Abstract: Objectives This study sought to establish a model for grading lesion difficulty in interventional chronic total occlusion (CTO) treatment. Background Owing to uncertainty of success of the procedure and difficulties in selecting suitable cases for treatment, performance of interventional CTO remains infrequent. Methods Data from 494 native CTO lesions were analyzed. To eliminate operator bias, the objective parameter of successful guidewire crossing within 30 min was set as an end point, instead of actual procedural success. All observations were randomly assigned to a derivation set and a validation set at a 2:1 ratio. The J-CTO (Multicenter CTO Registry of Japan) score was determined by assigning 1 point for each independent predictor of this end point and summing all points accrued. This value was then used to develop a model stratifying all lesions into 4 difficulty groups: easy (J-CTO score of 0), intermediate (score of 1), difficult (score of 2), and very difficult (score of ≥3). Results The set end point was achieved in 48.2% of lesions. Independent predictors included calcification, bending, blunt stump, occlusion length >20 mm, and previously failed lesion. Easy, intermediate, difficult, and very difficult groups, stratified by J-CTO score, demonstrated stepwise, proportioned, and highly reproducible differences in probability of successful guidewire crossing within 30 min (87.7%, 67.1%, 42.4%, and 10.0% in the derivation set and 92.3%, 58.3%, 34.8%, and 22.2% in the validation set, respectively). Areas under receiver-operator characteristic curves were comparable (derivation: 0.82 vs. validation: 0.76). Conclusions This model predicted the probability of successful guidewire crossing within 30 min very well and can be applied for difficulty grading.

Abstract: An anticonvulsant, carbamazepine (CBZ), is known to show incidences of cutaneous adverse drug reactions (cADRs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS). To identify a gene(s) susceptible to CBZ-induced cADRs, we conducted a genome-wide association study (GWAS) in 53 subjects with the CBZ-induced cADRs, including SJS, TEN and DIHS, and 882 subjects of a general population in Japan. Among the single nucleotide polymorphisms (SNPs) analyzed in the GWAS, 12 SNPs showed significant association with CBZ-induced cADRs, and rs1633021 showed the smallest P-value for association with CBZ-induced cADRs (P = 1.18 × 10⁻¹³). These SNPs were located within a 430 kb linkage disequilibrium block on chromosome 6p21.33, including the HLA-A locus. Thus, we genotyped the individual HLA-A alleles in 61 cases and 376 patients who showed no cADRs by administration of CBZ (CBZ-tolerant controls) and found that HLA-A*3101 was present in 60.7% (37/61) of the patients with CBZ-induced cADRs, but in only 12.5% (47/376) of the CBZ-tolerant controls (odds ratio = 10.8, 95% confidence interval 5.9-19.6, P = 3.64 × 10⁻¹⁵), implying that this allele has the 60.7% sensitivity and 87.5% specificity when we apply HLA-A*3101 as a risk predictor for CBZ-induced cADRs. Although DIHS is clinically distinguished from SJS and TEN, our data presented here have indicated that they share a common genetic factor as well as a common pathophysiological mechanism. Our findings should provide useful information for making a decision of individualized medication of anticonvulsants.

Abstract: Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.

Abstract: Objective The clinicopathological significance of four morphological types of intraductal papillary mucinous neoplasms of the pancreas (IPMNs; gastric, intestinal, pancreatobiliary and oncocytic) was assessed. Design Retrospective multicentre analysis of 283 surgically resected IPMNs. Results Of the 283 IPMNs, 139 were of the gastric type, 101 were intestinal, 19 were pancreatobiliary and 24 were oncocytic. These types were significantly associated with clinicopathological factors including sex (p=0.0032), age (p=0.00924), ectatic duct size (p=0.0245), detection of mural nodules (p=4.09×10 −6 ), histological grade (p −16 ), macroscopic types with differential involvement of the pancreatic duct system (p=3.91×10 −5 ), invasive phenotypes (p=3.34×10 −12 ), stage (p −16 ) and recurrence (p=0.00574). Kaplan–Meier analysis showed significant differences in patient survival by morphological type (p=5.24×10 −6 ). Survival rates at 5 and 10 years, respectively, were 0.937 (95% CI 0.892 to 0.984) for patients with gastric-type IPMNs; 0.886 (95% CI 0.813 to 0.965) and 0.685 (95% CI 0.553 to 0.849) for those with intestinal-type IPMNs; 0.839 (95% CI 0.684 to 1.000) and 0.734 (95% CI 0.526 to 1.000) for those with oncocytic-type IPMNs; and 0.520 (95% CI 0.298 to 0.909) and undetermined for those with pancreatobiliary-type IPMNs. Analysis by the Cox proportional hazards model comparing prognostic risks determined by stage and the morphological and macroscopic types indicated that staging was the most significant predictor of survival (p=3.68×10 −8 ) followed by the morphological type (p=0.0435). Furthermore, the morphological type remained a significant predictor in a subcohort of invasive cases (p=0.0089). Conclusion In this multicentre retrospective analysis, the morphological type of IPMN appears to be an independent predictor of patient prognosis.

Abstract: Dental biomaterials are widely used in all areas of routine dental practice. There are mainly two methods for their application. Firstly, dental biomaterials are placed into living tissues, such as teeth, to fill the space. Secondly, dental devices such as crown and bridge restorations and dentures are fabricated using various materials to restore the morphology and function of the dentition. Crown and bridge restorations are one of the main treatment methods used by general practitioners to achieve lifelike restoration of form and function. The recent introduction of osseointegrated implants has expanded the application of crown and bridge restorations for partially edentulous patients. Mechanical durability and precision fit are mandatory requirements for crowns and bridges. The development of various casting alloys and precise casting systems has contributed to the successful use of metal-based restorations. However, patient requests for more aesthetic and biologically 'safe' materials has led to an increased demand for metal-free restorations. There is also a growing demand to provide all-ceramic restorations more routinely. New materials such as highly sintered glass, polycrystalline alumina, zirconia based materials and adhesive monomers, will assist dentists to meet this demand. In addition, new fabrication systems combined with computer-assisted fabrication systems (dental CAD/CAM) and various networks are now available. Dental technology was centred on lost-wax casting technology but we now face a revolution in crown and bridge fabrication. This article reviews the history and recent status of dental CAD/CAM, the application of CAD/CAM fabricated tooth-coloured glass ceramic crowns, and the application of all-ceramic crowns and bridges using CAD/CAM fabricated zirconia based frameworks.

Abstract: Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&A are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan.

Abstract: Objective:The aim of this study was to elucidate the clinicopathological features and prognosis of mucinous cystic neoplasms (MCNs).Materials and Methods:We performed a multi-institutional, retrospective study on a collected series of patients with MCN pathologically defined by ovarian-type stroma.

Abstract: Summary Background and objectives Demand for hemodialysis among elderly patients is increasing worldwide. Although clinical care of this high-risk group is complex and challenging, no guidelines exist to inform hemodialysis practices. The Dialysis Outcomes and Practice Patterns Study (DOPPS) provides a unique opportunity to assess dialysis practices and associated outcomes among elderly versus younger patients on chronic in-center hemodialysis in 12 countries. Design, setting, participants, & measurements Clinical characteristics, dialysis practices, and outcomes of elderly versus younger patients were compared among participants in four DOPPS regions in 2005 through 2007. Results Although participant mean age increased over time in all DOPPS countries, the percentage of elderly varied widely. Overall, comorbidities and malnutrition were more common in the elderly. Fistulae were used less frequently among elderly versus younger patients in Europe and North America but not in Australia, New Zealand, and Japan. No difference in treatment time was observed between elderly and younger patients after normalizing for body weight. In all regions, ultrafiltration rates were lower among elderly patients. Elderly patients reported poorer quality of life with respect to the physical but not mental component scores. Mortality risk was three- to sixfold higher in the elderly group, whereas causes of death overall were similar for elderly and younger patients. Conclusions Elderly patients represent a different proportion of DOPPS participants across countries, possibly reflecting differences in policies and clinical practices. In general, hemodialysis practices in the elderly reflected each region9s clinical patterns, with some variation by age group depending upon the practice.

