Far-infrared rays control prostate cancer cells _in vitro_ and _in vivo_

We introduce a new effective method to control hormone refractory prostate cancer cells by using an activated rubber/resin form (RB), far-infrared ray emitter, with or without sodium butyrate (SB). The growth of three human prostate cancer cell lines (Du145, PC-3 and LNCaP) was suppressed _in vitro_ and _in vivo_ by using RB, and the cells were eradicated with RB + 3 mM SB. G1 arrest and apoptotic pathway proteins were induced by RB with intensified expressions of apoptosis - related mRNA on cDNA microarray. RB radiates the infra-red rays of the 4 to 25 [mu]m wavelengths to an object which exert a favorable influence on a cancer control. These results may render us a new therapeutic modality in hormone refractory prostate cancer

Trace Elements in Hair: Relevance to Air Pollution

Elemental concentrations of single hair samples taken from 2003 to 2012 had been evaluated by X-ray fluorescence for the assessment of the relation between calcium and cancer. Early results implied a mechanism linking hair and serum element concentrations with a shift in element levels over time. After 2009, pollution-attributable differences were seen in the levels of Ca, Sr, P, Cl, Br, K, S, elements under renal control by parathyroid hormone (PTH), as well as Cu, Zn, Ti. Especially, hair taken from February to March 2011 showed low [Cu] and [Zn] indicating about half of the normal serum level and often three orders of magnitude higher [Ti] than typical. These specimens also showed higher serum [S] than usual, and except for one patient with PTH-related disease, all the subjects had the normal or lower hair calcium than typical for earlier years. Almost all the subjects showed store-operated Ca channel gating. The pollution era is associated with an increase in hair Na, a decrease in K, and abnormally low P, suggesting a functional deterioration of Na+/K+-ATPase. These results can be attributed to increases in serum Ca and S coincident with breathing the polluted air; the incorporated Ca closes the ion channels of hair matrix cells but may be moved with P to bone, resulting in the abnormal P deficiency, likely producing an ATP shortage in serum. This insufficient ATP supply may result in inactivated molecular pumps and hypokalemia contributing to fatal ventricular fibrillation in patients with myocardial infarction. The pollution increase [S] in serum may be excreted by forming sulfide compounds with Cu and Zn, resulting in Cu deficiency necessary for making elastin to repair damage in blood vessels. The K and Cu deficiencies observed appear to account for the reported increase in infarction mortality after high-pollution days

Distinctive nuclear zone for RAD51-mediated homologous recombinational DNA repair

Genome-based functions are inseparable from the dynamic higher-order architecture of the cell nucleus. In this context, the repair of DNA damage is coordinated by precise spatiotemporal controls that target and regulate the repair machinery required to maintain genome integrity. However, the mechanisms that pair damaged DNA with intact template for repair by homologous recombination (HR) without illegitimate recombination remain unclear. This report highlights the intimate relationship between nuclear architecture and HR in mammalian cells. RAD51, the key recombinase of HR, forms spherical foci in S/G2 phases spontaneously. Using super-resolution microscopy, we show that following induction of DNA double-strand breaks RAD51 foci at damaged sites elongate to bridge between intact and damaged sister chromatids; this assembly occurs within bundle-shaped distinctive nuclear zones, requires interactions of RAD51 with various factors, and precedes ATP-dependent events involved the recombination of intact and damaged DNA. We observed a time-dependent transfer of single-stranded DNA overhangs, generated during HR, into such zones. Our observations suggest that RAD51-mediated homologous pairing during HR takes place within the distinctive nuclear zones to execute appropriate recombination

Development of D-to-D-to-P telemedicine at a remote island hospital using smart glasses

