Direct observation of imploded core heating via fast electrons with super-penetration scheme.

Fast ignition (FI) is a promising approach for high-energy-gain inertial confinement fusion in the laboratory. To achieve ignition, the energy of a short-pulse laser is required to be delivered efficiently to the pre-compressed fuel core via a high-energy electron beam. Therefore, understanding the transport and energy deposition of this electron beam inside the pre-compressed core is the key for FI. Here we report on the direct observation of the electron beam transport and deposition in a compressed core through the stimulated Cu Kα emission in the super-penetration scheme. Simulations reproducing the experimental measurements indicate that, at the time of peak compression, about 1% of the short-pulse energy is coupled to a relatively low-density core with a radius of 70 µm. Analysis with the support of 2D particle-in-cell simulations uncovers the key factors improving this coupling efficiency. Our findings are of critical importance for optimizing FI experiments in a super-penetration scheme.

Quantitative Survey of Laypersons' Attitudes Toward Organ Transplantation in Japan.

BACKGROUND: In comparison with foreign countries, living-organ transplantations (LOT) have been performed more frequently than dead organ transplants, including brain-dead organ transplantation (BOT) in Japan. This situation has given rise to organ transplantation tourism. Therefore, we clarify laypersons' preferences regarding organ transplantation that are producing the current situation in Japan, to suggest a possible framework for further efforts. METHODS: Voluntary completion of a quantitative and anonymous survey was promoted online (a sample size of 1030). The questionnaire had two types of variables concerning demographic characteristics and organ transplantation-related issues. RESULTS: LOT was favored over BOT. However, for willingness to donate to family members, the participants showed a significantly more positive attitude toward brain-dead organ donors (BODs) than living organ donors (LODs). In the evaluation of each transplantation technology, BOT and LOT were positioned in the middle, between transplantation that does not depend on others and the utilization of animal organs. CONCLUSIONS: Although LOT was favored over BOT, for participants hypothesized to be in a position to donate and receive organs, BODs received a conversely better reputation than LODs. Our survey and discussion suggest that the present conditions of organ transplantation in Japan might be because there is a lack of deliberation on transplantation tourism and LOT. Therefore, more surveys concerning LOT cases and the implications of avoidance of organs from brain-dead bodies, coupled with more discussions based on these surveys, are necessary to formulate a Japanese transplantation policy for the future.

The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control.

BACKGROUND: Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. METHODS: 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. RESULTS: People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p < 0.001). In regression models, cardiovascular risk factors accounted for attenuated ACh and SNP responses in CVD, whereas HbA1c accounted for the effects of T2DM. HbA1c was associated with ACh and SNP response after adjustment for cardiovascular risk factors (adjusted standardised beta (ß) -0.096, p = <0.008 and -0.135, p < 0.001, respectively). Pre-existing CVD did not modify this association (ß -0.099; p = 0.006 and -0.138; p < 0.001, respectively). Duration of diabetes accounted for the association between HbA1c and ACh (ß -0.043; p = 0.3), but not between HbA1c and SNP (ß -0.105; p = 0.02). CONCLUSIONS: In those with T2DM and CVD, good glycaemic control is still associated with better microvascular function, whereas in those with prolonged disease this association is lost. This suggests duration of diabetes may be a better surrogate for "advanced disease" than concomitant CVD, although this requires prospective validation.

Measures of atherosclerotic burden are associated with clinically manifest cardiovascular disease in type 2 diabetes: a European cross-sectional study.

