tbuckley/cabot-search huggingface dataset:
Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression
Authors: Maïté Rielland, David J. Cantor, Richard Graveline, Cristina Hajdu, Lisa Mara, Beatriz de Diego Diaz, George Miller, Gregory David
Journal: Journal of Clinical Investigation (2014)

Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional therapeutic approaches. We previously demonstrated that the histone deacetylase–associated protein SIN3B is essential for oncogene-induced senescence in cultured cells. Here, using a mouse model of pancreatic cancer, we have demonstrated that SIN3B is required for activated KRAS-induced senescence in vivo. Surprisingly, impaired senescence as the result of genetic inactivation of Sin3B was associated with delayed PDAC progression and correlated with an impaired inflammatory response. In murine and human pancreatic cells and tissues, levels of SIN3B correlated with KRAS-induced production of IL-1α. Furthermore, evaluation of human pancreatic tissue and cancer cells revealed that Sin3B was decreased in control and PDAC samples, compared with samples from patients with pancreatic inflammation. These results indicate that senescence-associated inflammation positively correlates with PDAC progression and suggest that SIN3B has potential as a therapeutic target for inhibiting inflammation-driven tumorigenesis.
Observations on Cardiac Arrythmias during Laparoscopy
Authors: D. B. Scott, D. G. Julian
Journal: BMJ (1972)

The incidence of cardiac arrhythmias occurring during laparoscopy was studied in 100 consecutive patients who received carbon dioxide to inflate the abdomen and compared with that in 45 patients in whom nitrous oxide was substituted for carbon dioxide. Seventeen patients receiving carbon dioxide and two receiving nitrous oxide developed multiple arrhythmias, the commonest variety being fusion beats due to ventricular ectopic beats. Blood gas determinations showed that carbon dioxide caused a significantly higher level of Paco(2) and a lower pH than did nitrous oxide.
Railroading in retinal vessels
Authors: P. D. L. John
Journal: BMJ (1967)

Bence Jones protein indicates further dedifferentiation " (misprinted as " differentia- tion " under Fig. 2).5 Irrespective of the proportion catabolized, Bence Jones proteinuria seems to carry a worse prognosis.I hope this has clarified the issue.-Iam, etc.,
ANALYSIS OF THE EXPERIMENTAL LESION OF CONNECTIVE TISSUE PRODUCED BY A COMPLEX OF C POLYSACCHARIDE FROM GROUP A STREPTOCOCCI
Authors: John H. Schwab
Journal: The Journal of Experimental Medicine (1962)

Specific antibody and a glucosaminidase enzyme react with the serologically active sites on C polysaccharide, and local injection of these reagents will neutralize the toxic effect of C polysaccharide complexes even after an interval of 24 to 72 hours. The cell wall lysins in S. albus filtrate and from phage-lysed Group C streptococci, break down the cell wall structure of Group A streptococci but leave the serological reactive sites of the C polysaccharide intact. These reagents lose much of their ability to neutralize the C polysaccharide toxin when superinjected after an interval of 4 hours following toxin injections. Toxic C polysaccharide cannot be recovered from an injection site by intercellular perfusion of the excised skin area after an interval of 1 to 4 hours following toxin injection. It is concluded that toxic particles of C polysaccharide complexes combine firmly with the dermal tissue of rabbits within 1 to 4 hours following intracutaneous injection. The cell wall lysins neutralize the toxin by reducing the particle size of C polysaccharide complexes. This minimum particle size is required for the initial reaction with tissue and when this has occurred these reagents are no longer able to influence the development of the lesion.
5-HYDROXYINDOLE COMPOUNDS IN THE CEREBROSPINAL FLUID OF PATIENTS WITH PSYCHIATRIC OR NEUROLOGICAL DISEASES
Authors: G.W. Ashcroft, T.B.B. Crawford, D. Eccleston, D.F. Sharman, ElizabethJ. Macdougall, J.B. Stanton, J.K. Binns
Journal: The Lancet (1966)
Risk factors for human hantavirus infection: Franco-Belgian collaborative case-control study during 1995-6 epidemic
Authors: N S Crowcroft, A Infuso, D Ilef, B Le Guenno, J-C Desenclos, F Van Loock, J Clement
Journal: BMJ (1999)

I is the presence or absence of significant intrinsic sympathomimetic activity, and S is the presence or absence of significant cardioselectivity.Similarly, is a constant, describes the overall treatment effect, describes the effect of intrinsic sympathomimetic activity, and describes the effect of cardioselectivity.
Physiological units and behavioral elements: Dynamic brains relate to dynamic behavior
Authors: Andreas Keil, Thomas Elbert
Journal: Behavioral and Brain Sciences (2000)

