Acanthamoeba containing endosymbiotic chlamydia isolated from hospital environments and its potential role in inflammatory exacerbation

Background: Environmental chlamydiae belonging to the Parachlamydiaceae are obligate intracellular bacteria that infect Acanthamoeba, a free-living amoeba, and are a risk for hospital-acquired pneumonia. However, whether amoebae harboring environmental chlamydiae actually survive in hospital environments is unknown. We therefore isolated living amoebae with symbiotic chlamydiae from hospital environments. Results: One hundred smear samples were collected from Hokkaido University Hospital, Sapporo, Japan; 50 in winter (February to March, 2012) and 50 in summer (August, 2012), and used for the study. Acanthamoebae were isolated from the smear samples, and endosymbiotic chlamydial traits were assessed by infectivity, cytokine induction, and draft genomic analysis. From these, 23 amoebae were enriched on agar plates spread with heatkilled Escherichia coli. Amoeba prevalence was greater in the summer-collected samples (15/30, 50%) than those of the winter season (8/30, 26.7%), possibly indicating a seasonal variation (p = 0.096). Morphological assessment of cysts revealed 21 amoebae (21/23, 91%) to be Acanthamoeba, and cultures in PYG medium were established for 11 of these amoebae. Three amoebae contained environmental chlamydiae; however, only one amoeba (Acanthamoeba T4) with an environmental chlamydia (Protochlamydia W-9) was shown the infectious ability to Acanthamoeba C3 (reference amoebae). While Protochlamydia W-9 could infect C3 amoeba, it failed to replicate in immortal human epithelial, although exposure of HEp-2 cells to living bacteria induced the proinflammatory cytokine, IL-8. Comparative genome analysis with KEGG revealed similar genomic features compared with other Protochlamydia genomes (UWE25 and R18), except for a lack of genes encoding the type IV secretion system. Interestingly, resistance genes associated with several antibiotics and toxic compounds were dentified. Conclusion: These findings are the first demonstration of the distribution in a hospital of a living Acanthamoeba carrying an endosymbiotic chlamydial pathogen

Alpha7 nicotinic ACh receptor mediated neuroprotective action by nicotine and GTS-21: An approach by the hippocampal organotypic slice cultures.

Nicotine, main constituent of tabaco, is known as a nicotinic acetylcholine receptor (nAChR) agonist and increases cognitive performance. 3-(2,4-dimethoxybenzylidene)-anabaseine (GTS-21) is derived from the marine worm toxin, anabaseine, and is alpha7-selective nAChR (D7-nAChR) agonist. Both nicotine and GTS-21 were expected as therapeutic agents of Alzheimer’s disease. Several studies showed that nicotine and GTS-21 protected neuron by activating nAChR, especially D7-nAChR. It has been reported that D7-nAChR has been shown to be an essential regulator of inflammation. The purpose of this study is to examine the neuroprotective and anti-inflammatory effects of nicotine and GTS-21 using organotypic hippocampal slice cultures. Kainic acid (KA, 5-50µM) induced concentration- and time-dependent neuronal cell death in the hippocampal organotypic slice cultures. The pretreatment with nicotine and GTS-21 tended to decrease in KA toxicity. In a CA3 area-specific analysis, pretreatment with nicotine resulted in significant inhibition of KA-induced neurotoxicity. The results suggest that nicotine may protect KA-induced neuronal cell death via D7-nAChR. We also examined anti-inflammatory effects of nicotine and GTS-21. Hippocampal slices were pretreated with nicotine or GTS-21, and then treated with lipopolysaccharide (LPS). LPS treatment induced concentration-dependent increases in TNFD and IL-1E gene expressions. LPS-induced TNFD gene expression, but not IL-1E was suppressed by GTS-21 pretreatment. These results suggest that D7-nAChR might be involved in the microglia activation towards a neuroprotective role by suppressing inflammatory cytokine

Latex Photoimmunoassay of Serum Ferritin

A basic analysis including recovery, reproducibility and dilution tests and clinical analysis of the latex photoimmunoassay, LPIA, produced acceptable results. One sample could be processed in a few minutes, which is a much shorter period of time than is required by the RIA or EIA, anzyme immunoassay. Sensitivity was a few nanograms per milliliter. The correlation coefficient with the IRMA was 0.973. Specificity was high and without the influence of various interfering factors in serum. The LPIA, therefore, seems to be a simple but reliable tool for estimating iron storage conditions and a tumor marker for rapidly screening of malignant diseases

Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling

Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson’s disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA–deficient Drosophila exhibits defects in neurotransmission during early developmental stages and progressive cell loss throughout the brain, including degeneration of the DA neurons. Lipid analysis of brain tissues reveals that the acyl-chain length of phospholipids is shortened by iPLA2-VIA loss, which causes endoplasmic reticulum (ER) stress through membrane lipid disequilibrium. The introduction of wild-type human iPLA2-VIA or the mitochondria–ER contact site-resident protein C19orf12 in iPLA2-VIA–deficient flies rescues the phenotypes associated with altered lipid composition, ER stress, and DA neurodegeneration, whereas the introduction of a disease-associated missense mutant, iPLA2-VIA A80T, fails to suppress these phenotypes. The acceleration of α-Syn aggregation by iPLA2-VIA loss is suppressed by the administration of linoleic acid, correcting the brain lipid composition. Our findings suggest that membrane remodeling by iPLA2-VIA is required for the survival of DA neurons and α-Syn stability

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy

Background The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone-naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). Methods At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer-specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5-year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5-year net CSS and OS survival gradually increased for all the patients. In patients given a 5-year survivorship, the conditional 5-year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) >= 2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions The conditional 5-year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient\u27s risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5-year follow-up. Conditional net survival can play a role in clinical decision-making, providing intriguing information for cancer survivors

Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer

We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2-4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specific survival (CSS) and overall survival (OS) were 7.08 and 6.47 years (median follow-up, 2.53 years), respectively. In the final optimal Cox model with serum biomarker levels treated as time-varying covariates, prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP) significantly increased the risk of poor survival in the context of both CSS and OS. Kaplan-Meier curves stratified by the three risk factors of high PSA, low Hb and high ALP desmondtated that median OS were not reached with none of these factors, 6.47 years with one or two factors, and 1.76 years with all three factors. Early changes in serum biomarker levels after ADT may be good prognostic markers for the survival of patients with mHSPC

Study on Water Science

In this study, we intended to clarify the effect of various treatments such as magnetic and ultraviolet light irradiation on acidic electrolyzed aqueous solutions and alkali halide aqueous solutions. The results indicated that the available chloride concentration of acidic electrolyzed aqueous solution was decreased by these treatments. It was proved that hydroxyl radicals and bound water varied by these treatments in the alkali halide aqueous solution. It was proved that the most effective treatment in aqueous solutions relates to the salt concentration in both the acidic electrolyzed aqueous solution and the alkali halide aqueous solution