BACKGROUND: There is a need to develop and validate surrogate markers of cardiovascular disease (CVD) in subjects with diabetes. The macrovascular changes associated with diabetes include aggravated atherosclerosis, increased arterial stiffness and endothelial dysfunction. The aim of this study was to determine which of these factors is most strongly associated with clinically manifest cardiovascular events. METHODS: Vascular changes were measured in a cohort of 458 subjects with type 2 diabetes (T2D) and CVD (myocardial infarction, stroke or lower extremity arterial disease), 527 subjects with T2D but without clinically manifest CVD and 515 subjects without T2D and with or without CVD. RESULTS: Carotid intima-media thickness (IMT) and ankle-brachial pressure index were independently associated with the presence of CVD in subjects with T2D, whereas pulse wave velocity and endothelial function provided limited independent additive information. Measurement of IMT in the carotid bulb provided better discrimination of the presence of CVD in subjects with T2D than measurement of IMT in the common carotid artery. The factors most significantly associated with increased carotid IMT in T2D were age, disease duration, systolic blood pressure, impaired renal function and increased arterial stiffness, whereas there were no or weak independent associations with metabolic factors and endothelial dysfunction. CONCLUSIONS: Measures of atherosclerotic burden are associated with clinically manifest CVD in subjects with T2D. In addition, vascular changes that are not directly related to known metabolic risk factors are important in the development of both atherosclerosis and CVD in T2D. A better understanding of the mechanisms involved is crucial for enabling better identification of CVD risk in T2D.

Dehydroepiandrosterone administration increased trabecular mass and dihydrotestosterone levels in the cancellous region of the tibia in young female rats.

The aim of the present study was to determine whether dehydroepiandrosterone (DHEA) administration affects bone mass and local sex hormone levels in the cancellous region of young female rats. Eleven female rats (6 weeks old) were randomly divided into 2 groups: control rats (CON, n=5) and rats treated with DHEA (DHEA, n=6). DHEA dissolved in sesame oil was administered to the DHEA group intraperitoneally at 20 mg DHEA/kg body weight, and the CON group was treated with vehicle only (sesame oil, 0.5 ml). The rats were treated with DHEA or vehicle for 3 consecutive days, followed by 1 day of no treatment. The experimental period was 8 weeks. According to dual-energy X-ray absorptiometry and high-resolution microcomputed tomography data, the DHEA group exhibited increased trabecular bone mineral density (BMD), bone volume, and tibial thickness compared to the findings in the CON group, whereas no effect was observed on cortical BMD or morphometry. The concentrations of free testosterone and estradiol in the cancellous region of the tibia did not differ between the 2 groups, but the DHT concentration was significantly higher in the DHEA group than in the CON group. These findings suggest that an increase in local DHT levels may stimulate an increase in trabecular bone mass during growth phases in female rats.

Hyperforin inhibits cell proliferation and differentiation in mouse embryonic stem cells.

OBJECTIVES: Hyperforin, a phloroglucinol derivative of St. John's Wort, has been identified as the major molecule responsible for this plant's products anti-depressant effects. It can be expected that exposure to St. John's Wort during pregnancy occurs with some frequency although embryotoxic or teratogenic effects of St. John's Wort and hyperforin have not yet been experimentally examined in detail. In this study, to determine any embryotoxic effects of hyperforin, we have attempted to determine whether hyperforin affects growth and survival processes of employing mouse embryonic stem (mES) cells (representing embryonic tissue) and fibroblasts (representing adult tissues). MATERIALS AND METHODS: We used a modified embryonic stem cell test, which has been validated as an in vitro developmental toxicity protocol, mES cells, to assess embryotoxic potential of chemicals under investigation. RESULTS: We have identified that high concentrations of hyperforin inhibited mouse ES cell population growth and induced apoptosis in fibroblasts. Under our cell culture conditions, ES cells mainly differentiated into cardiomyocytes, although various other cell types were also produced. In this condition, hyperforin affected ES cell differentiation into cardiomyocytes in a dose-dependent manner. Analysis of tissue-specific marker expression also revealed that hyperforin at high concentrations partially inhibited ES cell differentiation into mesodermal and endodermal lineages. CONCLUSIONS: Hyperforin is currently used in the clinic as a safe and effective antidepressant. Our data indicate that at typical dosages it has only a low risk of embryotoxicity; ingestion of large amounts of hyperforin by pregnant women, however, may pose embryotoxic and teratogenic risks.

Differential genetic responses to ionizing irradiation in individual families of Japanese medaka, Oryzias latipes.

Although no statistically significant hereditary effects have yet been detected in the children of survivors from the atomic bombings in Hiroshima and Nagasaki, recent animal studies have found that exposure to ionizing radiation can cause genomic and epigenomic instability in the exposed individuals, as well as their offspring, and therefore, may have much larger genetic effects than predicted by earlier studies. When individuals are exposed to various environmental insults, including radiation, individual sensitivity to the insults often varies. Variance in germ-line response to radiation among individuals has been widely recognized, but it is difficult to address due to the use of inbred strains and the limited number of offspring that can be produced by a pair of mice, the common model used to study genetic effects of radiation. Herein is the first study to examine individual family responses to ionizing radiation using a parent-pedigree approach in an outbred strain of a vertebrate model, the Japanese medaka fish. Changes in frequencies of radiation-induced germline mutations at nine microsatellite loci were examined in the same families before and after exposure to one of four acute doses of ionizing radiation (0.1, 0.5, 2.5, 5Gy, plus sham-exposed controls). Families varied significantly in pre-exposure mutation frequencies and responses to irradiation, but germline mutations were elevated in at least one family after 0.1, 0.5, and 5Gy exposures. Variance among individuals in sensitivity to radiation is well documented for many endpoints, and our work now extends these endpoints to include germ-line mutations. Further studies are needed to elucidate dose response, effects at varying stages of spermatogenesis, and the mechanisms underlying the variance in these individual responses to radiation.

A cubic-anvil high-pressure device for pulsed neutron powder diffraction.

A compact cubic-anvil high-pressure device was developed for in situ neutron powder diffraction studies. In this device, a cubic shaped pressure medium is compressed by six anvils, and neutron beams pass through gaps between the anvils. The first high-pressure experiment using this device was conducted at J-PARC and clearly showed the neutron diffraction patterns of Pb. Combining the cubic-anvil high-pressure device with a pulsed neutron source will prove to be a useful tool for neutron diffraction experiments.

Exercise in, and adaptations to a cold environment have no effect on SIgA.

AIM: The authors hypothesized that inconsistent SIgA response to exercise is caused by the different adaptative status of subjects to a cold environment. The purposes of the study were to examine whether moderate-intense exercise in a cold environment decreases SIgA and whether adaptation to a cold environment has any effect on SIgA. METHODS: Young male skaters, short track (N=9) and inline (N=10), participated in this study. All subjects cycled for 60 min at 65% VO(2max) in cold (ambient temperature: 5 +or - 1 degrees Celsius, relative humidity 41 + or - 9%) and thermoneutral (ambient temperature: 21 + or - 1 degrees Celsius, relative humidity 35 + or - 5%) conditions. Saliva samples were collected as follows: before and after 1hour of environmental exposure; immediately, 30-min, 60-min and 120-min after the exercise. RESULTS AND CONCLUSIONS: Salivary SIgA and saliva flow rate decreased after the exercise in both groups only in thermoneutral conditions. The SIgA secretion rate did not decrease after moderate-high intensity exercise in a cold environment, and the SIgA response to exercise was not affected by the different adaptative status of subjects to the cold environment.

DHEA improves impaired activation of Akt and PKC zeta/lambda-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes rats.

AIM: Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5alpha-dihydrotestosterone (DHT). It induced activation of glucose metabolism-related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC zeta/lambda)-glucose transporter-4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear. METHODS: Using streptozotocin (STZ)-induced rats with type 1 diabetes mellitus, we tested the hypothesis that a single bout of DHEA injection in the rats improves hyperglycaemia and muscle GLUT4-regulated signalling pathway. After 1 week of STZ injection (55 mg kg(-1)) with male Wistar rats, fasting glucose concentrations were determined in a blood sample taken from the tail vein. Blood glucose levels were then monitored for 180 min after DHEA or sesame oil (control) was injected (n = 10 for each group). RESULTS: Blood glucose levels decreased significantly for 30-150 min after 2 mg DHEA injection in the STZ rats. In the skeletal muscle, expression and translocation of GLUT4 protein, phosphorylation of Akt and PKC zeta/lambda, and phosphofructokinase and hexokinase enzyme activities increased significantly by DHEA injection. However, DHEA-induced improvements in Akt and PKC zeta/lambda-GLUT4 pathways were blocked by a DHT inhibitor. CONCLUSION: These results suggest that a single bout of DHEA injection can improve hyperglycaemia and activate the glucose metabolism-related signalling pathway via Akt and PKC zeta/lambda-GLUT4 proteins of skeletal muscles in rats. Moreover, these results show that a DHEA-induced increase in muscle glucose uptake and utilization might contribute to improvement in hyperglycaemia in type 1 diabetes mellitus.

Communication of radiation-induced signals in vivo between DNA repair deficient and proficient medaka (Oryzias latipes).

Radiation-induced bystander effects are established consequences of exposure to ionizing radiation. The operation of this mechanism has been seen in vitro and also between fish, mammals, and plants in vive where stress signals from treated organisms induce responses in neighbors. In vitro research shows that DNA repair deficient cells produce more toxic bystander responses. To test this in vivo two strains of Japanese medaka were tested. One is a mutant, repair deficient strain (ric2) and the other, the wildtype repair proficient strain (CAB). Irradiated fish swam with unirradiated partners in a strain mix and match protocol. The data suggest that medaka produce signals, when exposed to radiation, that induce unirradiated fish ofthe same strain swimming with them to produce an altered response to that seen in bystanders to sham irradiated fish. More apoptosis was seen in bystanders to repair deficient fish. When the strains are mixed, the bystanders of either strain respond like the donor strain. Measurements of Bcl-2 and cmyc proteins in the explants confirmed these observations. A possible role for p53 was also identified in that the use of reporters with mutant p53 demonstrated that CAB signals killed all the reporter cells by apoptosis. Use of a similar but p53 wildtype cell line had no such effect. The data add to the body of knowledge showing that bystander signals operate at hierarchical levels of organization greater than the individual and may therefore have relevance in radioecology and (eco)systems biology.

MRI evaluation of body composition changes in wrestlers undergoing rapid weight loss.

PURPOSE: Changes in body composition of college wrestlers undergoing rapid weight reduction were evaluated over time using magnetic resonance imaging (MRI). METHODS: This study evaluated 12 wrestlers (male, 18-22 years of age) who participated in Japan's 2005 intercollegiate wrestling tournament. For this study, MRI (of the right femoral region and the trunk), as well as measurements of body weight, body fat percentage and body water content, were performed 1 month and 1 week prior to the weigh-in, on the day of the weigh-in, on the day of the match (after the match), and 1 week after the weigh-in. A survey of food and fluid intake was also conducted. RESULTS: Several variables were significantly lower on the day of the weigh-in than one month prior: body weight (p<0.01, -7.3% (SD 1.6%)); body fat (p<0.05, -9.3 (5.8)%); body water content (p<0.01, -5.9 (1.6)%); trunk cross-section (p<0.01, -13.2 (4.4)%), including separate measurements of trunk viscera, trunk muscle, and trunk fat; quadriceps muscle; lower subcutaneous; and food intake (p<0.01, 122 (20)). At 1 week after the match, all metrics had recovered to their levels measured 1 month before the weigh-in. Certain variables that were highly sensitive to hydration recovered more rapidly: they had reached their initial levels when measured immediately after the match. CONCLUSION: Rapid weight reduction reduced the wrestlers' cross-sectional areas of muscle and fat tissues, which tended to recover through rehydration after the weigh-in. These results suggest that rapid weight reduction of wrestlers induced changes in different regions of the body.

A rat model of saliva secretory immunoglobulin: a suppression caused by intense exercise.

We aimed to develop a valid model of immunosuppression induced by intense exercise in rats. Rats were divided into three groups. In the rest (Rest) group, saliva was collected from resting rats on 4 consecutive days. In the exercise (Ex) group, rats ran on a treadmill until exhaustion (exercise time: 60.0 +/- 3.7 min), and their saliva was collected before and after exercise; the salivary glands were removed after exercise. In the control (Con) group, saliva collection and gland removal were also performed, but the rats did not exercise. Secretory immunoglobulin A (SIgA) concentrations in saliva and polymeric immunoglobulin receptor (pIgR) mRNA expression in the glands were measured. There was no significant change in SIgA concentration in the Rest group over 4 days. In the Ex group, SIgA concentration decreased significantly after exercise compared with before, whereas there was no significant change in the Con group. The expression of pIgR mRNA was significantly lower in the Ex group post-exercise than in the Con group. Our procedure for saliva collection appeared suitable, and the exercise-induced SIgA suppression was probably caused by a decline in pIgR mRNA expression. We propose to use this reproducible and reliable rat model of exercise-induced SIgA suppression in future studies.

[Repair of paravalvular leak after a third mitral valve replacement].

This study reports on a 57-year-old woman who underwent a 3rd mitral valve replacement and presented with complaints of fatigue. Laboratory examination revealed severe hemolytic anemia, and trans-esophageal echocardiography revealed a paravalvular leak (PVL) around the prosthetic valve at the posterior trigone in the mitral position. PVL was regarded as the cause of hemolytic anemia. At surgery, a small tissue defect was detected around the calcified posterior trigone of the mitral annulus with no evidence of infective endocarditis. The mitral PVL was successfully repaired with suture closure of the annular defect. The postoperative course was uneventful: postoperative echocardiography revealed no evidence of PVL, and the hemolytic anemia subsided.

[Ascending aortic aneurysm following aortic valve replacement due to aortitis syndrome; report of a case].

A 60-year-old woman had previously undergone aortic valve replacement for aortic regurgitation. As the aortic wall was elastic hard, inflammatory change was suspected; therefore, we undertook a partial biopsy of the ascending aortic wall and the intraoperative pathological specimens were compatible with aortitis syndrome. As there was no active inflammatory change, she was diagnosed as inactive aortitis syndrome and steroid therapy was not applied. Seven years later, a follow-up computed tomography (CT) showed an ascending aortic aneurysm of 65 mm in diameter. Aortic root replacement was planned based on a clinical diagnosis of an aneurysm of the ascending aorta. The patient was discharged without complication 21 days after surgery. It is possible that an inactive stage of aortitis may lead to late dilatation of the ascending aorta; therefore, careful postoperative follow-up is necessary in such cases.

Changes of pituitary, adrenal and gonadal hormones during competition among female soccer players.

AIM: This study was intended to investigate various hormones during competition among female athletes. METHODS: Subjects were elite female soccer players (n=9). Blood samples and profiles of mood states (POMS) were obtained before (Pre), during 3 days of competition (Competition), and after competition (Post-3 days). Serum concentrations were determined for dehydroepiandrosterone sulfate (DHEAS), cortisol (C), prolactin (PRL), testosterone (T), adrenocorticotropic hormone (ACTH), luteinising hormone (LH), and follicle stimulating hormone (FSH). RESULTS: Levels of C and PRL increased significantly during competition (2nd: P<0.05; 3rd: P<0.01) compared with Pre. Levels of LH increased significantly during competition (3rd day) compared with Pre (P<0.05). Levels of DHEAS changed significantly during competition, whereas levels of T, ACTH, and FSH were unchanged during competition. The fatigue score of POMS increased significantly during competition (2nd day) compared with Pre (P<0.05). CONCLUSIONS: We demonstrated that competitive stress affected hormonal status in female athletes. These findings suggest that hormonal changes reflect physical and mental stress during competition.

[Cardiac papillary fibroelastomas: report of 2 cases].

We report 2 cases of cardiac papillary fibroelastomas in adults. Case 1: A 61-year-old man was admitted because echocardiography showed a 1 cm pedunculated papillary tumor in the left atrium. In an operation, it was located in the left atrium near the mitral valve and was resected along with a 5 mm margin of endocardium. Case 2: A 60-year-old woman had a 1 cm mobile tumor in the right ventricle near the tricuspid valve located by echocardiography in a preoperative examination of a ventricular septal defect. In an operation, a pedunculated tumor located in the right ventricle was resected. In these 2 cases, histopathology showed the tumor to be a papillary fibroelastoma. Almost all cardiac papillary fibroelastoma are closely related to the cardiac valve, but in these cases, the tumors were located in the left atrium, and the right ventricle, respectively, which is quite rare.

Significance of the transcription factor KLF5 in cardiovascular remodeling.

Structural remodeling of the heart and blood vessels is an important pathologic process in the development of many cardiovascular diseases. However, transcriptional regulation of altered gene expression during cardiovascular remodeling is not well understood. We previously isolated KLF5/basic transcription element-binding (BTEB)2, a Krüppel-like factor, as a transcription factor that binds the promoter of the embryonic smooth muscle myosin heavy chain gene (SMemb). KLF5 activates many genes inducible during cardiovascular remodeling, such as platelet-derived growth factor (PDGF)-A/B, Egr-1, plasminogen activator inhibitor-1 (PAI-1), inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) receptors. KLF5 is abundantly expressed in embryonic smooth muscles and is down-regulated with vascular development, but reinduced in proliferative neointimal smooth muscles in response to vascular injury. In KLF5 gene-targeted mice, homozygotes die at an early embryonic stage whereas heterozygotes are apparently normal. However, in response to external stress, arteries of heterozygotes exhibit diminished levels of smooth muscle and adventitial cell activation. Furthermore, angiotensin II-induced cardiac hypertrophy and fibrosis are attenuated in heterozygotes. KLF5 activities are regulated by many transcriptional regulators and nuclear receptors, such as retinoic acid receptor-alpha (RAR alpha), NF-kappaB, PPAR gamma, p300, and SET. Interestingly, RAR alpha agonist suppresses KLF5 and cardiovascular remodeling, whereas RAR alpha antagonist activates KLF5 and induces angiogenesis. These results indicate that KLF5 is an essential transcription factor in cardiovascular remodeling and a potential therapeutic target for cardiovascular disease.

Morphologic evaluation of the antitumor activity of photodynamic therapy (PDT) using mono-L-aspartyl chlorin e6 (NPe6) against uterine cervical carcinoma cell lines.

In order to elucidate the antitumor effect and mechanism of action of photodynamic therapy (PDT) using the photosensitizing agent mono-L-aspartyl chlorin e6 (NPe6) and a semiconductor laser, we conducted a morphologic study on uterine cervical cancer cell lines. First, tumor shrinkage was confirmed in a tumor growth inhibition test. Next, morphologic changes after PDT were examined, and since the major change appeared to be tumor necrosis secondary to obstruction of the blood vessels around the tumor, an NPe6 cell uptake experiment was performed. The results confirmed that a significantly greater amount of NPe6 was incorporated by human umbilical vein endothelial cells (HUV-EC1) and the cervical cancer cell lines than by human umbilical cord-derived fibroblasts. Based on these findings it was concluded that NPe6 possesses tumor affinity, and necrosis secondary to vascular obstruction was postulated to be the principal mechanism of the antitumor effect of PDT using NPe6.