tbuckley/cabot-search huggingface dataset:
SP0014 Healthy Work Life Expectancy in Older Adults with Arthritis: How Long Can People with Arthritis Work for and what Maintains Work Participation Till Old Age
Authors: R. Wilkie
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> People in Europe are living longer. On the basis of this, European Union targets and national government policy aim to increase the number of older adults in work and extend working life. However, if increases in working life are accompanied by an increase in time spent with musculoskeletal conditions, such targets will be difficult to realise, with implications for older workers, clinicians, employers, health providers and government policy. Of particular concern are musculoskeletal disorders, such as osteoarthritis; the most common joint condition in adults and a frequent cause of joint pain and disability in older adults. Extensions to working life raises the likelihood that the prevalence of adults in employment with osteoarthritis will increase. However the extent to which osteoarthritis will impact on their ability to stay healthy and in work is unclear. Measuring work capability in older people is challenging. However, population health indicators (e.g. healthy life expectancy) were developed to assess whether gains in life expectancy are years of healthy or unhealthy life. Healthy Working Life Expectancy (HWLE) is a longevity statistic that captures the number of years an average person aged between 50 and 70 years can expect to be both working and healthy. HWLE has been compared across European countries and over time using European Community Household Panel (ECHP). This presentation describes a study which explores (i) the impact of osteoarthritis on Healthy Work Life Expectancy in older adults and (ii) the factors that decrease HWLE in older adults with osteoarthritis. <h3>Disclosure of Interest</h3> None Declared
Abstract 481: Oligodeoxynucleotides expressing Poly-G motifs promote anti-tumor activity through the up-regulation of IL-2.
Authors: Nobuaki Kobayashi, Dennis M. Klinman, Masahiro Sasaki, Takeshi Kaneko, Yoshiaki Ishigatsubo, Hidekazu Shirota
Journal: Cancer Research (2013)

Abstract The primary goal of cancer immunotherapy is to elicit an immune response capable of eliminating the tumor. One approach towards accomplishing that goal utilizes general (rather than tumor-specific) immunomodulatory agents to boost the number and activity of pre-existing cytotoxic T lymphocytes. We find that the intra-tumoral injection of poly-G ODN has such an effect, boosting anti-tumor immunity and promoting tumor regression. The anti-tumor activity of poly-G ODN was mediated through CD8 T cells in a TLR9 independent manner. Mechanistically, poly-G ODN directly induced the phosphorylation of Lck (an essential element of the T cell signaling pathway), thereby enhancing the production of IL-2 and CD8 T cell proliferation. These findings establish poly-G ODN as a novel type of cancer immunotherapy. Citation Format: Nobuaki Kobayashi, Dennis M. Klinman, Masahiro Sasaki, Takeshi Kaneko, Yoshiaki Ishigatsubo, Hidekazu Shirota. Oligodeoxynucleotides expressing Poly-G motifs promote anti-tumor activity through the up-regulation of IL-2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 481. doi:10.1158/1538-7445.AM2013-481
Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis
Authors: Neng-Yu Lin, Alfiya Distler, Christian Beyer, Ariella Philipi-Schöbinger, Silvia Breda, Clara Dees, Michael Stock, Michal Tomcik, Andreas Niemeier, Francesco Dell'Accio, Kolja Gelse, Mark P Mattson, Georg Schett, Jörg HW Distler
Journal: Annals of the Rheumatic Diseases (2016)

Objectives Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. Methods Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. Results Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. Conclusions Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA.
Catch the drift. Assessing risk from pesticide spraying.
Authors: W Conard Holton
Journal: Environmental Health Perspectives (2000)

Sins of the FatherParentalSmoking and Childhood Cancer Exposure to passive (or environmental) tobacco smoke has been implicated in numerous childhood ailments ranging from low birth weight to middle ear disease.Passive smoke has also been suspect- ed, but not proven, to increase the risk of childhood cancer.Clarifying this issue is crucial not only for the protection of chil- dren's health but also for the fashioning of policy concerning smoking in public and private facilities.In this month's issue, Paolo Boffetta and colleagues present their meta-analysis of the results of more than 30 studies on the association between expo- sure to tobacco smoke from parental smoking during pregnancy and cancer in childhood ].The biological plausibility of the association between passive tobacco smoke and childhood cancer is based on studies that show that children do take in tobacco components-including carcino- gens and mutagens-when exposed to tobacco smoke during both gestation and childhood.Activation of procarcinogens in human fetal and placental tissues has been demonstrated, as has smoke- induced damage to DNA in human placenta.In conducting their meta-analysis, the authors searched the med- ical literature for epidemiological studies on childhood cancer where A meta-analysis of studies, though limited, indicates incras of cancer in children exposed to tobacco smoke from parental smoking9.
Fever in Immunocompromised Patients
Authors: P A Pizzo
Journal: New England Journal of Medicine (1999)

The past two decades have witnessed an increase in the number of patients who are immunocompromised as a consequence of a primary or secondary immunodeficiency disorder or from the use of agents that depress one or more components of the immune system. Broadly defined, an immunocompromised host has an alteration in phagocytic, cellular, or humoral immunity that increases the risk of an infectious complication or an opportunistic process such as a lymphoproliferative disorder or cancer.1 Patients may also be immunocompromised if they have an alteration or breach of their skin or mucosal defense barriers that permits microorganisms to cause either . . .
Spontaneous Osteogenic Sarcoma in a Stumptail (&lt;italic&gt;Macaca arctoides&lt;/italic&gt;) Monkey&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Charles F. Chesney, James R. Allen
Journal: JNCI Journal of the National Cancer Institute (1972)

A focal enlargement of the lateral surface of the maxilla was noted in a stumptail (Macaca arctoides) monkey immediately on arrival from the importer. The cancer grew for the next 15 months until the monkey was killed when mastication became difficult. Frequent clinico-pathologic examinations and biopsies were performed, but no therapeusis was attempted. The light and electron microscopic features of the growth were characteristic of an osteogenic sarcoma.
P49 Tuberculosis in Birmingham is Seasonal
Authors: GCKW Koh, G Hawthorne, H Kunst, M Dedicoat
Journal: Thorax (2012)

<h3>Background</h3> Birmingham is a large industrial city with migrant populations from Pakistan, India, Somalia and Eritrea. Central Birmingham is highly endemic for tuberculosis (TB) with an annual incidence 80 per 100,000. TB is therefore a disease of major public health importance in Birmingham. <h3>Objectives</h3> We sought to determine the contribution of seasonal variation to TB incidence in Birmingham. <h3>Methods</h3> Information was collected prospectively on all adult TB notifications for Birmingham covering the thirty-year period from 1980 to 2009. Unmeasured component models were used to decompose incidence data into seasonal and long term trends. <h3>Results</h3> There were 10,892 cases of tuberculosis notified during the study period from winter 1988/9 to autumn 2009. There was strong evidence for seasonality in tuberculosis notifications with peaks occurring every summer (Figure 1, AICD 10.5). This seasonality was apparent in both pulmonary and extra pulmonary tuberculosis (AICD 12.1 and 11.0, respectively). There was no support for seasonality in UK-born cases (AICD –12.0), but seasonality was apparent in non-UK born cases (AICD 11.8). <h3>Discussion and Conclusion</h3> TB notifications peak every summer and may plausible be linked to conditions in the preceding winter. Winter crowding may lead to increased transmission of tuberculosis, which then manifests as active TB in the summer. Alternatively, reduced exposure to sunshine during the winter and decreased vitamin D levels may result in impaired host defence to tuberculosis. The potential link between seasons and vitamin D levels is interesting, because vitamin D supplementation of at-risk populations is a plausible public health intervention.
MYOCARDIAL BRIDGING IS ASSOCIATED WITH WORSE IN-HOSPITAL OUTCOME IN PATIENTS WITH TAKOTSUBO CARDIOMYOPATHY
Authors: Ken Kato, Yuichi Saito, Yoshiaki Sakai, Iwao Ishibashi, Toshiharu Himi, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2016)
P467P2X7-MMP9 pathway in atherosclerosis: set up and characterization of ex-vivo and in vitro human vascular models
Authors: ME Mantione, M Lombardi, D Baccellieri, R Castellano, M Kamami, D Ferrara, R Chiesa, O Alfieri, C Foglieni
Journal: Cardiovascular Research (2014)

