tbuckley/cabot-search huggingface dataset:
Current Serum Levels of 2,3,7,8-Tetrachlorodibenzo-p- dioxin in Phenoxy Acid Herbicide Applicators and Characterization of Historical Levels
Authors: E. S. Johnson, W. Parsons, C. R. Weinberg, D. L. Shore, J. Mathews, D. G. Patterson, L. L. Needham
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Workers who sprayed phenoxy acid herbicides, especially those who sprayed before 1975, may have been exposed to significant amounts of 2, 3, 7, 8-tetrachlorodi-benzo- p -dioxin (TCDD), a potent animal carcinogen present in herbicide preparations as a contaminant. Purpose : The aims of this study were ( a ) to determine serum levels of TCDD in a representative sample of workers occupationally exposed to the agent during the spraying of phenoxy acid herbicides; ( b ) to compare serum levels in workers exposed before 1965, when concentrations in herbicide products were unregulated and high, with levels in workers exposed after 1974, when concentrations were lower as a result of government regulations worldwide; and ( c ) to examine the correlation, if any, between serum levels and duration of employment in spraying. Methods : Thirty-seven subjects were randomly selected from a group of 654 men who had sprayed the herbicides 2, 4, 5-trichlorophen-oxyacetic acid (2, 4, 5-T) and 2, 4-dichlorophenoxyacetic acid (2, 4-D) in Australia for at least 12 months. The workers were classified as follows: eight who sprayed only before 1965, nine who sprayed only during the period after 1964 and before 1975, and 20 who sprayed during the period after 1974 and before 1991. Serum from the workers was analyzed for TCDD by high-resolution gas chro-matography and high-resolution mass spectrometry at a detection limit of 0.6 parts per trillion (ppt) on a lipid-weight basis. In addition, rates of exposure to TCDD were estimated, as were TCDD serum concentrations at termination of employment and intensity of herbicide use. Results : Only one worker, with a serum TCDD level of 34 ppt, had a serum level higher than the maximum level of 26 ppt reported for the general population. As suming a half-life of 7.1 years, we estimated the mean exposure rates to be 2.7, 2.3, and 0.06 ppt/mo for the three epochs, respectively. We found the highest serum level of TCDD at the time of cessation of employment to be 329 ppt. Calendar period and intensity of use of 2, 4, 5-T and 2, 4-D were statistically significant determinants of rate of exposure to TCDD, but 2, 4-D was associated with exposure rate only for the pre-1975 periods. Estimated rates prior to 1965 were more than an order of magnitude higher than those after 1974. Conclusion : The highest estimated exposure rate was 20.7 ppt/mo, which suggests that some sprayers may have been exposed to levels comparable with those that produce cancer in laboratory animals. [J Natl Cancer Inst 84: 1648–1653, 1992]
How well do we care for patients with end stage chronic obstructive pulmonary disease (COPD)? A comparison of palliative care and quality of life in COPD and lung cancer
Authors: J M Gore
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Patients with severe chronic obstructive pulmonary disease (COPD) have a poor quality of life and limited life expectancy. This study examined whether these patients were relatively disadvantaged in terms of medical and social care compared with a group with inoperable lung cancer. <h3>METHODS</h3> An open two group comparison was made of 50 patients with severe COPD (forced expiratory volume in one second (FEV<sub>1</sub>) &lt;0.75 l and at least one admission for hypercapnic respiratory failure) and 50 patients with unresectable non-small cell lung cancer (NSCLC). A multi-method design was used involving standardised quality of life tools, semi-structured interviews, and review of documentation. <h3>RESULTS</h3> The patients with COPD had significantly worse activities of daily living and physical, social, and emotional functioning than the patients with NSCLC (p&lt;0.05). The Hospital Anxiety and Depression Scale (HADS) scores suggested that 90% of patients with COPD suffered clinically relevant anxiety or depression compared with 52% of patients with NSCLC. Patients were generally satisfied with the medical care received, but only 4% in each group were formally assessed or treated for mental health problems. With regard to social support, the main difference between the groups was that, while 30% of patients with NSCLC received help from specialist palliative care services, none of the patients with COPD had access to a similar system of specialist care. Finally, patients in both groups reported a lack of information from professionals regarding diagnosis, prognosis and social support, although patients9 information needs were disparate and often conflicting. <h3>CONCLUSION</h3> This study suggests that patients with end stage COPD have significantly impaired quality of life and emotional well being which may not be as well met as those of patients with lung cancer, nor do they receive holistic care appropriate to their needs.
The cyclin D1 proto-oncogene is sequestered in the cytoplasm of mammalian cancer cell lines
Authors: John P Alao, Simon C Gamble, Alexandra V Stavropoulou, Karen M Pomeranz, Eric W-F Lam, R Charles Coombes, David M Vigushin
Journal: Molecular Cancer (2006)

Abstract Background The cyclin D1 proto-oncogene is an important regulator of G1 to S-phase transition and an important cofactor for several transcription factors in numerous cell types. Studies on neonatal cardiomyocytes and postmitotic neurons indicate that the activity of cyclin D1 may be regulated through its cytoplasmic sequestration. We have demonstrated previously, that TSA induces the ubiquitin-dependent degradation of cyclin D1 in MCF-7 breast cancer cells. Additional studies were initiated in order to further investigate the effect of TSA on cyclin D1 regulation using sub-cellular fractionation techniques. Results Our studies revealed cyclin D1 to be localized predominantly within the cytoplasmic fraction of all cell lines tested. These observations were confirmed by confocal microscopy. GSK3β was found to be localized within both the nucleus and cytoplasm throughout the cell cycle. Inhibition of GSK3β or CRM1-dependent nuclear export resulted in only modest nuclear accumulation, suggesting that the cytoplasmic localization of cyclin D1 results from the inhibition of its nuclear import. Conclusion We have shown by several different experimental approaches, that cyclin D1 is in fact a predominantly cytoplasmic protein in mammalian cancer cell lines. Recent studies have shown that the cytoplasmic sequestration of cyclin D1 prevents apoptosis in neuronal cells. Our results suggest that cytoplasmic sequestration may additionally serve to regulate cyclin D1 activity in mammalian cancer cells.
KIF5B-ALK, a Novel Fusion Oncokinase Identified by an Immunohistochemistry-based Diagnostic System for ALK-positive Lung Cancer
Authors: Kengo Takeuchi, Young Lim Choi, Yuki Togashi, Manabu Soda, Satoko Hatano, Kentaro Inamura, Shuji Takada, Toshihide Ueno, Yoshihiro Yamashita, Yukitoshi Satoh, Sakae Okumura, Ken Nakagawa, Yuichi Ishikawa, Hiroyuki Mano
Journal: Clinical Cancer Research (2009)

EML4-ALK is a transforming fusion tyrosine kinase, several isoforms of which have been identified in lung cancer. Immunohistochemical detection of EML4-ALK has proved difficult, however, likely as a result of low transcriptional activity conferred by the promoter-enhancer region of EML4. The sensitivity of EML4-ALK detection by immunohistochemistry should be increased adequately.We developed an intercalated antibody-enhanced polymer (iAEP) method that incorporates an intercalating antibody between the primary antibody to ALK and the dextran polymer-based detection reagents.Our iAEP method discriminated between tumors positive or negative for EML4-ALK in a test set of specimens. Four tumors were also found to be positive for ALK in an archive of lung adenocarcinoma (n = 130) and another 4 among fresh cases analyzed in a diagnostic laboratory. These 8 tumors were found to include 1 with EML4-ALK variant 1, 1 with variant 2, 3 with variant 3, and 2 with previously unidentified variants (designated variants 6 and 7). Inverse reverse transcription-PCR analysis revealed that the remaining tumor harbored a novel fusion in which intron 24 of KIF5B was ligated to intron 19 of ALK. Multiplex reverse transcription-PCR analysis of additional archival tumor specimens identified another case of lung adenocarcinoma positive for KIF5B-ALK.The iAEP method should prove suitable for immunohistochemical screening of tumors positive for ALK or ALK fusion proteins among pathologic archives. Coupling of PCR-based detection to the iAEP method should further facilitate the rapid identification of novel ALK fusion genes such as KIF5B-ALK.
Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma
Authors: Isabel Ben-Batalla, Alexander Schultze, Mark Wroblewski, Robert Erdmann, Michael Heuser, Jonas S. Waizenegger, Kristoffer Riecken, Mascha Binder, Denis Schewe, Stefanie Sawall, Victoria Witzke, Miguel Cubas-Cordova, Melanie Janning, Jasmin Wellbrock, Boris Fehse, Christian Hagel, Jürgen Krauter, Arnold Ganser, James B. Lorens, Walter Fiedler, Peter Carmeliet, Klaus Pantel, Carsten Bokemeyer, Sonja Loges
Journal: Blood (2013)
Blockade of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) down-regulates induction of contact sensitivity by haptenated epidermal cells
Authors: I. KATAYAMA, T. MATSUNAGA, H. YOKOZEKI, K. NISHIOKA
Journal: British Journal of Dermatology (1997)

Journal Article Blockade of costimulatory molecules B7‐1 (CD80) and B7‐2 (CD86) down‐regulates induction of contact sensitivity by haptenated epidermal cells Get access I. KATAYAMA, I. KATAYAMA Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Yushima, Bunkyo‐ku, Tokyo, Japan Dr I.Katayama, Department of Dermatology, Nagasaki University School of Medicine 1‐7‐1, Sakamoto Nagasaki, Japan 852. Search for other works by this author on: Oxford Academic Google Scholar T. MATSUNAGA, T. MATSUNAGA Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Yushima, Bunkyo‐ku, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar H. YOKOZEKI, H. YOKOZEKI Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Yushima, Bunkyo‐ku, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar K. NISHIOKA K. NISHIOKA Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Yushima, Bunkyo‐ku, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 136, Issue 6, 1 June 1997, Pages 846–852, https://doi.org/10.1046/j.1365-2133.1997.01842.x Published: 01 June 1997 Article history Accepted: 24 December 1996 Published: 01 June 1997
Relationships of immunoglobulins E and G sensitization to respiratory function in dairy farmers
Authors: V Westeel, S Julien, C De Champs, JC Polio, F Mauny, R Gibey, JJ Laplante, JM Aiache, A Depierre, JC Dalphin
Journal: European Respiratory Journal (2000)

An impairment of respiratory function has been demonstrated in dairy farmers. The objective of this study was to evaluate the relationship of allergy to respiratory function in dairy farmers in a longitudinal study conducted in the Doubs (France). A cohort of male dairy farmers constituted in 1990 was re-evalued in 1995. Subjects completed a medical and occupational questionnaire, and a spirometry test in both 1990 and 1995, in 1995 they were also subjected to immunological tests. Relationships between immunological variables and respiratory function were studied by a multiple linear regression model adjusted for age, smoking status, respiratory symptoms, altitude and occupational exposure. Amongst the 394 subjects of the initial cohort, 330 were included in the longitudinal study and 320 had immunological tests. Log immunoglobulin (Ig) E was negatively correlated with the 1995 respiratory function parameters (p&lt;0.05 for forced expiratory volume in one second (FEV1) and FEV1/vital capacity (VC). Immunoglobulin (Ig) G response to Aspergillus fumigatus detected by enzyme-linked immunosorbent assay (ELISA) was negatively correlated to 1995 respiratory function parameters (VC: p&lt;0.01; FEV1: p&lt;0.001; FEV1/VC: p&lt;0.01). There was a positive relationship between IgG antibodies against Aspergillus fumigatus and the mean annual decline in FEV1 (p&lt;0.01) and FEV1/VC (p&lt;0.01). To conclude, allergy may play a role in the impairment of respiratory function in dairy farmers of the Doubs and sensitization to Aspergillus fumigatus seems to constitute an independent risk factor for the development of airflow obstruction in this occupational setting.
Position statement—altitude training for improving team-sport players’ performance: current knowledge and unresolved issues
Authors: Olivier Girard, Markus Amann, Robert Aughey, François Billaut, David J Bishop, Pitre Bourdon, Martin Buchheit, Robert Chapman, Michel D'Hooghe, Laura A Garvican-Lewis, Christopher J Gore, Grégoire P Millet, Gregory D Roach, Charli Sargent, Philo U Saunders, Walter Schmidt, Yorck O Schumacher
Journal: British Journal of Sports Medicine (2013)

Despite the limited research on the effects of altitude (or hypoxic) training interventions on team-sport performance, players from all around the world engaged in these sports are now using altitude training more than ever before. In March 2013, an Altitude Training and Team Sports conference was held in Doha, Qatar, to establish a forum of research and practical insights into this rapidly growing field. A round-table meeting in which the panellists engaged in focused discussions concluded this conference. This has resulted in the present position statement, designed to highlight some key issues raised during the debates and to integrate the ideas into a shared conceptual framework. The present signposting document has been developed for use by support teams (coaches, performance scientists, physicians, strength and conditioning staff) and other professionals who have an interest in the practical application of altitude training for team sports. After more than four decades of research, there is still no consensus on the optimal strategies to elicit the best results from altitude training in a team-sport population. However, there are some recommended strategies discussed in this position statement to adopt for improving the acclimatisation process when training/competing at altitude and for potentially enhancing sea-level performance. It is our hope that this information will be intriguing, balanced and, more importantly, stimulating to the point that it promotes constructive discussion and serves as a guide for future research aimed at advancing the bourgeoning body of knowledge in the area of altitude training for team sports.
Appropriateness of colonoscopy in Europe (EPAGE II) – Presentation of methodology, general results, and analysis of complications
Authors: P. Juillerat, I. Peytremann-Bridevaux, J.-P. Vader, C. Arditi, S. Schusselé Filliettaz, R. Dubois, J.-J. Gonvers, F. Froehlich, B. Burnand, V. Pittet
Journal: Endoscopy (2009)

Appropriate use of colonoscopy is a key component of quality management in gastrointestinal endoscopy. In an update of a 1998 publication, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE II) defined appropriateness criteria for various colonoscopy indications. This introductory paper therefore deals with methodology, general appropriateness, and a review of colonoscopy complications.The RAND/UCLA Appropriateness Method was used to evaluate the appropriateness of various diagnostic colonoscopy indications, with 14 multidisciplinary experts using a scale from 1 (extremely inappropriate) to 9 (extremely appropriate). Evidence reported in a comprehensive updated literature review was used for these decisions. Consolidation of the ratings into three appropriateness categories (appropriate, uncertain, inappropriate) was based on the median and the heterogeneity of the votes. The experts then met to discuss areas of disagreement in the light of existing evidence, followed by a second rating round, with a subsequent third voting round on necessity criteria, using much more stringent criteria (i. e. colonoscopy is deemed mandatory).Overall, 463 indications were rated, with 55 %, 16 % and 29 % of them being judged appropriate, uncertain and inappropriate, respectively. Perforation and hemorrhage rates, as reported in 39 studies, were in general < 0.1 % and < 0.3 %, respectivelyThe updated EPAGE II criteria constitute an aid to clinical decision-making but should in no way replace individual judgment. Detailed panel results are freely available on the internet (www.epage.ch) and will thus constitute a reference source of information for clinicians.
Use of clinical syndromes to target antibiotic prescribing in seriously ill children in malaria endemic area: observational study
Authors: James A Berkley, Kathryn Maitland, Isaiah Mwangi, Caroline Ngetsa, Saleem Mwarumba, Brett S Lowe, Charles RJC Newton, Kevin Marsh, J Anthony G Scott, Mike English
Journal: BMJ (2005)

To determine how well antibiotic treatment is targeted by simple clinical syndromes and to what extent drug resistance threatens affordable antibiotics.Observational study involving a priori definition of a hierarchy of syndromic indications for antibiotic therapy derived from World Health Organization integrated management of childhood illness and inpatient guidelines and application of these rules to a prospectively collected dataset.Kilifi District Hospital, Kenya.11,847 acute paediatric admissions.Presence of invasive bacterial infection (bacteraemia or meningitis) or Plasmodium falciparum parasitaemia; antimicrobial sensitivities of isolated bacteria.6254 (53%) admissions met criteria for syndromes requiring antibiotics (sick young infants; meningitis/encephalopathy; severe malnutrition; very severe, severe, or mild pneumonia; skin or soft tissue infection): 672 (11%) had an invasive bacterial infection (80% of all invasive bacterial infections identified), and 753 (12%) died (93% of all inpatient deaths). Among P falciparum infected children with a syndromic indication for parenteral antibiotics, an invasive bacterial infection was detected in 4.0-8.8%. For the syndrome of meningitis/encephalopathy, 96/123 (76%) isolates were fully sensitive in vitro to penicillin or chloramphenicol.Simple clinical syndromes effectively target children admitted with invasive bacterial infection and those at risk of death. Malaria parasitaemia does not justify withholding empirical parenteral antibiotics. Lumbar puncture is critical to the rational use of antibiotics.
TLR7 stimulation in human plasmacytoid dendritic cells leads to the induction of early IFN-inducible genes in the absence of type I IFN
Authors: Jérémy Di Domizio, Ariane Blum, Maighread Gallagher-Gambarelli, Jean-Paul Molens, Laurence Chaperot, Joël Plumas
Journal: Blood (2009)
Outcome in hemoglobin SC disease: A four‐decade observational study of clinical, hematologic, and genetic factors
Authors: Darleen R. Powars, Alan Hiti, Emily Ramicone, Cage Johnson, Linda Chan
Journal: American Journal of Hematology (2002)