Nunez is to be applauded for putting forward a theoretical brain model. In order to improve any model it needs to be experimentally testable. The model presented in the target article suffers from insufficient clarity as to how new experimental designs could be derived. This is a consequence of neglecting the purpose of the brain, which is to produce effective and adaptive behavior. It might be possible to overcome this drawback by including Hebb-based modeling.
IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications
Authors: Anna Vardi, Andreas Agathangelidis, Lesley-Ann Sutton, Maria Chatzouli, Lydia Scarfò, Larry Mansouri, Vassiliki Douka, Achilles Anagnostopoulos, Nikos Darzentas, Richard Rosenquist, Paolo Ghia, Chrysoula Belessi, Kostas Stamatopoulos
Journal: Clinical Cancer Research (2013)

Immunoglobulin G-switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires.Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively.G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of (i) overuse of the IGHV4-34 and IGHV4-39 genes and (ii) differential somatic hypermutation (SHM) load. Repertoire differences were also found when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and #8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior.G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated.
Abstract 5150: JMJD3 suppresses progression of colorectal carcinoma by regulating cell cycle and anti-apoptosis
Authors: Ryuma Tokunaga, Shigeki Nakagawa, Yasuo Sakamoto, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba
Journal: Cancer Research (2014)

Abstract Background: JMJD3 has been known to play important roles in transcriptional regulation and cell proliferation by demethylating histone3 lysin27 (H3K27) in various cancers. However, the mechanism underlying JMJD3-mediated transcriptional regulation and the relation with prognosis were unclear in colorectal carcinoma. Here, we investigated the expression of JMJD3 in clinical samples and the function of JMJD3 in colorectal carcinoma cell lines. Methods: Quantitative real-time PCR were performed to check the expression of JMJD3 mRNA using the carcinoma and normal colorectal tissue in 14 colorectal carcinoma patients who underwent a curative surgery. In vitro analysis, we investigated the expression of JMJD3 in colorectal carcinoma cell lines by Western Blotting, and we knocked down the expression of JMJD3 by using small interfering RNA in Colo201 and colo320. The influence of JMJD3 on cell growth, apoptosis and cell cycle was assessed by growth assay, apoptosis assay and cell cycle analysis. We checked the changes of cell cycle related genes by real time PCR. Results: In clinical samples, the expression of JMJD3 in carcinoma tissue was significantly lower than in normal tissue (P=0.02). In vitro analysis, we knocked down the expression of JMJD3 by siRNA targeting JMJD3 and checked the reduction on mRNA and protein level. Knockdown of JMJD3 significantly increased cell proliferation (P=0.02), reduced apoptosis (P=0.003), and increased G2/M phase population (P = 0.05) which was detected by FACS. Moreover, knockdown of JMJD3 significantly decreased the expression of p15INK4B in quantitative real-time PCR. Conclusion: We showed the expression of JMJD3 in carcinoma tissue was lower than in normal tissue and demonstrated that the down-regulation of JMJD3 resulted in the increase of cell proliferation, acceleration of cell cycle and anti-apoptosis in vitro analysis. These results suggest that JMJD3 is a tumor suppressor gene for colorectal carcinoma. Note: This abstract was not presented at the meeting. Citation Format: Ryuma Tokunaga, Shigeki Nakagawa, Yasuo Sakamoto, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. JMJD3 suppresses progression of colorectal carcinoma by regulating cell cycle and anti-apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5150. doi:10.1158/1538-7445.AM2014-5150
Pethidine and the Triple Response
Authors: B. L. Finer, M. W. Partington
Journal: BMJ (1953)

CLOSTRIDIAL MYOSITIS BJmo-431 the organism being a normal inhabitant of the intestinal tract of man.The customary brief skin " cleansing " with alcohol would not be sufficient to kill spores.Alternatively, the organism may have been present in any of the injection solutions or apparatus; proof of this is impossible to obtain.SummaryMyositis due to Clostridium welchii infection was found in the region of injections of sodium sulphathiazole at the post-mortem examination of a man who died of acute coronary thrombosis.It is believed that the very alkaline solution of sulphathiazole was responsible for muscle necrosis, and that accidentally introduced infection of a necrotic focus led to gas-gangrene.The possible source of the infection is mentioned, and some simple experiments in the culture of Cl. welchii at vary- ing pH values are described.
Authors' reply to Hull
Authors: J. Hollowell, E. Schroeder, S. Petrou, P. Brocklehurst
Journal: BMJ (2012)

Hull criticises Birthplace as flawed because it did not deal with questions about antepartum stillbirth and elective caesareans.1 2 We agree that maternity service configuration requires evidence about a broad range of issues; however, this study was commissioned to answer a specific set of unanswered questions related to the safety of planned place of birth. The analyses to answer these questions are not …
Paradigms for Primary Prevention of Ovarian Carcinoma
Authors: M. N. Barnes, W. E. Grizzle, C. J. Grubbs, E. E. Partridge
Journal: CA A Cancer Journal for Clinicians (2002)

Objective: To provide the clinician with current concepts regarding prevention of ovarian cancer. Specifically, in this review, we provide a rationale for chemoprevention of ovarian cancer, a description of promising chemopreventive agents, and an overview of surgical strategies used in the prevention of ovarian cancer. Data Sources: A computerized search of articles published through December 2001 was performed using the MEDLINE database from the period of 1966 to present. Search terms utilized included ovarian neoplasms, primary prevention, chemoprevention, oral contraceptives, NSAIDs, retinoids, ovariectomy, and tubal sterilization. Additional sources were identified through cross-referencing. Methods of Study Selection: All identified references relevant to prevention of ovarian carcinoma were reviewed. Tabulation, Integration, and Results: Each reference was reviewed to determine the relevant contribution to the fundamental science of ovarian cancer prevention. Particular attention was paid to those studies that offered insight into the development of translational trials in ovarian cancer chemoprevention. Conclusions: Investigation into chemoprevention for ovarian cancer represents a vastly underdeveloped area of research. Continued research efforts toward identification of novel compounds will accelerate the progress of clinical trials in this neglected area of investigation.
Abstract 2032: A novel function of WW domain binding protein 2 (WBP2) in regulating cytoskeletal function and cellular division through binding to co-chaperone BAG3
Authors: Andrea K. McCollum, Mathew G. Angelos, Andrea D. Fischione, Marco Mineo, Elise C. Kohn
Journal: Cancer Research (2012)

Abstract BAG3, a BAG co-chaperone family member, co-localizes with actin microfilaments and influences processes that involve actin function, including adhesion and migration. Because actin function regulates cell division, we hypothesized that the BAG3 WW-domain regulates cellular division through its cytoskeletal association. We show that BAG3 co-localizes with leading lamellipodia exclusively during G2 and mitosis phases. Co-immunoprecipitation of BAG3 and pulldown of GST-tagged BAG3 WW-domain confirmed that BAG3 WW-domain association with actin increased during G2 and mitosis relative to asynchronous cells. Deletion of the BAG3 WW-domain caused an abnormal cellular morphology, degenerate F-actin organization, longer doubling time (p&amp;lt;0.05, n=4), and three-fold increase in polynucleated cells relative to empty vector and full length-BAG3 (FL-BAG3; p&amp;lt;0.001, n=3). We confirmed polyploidy development and absence of cytokinesis in αWW-BAG3 cells by live-cell imaging, and observed mitotic delay relative to control and FL-BAG3 cells. To identify a potential regulation mechanism for BAG3-actin binding, we identified WBP2 as a novel BAG3 WW domain interacting protein in a yeast two-hybrid assay. BAG3 and WBP2 co-immunoprecipitated only in G1 and S phases, indicating cell cycle-specific BAG3-WBP2 binding. WBP2 silencing caused indiscriminate BAG3 co-immunoprecipitation with actin across all cell cycle phases, suggesting that association with WBP2 prevents BAG3-actin binding. We are the first to identify a function for WBP2, which our data show regulates BAG3 WW-domain association with actin in a cell cycle-specific manner. Because actin dysfunction has been proposed to contribute to chromosomal instability and tumor formation, the WW-domain of BAG3 is a potential target to reduce abnormal cell division. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2032. doi:1538-7445.AM2012-2032
'Lox on neovascularization': leukotrienes as mediators in endothelial biology
Authors: D. G.M. Molin, N. M.S. van den Akker, M. J. Post
Journal: Cardiovascular Research (2010)

Leukotrienes comprise the 5-lipoxygenase (5-LOX)-derived family of short-lived lipid mediators that modulate inflammatory cell reactivity and vascular function under both physiological and pathophysiological conditions (for overview, see Poeckel and Funk1). The leukotriene LTA4 is synthesized from arachidonic acid by 5-LOX in conjunction with 5-LOX-activation protein (FLAP; Figure 1A ). Next, LTA4 is converted by LTA4 hydrolase to LTB4, or by LTC4 synthase to LTC4, which through hydrolysis can give rise to LTD4 and LTE4, respectively. BLT1/2 and CysLT1/2 are the main leukotriene receptors that specifically bind the respective leukotriene LTB4 and the cysteinyl leukotrienes LTC4, LTD4, and LTE4. Upon activation, both BLT and CysLT activate a G-protein response (via Gq and Gi), eliciting a potent increase in intracellular calcium levels and a decrease in cyclic AMP levels, and initiating kinase activation (i.e. ERK1/2) and cellular responses such as differentiation, migration, and chemotaxis ( Figure 1B ).



Figure 1 
( A ) Overview of the 5-LOX leukotriene pathway showing the enzymes, leukotrienes, and receptor interactions. Note that LTA4 can be provided to neighbouring cells for transcellular biosynthesis. ( B ) Hypothetical model of the interplay between LTB4, 12-( S )-HETE, and the BLT receptor in endothelial-related ESCs. In this model, LTB4 can be provided by myeloid cells or endothelial precursors themselves via transcellular biosynthesis of LTA4. 12-( S )-HETE production is dependent on VEGF-A signalling and vice versa. Both 12-( S )-HETE and LTB4 can activate BLT receptors and via ERK1/2 will … 



*Corresponding author. Tel: +31 43 3881085; fax: +31 43 3884166, Email: m.post{at}fys.unimaas.nl
Statistical properties of a two-stage model of carcinogenesis.
Authors: C J Portier
Journal: Environmental Health Perspectives (1987)

Some of the statistical properties of a simple two-stage model of carcinogenesis are explored. The implications of additive treatment effects versus independent treatment effects on the shape of the dose-response curve are considered. Response that is low-dose linear results in the cases where the mutation rates are affected by dose or in the cases where treatment changes the birth rate/death rate of initiated cells in an additive fashion. Independent treatment effects lead to non-low-dose linear response when the survival of initiated cells is affected by treatment. A computer simulation experiment was performed that examined the ability of animal carcinogenesis data to differentiate between various forms of this simple two-stage model. It is shown that animal carcinogenicity experiments do not contain enough data to adequately describe the difference between these two types of effects.
Perspectives for Cancer Prevention With Natural Compounds
Authors: A.R.M. Ruhul Amin, Omer Kucuk, Fadlo R. Khuri, Dong M. Shin
Journal: Journal of Clinical Oncology (2009)

Cancer is the second leading cause of death in the United States. Despite the estimated 565,650 deaths in 2008 of Americans as a result of cancer, it is mostly a preventable disease. Simply by modification of diet, maintenance of optimum body weight, and regular physical activity, 30% to 40% of all instances of cancer could be prevented. Modification of diet alone by increasing vegetable and fruit intake could prevent 20% or more of all cases of cancer and may potentially prevent approximately 200,000 cancer-related deaths annually. Because of their safety, low toxicity, antioxidant properties, and general acceptance as dietary supplements, fruits, vegetables, and other dietary elements (phytochemicals and minerals) are being investigated for the prevention of cancer. Extensive research over the past several decades has identified numerous dietary and botanical natural compounds that have chemopreventive potential. In this review, we discuss promising natural chemopreventive compounds, their molecular targets, and their mechanisms, which may help the further design and conduct of preclinical and clinical trials.
Increased mortality among Danish women: population based register study
Authors: K. Juel
Journal: BMJ (2000)

annually.This is about 35 US cents (23 pence) per capita and is considerably less than the 18 US dollars per capita spent in the United States. 8 An analyst of the tobacco industry suggests that British-American Tobacco considers the market in Mauritius saturated, with little potential for increases in volume, and with no new market segments to be opened up there is limited scope for product differentiation.Limited opportunity to break the strong cultural resistance to women smoking is seen.This suggests that Mauritius has avoided massive promotional activity by tobacco companies compared with other developing nations.In the absence of this, any health promotion and legislative efforts, including tax increases, seem to have been more effective and sustained than elsewhere. 1 4 Mauritius is a rapidly developing country that has made great gains in tobacco control in the absence of the expensive antismoking campaigns seen in developed countries.It seems that a lack of excessive promotional activity by tobacco companies has led to more effective legislative and health promotion efforts.Increased taxes in conjunction with slower economic growth may have played a major part in reducing smoking behaviour.Reductions in smoking prevalence across income categories support this supposition.These observations support the premise that curbing the efforts of tobacco companies in low and middle income countries is central to initiatives for tobacco control.We thank the people of Mauritius, Australia, and Finland who have been involved in the planning and conduct of noncommunicable disease research activities in Mauritius since 1987.Contributors: HSC conceived the rationale for this paper, analysed the data, and wrote the paper.JWW assisted in data analysis and in critical review of the manuscript.MPdeC planned and coordinated the 1998 survey
Unnecessary hospitalization in a psychiatric rehabilitation unit.
Authors: K. Shotliff, A. Prasad, D. Mukherjee
Journal: BMJ (1992)

consent, as they move within the NHS, house officers may be unaware that they are not protected against prescribed diseases such as tuberculosis and hepatitis B. It may well be that Lewisham Hospital's handbook mentions the occupational health department.Luisa Dillner's review of Stress and the Medical Profession seems to confirm my views.2The pen- ultimate paragraph suggests that doctors need an accessible counselling service and an occupational health service that is geared to recognising stress.The standard and quality of occupational health services vary considerably within the NHS, but it is essential that all staff, including doctors, become more aware of the services they offer.