Atherosclerotic plaque rupture with thrombosis is a major cause of cardiovascular events. The natural history of plaque progression is still unknown and the plaque destabilization unpredictable. We have recently suggested that P2X7 purinergic receptor expressed in carotid plaques (CP) might play a role a role in the pathogenesis of atherosclerosis. P2X7 activation by ATP leads to a broad spectrum of effects, including membrane blebbing, tissue factor (TF)-dependent thrombosis in mice, metalloproteases (MMPs) activation and release. MMPs deregulation may alter extracellular matrix network, affect vascular smooth muscle cell (VSMC) migration, contributing to plaque rupture. To study the P2X7 pathway role in MMPs regulation and in CP progression to thrombosis we developed functional models. We setup and characterized an ex-vivo tissue culture model, using human explants from either atherosclerotic (CP) or not (internal mammary artery, IMA) vessels of patients submitted to carotid endoarterectomy or to coronary artery bypass surgery. The preservation of vascular features in ex-vivo culture was verified at different time points (from 24 hours to 15 days) by evaluating the morphology (Hematoxylin/Eosin, Movat's), and the expression of wall cells (aSMA, sm22, Vimentin, CD68, FSP1) and extracellular matrix markers (Collagen type I), of P2X7, MMP9 and TF by confocal microscopy and/or biochemistry. ATP quantification and gel zymography in tissue protein extracts and culture supernatants evaluated the metabolic activity and the MMPs-related gelatinolysis of cultured vessels. A time frame of 4 days was identified as the maximum for structurally and functionally preserved vessel ex-vivo culture; functional loss was seen at day7, morphology alteration at days 10 and 15. P2X7 and MMP9 were previously detected in CP intima-media, thus to perform targeted functional studies we obtained VSMC from ateromasic areas of CP and from IMA. IMA fragments released cells for up to 3 months, CP for up to 2 months. VSMC were characterized similarly to tissue cultures; when freshly-explanted or at passage1, VSMC displayed P2X7, MMP9 molecules expression and gelatinolytic activity. At further passages P2X7 was undetected or unmounted on membrane, MMP9 expression and gelatinolysis absent. Treatment with ATP (50-200mM, 24hours), P2X7 antagonists (KN62, A74003) affected cell metabolism and gelatinolysis but not P2X7 expression. Our data showed that CP and IMA ex-vivo cultures and primary VSMC in vitro cultures represent suitable functional models to investigate the role of P2X7-MMP9 pathway in vascular pathology.
Cancer prevention by synthetic food dyes
Authors: Gayle Orner, Michael Simonich, Ulrich Harttig, Jerry Hendricks, George Bailey
Journal: Cancer Research (2008)

3814  Synthetic food dyes are present at high levels in many foods. The average American consumes over 10 grams of these food additives each day. There is considerable public interest in potential adverse health effects of synthetic food dyes. Extensive research has been conducted to ensure that the currently approved food dyes do not cause cancer. However, the possibility that these agents might inhibit cancer has not yet been addressed. Based on their chemical structures, we hypothesized that certain synthetic food dyes may form complexes with planar chemical carcinogens and inhibit carcinogen uptake in a manner similar to that of the successful cancer chemopreventive agent chlorophyllin (CHL). Five food dyes were compared in vitro for their ability to modulate dibenzo[a,l]pyrene (DBP) and aflatoxin B1 (AFB1)-induced mutagenicity. FDA approved (FD&C) Blue No. 2 (Blue 2) and Red No. 40 (Red 40) each inhibited mutagenicity of DBP and AFB1 in bacterial reverse mutation assays. The concentration of Blue 2 producing 50% inhibition of mutagenicity (IC50) towards DBP was 12 nmol/plate. The IC50s for AFB1-induced mutagenicity were 49 and 58 nmol/plate for Red 40 and Blue 2, respectively. Blue 2 and Red 40 were then tested towards AFB1-induced carcinogenicity. Rainbow trout fry were fed diets containing 40 ppb AFB1 alone or in combination with one of the food dyes (at 2000 or 4000 ppm) for one month. Nine months later trout were sampled and livers examined for the presence of tumors. AFB1-induced tumor incidence was significantly inhibited by co-treatment with either Red 40 (2000 ppm) or Blue 2 (2000 or 4000 ppm). Protection provided by the food dyes was comparable to that provided by 2000 ppm CHL. These results suggest that the synthetic food dyes Blue 2 and Red 40 may be effective cancer preventive agents.
Importance of Lateral and Steric Stabilization of Polyelectrolyte Gene Delivery Vectors for Extended Systemic Circulation
Authors: David Oupicky, Manfred Ogris, Kenneth A. Howard, Philip R. Dash, Karel Ulbrich, Leonard W. Seymour
Journal: Molecular Therapy (2002)

Gene therapy for systemic diseases requires intravenous administration, but existing vectors are not suitable for systemic delivery, often showing rapid elimination from the bloodstream that restricts potential transfection sites to "first-pass" organs. To develop long-circulating vectors, here we have compared polyplexes containing DNA and poly-L-lysine (PLL) or polyethylenimine (PEI), surface-modified with either monovalent polyethylene glycol (PEG) or multivalent copolymers of <i>N</i>-(2-hydroxypropyl)methacrylamide (PHPMA), correlating their biophysical properties with their distribution following intravenous injection. A key difference between the two types of coating is the introduction of lateral stabilization by surface attachment of multivalent PHPMA, in addition to the steric stabilization provided by both types of polymers. The α-half-life for bloodstream clearance of polycation/DNA polyplexes (typically <5 minutes in mice) could be extended using multivalent PHPMA coating to >90 minutes. We found that the dose administered, as well as the amount and molecular weight of the coating PHPMA, had important effects on circulation properties. Multivalent PHPMA coating allows, for the first time, considerably extended circulation time using polyplex systems—a prerequisite for systemic gene delivery.
Abstract 3877: FTSJ2, a putative ribosomal RNA methyltransferase, suppressed cell invasion and migration in cancer cell line
Authors: Cheng-Wei Lai, Ken-Yo Lin, Fang-Jiue Liou, Hsiao-Ling Chen, Ju-Chien Cheng, Chuan-Mu Chen
Journal: Cancer Research (2011)