Abstract: Aims/hypothesis Several lines of evidence suggest that incretin-based therapies suppress the development of cardiovascular disease in type 2 diabetes. We investigated the possibility that glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can prevent the development of atherosclerosis in Apoe −/− mice.

Abstract: Thymic stromal lymphopoietin (TSLP) triggers dendritic cell--mediated T helper (Th) 2 inflammatory responses. A single-nucleotide polymorphism (SNP), rs3806933, in the promoter region of the TSLP gene creates a binding site for the transcription factor activating protein (AP)-1. The variant enhances AP-1 binding to the regulatory element, and increases the promoter--reporter activity of TSLP in response to polyinosinic-polycytidylic acid (poly[I:C]) stimulation in normal human bronchial epithelium (NHBE). We investigated whether polymorphisms including the SNP rs3806933 could affect the susceptibility to and clinical phenotypes of bronchial asthma. We selected three representative (i.e., Tag) SNPs and conducted association studies of the TSLP gene, using two independent populations (639 patients with childhood atopic asthma and 838 control subjects, and 641 patients with adult asthma and 376 control subjects, respectively). We further examined the effects of corticosteroids and a long-acting β(2)-agonist (salmeterol) on the expression levels of the TSLP gene in response to poly(I:C) in NHBE. We found that the promoter polymorphisms rs3806933 and rs2289276 were significantly associated with disease susceptibility in both childhood atopic and adult asthma. The functional SNP rs3806933 was associated with asthma (meta-analysis, P = 0.000056; odds ratio, 1.29; 95% confidence interval, 1.14-1.47). A genotype of rs2289278 was correlated with pulmonary function. Moreover, the induction of TSLP mRNA and protein expression induced by poly(I:C) in NHBE was synergistically impaired by a corticosteroid and salmeterol. TSLP variants are significantly associated with bronchial asthma and pulmonary function. Thus, TSLP may serve as a therapeutic target molecule for combination therapy.

Abstract: BACKGROUND: Plasma concentrations of small dense (sd)-LDL are associated with the prevalence of cardiovascular events. However, the special equipment and long assay times required for sd-LDL measurement have hindered its clinical application. Herein, we report development of a simple homogeneous assay for sd-LDL-cholesterol (C) adaptable to autoanalyzers. MATERIALS AND METHODS: We identified suitable surfactants and phospholipases by screening for those selective for the sd-LDL fraction (d 1.044–1.063 kg/L) and for the dissociation of other lipoproteins, including large buoyant LDL (lb-LDL). Principal characteristics of this assay were compared with ultracentrifugal isolation of LDL subfractions and with our previous heparin-magnesium precipitation assay for sd-LDL. We measured sd-LDL-C concentrations in 460 healthy, normolipidemic individuals. RESULTS: We used a polyoxyethylene benzylphenyl ether derivative to dissociate triglyceride-rich lipoproteins and HDLs, whereas sphingomyelinase proved most effective for dissociation of lb-LDL from LDL owing to the higher sphingomyelin content in the lb-LDL subfractions. A polyoxyethylene styrenephenyl ether derivative protected sd-LDL against the dissociative actions of sphingomyelinase and cholesterol oxidase/esterase during an initial incubation step. Next, polyoxyethylene alkyl ether dissociated sd-LDL-C and the cholesterol released from sd-LDL were subsequently measured by using cholesterol oxidase/esterase. The homogeneous method correlated excellently with ultracentrifugation for sd-LDL-C ( y = 0.99 x – 0.09, R 2 = 0.91, n = 60) and exhibited within-run precision CVs <1.1%. The distribution of sd-LDL-C was skewed, and the central 95% of sd-LDL-C concentrations ranged from 0.24 to 0.88 mmol/L (9.4–34.0 mg/dL). CONCLUSIONS: The homogeneous assay allows reproducible measurement of sd-LDL-C within 10 min and appears promising in further investigations of the clinical significance of sd-LDL-C.

Abstract: Most cases of frontotemporal lobar degeneration (FTLD) are characterized by abnormal intracellular accumulation of either tau or TDP-43 protein. However, in ~10% of cases, composed of a heterogenous collection of uncommon disorders, the molecular basis remains to be uncertain. We recently discovered that the pathological changes in several tau/TDP-43-negative FTLD subtypes are immunoreactive (ir) for the fused in sarcoma (FUS) protein. In this study, we directly compared the pattern of FUS-ir pathology in cases of atypical FTLD-U (aFTLD-U, N = 10), neuronal intermediate filament inclusion disease (NIFID, N = 5) and basophilic inclusion body disease (BIBD, N = 8), to determine whether these are discrete entities or represent a pathological continuum. All cases had FUS-ir pathology in the cerebral neocortex, hippocampus and a similar wide range of subcortical regions. Although there was significant overlap, each group showed specific differences that distinguished them from the others. Cases of aFTLD-U consistently had less pathology in subcortical regions. In addition, the neuronal inclusions in aFTLD-U usually had a uniform, round shape, whereas NIFID and BIBD were characterized by a variety of inclusion morphologies. In all cases of aFTLD-U and NIFID, vermiform neuronal intranuclear inclusions (NII) were readily identified in the hippocampus and neocortex. In contrast, only two cases of BIBD had very rare NII in a single subcortical region. These findings support aFTLD-U, NIFID and BIBD as representing closely related, but distinct entities that share a common molecular pathogenesis. Although cases with overlapping pathology may exist, we recommend retaining the terms aFTLD-U, NIFID and BIBD for specific FTLD-FUS subtypes.

Abstract: Currently, successful treatment of chronic total occlusion (CTO) seems markedly improved, due to several new techniques and dedicated device developments. However, this improved success rate is often limited to procedures performed by skilled, highly experienced operators. To improve the overall success rate of percutaneous coronary intervention of CTO from a worldwide perspective, a deeper understanding of CTO histopathology might offer insights into the development of new techniques and procedural strategies. In this review, CTO histopathology and wire techniques are discussed on the basis of the fundamental concepts of antegrade and retrograde approaches. Although details pertaining to wire manipulation are very difficult to explain objectively, we tried to describe this as best as possible in this article. Finally, a systematic review of the current standard CTO strategy is provided. Hopefully, this article will enhance the understanding of this complex procedure and, consequently, promote safe and effective CTO-percutaneous coronary intervention for patients who present with this challenging lesion subset.

Abstract: Background Matricellular proteins, including periostin, are important for tissue regeneration. Methods and Findings Presently we investigated the function of periostin in cutaneous wound healing by using periostin-deficient (−/−) mice. Periostin mRNA was expressed in both the epidermis and hair follicles, and periostin protein was located at the basement membrane in the hair follicles together with fibronectin and laminin γ2. Periostin was associated with laminin γ2, and this association enhanced the proteolytic cleavage of the laminin γ2 long form to produce its short form. To address the role of periostin in wound healing, we employed a wound healing model using WT and periostin−/− mice and the scratch wound assay in vitro. We found that the wound closure was delayed in the periostin−/− mice coupled with a delay in re-epithelialization and with reduced proliferation of keratinocytes. Furthermore, keratinocyte proliferation was enhanced in periostin-overexpressing HaCaT cells along with up-regulation of phosphorylated NF-κB. Conclusion These results indicate that periostin was essential for keratinocyte proliferation for re-epithelialization during cutaneous wound healing.

Abstract: Previous studies in several different trigeminal nerve injury/inflammation models indicated that the hyperexcitability of primary afferent neurons contributes to the pain pathway underlying mechanical allodynia. Although multiple types of voltage-gated ion channels are associated with neuronal hyperexcitability, voltage-gated K+ channels (Kv) are one of the important physiological regulators of membrane potentials in excitable tissues, including nociceptive sensory neurons. Since the opening of K+ channels leads to hyperpolarization of cell membrane and a consequent decrease in cell excitability, several Kv channels have been proposed as potential target candidates for pain therapy. In this review, we focus on common changes measured in the Kv channels of several different trigeminal neuropathic/inflammatory pain animal models, particularly the relationship between changes in Kv channels and the excitability of trigeminal ganglion (TRG) neurons. We also discuss the potential of Kv channel openers as therapeutic agents for trigeminal neuropathic/inflammatory pain, such as mechanical allodynia.

Abstract: To cite this article: Ohta K, Bousquet P-J, Aizawa H, Akiyama K, Adachi M, Ichinose M, Ebisawa M, Tamura G, Nagai A, Nishima S, Fukuda T, Morikawa A, Okamoto Y, Kohno Y, Saito H, Takenaka H, Grouse L, Bousquet J. Prevalence and impact of rhinitis in asthma: SACRA, a cross-sectional nation-wide study in Japan. Allergy 2011; 66: 1287–1295. Abstract Background: Asthma and rhinitis are common co-morbidities everywhere in the world but nation-wide studies assessing rhinitis in asthmatics using questionnaires based on guidelines are not available. Objective: To assess the prevalence, classification, and severity of rhinitis using the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria in Japanese patients with diagnosed and treated asthma. Methods: The study was performed from March to August 2009. Patients in physicians’ waiting rooms, or physicians themselves, filled out questionnaires on rhinitis and asthma based on ARIA and Global Initiative for Asthma (GINA) diagnostic guides. The patients answered questions on the severity of the diseases and a Visual Analog Scale. Their physicians made the diagnosis of rhinitis. Results: In this study, 1910 physicians enrolled 29 518 asthmatics; 15 051 (51.0%) questionnaires were administered by physician, and 26 680 (90.4%) patients were evaluable. Self- and physician-administered questionnaires gave similar results. Rhinitis was diagnosed in 68.5% of patients with self-administered questionnaires and 66.2% with physician-administered questionnaires. In this study, 994 (7.6%) patients with self-administered and 561 (5.2%) patients with physician-administered questionnaires indicated rhinitis symptoms on the questionnaires without a physician’s diagnosis of rhinitis. Most patients with the physician’s diagnosis of rhinitis had moderate/severe rhinitis. Asthma control was significantly impaired in patients with a physician’s diagnosis of rhinitis for all GINA clinical criteria except exacerbations. There were significantly more patients with uncontrolled asthma as defined by GINA in those with a physician’s diagnosis of rhinitis (25.4% and 29.7%) by comparison with those without rhinitis (18.0% and 22.8%). Conclusion: Rhinitis is common in asthma and impairs asthma control.

Abstract: Twenty-nine IMP-type β-lactamases (IMPs) have been identified in at least 26 species of clinically important Gram-negative bacilli from more than 24 countries/regions. Most of bla(IMP) genes are harbored by class 1 integrons that are usually embedded in transposons and/or plasmids, footnoting their horizontal transfer and worldwide distribution. bla(IMP) genes usually co-exist with other resistance genes, such as aacA, catB, and bla(OXA), resulting in multi-drug resistance. Compared to other gene cassettes, 76.3% of the bla(IMP) gene cassettes are located adjacent to Pc promoter of the class 1 integrons, indicating that the bla(IMP) genes are readily expressed in most of bacterial hosts.