Background: Medical resources on remote islands are limited, which makes it difficult for patients to receive specialized medical care.Purpose: This study aimed to develop and evaluate a method to perform doctor-to-doctor-to-patient (D-to-D-to-P) telemedicine.Methods: The-D-to-D-to-P telemedicine was implemented to provide specialized medical support from a neurologist at Nagasaki University Hospital to a rural physician wearing camera-equipped smart glasses at Goto Chuoh Hospital on a remote island, which was called a virtual neurological outpatient (VNO). For the first six months, the rural physician independently saw patients with Parkinson’s disease (PD), and then for the next six months, VNO was implemented. Comparisons were made before and after the implementation of the VNO. Next, by adding a 4 K overhead camera, in-person examinations of a single outpatient were compared between the rural physician with VNO and another neurologist unrelated to the VNO.Results: The clinical efficacy of VNO was not superior to no VNO, but had a learning effect on rural physicians and was satisfactory for patients. By adding a 4 K overhead camera to the VNO, the accuracy of the in-person examination by the rural physician was shown to be equivalent to that of an in-person neurologist.Conclusion: VNO using smart glasses could be applied for D-to-D-to-P telemedicine in neurology. However, to promote telemedicine on remote islands, it will be necessary to improve the system to make it more accessible to rural physicians

Complete Response Using Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma with Multiple Lymph Node and Bone Metastases: A Case Report

Hepatocellular carcinoma（HCC）is the sixth most commonly diagnosed cancer worldwide. Sorafenib is an oral multikinase inhibitor used in the palliative treatment of advanced HCC. However, there were no reported cases of complete response（CR）from two previous large phaseⅢ clinical trials. Here, we report a case of CR in a patient with advanced HCC with multiple lymph node and bone metastases, treated with sorafenib monotherapy for 8 months. To our knowledge, this is the first evidence showing CR following sorafenib monotherapy for HCC with bone metastasis

Genome Sequence of a Mesophilic Hydrogenotrophic Methanogen Methanocella paludicola, the First Cultivated Representative of the Order Methanocellales

We report complete genome sequence of a mesophilic hydrogenotrophic methanogen Methanocella paludicola, the first cultured representative of the order Methanocellales once recognized as an uncultured key archaeal group for methane emission in rice fields. The genome sequence of M. paludicola consists of a single circular chromosome of 2,957,635 bp containing 3004 protein-coding sequences (CDS). Genes for most of the functions known in the methanogenic archaea were identified, e.g. a full complement of hydrogenases and methanogenesis enzymes. The mixotrophic growth of M. paludicola was clarified by the genomic characterization and re-examined by the subsequent growth experiments. Comparative genome analysis with the previously reported genome sequence of RC-IMRE50, which was metagenomically reconstructed, demonstrated that about 70% of M. paludicola CDSs were genetically related with RC-IMRE50 CDSs. These CDSs included the genes involved in hydrogenotrophic methane production, incomplete TCA cycle, assimilatory sulfate reduction and so on. However, the genetic components for the carbon and nitrogen fixation and antioxidant system were different between the two Methanocellales genomes. The difference is likely associated with the physiological variability between M. paludicola and RC-IMRE50, further suggesting the genomic and physiological diversity of the Methanocellales methanogens. Comparative genome analysis among the previously determined methanogen genomes points to the genome-wide relatedness of the Methanocellales methanogens to the orders Methanosarcinales and Methanomicrobiales methanogens in terms of the genetic repertoire. Meanwhile, the unique evolutionary history of the Methanocellales methanogens is also traced in an aspect by the comparative genome analysis among the methanogens

The Japanese Clinical Practice Guideline for acute kidney injury 2016

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search

ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot

Chromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, increases the incidence of chromosome translocations. However, how ATM protects cells from chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide, a topoisomerase II poison. Here we show that ATM deficiency results in the excessive binding of the DNA recombination protein RAD51 at the translocation breakpoint hotspot of 11q23 chromosome translocation after etoposide exposure. Binding of Replication protein A (RPA) and the chromatin remodeler INO80, which facilitate RAD51 loading on damaged DNA, to the hotspot were also increased by ATM deficiency. Thus, in addition to activating DNA damage signaling, ATM may avert chromosome translocations by preventing excessive loading of recombinational repair proteins onto translocation breakpoint hotspots

Probiotic Bifidobacterium breve Induces IL-10-Producing Tr1 Cells in the Colon

Specific intestinal microbiota has been shown to induce Foxp3+ regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103+ dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103+ DCs from Il10−/−, Tlr2−/−, and Myd88−/− mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103+ DCs failed to induce IL-10 production from co-cultured Il27ra−/− T cells. B. breve treatment of Tlr2−/− mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103+ DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4+ T cells from wild-type mice, but not Il10−/− mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells