Preceding actin denaturation accelerates myosin denaturation in tilapia myofibrils in frozen storage

Myosin and actin denaturation (0.1 M NaCl, 20 mM Tris-HCl, pH 7.5) of tilapia myofibrils (Mf) during frozen storage at -10, -20, and -40 A degrees C was studied. Ca2+-ATPase inactivation was rapid at -10 A degrees C but very slow at -20 and -40 A degrees C. Myosin retained its solubility at 0.5 M NaCl even after Ca2+-ATPase inactivation. The amount of subfragment-1 generated from the Mf by chymotryptic digestion decreased with decreasing Ca2+-ATPase inactivation. The amount of rod produced in the frozen Mf remained at a high level, explaining the high salt solubility of myosin. Actin denaturation occurred in the Mf during freezer storage, as revealed by chymotrypic digestion patterns that showed a decreased actin content in the digest, and occurred much faster than Ca2+-ATPase inactivation. Analysis of tilapia meat during freezer storage revealed that Ca2+-ATPase inactivation was very slow in the frozen tissue and was ninefold slower at -10 A degrees C than at -20, and -40 A degrees C. Practically no actin denaturation occurred in the frozen meat. Based on these results, we conclude that native actin in frozen meat protects myosin from denaturation during the frozen storage period but that such protection by actin does not extend to Mf due to rapid actin denaturation. Consequently, the Ca2+-ATPase inactivation rate in Mf represents that of myosin itself-with no protection provided by actin. Therefore, the myosin denaturation rate obtained with Mf should not be used for frozen meat. Mf suspended in 0.1 M NaCl is not a suitable model by which to obtain the myosin denaturation rate in frozen fish meat

Disaster management education approach possibilities with school safety perspectives

Past disasters such as the Great Hanshin-Awaji Earthquake in January 17, 1995 has increased awareness of the need for protection against natural disasters. Including the recent climatic phenomena like torrential rains and tornado, Japan is prone to various types of natural disasters such as windstorm and flood, earthquake and tsunami-earthquake, active volcano and sediment disaster. Particularly, in the near future, there is a high possibility of the Nankai Earthquake and the Tonankai Earthquake, and therefore, the need of disaster management education for children who did not experience disasters is now increasing. However, the present situation of disaster management education is actively practiced only by some dedicated citizens and disaster-related people, a small fraction of the Japanese nation. In order to make disaster management education more effective and universally, it should add to the curricula for compulsory education. With the revision of the School Health and Safety Act in 2009, the possibilities of disseminating disaster management education are considered here

Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum

Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK), which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20 min) and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice

Optic Neuritis Possibly Induced by Anti-PD-L1 Antibody Treatment in a Patient with Non-Small Cell Lung Carcinoma

Background: Recent immune therapy with checkpoint inhibitors (CPIs) has demonstrated remarkable antitumor effects on specific tumors, such as malignant lymphoma and non-small cell lung carcinoma. By contrast, CPIs cause an imbalance in the immune system, triggering a wide range of immunological side effects termed immune-related adverse effects (irAEs). Here, we report a rare case of optic neuritis and hypopituitarism during anti-programmed death-ligand 1 (PD-L1) antibody treatment. Case Presentation: A patient with non-small cell lung carcinoma received anti-PD-L1 antibody treatment every 3 weeks; however, the patient started experiencing headaches, general fatigue, anorexia, and diarrhea approximately 1 year after the initiation of the treatment. Moreover, sudden visual loss of the right eye occurred 1 week after the interruption of the anti-PD-L1 antibody treatment. MRI findings showed gadolinium enhancement in the left optic nerve, but no enlargement of the pituitary gland and stalk. Laboratory data showed decreased serum adrenocorticotropic hormone (ACTH), cortisol, and free T4 levels, and a hormone tolerance test indicated hypopituitarism, hypothyroidism, and hypoadrenocorticism. The central scotoma caused by optic neuritis completely disappeared immediately after a course of steroid pulse therapy, and no recurrence occurred up to 2 years after initiation of the steroid pulse therapy while replacement therapy for hypothyroidism and hypoadrenocorticism was continued. Conclusions: The patient presented with optic neuritis and hypopituitarism, possibly due to irAEs of the anti-PD-L1 antibody treatment. Steroid pulse therapy was effective for optic neuritis, suggesting underlying immunological mechanisms. Neurological complications including optic neuritis should be considered when examining patients with cancer undergoing CPI treatment