Abstract The E. coli heat shock protein which is called ribosomal RNA large subunit methyltransferase J (RrmJ) responsible for the 2’-O-ribose methylation of A-loop U2552 in the 23S rRNA. This gene is highly conserved from Prokaryota to Eukaryota. In human, three closed homologues of RrmJ have been identified and designated as FTSJ1, FTSJ2 and FTSJ3. In this study, we characterized mammalian FTSJ2 from the amino acid sequences alignment to the mitochondrial localization, and suggested the similar function to RrmJ. The RT-PCR results showed that there were much lower FTSJ2 mRNA expression in eight hepatoma cell lines (HepG2, Hep3B, HHCM, Huh7, 22T, 59T, SK-Hep1, PLC/PRF/5) and one medulloblastoma cell line (Te671), compared with the expression level in normal liver tissue. Subsequently, after the medulloblastoma cells were transfected with FTSJ2 overexpression vector, the FTSJ2-overexpressed Te671 cells (FTSJ2/Te671) showed the inhibition effects of cell migration and invasion in vitro. In addition, this also caused the rearrangement of F-action in FTSJ2/Te671 detected by immunofluorescence. However, recent study showed that FTSJ2 may involve in tumourigenesis, and FTSJ2 gene was activated in non-small cell lung cancer. Thus, we proposed that FTSJ2 may play different roles in different tissues during tumourigenesis through the catalysis of ribosomal RNA methylation in mitochondria. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3877. doi:10.1158/1538-7445.AM2011-3877
Abstract B60: Suppressing malignant progression of prostate cancer by inhibiting expression of OPN and S100A4
Authors: Yu Zhang, Shiva S. Forootan, Christopher Foster, Youqiang Ke
Journal: Cancer Research (2009)

Abstract The potential of using OPN and S100A4 as therapeutic targets has been tested in this study. Constructs expressing short silencing RNAs targeting OPN and S100A4 respectively were transfected into DU145 cells which express high levels of both OPN and S100A4 prior to the transfection. In the two established S100A4 transfectant lines, named SDRC2 and SDRC11 respectively, the level of S100A4 was reduced by 28- and 4- fold, compared with the control. In the two OPN-suppressed transfectants, named ODRC4 and ODRC10 respectively, the expression of OPN was either reduced by 8 times or almost completely suppressed. When tested in vitro, suppression of either OPN or S100A4 significantly inhibited the tumourigenicity and invasiveness, but not the motility and proliferation rate of the cancer cells. When inoculated in nude mice, all OPN-suppressed and S100A4-suppressed transfectants produced smaller tumors compared to the control group. Tumors produced by ODRC4 cells and ODRC10 cells showed significant reduction by 6- and 2.8- times in the average size compared to the control; and the difference between the average size of the tumors produced by OPN-moderately-suppressed ODRC4 cells and that produced by OPN-highly-suppressed ODRC10 cells was significant. The average size of tumors produced by S100A4-moderately-suppressed SDRC11 cells was reduced by 7.3 times while that produced by S100A4-highly-suppressed SDRC2 cells was only mild. Western blot and immunocytochemistry staining showed that the patterns of OPN and S100A4 expressions in tumor tissues were very similar to those correspondent cell lines inoculated. These results suggested that the inhibition of either OPN or S100A4 can suppress tumourigenicity of prostate cancer cells. While the tumor sizes appeared to be reduced as the reducing level of OPN, the tumor-suppressing and the S100A4-reduction did not exhibit a linear relationship. While the maximum tumor suppression was achieved when the level of S100A4 was reduced to the level similar to that expressed in benign cells, further S100A4 suppression did not appear to have any further effect on tumor size. Separate studies on the relationship between OPN and S100A4 indicated that S100A4 and OPN may promote the development and malignancy progression of prostate cancer in a coordinated manner. Our work suggested that both S100A4 and OPN may be potential targets for tumorgenecity-suppression. Citation Information: Cancer Res 2009;69(23 Suppl):B60.