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The Prostate Cancer Cohort Consortium (PC3) Working Group proposed a definition for aggressive prostate cancer (PC) for aetiologic epidemiologic research. We aimed to validate this definition as well as a second approach utilising only information on stage at diagnosis. First primary PCs diagnosed 2004 − 2009 in the population-based Janus Serum Bank (JSB) cohort were identified by linkage to the population-based Cancer Registry of Norway (CRN) (n = 3568). The CRN and Norwegian Prostate Cancer Registry provided clinicopathological data for these cases. Approach 1 classified PC as aggressive if it was clinically T4, or N1, or M1, or had a Gleason score ≥8 at diagnosis (as proposed). Approach 2 classified PC as aggressive if CRN stage at diagnosis was 'regional spread' or 'distant metastases'. Both approaches were validated by calculating the sensitivity and positive predictive value (PPV) against PC-death within 10 years of diagnosis. Overall, 555 died from PC within 10 years. Approach 1 classified 24.7% of cases as aggressive and 13.6% were unclassified due to missing information. Approach 2 classified 19.6% as aggressive and 29% were unclassified. Sensitivity was highest for Approach 1 (0.76, 95% CI: 0.72 − 0.80 vs 0.69, 95% CI: 0.64 − 0.73), while PPVs were similar for both approaches (0.43, 95% CI: 0.40 − 0.46 and 0.40, 95% CI: 0.36 − 0.44). We observed similarly high sensitivity and higher PPVs than those reported by the PC3 Working Group. The proposed definition of aggressive PC was applicable and valid in the JSB cohort. Stage at diagnosis can be useful if data on cTNM or Gleason score is unavailable. [ABSTRACT FROM AUTHOR]

An error‐free wireless transmission of a 9 Gbit/s on–off keying modulated signal as well as a 4 k video signal is demonstrated using resonant tunnelling diodes as active elements in both the transmitter and the receiver. The employed system and the modulation scheme enabling the high data rate are discussed. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) has been associated with both a myeloid lineage commitment and favorable prognosis in patients with acute myeloid leukemia (AML). DNA methyltransferase inhibitors (decitabine and zeburaline) induced MPO gene promoter demethylation and MPO gene transcription in AML cells with low MPO activity. Therefore, MPO gene transcription was directly and indirectly regulated by DNA methylation. A DNA methylation microarray subsequently revealed a distinct methylation pattern in 33 genes, including DNA methyltransferase 3 beta (DNMT3B), in CD34-positive cells obtained from AML patients with a high percentage of MPO-positive blasts. Based on the inverse relationship between the methylation status of DNMT3B and MPO, we found an inverse relationship between DNMT3B and MPO transcription levels in CD34-positive AML cells (P=0.0283). In addition, a distinct methylation pattern was observed in five genes related to myeloid differentiation or therapeutic sensitivity in CD34-positive cells from AML patients with a high percentage of MPO-positive blasts. Taken together, the results of the present study indicate that MPO may serve as an informative marker for identifying a distinct and crucial DNA methylation profile in CD34-positive AML cells. [ABSTRACT FROM AUTHOR]

Background: During 2005-2007, we experienced sporadic isolations of multidrug-resistant (MDRP) Pseudomonas aeruginosa from wards in a general hospital in Hiroshima. The objective of this study was to analyze epidemiology relationships and the mode of spread of the strains. Methods: Clonality was assessed using pulsed-field gel electrophoresis (PFGE) and serotyping. MICs were determined using the microdilution broth method. Investigations of the affected patients' movements and environmental sampling from the affected wards were conducted. Results: An abrupt increase in MDRP isolations began at the end of 2005 and ended in February 2007. A total of 25 MDRP strains were sporadically isolated from nine wards. Fourteen strains were genotypically and serologically identical. Analysis of the patients' movements identified that six of the 14 MDRP-positive patients became positive for MDRP when they were in the intensive care unit (ICU), and two became positive after the patients moved from the ICU to another nursing unit. Four MDRP strains were isolated from patients who did not stay in the ICU and were in ward E6, which had the second highest number of isolations. In July 2006, environmental sampling of the hospital identified a toilet brush in ward E6 that was contaminated with MDRP that was genotypically and serologically identical to the clinical isolates. Conclusions: Our study suggests that the sporadic increase in MDRP isolates during 2005-2007 in the general hospital in Hiroshima was due to an epidemic of an MDRP clone. Continuity and spread of infection was probably due to cross infection and contamination in the hospital with the MDRP strain. [ABSTRACT FROM AUTHOR]

Ohara M, Miyauchi M, Tsuruda K, Takata T, Sugai M. Topical application of Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces cell cycle arrest in the rat gingival epithelium in vivo . J Periodont Res 2011; 46: 389-395. © 2011 John Wiley & Sons A/S Aggregatibacter actinomycetemcomitans is one of the etiological pathogens implicated in the onset of periodontal disease. This pathogen produces cytolethal distending toxin (CDT) that acts as a genotoxin to induce cell cycle arrest and cellular distension in cultured cell lines. Therefore, CDT is a possible virulence factor; however, the in vivo activity of CDT on periodontal tissue has not been explored. Here, CDT was topically applied into the rat molar gingival sulcus; and the periodontal tissue was histologically and immunohistochemically examined. Recombinant purified A. actinomycetemcomitans CDT was applied to gingival sulcus of male Wistar rats and tissue samples were immunohistochemmically examined. One day after application, infiltration of neutrophils and dilation of blood vessels in the gingival connective tissue were found. At day three, desquamation and detachment of cells in the junctional epithelium was observed. This abrasion of junctional epithelium was not observed in rats treated with mutated CDT, in which a His274Ala mutation is present in the CdtB subunit. This indicates the tissue abrasion may be caused by the genotoxicity of CdtB. Expression of the proliferating cell nuclear antigen (PCNA), a marker for proliferating cells, was significantly suppressed using CDT treatment in the junctional epithelium and gingival epithelium. Using the rat model, these data suggest CDT intoxication induces cell cycle arrest and damage in periodontal epithelial cells in vivo. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm etiologically associated with human T-lymphotropic virus type-1 (HTLV-1), is resistant to treatment. In this study, we examined the effects of a new inhibitor of deacetylase enzymes, LBH589, on ATLL cells. LBH589 effectively induced apoptosis in ATLL-related cell lines and primary ATLL cells and reduced the size of tumors inoculated in SCID mice. Analyses, including with a DNA microarray, revealed that neither death receptors nor p53 pathways contributed to the apoptosis. Instead, LBH589 activated an intrinsic pathway through the activation of caspase-2. Furthermore, small interfering RNA experiments targeting caspase-2, caspase-9, RAIDD, p53-induced protein with a death domain (PIDD) and RIPK1 (RIP) indicated that activation of RAIDD is crucial and an event initiating this pathway. In addition, LBH589 caused a marked decrease in levels of factors involved in ATLL cell proliferation and invasion such as CCR4, IL-2R and HTLV-1 HBZ-SI, a spliced form of the HTLV-1 basic zipper factor HBZ. In conclusion, we showed that LBH589 is a strong inducer of apoptosis in ATLL cells and uncovered a novel apoptotic pathway initiated by activation of RAIDD. [ABSTRACT FROM AUTHOR]

Shopping carts and handheld shopping baskets in supermarkets are subject to accidental bacterial contamination through contacts with a variety of food. We investigated the prevalence of Staphylococcus aureus on the handles of handheld shopping baskets in four supermarkets distantly located in Osaka district, Japan. Fifty two strains of Staph. aureus were isolated from 760 basket handles. Among these, six strains were positive for staphylococcal enterotoxin B (SEB) production, representing 12% of total. This SEB producer ratio is considerably higher than among Staph. aureus isolated from nasal swabs of the supermarket workers (2%) and from independently collected clinical specimens (4%). These SEB-producing Staph. aureus strains from the basket handles are clonal and belong to ST12. Coagulase typing showed that they are in group VII, which is the most common cause of food poisoning in Japan. Biofilm assays indicated that SEB gene ( seb)-positive strains including this clone produced a significantly higher amount of biofilm than seb-negative strains. The frequent isolation of seb-positive Staph. aureus on shopping basket handles raises the possibility that they could be a hidden reservoir for Staph. aureus with a potential to cause food poisoning and draws attention to the importance of shopping basket sanitation. [ABSTRACT FROM AUTHOR]

It has been reported that the induction of cellular senescence through p53 activation is an effective strategy in tumor regression. Unfortunately, however, tumors including adult T-cell leukemia/lymphoma (ATL) have disadvantages such as p53 mutations and a lack of p16(INK4a) and/or p14(ARF). In this study we characterized Nutlin-3a-induced cell death in 16 leukemia/lymphoma cell lines. Eight cell lines, including six ATL-related cell lines, had wild-type p53 and Nutlin-3a-activated p53, and the cell lines underwent apoptosis or cell-cycle arrest, whereas eight cell lines with mutated p53 were resistant. Interestingly, senescence-associated-beta-galactosidase (SA-beta-gal) staining revealed that only ATL-related cell lines with wild-type p53 showed cellular senescence, although they lack both p16(INK4a) and p14(ARF). These results indicate that cellular senescence is an important event in p53-dependent cell death in ATL cells and is inducible without p16(INK4a) and p14(ARF). Furthermore, knockdown of Tp53-induced glycolysis and apoptosis regulator (TIGAR), a novel target gene of p53, by small interfering RNA(siRNA) indicated its important role in the induction of cellular senescence. As many patients with ATL carry wild-type p53, our study suggests that p53 activation by Nutlin-3a is a promising strategy in ATL. We also found synergism with a combination of Nutlin-3a and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), suggesting the application of Nutlin-3a-based therapy to be broader than expected. [ABSTRACT FROM AUTHOR]

Despite the significant implication of apoptosis in tumorigenesis, there is no biomarker to assess the extent of ongoing apoptosis in vivo for hematological malignancies. We investigated the potential of serum cytochrome c (cyto-c) as a biomarker for apoptosis. Cyto-c and lactate dehydrogenase (LD) were released into the culture medium from apoptotic cells induced by tumor necrosis factor-related apoptosis-inducing ligand in a time-dependent manner in vitro, with different kinetic patterns. Only one-third of 153 patients with hematological malignancies showed high levels of serum cyto-c (>20 ng/ml). Although serum cyto-c level was roughly correlated to serum LD activity, their different kinetic patterns from serial measurements indicated that serum cyto-c rather than LD is a more sensitive indicator for tracking changes of tumor status. Furthermore, serum cyto-c level stratified patients with acute adult T-cell leukemia into favorable and unfavorable subgroups with 5-year survival rates of 67% vs. 11%. In conclusion, serum cyto-c may provide a fast real-time biomarker for tracking changes of tumor status involved in apoptotic cell death, but lacking disease or cell-type specificity. [ABSTRACT FROM AUTHOR]

Introduction: The current detection methods for periodontopathogens mainly use polymerase chain reactions. However, there are few methods available for visualizing the bacteria that impact on patients with periodontal disease for use in health education. The purpose of this study was to develop a specific detection method to visualize periodontopathogenic bacteria. Methods: Fluorescently-labeled oligonucleotide probes directed to specific 16S ribosomal RNA (rRNA) sequences of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were synthesized. Cultured individual bacterial species were fixed with 4% paraformaldehyde and smeared on glass slides. Fluorescein isothiocyanate-labeled oligonucleotide probes were hybridized under stringent conditions with smeared whole cells, and then probe specificity was investigated by epifluorescence microscopy. Results: Comparatively long (50-mer) oligonucleotide probes for P. gingivalis and A. actinomycetemcomitans were designed. These probes clearly hybridized with 16S rRNA of the target species in situ and single bacterial cells were detectable visually. The probes exhibited no cross-hybridization against the additional organisms that were closely related to the target species. Conclusions: The fluorescence in situ hybridization technique is a specific and reliable method by which to visually identify the target organisms. The oligonucleotide probes designed in this study will be useful for detecting P. gingivalis and A. actinomycetemcomitans populations. [ABSTRACT FROM AUTHOR]

The analytical methods of Southern blot hybridization (SBH) and the polymerase chain reaction (PCR) for complementarity determining region-3 (CDR3) are fundamental for detecting IgH gene rearrangement. However, there are problems stemming from the characteristics of both methods; especially, the long turn around time (TAT) because of the complex process in the SBH, and the low analytical sensitivity for amplicons in the PCR. Thus, to improve the PCR procedure, we investigated the application of detecting the clonal amplicons based on the different melting Temperature ( Tm) in internal melting domains corresponding to the CDR3 hypervariable region. Our new protocol is based on the combination of a LightCycler Technology with high-speed amplification, and Idaho-Technology with rapid and high-resolution melting curve analysis (MCA), designated PCR-MCA. This method can provide the results within 3 h with an analytical sensitivity of 10−3. The diagnostic sensitivity and specificity relative to the results documented with the SBH analysis were 89.2% and 100%, respectively. This indicates that the new protocol of PCR-MCA is acceptable for clinical testing; especially, PCR-MCA is relevant in terms of the rapid and sensitive detection of IgH clonality within amplicons. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells, but not in normal cells, and hence TRAIL has recently emerged as a novel anti-cancer agent. Adult T-cell leukaemia lymphoma (ATLL) is a neoplasm of T-lymphocyte origin aetiologically associated with human T-lymphotropic virus type 1 (HTLV-I), and is resistant to standard anti-cancer therapy. We thus characterized the sensitivity of ATLL cells to TRAIL in this study. Although most primary ATLL cells and cell lines expressed TRAIL death receptors on their surface, they showed only restricted sensitivity to TRAIL. Among the 10 ATLL cell lines examined, one was sensitive, but two had insufficient death-receptor expression, two had an unknown resistant mechanism with abrogation of the death signal upstream of caspase-8, and the remaining five showed attenuation of the signal in both extrinsic and intrinsic pathways by X-linked inhibitor of apoptosis and Bcl-2/Bcl-xL respectively. Furthermore, the level of HTLV-I tax expression was significantly correlated to TRAIL resistance. Interestingly, ATLL cells themselves expressed TRAIL on the cell surface. Constitutive production of TRAIL may offer resistance, thus allowing the development of TRAIL-resistant ATLL cells. Consequently, the resistant mechanism in ATLL cells against TRAIL was assigned to multiple factors and was not explained by a definitive single agent. [ABSTRACT FROM AUTHOR]

We have developed a prototype time-of-flight neutral gas mass spectrometer that simultaneously measures the density and the velocity distribution function of each mass species, using the time-of-flight and the two-dimensional spatial distribution of the ionized particles on a charge-coupled device (CCD). We confirmed the feasibility of the velocity distribution measurement in a vacuum chamber using room-temperature Ar gas, by measuring the spatial distribution of the ionized Ar on the CCD and inferring the corresponding velocity distribution of the incident Ar. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We examined the cytotoxicity in culture medium of Actinobacillus actinomycetemcomitans against the human monocyte-macrophage-like cell line U937 using the trypan blue exclusion test and WST-1 test. We found that A. actinomycetemcomitans Y4 showed the highest cytotoxic activity among the three different serotype strains and the cytotoxic effects of both bacterial cells and culture supernatants in A. actinomycetemcomitans Y4 were stronger on phorbol-12-myristate 13-acetate (PMA)-induced U937 cells than uninduced U937 cells. Morphological changes in PMA-induced U937 cells treated with culture supernatants differed from those treated with leukotoxin, and a difference in the susceptibility to 56 °C heat treatment was found between culture supernatants and leukotoxin. The cytotoxic activity by WST-1 was determined more rapidly and strongly than that by trypan blue assay. These findings suggested that the cytotoxic effect of A. actinomycetemcomitans was influenced by the differentiation of U937 cells and may be more potent on the respiratory chain than the cell membrane. [ABSTRACT FROM AUTHOR]

An ion emission instrument has been developed to actively control the electrostatic surface potential of a spacecraft in orbit. Spacecraft surfaces tend to charge positive when their conductive surfaces are partially sunlit, and photoelectrons emitted, and the spacecraft is positioned outside of the very dense plasma region which is referred to as plasmasphere. A small, lightweight instrument with a lifetime of more than 10[sup 4] h at a nominal emission current of 10 µA was the design goal. The ion emitter is based on the liquid metal ion source principle; a constant stream of liquified indium is evaporated from the tip of a needle and ionized; the ions are then extracted by a strong electric field. The size of the instrument is about 18 by 15 by 23 cm (length×width[sub ]height) and the entire instrument weighs about 1.9 kg and consumes 2.4 W of electrical power in the nominal emission mode. An instrument of this type is already operational on the Japanese Geotail spacecraft, while five more instruments are at the stage of flight model assembly for integration on the Russian Interball satellite and the ESA/NASA four-spacecraft Cluster mission. The Geotail instrument is functioning as expected. Preliminary results show that the ion emitter is able to reduce surface potentials of +70 V (highest value observed up to now) down to 2-4 V. [ABSTRACT FROM AUTHOR]