Predictors and prognosis of paroxysmal atrial fibrillation in general practice in the UK

BACKGROUND: Natural history of paroxysmal atrial fibrillation (AF) is not very well documented. Clinical experience suggests that paroxysmal AF could progress to chronic AF with estimates ranging between 15 and 30% over a period of 1–3 years. We performed an epidemiologic study to elucidate the natural history of paroxysmal AF, this study estimated its incidence in a general practice setting, identified associated factors and analyzed the progression into chronic AF as well as the mortality rate. METHODS: Using the UK General Practice Research Database (GPRD), we identified patients aged 40–89 years with a first-recorded episode of paroxysmal AF during 1996. Risk factors were assessed using 525 incident paroxysmal AF cases confirmed by the general practitioner (GP) and a random sample of controls. We follow-up paroxysmal AF patients and estimated their mortality rate and progression to chronic AF. RESULTS: The incidence of paroxysmal AF was 1.0 per 1,000 person-years. Major risk factors for paroxysmal AF were age and prior valvular heart disease, ischaemic heart disease, heart failure and hyperthyroidism. During a mean follow-up of 2.7 years, 70 of 418 paroxysmal AF patients with complete information progressed to chronic AF. Risk factors associated with progression were valvular heart disease (OR 2.7, 95% CI 1.2–6.0) and moderate to high alcohol consumption (OR 3.0, 95% CI 1.1–8.0). Paroxysmal AF patients did not carry an increased risk of mortality, compared to an age and sex matched sample of the general population. There was a suggestion of a small increased risk among patients progressing to chronic AF (RR 1.5, 96% CI 0.8–2.9). CONCLUSION: Paroxysmal AF is a common arrhythmia in the general practice setting, increasing with age and commonly associated with other heart diseases. It sometimes is the initial presentation and then progress to chronic AF. A history of valvular heart disease and alcohol consumption are associated with this progression

Nationwide retrospective observational study of idiopathic dendriform pulmonary ossification : clinical features with a progressive phenotype

Background: Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO. Methods: We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO. Results: Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22-56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. )) at diagnosis. Nearly 80% of the subjects wereasymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. Conclusions: IDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO

Research on the Standardization of Disaster-preparedness and Crisis-management Systems of Local Governments

The Tohoku Great earthquake and tsunami, which struck on March 11, 2011, along with the resulting nuclear accident at Fukushima Daiichi Power Plant, inflicted major damage on Japan. The disaster has had an extremely huge impact on Japanese society, and interest among citizens and the government in creating a safe and secure society is currently at an all-time high. Many of the administrative offices of disaster-hit municipalities also sustained damage, with a large number of administrative officers among the casualties and operations throw into disarray. In order to overcome these circumstances, this disaster prompted local governments to provide each other with a range of support. However, they faced unprecedented circumstances and adequate systems were not in place on either the sides of those giving support or those receiving support, in many cases leading to a state of major confusion. Disaster support between local governments involves cooperative operations between the organizations involved. In order for different organizations to carry out these cooperative operations smoothly, it is essential for conditions to be put in place that will allow them to carry out disaster activities based on a shared awareness. In the U.S., we see progress being made in standardizing and unifying terminology, organizational forms and information systems under the Incident Command System (ICS). In Japan, however, the disaster-preparedness and crisis-management systems of local government are all different, which accounts in part for the confusion experienced during the Tohoku Great Earthquake and Tsunami. In this research, I analyze the current status of disaster-preparedness and crisis-management organizations and agencies of local governments in Japan, and propose an optimum model for standardizing these at the national level

Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung

BackgroundAldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer’s diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined.MethodsWe examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 −/− mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 −/− mice.ResultsIn humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 −/− and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 −/− mice. Aldh2 −/− tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 −/− mice than in WT mice.ConclusionsALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a “premature lung aging” effect

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified