyama is one of the most famous and best-researched mid-Holocene (mid-Jomon) archaeological sites in Japan, because of a large community of people for a long period. Archaeological studies have shown that the Jomon people inhabi1ted the Sannai-Maruyama site from 5.9 to 4.2 ± 0.1 cal kyr BP However, a continuous record of the terrestrial and marine environments around the site has not been available. Core KT05-7 PC-02, was recovered from Mutsu Bay, only 20 km from the site, for the reconstruction of high-resolution time series of environmental records, including sea surface temperature (SST). C37 alkenone SSTs showed clear fluctuations, with four periods of high (8.4–7.9, 7.0–5.9, 5.1–4.1, and 2.3–1.4 cal kyr BP) and four of low (−8.4, 7.9–7.0, 5.9–5.1, and 4.1–2.3 cal kyr BP) SST. Thus, each SST cycle lasted 1.0–2.0 kyr, and the amplitude of fluctuation was about 1.5–2.0 °C. Total organic carbon (TOC) and C37 alkenone contents, and the TOC/total nitrogen ratio indicate that marine biogenic production was low before 7.0 cal kyr BP, but was clearly increased between 5.9 and 4.0 cal kyr BP, because of stronger vertical mixing. During the period when the community at the site prospered (between 5.9 and 4.2 ± 0.1 cal kyr BP), the terrestrial climate was relatively warm. The high relative abundance of pollen of both Castanea and Quercus subgen. Cyclobalanopsis supports the interpretation that the local climate was optimal for human habitation. Between 5.9 and 5.1 cal kyr BP, in spite of warm terrestrial climates, the C37 alkenone SST was low; this apparent discrepancy may be attributed to the water column structure in the Tsugaru Strait, which differed from the modern condition. The evidence suggests that at about 5.9 cal kyr B.P, high productivity of marine resources such as fish and shellfish and a warm terrestrial climate led to the establishment of a human community at the Sannai-Maruyama site. Then, at about 4.1 ± 0.1 cal kyr BP, abrupt marine and terrestrial cooling, indicated by a decrease of about 2 °C in the C37 alkenone SST and an increase in the pollen of taxa of cooler climates, led to a reduced terrestrial food supply, causing the people to abandon the site. The timing of the abandonment is consistent with the timing (around 4.0–4.3 cal kyr BP) of the decline of civilizations in north Mesopotamia and along the Yangtze River. These findings suggest that a temperature rise of ∼2 °C in this century as a result of global warming could have a great impact on the human community and especially on agriculture, despite the advances of contemporary society.

In order to investigate fatigue characteristics of vulcanized natural rubber, fatigue tests were carried out under various stress ratios R. It was considered that the fatigue cracks were initiated from defects in very early stage of total life. The fatigue life was nearly equal to the fatigue crack propagation life and the propagation process was independent of R. The crack growth rate was proportional to the crack length to about the first power, when the crack length was defined as the length of the direction perpendicular to the loading direction. The crack propagation mode was dependent on R. Under 0

In order to investigate fatigue characteristics of vulcanized natural rubber (NR), fatigue tests are carried out under various stress ratios R and variable loading. In this paper, fatigue crack propagation life is predicted depending on fatigue crack propagation behavior, because the fatigue life is almost the fatigue crack propagation life. Two essential assumptions for the application of Miner's rule are satisfied. It is considered that Miner's rule can predict the fatigue life safely under two-step loading, because the fatigue damage location is depending on R. Under complex variable loading, it is considered that the crack growth rate under 0

Introduction: Suppressor of cytokine signaling-3 (SOCS3) is a cytokine-inducible negative regulator of JAK-STAT signaling pathway. Cardiac-specific SOCS3 deficient mice (SOCS3-CKO) spontaneously develop cardiac dysfunction with advanced age. Hypothesis: We thus evaluated the underlying mechanism of age-related cardiac dysfunction in SOCS3-cKO mice. Methods: To create SOCS3-CKO mice, SOCS3-flox mice were bred with mice harboring a transgene encoding Cre recombinase driven by the α-myosin heavy chain promoter. Cardiac fibrosis was measured by Sirius-red staining. We evaluated autophagy induction by western blot using an antibody raised against microtubule-associated protein light chain 3 (LC3). Results: SOCS3-CKO mice were born at the expected Mendelian ratio, but developed cardiac dysfunction estimated by echocardiogram from 25 weeks of age. Cardiac fibrosis was greater in SOCS3-CKO mice compared to control mice (p Conclusions: These results suggest that age-related cardiac dysfunction in SOCS3-CKO mice may be due to impaired autophagy through sustained STAT3 activation.

Introduction: In patients with acute heart failure, pleural fluid localized in an inter-pleural fissure produces a mass on chest X-ray, which mimics a tumor. Case Presentation: Such masses have been designated as vanishing tumors of the lung. It is extremely rare that a vanishing tumor occurs in the apex of the lung. Conclusions: This is the first case report of a vanishing tumor in the right pulmonary apex.

The Okhotsk Sea plays a significant role in climatic and oceanic environmental change on regional and global scales. The fluctuation in pollen and spores abundances was investigated in order to reconstruct terrestrial and ocean environmental change during the Holocene. Fluctuation of the total abundance and assemblage of most of pollen and spores reflects terrestrial environmental change along the coastal area of the southern Okhotsk Sea. On the other hand, the abundance of Cryptomeria , Cyclobalanopsis and Castanopsis pollen from plants which are not currently growing in Hokkaido, is suggested to be a good proxy for the intensity of the Tsushima Current. Relatively warm pollen assemblages characterize Periods 1 (calendar age 7240–3050 yr BP) and 3 (150–0 yr BP) while a relatively cold pollen assemblage characterizes Period 2 (3050–150 yr BP). Three warm sub-periods 1a (7240–6500 yr BP), 1c (5900–4550 yr BP) and 1e (4300–3550 yr BP) are associated with relatively strong intensity of the Tsushima Current, transgression, and the occurrence of bivalves living in warm conditions. Continuous cooling started 3000 yr BP. The area remained so cold that the intensified Tsushima Current (2800–2400 and 1700–1400 yr BP) would have made little difference to terrestrial warming in the southern Okhotsk Sea. In the uppermost samples, a large increase in total abundance of pollen and spores may be partly attributed to the modern global warming effect.

The data on interactive actions between running vehicles should be obtained when making microscopic traffic simulation models based on Car Following Theory. In this paper, the data collection method using GPS is proposed. The GPS device installed to each car observes the velocity and location every second and based on those data, the headway and the reaction time-lag data can be calculated. Using this method, the data on various kind of traffic conditions and road conditions can be obtained. The usefulness of the method is apparent by applying the data to our microscopic traffic simulation model.

An N2O-saturated aqueous solution containing 2''-dG and the spin trap agent PBN was examined by ESR and HPLC-ECD methods after X irradiation. ESR examination showed that the ESR spectrum obtained consisted of signals due to the PBN-OH and PBN-H adducts. The signal intensity of PBN-H adducts was larger in the presence of 2''-dG than in the absence of 2''-dG, while that of PBN-OH adducts was smaller in the presence of 2''-dG than in the absence of 2''-dG. When the OH-radical-induced 8-oxodG was measured by HPLC-ECD, the yield of 8-oxodG was found to be enhanced about twofold in the presence of PBN. By contrast, usual OH-radical scavengers (DMSO, sodium formate and mannitol) inhibited the formation of 8-oxodG beyond expectation. The enhancement of the yield of PBN-H adducts by 2''-dG and the enhancement of the 8-oxodG formation by PBN were explained by the electron transfer and subsequent proton transfer reactions from OH-radical-induced guanine-N7 radicals to PBN to form 8-oxodG and PBN-H. The present study led us to conclude that PBN reacted with the precursor radical of 8-oxodG to accelerate the formation of 8-oxodG, while OH-radical scavengers reacted with it to diminish the formation of 8-oxodG.

In the present study we demonstrated the protective effects of the spin-trapping agent α-phenyl-tert-butyl nitrone (PBN) against fulminant hepatitis with jaundice in LEC rats. In LEC rats an excess amount of copper is accumulated in the liver and causes hepatitis with severe jaundice. PBN was subcutaneously administered every 2 d at the concentration of 128 mg/kg, beginning with 13-week-old rats and continuing for 17 weeks. PBN prevented the loss of body weight, reduced death rate, and suppressed the increase in GTP and GOT values reflecting hepatic cell destruction. Ocular inspection also confirmed the suppressive effects of PBN on jaundice. In parallel with these phenomena, the amounts of thiobarbituric acid-reactive substances (TBARS) in livers of PBN-administered rats were found to be lower than those of non-PBN-administered rats. Little histological changes were observed in PBN-administered rats in comparison with non-PBN-administered rats. The protective effect of PBN on the formation of oxidative damage in liver DNA was observed but not so remarkable as that on lipid peroxidation. From these results, it was concluded that PBN had the liver-protective effects against fulminant hepatitis with jaundice. This suggested that free radicals play an important role in abnormally accumulated copper-induced liver injury and that PBN potentially has therapeutic value for the treatment of hepatitis.

Lysyl oxidase (LOX) and LOX-like protein-1 (LOXL-1) are extracellular matrix-embedded amine oxidases that have critical roles in the cross-linking of collagen and elastin. LOX family proteins are abundantly expressed in the remodeled heart of animals and humans and are implicated in cardiac fibrosis; however, their role in cardiac hypertrophy is unknown. In this study, in vitro stimulation with hypertrophic agonists significantly increased LOXL-1 expression, LOX enzyme activity and [(3)H] leucine incorporation in neonatal rat cardiomyocytes. A LOX inhibitor, beta-aminopropionitrile (BAPN), inhibited agonist-induced leucine incorporation in cardiomyocytes in vitro, suggesting the involvement of LOXL-1 in cardiomyocyte hypertrophy. Abdominal aortic constriction in rats produced left ventricular hypertrophy in parallel with LOXL-1 mRNA upregulation. And BAPN administration significantly inhibited angiotensin II-induced cardiac hypertrophy in vivo. These results suggest a role of LOXL-1 in cardiac hypertrophy in vivo. We generated transgenic mice with cardiomyocyte-specific expression of LOXL-1. LOXL-1 transgenic mice pups were born normally and grew to adulthood without increased mortality; these mice exhibited a greater left ventricle to body weight ratio, larger myocyte diameter, and more brain natriuretic peptide expression than their wild-type littermates. Echocardiography revealed that the LOXL-1 transgenic mice also had greater wall thickness with preserved cardiac contraction. Our results indicate a possible fundamental role of LOXL-1 in cardiac hypertrophy.

Morphological structures produced by the phase separation of polystyrene/poly(2-chlorostyrene) blend bilayer films has been studied by electron microscopy

Cannulation of the ascending aorta is the recognized method to achieve arterial return during cardiopulmonary bypass. Mediastinal infection after cardiac surgery can cause disruption at the point of insertion, and give rise to a pseudoaneurysm in the ascending aorta. Although rare, a pseudoaneurysm can occur without clear evidence of infection. Here we report two cases that received aortic valve replacement and that developed ascending aortic aneurysms after surgery. Based on our clinical findings, these aneurysms were related to the arterial cannulation into the aorta and not to any infection.

Currently, poststernotomy mediastinitis frequently is being treated by debridement and immediate closure with omental drainage. This method is useful, but subcutaneous infection occasionally occurs. Divided omental transfer to the presternal space may be helpful in preventing this complication.

We report herein the unusual case of a patient in whom postoperative angiography following coronary artery bypass grafting (CABG) revealed a lateral origin of the right internal thoracic artery (ITA) and a normal origin of the left ITA, both of which were demonstrated to be patent and did not follow a tortuous course. The CABG had involved revascularization of the left anterior descending artery (LAD) with the right ITA, and the obtuse marginal artery with the left ITA. The patient had an uneventful postoperative course and developed no respiratory symptoms.

Aqueous DNA solutions with or without the spin trap alpha-phenyl-N-tert-butylnitrone (PBN) were exposed to gamma-rays at 77 K. After thawing the solutions, three experiments were carried out to confirm the generation of OH radicals in the hydration layer of DNA and to examine whether they act as an inducer of DNA strand breaks and base alterations. Observation with the ESR-spin trapping method showed ESR signals from PBN-OH adducts in the solution containing PBN and DNA, but there were few signals in the solution containing PBN alone, suggesting that reactive OH radicals were produced in the hydration layer of gamma-irradiated DNA and were effectively scavenged by PBN, and that unreactive OH radicals were produced in the free water layer of gamma-irradiated DNA. Agarose gel electrophoresis of DNA proved that PBN had no effect on the formation of strand breaks, whereas examination with the high-performance liquid chromatography-electrochemical detection (HPLC-ECD) method showed that PBN suppressed the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). From these results it was concluded that OH radicals generated in the hydration layer of gamma-irradiated DNA did not induce DNA strand breaks but induced base alterations.

A spin-trapping method combined with enzymatic digestion and high-performance liquid chromatography was employed to detect hydroxyl-radical-induced precursors of strand breaks in oligonucleotides ((dC)10 and (dT)10) as DNA models. Radicals produced as precursors of both strand breaks and base alterations were first trapped by the spin trap 2-methyl-2-nitrosopropane. The oligonucleotides containing spin adducts were subsequently digested by snake venom phosphodiesterase to release low-molecular-weight nitroxide fragments. In this way, several spin adducts were separated by high-performance liquid chromatography. In both oligonucleotides, ESR spectra attributable to the spin adducts derived from trapping of a precursor radical of strand breaks (the C4'-sugar radical) were observed. To further confirm this assignment, the induction of strand breaks was examined by polyacrylamide gel electrophoresis of 5'-32P-end-labeled oligonucleotides. Autoradiograms of the gels showed that the fragments corresponding to monomers to 9mers were formed in both oligonucleotides. When experiments were carried out under conditions in which hydroxyl radicals reacted with oligomers in the presence of the spin trap, the spin trap was found to suppress the fragmentation more than it did by scavenging hydroxyl radicals, indicating that the precursor radical of strand breaks (the C4' radical) was trapped. The present experiments showed that the spin-trapping method combined with gel electrophoresis was a good approach to identify sites of radical damage which cause strand breaks in oligonucleotides (probably in DNA).

A 23-year-old man underwent a tracheostomy. A massive hemorrhage from the tracheostomy site occurred 50 days later. An emergency operation was immediately performed and an erosion was noted on the innominate artery. The artery was divided and the hemorrhage was successfully stopped.