We present estimations for the amounts of Arcobacter (A. butzleri, A. cryaerophilus and A. skirrowii) and Campylobacter (C. jejuni, C. coli and C. fetus) species in retail chicken, pork and beef meat ...using PCR‐MPN. Arcobacter butzleri, A. cryaerophilus and C. jejuni were found in 100, 60 and 55% of chicken samples, respectively. No other Arcobacter or Campylobacter species were found in chicken. The MPNs of A. butzleri, A. cryaerophilus and C. jejuni were greater than 103 per 100 g in 50, 0 and 5% of samples, respectively. The MPN of A. butzleri was higher than that of C. jejuni in 95% of samples. In pork, A. butzleri and A. cryaerophilus were detected in 10 and 11 (50 and 55%) of 20 samples, respectively. No other Arcobacter or Campylobacter species were found in pork. Only one pork sample had more than 103 MPN per 100 g of A. cryaerophilus. For beef, only two samples tested positive for A. cryaerophilus, at 4600 and 92 MPN per 100 g. Overall, we found that the presence and MPNs of Arcobacter species are very high in chicken. In contrast, the positive ratios of Arcobacter in pork were high as chicken samples, but MPNs were lower than in chicken.
Significance and Impact of the Study: Arcobacter are isolated from patients with diarrhoea and gastrointestinal diseases. However, whether Arcobacter relate with food‐borne disease or not has not been clarified. There were few studies that investigated the numbers of Arcobacter in foods. In this study, the numbers of Arcobacter and Campylobacter in retailed meat were investigated. The results in this study showed that both the number and the contamination ratio of A. butzleri surpassed that of Campylobacter, a well‐established food‐borne pathogen. This result indicated that even if Arcobacter relates with food‐borne disease, the pathogenesis of A. butzleri may be weaker than that of C. jejuni.
Intake of a small dose of foodborne pathogens can cause infection. In this study, an estimation of the infectious dose of the pathogens was obtained by conducting microbiological risk assessments. ...The contamination levels of foodborne pathogens were analysed in 17 outbreaks of Salmonella, Escherichia coli O157, enterotoxigenic E. coli, Vibrio parahaemolyticus, and Campylobacter jejuni occurring in Japan between 2004 and 2006. The infectious dose was estimated in 14 of the 17 outbreaks utilizing existing data. In three outbreaks of Salmonella infection in which the infection rate was 89–100%, the dose of the ingested pathogens was estimated to be 259 000–14 000 000 000 c.f.u. In other outbreaks of Salmonella infection, the infection rate and dose of the ingested pathogens were 10–66·4% and 81–1560 c.f.u. or most probable number (MPN), respectively. The ingested Salmonella dose is likely to be related to the infection rate; however, storage conditions should be taken into account when making this determination. In an outbreak of E. coli O157 infection, the infection rate and ingestion dose were 100% and 2 to <9 c.f.u., respectively, while in an outbreak of enterotoxigenic E. coli infection, they were 93% and 25–1000 c.f.u., respectively. Finally, in an outbreak of C. jejuni infection, the infection rate and ingestion dose were 37·5% and 360 MPN, respectively. These results will be particularly valuable for risk assessment.
Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, ...we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation. Particularly, the expression of Cd44, a liver cancer stem marker, was regulated by AP-1 in a Kdm3a-dependent manner. We identified Cd44-positive hepatocytes with epithelial-mesenchymal transition-related expression profiles in the Pik3ca Tg liver and confirmed their in vivo tumorigenic capacity. Notably, the number and tumor-initiating capacity of Cd44-positive hepatocytes were governed by Kdm3a. As a mechanism in Kdm3a-dependent AP-1 transcription, Kdm3a recruited c-Jun to the AP-1 binding sites of Cd44, Mmp7 and Pdgfrb without affecting c-Jun expression. Moreover, Brg1, a component of the SWI/SNF chromatin remodeling complex, interacted with c-Jun in a Kdm3a-dependent manner and was bound to the AP-1 binding site of these genes. Finally, KDM3A and c-JUN were co-expressed in 33% of human premalignant lesions with PI3K activation. Our data suggest a critical role for KDM3A in the PI3K/AP-1 oncogenic axis and propose a novel strategy for inhibition of KDM3A against liver tumor development under PI3K pathway activation.
Epithelial-mesenchymal transition (EMT) is a crucial process in cancer progression that provides cancer cells with the ability to escape from the primary focus, invade stromal tissues and migrate to ...distant regions. Cell lines that lack E-cadherin show increased tumorigenesis and metastasis, and the expression levels of E-cadherin and Snail correlate inversely with the prognosis of patients suffering from breast cancer or oral squamous cell carcinoma (OSCC). Moreover, recent studies have shown that most EMT cases are regulated by soluble growth factors or cytokines. Among these factors, fibroblast growth factors (FGFs) execute diverse functions by binding to and activating members of the FGF receptor (FGFR) family, including FGFR1-4. Fibroblast growth factor receptor 1 is an oncoprotein that is involved in tumorigenesis, and PD173074 is known to be a selective inhibitor of FGFR1. However, the roles of FGFR1 and FGFR1 inhibitors have not yet been examined in detail.
Here, we investigated the expression of FGFR1 in head and neck squamous cell carcinoma (HNSCC) and the role of the FGFR1 inhibitor PD173074 in carcinogenesis and the EMT process.
Fibroblast growth factor receptor 1 was highly expressed in 54% of HNSCC cases and was significantly correlated with malignant behaviours. Nuclear FGFR1 expression was also observed and correlated well with histological differentiation, the pattern of invasion and abundant nuclear polymorphism. Fibroblast growth factor receptor 1 was also overexpressed in EMT cell lines compared with non-EMT cell lines. Furthermore, treatment of HOC313 cells with PD173074 suppressed cellular proliferation and invasion and reduced ERK1/2 and p38 activation. These cells also demonstrated morphological changes, transforming from spindle- to cobble stone-like in shape. In addition, the expression levels of certain matrix metalloproteinases (MMPs), whose genes contain activator protein-1 (AP-1) promoter sites, as well as Snail1 and Snail2 were reduced following PD173074 treatment.
Taken together, these data suggest that PD173074 inhibits the MAPK pathway, which regulates the activity of AP-1 and induces MET. Furthermore, this induction of MET likely suppresses cancer cell growth and invasion.
The tumor immune microenvironment (TIME) of lung cancer brain metastasis is largely unexplored. We carried out immune profiling and sequencing analysis of paired resected primary tumors and brain ...metastases of non-small-cell lung carcinoma (NSCLC).
TIME profiling of archival formalin-fixed and paraffin-embedded specimens of paired primary tumors and brain metastases from 39 patients with surgically resected NSCLCs was carried out using a 770 immune gene expression panel and by T-cell receptor beta repertoire (TCRβ) sequencing. Immunohistochemistry was carried out for validation. Targeted sequencing was carried out to catalog hot spot mutations in cancer genes.
Somatic hot spot mutations were mostly shared between both tumor sites (28/39 patients; 71%). We identified 161 differentially expressed genes, indicating inhibition of dendritic cell maturation, Th1, and leukocyte extravasation signaling pathways, in brain metastases compared with primary tumors (P < 0.01). The proinflammatory cell adhesion molecule vascular cell adhesion protein 1 was significantly suppressed in brain metastases compared with primary tumors. Brain metastases exhibited lower T cell and elevated macrophage infiltration compared with primary tumors (P < 0.001). T-cell clones were expanded in 64% of brain metastases compared with their corresponding primary tumors. Furthermore, while TCR repertoires were largely shared between paired brain metastases and primary tumors, T-cell densities were sparse in the metastases.
We present findings that suggest that the TIME in brain metastases from NSCLC is immunosuppressed and comprises immune phenotypes (e.g. immunosuppressive tumor-associated macrophages) that may help guide immunotherapeutic strategies for NSCLC brain metastases.
•On March 11th 2011 the Fukushima Daiichi Units 1 to 3 experienced station black out. This set in motion a chain of events leading to core meltdown.•Radioactive materials were released to the ...environment.•TEPCO has made many efforts to investigate the accident progressions.•Up to date no perfect calculations exists due to lack of knowledge of BWR phenomena.•Comparison between calculations and findings emphasize model development direction.
On March 11th 2011 the Great East Japan Earthquake and Tsunami hit the Fukushima Daiichi Nuclear Power Station. The Fukushima Daiichi Units 1 to 3 lost all DC and AC power supplies, which set in motion a chain of events that led to releases of radioactivity to the environment. Since then, TEPCO has made many efforts to investigate the accident progressions and the status of the reactors and containment vessels, mainly by using severe accident analysis code, such as MAAP, MELCOR and SAMPSON. However, there still exist several tens of unsolved issues to be investigated for the fully understanding of the accident. In recent years, massive amounts of information of the accident plants were obtained through the investigation activities by using robots or other devices. The investigation results suggested us the possibilities that some phenomena identifications established before the accident were incorrect. And also, there are many difficulties to reproduce the accident progressions of the Fukushima Daiichi unit 1 to 3, due to lack of knowledge real BWR plant accident phenomena. In this paper, we will introduce the special characteristics, which made difficult to reproduce the accident. And we will discuss how to use the investigation results obtained in Fukushima Daiichi NPP for the SA code validation by comparing with investigation results and calculation results.
Consumption of seafood contaminated with Vibrio parahaemolyticus causes foodborne infections, which are on the rise owing to increased consumption of raw seafood in Asia, Europe, North America, and ...other regions. V. parahaemolyticus infections have been common in Japan since the 1960s. Following an epidemic in 1997, the Japanese Ministry of Health, Labour, and Welfare instituted regulations for seafood in 1999, which appear to be reducing V. parahaemolyticus infections. In this review, we describe the scientific findings for these regulations. Analyses of the V. parahaemolyticus serotypes and isolate characteristics in samples from infected patients and contaminated seafood are discussed. In addition, based on the results of a survey, we show that new food safety regulations have led to improvements in food hygiene at many seafood retail shops, food service facilities, and restaurants. This example from Japan could be of immense help to control foodborne infections in other countries.
Background and purpose
Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the ...microtubule‐binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, 18FTHK‐5351, which we have recently developed.
Methods
Paraffin‐embedded brain sections of the patients with PSP were used for autoradiography with 3HTHK‐5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with 18FTHK‐5351. To detect amyloid‐β deposition, PET imaging with Pittsburgh compound B was also performed.
Results
Autoradiography in the brain sections of patients with PSP demonstrated 3HTHK‐5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable 18FTHK‐5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP.
Conclusions
We conclude that 18FTHK‐5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.
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