Abstract Over the past 40 years, we observed 284 subjects with hemoglobin SC disease (Hb SC) for 2,837 person‐years. We examined the association of the course of clinical events with hematologic and genetic factors. The mean entry age was 21 years, although 15% entered before one year of age. The mean Hb concentration was 11.3 g/dL, the mean fetal hemoglobin was 2.5%, and the mean MCV was 84.4 fL. Twenty‐five subjects died at a median age of 37 years. Chronic organ‐specific complications occurred in 112 subjects (39.4%), with advanced retinopathy in 65 subjects (22.9%) and osteonecrosis (avascular necrosis) in 42 subjects (14.8%). We identified the β‐globin haplotypes in 82 subjects and the α‐gene status in 79. Twenty‐nine percent had α‐thalassemia‐2. The β CI haplotype was present in 85.4%. We found a decreased incidence of retinopathy in the β CI subjects compared to the non‐β CI subjects (33% vs. 67%; P = 0.049) with a later mean onset age (29 years vs. 21 years; log‐rank test, P = 0.026). We also found a consistent pattern of decreased morbidity in subjects who had α‐thalassemia‐2 in comparison to those who did not. We found a reduced risk of chronic organ‐specific complications (log‐rank test, P = 0.003), lower incidence of sickle crisis (48% vs. 80%, P = 0.001), later onset of gallbladder disease (age of onset: 55 years vs. 34 years; P = 0.055), and lower risk of osteonecrosis (log‐rank test, P = 0.024). Our findings suggest that Hb SC subjects who have not inherited α‐thalassemia‐2 might benefit from erythrocyte rehydration therapy. Am. J. Hematol. 70:206–215, 2002. © 2002 Wiley‐Liss, Inc.
Epidemiology of appendicectomy in primary sclerosing cholangitis and ulcerative colitis: its influence on the clinical behaviour of these diseases
Authors: T H J Florin
Journal: Gut (2004)

<b>Background and aims:</b> Appendicectomy and smoking are environmental factors that are known to influence ulcerative colitis (UC). The phenotype of UC is different in patients with coexistent primary sclerosing cholangitis (PSC). This study investigates the interaction of appendicectomy and PSC on the epidemiology and clinical behaviour of colitis. <b>Methods:</b> Patients were from the Brisbane IBD Research Group database. Controls were from the Australian twin registry. Seventy eight PSC-inflammatory bowel disease (PSC-IBD) patients, 12 pure PSC, and 294 UC patients were matched with 1466 controls by sex and birth cohort that comprised randomly selected twins from each twin pair. The effects of appendicectomy, smoking, or PSC on the onset of disease, disease extent, disease severity (as identified by immunosuppression-colectomy or liver transplant), and disease related complications (high grade dysplasia, colorectal cancer, or cholangiocarcinoma) were investigated using univariate and multiple logistic regression analyses. <b>Results:</b> PSC-IBD patients had a more extensive colitis than UC patients (p&lt;0.0001) but required less immunosuppression (p = 0.007), which was independent of disease extent. They were more likely to have high grade dysplasia or colorectal cancer (p = 0.029) than UC patients. Appendicectomy rates in the PSC groups were not different from the control groups (p = 0.72, 0.76), which was in sharp contrast with UC where the rate was four times less (p = 0.0001). Prior appendicectomy appeared to be associated with an approximate five year delay in the onset of intestinal (PSC-IBD or UC) or hepatic (PSC) disease, which was independent of smoking. Appendicectomy did not independently alter the extent or severity of disease in PSC. In contrast, prior appendicectomy in UC was associated with more extensive disease but with a lesser requirement for immunosuppression or colectomy for the treatment of colitis (p = 0.004). There were trends for high grade dysplasia or colorectal cancer with appendicectomy in both PSC-IBD and UC. Although these trends were not statistically significant, colorectal cancer appeared more frequent with appendicectomy in a meta-analysis of the available UC data from this and another Australian study. <b>Conclusions:</b> In contradistinction to UC, appendicectomy did not significantly influence the prevalence of the PSC groups, or the extent of colitis in PSC-IBD, but as with UC, did appear to delay their onset. The extensive milder colitis, which is characteristic of PSC-IBD, relates to other poorly understood factors. Further prospective studies are required to determine any influence of appendicectomy on the extent of colitis in IBD and an associated dysplasia or colorectal cancer.