Abstract: Bone morphogenetic proteins (BMPs) possess osteoinductive activities and are useful for clinical treatments, including bone regeneration. We found that transforming growth factor (TGF)-β1 strongly enhances the osteoinductive activity of BMP-2. Collagen sponges containing 5 μg of BMP-2 were implanted into mouse muscle tissues, after which lump-like masses appeared and grew until day 7. Subsequently, calcification occurred in the lump-like masses by day 14. Addition of 50 ng of TGF-β1 to the BMP-2-containing sponges markedly accelerated the growth of the lump-like masses and resulted in a fivefold increase in total bone volume as compared with BMP-2 alone. The number of osteoblasts in ectopic bone tissues at 14 days after implantation induced by BMP-2+TGF-β1 was twofold greater than that with BMP-2 alone, whereas the number of osteoclasts was decreased by half. On the other hand, TGF-β1 accelerated the differentiation of both osteoblasts and osteoclasts in the early stage (2-7 days after implantation) of ectopic bone formation. We also implanted collagen sponges into bone defects surgically created in mouse calvaria. Sponges containing 2.5 μg of BMP-2 and 25 ng of TGF-β1 caused complete filling of the defects with orthotopic bone, whereas those containing 2.5 μg of BMP-2 alone caused only partial filling. These results suggest that TGF-β1 enhances BMP-2-induced ectopic bone formation by accelerating the growth of lump-like masses, and regulates osteoblast and osteoclast generation. Our findings may contribute to the development of a new treatment method for skeletal disorders.

Abstract: Growing rice is an important socio-economic activity. Rice proteomics has achieved a tremendous progress in establishing techniques to proteomes of almost all tissues, organs, and organelles during the past one decade (year 2000-2010). We have compiled these progresses time to time over this period. The present compilation discusses proteomics research in rice published between 1st April 2008 and 30th July 2010. Progress continues mainly towards protein cataloging deep into the proteome with high-confident protein assignment and some functional significance than ever before by (i) identifying previously unreported/low-abundance proteins, (ii) quantifying relative/absolute values of proteins, (iii) assigning protein responses to biotic/abiotic stresses, (iv) protein localization into organelles, (v) validating previous proteomes and eliminating false-positive proteins, and (vi) discovering potential biomarkers for tissues, organs, organelles, and for screening transgenic plants and food-safety evaluation. The notable achievements in global mapping of phosphorylation sites and identifying several novel secreted proteins into the extracellular space are worth appreciating. Our ever-increasing knowledge on the rice proteomics is beginning to impact the biology of not only rice, but also crops and plants. These major achievements will be discussed in this review keeping in mind newcomers, young, and established scientists in proteomics and plants.

Abstract: To demonstrate the reasons for low morbidity and mortality from coronary artery disease (CAD) and reconfirm the effectiveness of the Japanese dietary lifestyle for preventing CAD, we herein review the CAD risk transition, and post-war changes in Japanese food and nutrient intake. Large-scale cohort studies in Japan were selectively reviewed. Low serum total cholesterol contributed to preventing CAD, and decreased blood pressure was the major factor favoring stroke reduction. Japanese consumed more plant and marine origin foods, but fewer animal foods with saturated fatty acids (SFA) during the 1960-70s than in recent decades. Adequate control of total energy with restriction of saturated fatty acids from animal foods, increased intake of n-3 polyunsaturated fatty acids, including fish, soybean products, fruits and vegetables together with low salt intake are responsible for promoting CAD and stroke prevention. A diet with adequate total calories and increased intake of fish and plant foods, but decreased intake of refined carbohydrates and animal fat, a so-called Japan diet, appears to be quite effective for prevention of CAD risk factors and is recommended as dietary therapy for preventing CAD.

Abstract: NK cells are effector lymphocytes playing a critical role in the natural resistance against tumors. However, the precise mechanisms underlying NK cell-mediated natural resistance against tumor metastasis are still unrevealed. B16 cells, mouse melanoma cells, were resistant to freshly isolated NK cell-mediated killing; nevertheless, NK cells were critical for natural resistance against experimental lung metastasis of B16 cells. We found that lung metastasis was increased significantly in IFN-γ(-/-) mice but not pfp(-/-), IFN-αR(-/-), or IL-12/IL-18(-/-) mice. Interestingly, freshly isolated lung NK cells, but not spleen or liver NK cells, displayed augmented IFN-γ production after B16 inoculation. Adoptive transfer of pfp(-/-) NK cells, but not IFN-γ(-/-) NK cells, significantly decreased B16 lung metastasis in IFN-γ(-/-) and pfp/IFN-γ(-/-)mice. Lung metastases of IFN-γRDN B16 was also increased in NK cell-depleted or IFN-γ(-/-) mice, suggesting that the IFN-γ response of host cells was required in the NK cell and IFN-γ-mediated antimetastatic effect. Our results demonstrate that IFN-γ production from lung resident NK cells is a key response in the natural resistance to the experimental lung metastasis of NK cell-resistant tumor cells.

Abstract: Ozone (O3) is known to have existed in the atmosphere since ancient times and has played a critical role in the survival of life on the Earth. In the stratosphere, O3 plays an extremely important and beneficial role in screening the lower layers of the atmosphere and the surface of the Earth from the sun’s harmful ultraviolet radiation. In the troposphere, and especially near the surface of the Earth, O3 is not beneficial. Ozone has been shown to be harmful to human health, vegetation and crop productivity (Dentener et al. 2006). In the past few decades, tropospheric O3 has emerged as a major secondary ­pollutant due to increased emissions of its precursors, e.g., nitrogen oxides (NO x ; x = 1 or 2) and volatile organic compounds (VOCs) (Ashmore 2005). High concentrations of O3 are associated with hot sunny weather. Such high concentrations of O3 are frequently observed in tropical areas where conditions are favorable for O3 formation (Jain et al. 2005; Tiwari et al. 2008). The adverse effects of O3 were first identified in grapevines (Richards et al. 1958), and it is now recognized as the most important rural air pollutant affecting human health, vegetation, or material that is susceptible to oxidation (Ashmore 2005; Fuhrer and Booker 2003; Karnosky et al. 2007; Karlsson et al. 2003; Laurence and Andersen 2003; Matyssek and Sandermann 2003).

Abstract: According to many prospective cohort studies and meta-analyses of those studies, physical inactivity and/or low levels of physical fitness are associated with an elevated risk for the development of metabolic syndrome, type 2 diabetes, hypertension, coronary artery disease (CAD), and stroke, and with an increased risk of cardiovascular disease (CVD) mortality and all-cause mortality. Most of these analyses, however, were conducted on non-Japanese populations in the West. This report summarizes prospective observational and clinical studies in Japan. The annual national nutrition survey has shown a gradual decline in the number of walking steps in both genders and in all age groups over the last 10 years. While exercise habits have been gradually increasing in the elderly, only one-fifth of young and middle-aged people undertake leisure-time physical activity. Prospective cohort studies have shown that increased physical fitness and greater physical activity in either daily life or leisure time are of benefit in preventing all-cause mortality and CVD mortality. The daily number of walking steps is positively associated with HDL cholesterol levels and negatively associated with triglyceride levels. According to a random-effects model meta-analysis of 4 randomized controlled trials comparing supervised aerobic exercise training with non-exercise control in subjects without CAD, exercise resulted in a significant increase in HDL-cholesterol (10.01 mg/dL, 95% CI 5.38 to 14.65, p< 0.0001). While this confirms the importance of physical activity in preventing CVD mortality and all-cause mortality, the levels of physical activity are on a declining trend in Japan, particularly among the young.