tbuckley/cabot-search huggingface dataset:
The views of doctors on their working lives: a qualitative study
Authors: Ian Watt, Sarah Nettleton, Roger Burrows
Journal: Journal of the Royal Society of Medicine (2008)

Summary Objective To describe doctors' views on, and responses to, their professional working lives in the UK National Health Service (NHS). Design Qualitative study using semi structured interviews. Setting Two district hospitals and primary care settings in the North of England. Participants Fifty-two doctors participated in the study – 47 worked in hospital and five worked in general practice. Main outcome measures Qualitative information regarding doctors' views on their working lives. Results The study provided insights into the views of their working lives of a sample of doctors in the NHS. Feelings they articulated contained a number of ambivalences. Feelings about the future were coloured by concerns about the impact of regulatory changes and processes of modernization on the experiential knowledge of doctors. Conclusions These insights into doctors' views of their working lives might usefully inform those involved in the planning and overseeing of changes to health service structures and systems.
Bronchodilator combinations for COPD: real hopes or a new Pandora’s box?
Authors: Nicolas Roche, Pascal Chanez
Journal: European Respiratory Journal (2013)

The SHINE study describes the effect of dual vs single bronchodilation in COPD, but what does this mean for patients?http://ow.ly/plAHX Rationale for bronchodilator combinations in COPDWhile bronchodilators are considered the cornerstone of COPD pharmacological treatment, there is a clear pharmacological rationale for combining b 2 -agonists and anti-muscarinic agents, as recently reviewed [7].
GSTM1 and GSTP1 and respiratory health in asthmatic children exposed to ozone
Authors: I. Romieu, M. Ramirez-Aguilar, J. J. Sienra-Monge, H. Moreno-Macias, B. E. del Rio-Navarro, G. David, J. Marzec, M. Hernandez-Avila, S. London
Journal: European Respiratory Journal (2006)

Acute exposure to ozone has been related to a wide spectrum of health effects in susceptible individuals. Genetic factors may influence interindividual variation in ozone response. The current authors investigated the relationships between common polymorphisms in two genes involved in response to oxidative stress, i.e. glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), and both respiratory symptoms and lung function in response to ozone among childhood asthmatics. A total of 151 asthmatic children, who were participants in a randomised controlled trial of antioxidant vitamin supplementation in Mexico City, were studied. Children were genotyped using PCR methods and followed from October 1998-April 2000. Increases in reported breathing difficulty were associated with ozone exposure in children with GSTM1 null (8%, 95% confidence interval (CI) 1-15%, per 20-ppb increase in 1-h maximum daily average over 7 days) or GSTP1 Valine/Valine (Val/Val) genotypes (14%, 95% CI 5-25%). In children with both GSTM1 null and GSTP1 Val/Val genotypes, the increase in breathing difficulty associated with a 20-ppb increase in ozone exposure was even greater (21%, 95% CI 5-39%). GSTP1 genotypes were not significantly associated with ozone-related lung function changes. In conclusion, asthmatic children with glutathione S-transferase M1 null and glutathione S-transferase P1 Valine/Valine genotypes appear more susceptible to developing respiratory symptoms related to ozone exposure.
TOBACCO DEPENDENCE TREATMENTS: Review and Prospectus
Authors: S. Shiffman, K. M. Mason, J. E. Henningfield
Journal: Annual Review of Public Health (1998)

Cigarette smoking continues to place an enormous burden on US health systems. The treatment of tobacco-dependent persons is vital to the public health, since unmitigated smoking could lead to the development of disease and premature death in as many as 20 million current smokers in the United States. Much of this tobacco-related morbidity and mortality could be prevented by the application of existing treatments, as well as newer ones. Access to safe and effective treatments was significantly expanded in 1996, when two forms of nicotine replacement therapy (NRT), the nicotine gum and patch, became available for over-the-counter sale. Expanded access has led to significantly increased utilization and quitting. Even with these advances, however, the scope of this tobacco dependence demands that we explore alternative treatment strategies, including exposure reduction therapy (ERT) as a possible option for smokers not currently making quit attempts. In this review, we present principles to guide the development of such a therapy, and for its application, should it be proven effective.
Expression and Function of Recombinant Endothelial Nitric Oxide Synthase Gene in Canine Basilar Artery
Authors: Alex F.Y. Chen, Timothy O’Brien, Masato Tsutsui, Hiroyuki Kinoshita, Vincent J. Pompili, Thomas B. Crotty, David J. Spector, Zvonimir S. Katusic
Journal: Circulation Research (1997)

Endothelial NO synthase (eNOS) is an enzyme responsible for the production of a potent vasodilator and a key regulator of vascular tone, NO. In peripheral arteries, expression of a recombinant eNOS gene increases production of NO in the blood vessel wall. This approach appears to be a promising strategy for gene therapy of cerebrovascular disease. The major objective of the present study was to determine whether a recombinant eNOS gene (AdCMVNOS) can be functionally expressed in cerebral arteries. Replication-defective recombinant adenovirus vectors encoding bovine eNOS and Escherichia coli beta-galactosidase (AdCMVLacZ) genes, driven by the cytomegalovirus promoter, were used for ex vivo gene transfer. Rings of canine basilar artery were incubated with increasing titers of the vectors in MEM. Twenty-four or forty-eight hours after gene transfer, expression and function of AdCMVNOS were evaluated by (1) immunohistochemical staining, (2) isometric tension recording, and (3) cGMP radioimmunoassay. Transfection with AdCMVNOS resulted in the expression of recombinant eNOS protein in the vascular adventitia and endothelium, associated with significantly reduced contractile responses to UTP and enhanced endothelium-dependent relaxation to calcium ionophore A23187. Basal production of cGMP was significantly increased in the transfected vessels. The reduced contractions to UTP with increased cGMP production were reversed by a NOS inhibitor, N G -monomethyl-L-arginine. Contractions to UTP or production of cGMP were not affected in arteries transfected with AdCMVLacZ reporter gene. The results of the present study represent the first successful transfer and functional expression of recombinant eNOS gene in cerebral arteries. Our findings suggest that cerebral arterial tone can be modulated by recombinant eNOS expression in the vessel wall. (Circ Res. 1997;80:327-335.)
International Union of Pharmacology. XIII. Classification of Histamine Receptors
Authors: S.J. Hill, C.R. Ganellin, H. Timmerman, J.C. Schwartz, N.P. Shankley, J.M. Young, W. Schunack, R. Levi, H.L. Haas
Journal: Pharmacological Reviews (1997)

The classification of histamine receptors has to date been based on rigorous classical pharmacological analysis, and as yet, the classification of the three histamine receptors that have been defined by this process, (i.e., the H1-, H2-, and H 3-receptors) have not been added to because of more
The Other-Race Effect in Face Processing Among African American and Caucasian Individuals With Schizophrenia
Authors: Amy E. Pinkham, Noah J. Sasson, Monica E. Calkins, Jan Richard, Paul Hughett, Raquel E. Gur, Ruben C. Gur
Journal: American Journal of Psychiatry (2008)

Objective: Studies of emotion recognition abilities in schizophrenia show greater impairment for non-Caucasians with schizophrenia compared with Caucasians. These studies, however, included only Caucasian faces as stimuli. There is evidence from healthy individuals for a performance disadvantage on face memory and emotion recognition when processing faces from a different ethnicity. The authors sought to measure the "other-race effect" in schizophrenia, which could account for previous findings and provide information about sensitivity to such social cues in patients. Method: The study included 540 participants from four groups: African Americans with schizophrenia (N=135), Caucasians with schizophrenia (N=135), African American community comparison subjects (N=135), and Caucasian community comparison subjects (N=135). All participants completed face recognition and facial emotion identification tasks that included both Caucasian and African American faces as stimuli. Results: Although comparison participants performed better than individuals with schizophrenia across all tasks, both comparison participants and participants with schizophrenia exhibited a strong and significant other-race effect for face memory and emotion recognition. The magnitude of the other-race effect did not differ between these two groups. Conclusions: These findings reveal an intact other-race effect in patients with schizophrenia and highlight a methodological concern in the measurement of face processing abilities in schizophrenia, namely, that findings of greater impairment in African American patients are spurious when Caucasian faces are used as stimuli. Despite overall impairments in face memory and emotion recognition, the presence of a normative other-race effect in schizophrenia may reflect typical experiences with faces during development.
Subnormal activation of phagocytes by complement in chronic inflammatory bowel disease? Neutrophil chemotaxis to complement split product C5a.
Authors: J Elmgreen
Journal: Gut (1984)

The capacity of circulating phagocytes for activation by complement was investigated in consecutive, untreated cases of chronic inflammatory bowel disease. The major complement derived chemotactic factor, C5a, served as chemoattractant in dose response studies of neutrophil chemotaxis. A similar, significantly decreased sensitivity and peak response was revealed in patients with Crohn's disease and ulcerative colitis. This subnormal function of neutrophils could be shown even in cases of complete clinical remission. Chemotactic response to casein and spontaneous motility was within the normal range showing an unaffected basic cell function of neutrophils in the patients. The study shows a dysfunction of phagocytic cells, related to potentially important phlogistic mediators, in chronic inflammatory bowel disease.
Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis
Authors: Jonathan Cools-Lartigue, Jonathan Spicer, Braedon McDonald, Stephen Gowing, Simon Chow, Betty Giannias, France Bourdeau, Paul Kubes, Lorenzo Ferri
Journal: Journal of Clinical Investigation (2013)

The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.
RNAdjuvant®, a novel, highly-potent RNA-based adjuvant, combines strong immunostimulatory capacities with a favorable safety profile
Authors: Regina Heidenreich, Keyvan Mehr, Janine Noth, Sven Koch, Henoch Hong, Karl Melber, Angelika Daehling, Tilmann Roos, Johannes Lutz, Aleksandra Kowalczyk, Patrick Baumhof, Birgit Scheel, Söhnke Voss, Karl-Josef Kallen, Mariola Fotin-Mleczek, Ulrike Gnad-Vogt
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Purified recombinant proteins and peptides, which are currently under development in various anti-cancer vaccination approaches, lack sufficient immunogenicity. Therefore, potent adjuvants are needed to induce strong and persistent anti-tumor immunity. However, currently only few
Eosinophilic inflammation in sputum of poorly controlled asthmatics
Authors: M. Romagnoli, I. Vachier, P. Tarodo de la Fuente, H. Meziane, C. Chavis, J. Bousquet, P. Godard, P. Chanez
Journal: European Respiratory Journal (2002)

Despite full effective treatment, asthmatic patients often present with poorly controlled asthma. Airway eosinophilia is associated with asthma, but its relationship with asthma control is still undetermined. To investigate the relationship between airway eosinophilia and asthma control, cellular and biochemical markers of airway inflammation were measured in 19 subjects with poorly controlled asthma, 16 subjects with asthma under control and eight normal volunteers. The severity of asthma was mild-to-moderate persistent in 23 patients (14 poorly controlled) and severe prednisone-dependent in 12 subjects (five poorly controlled). Induced sputum was analysed for total and differential cell counts, leukotriene E4 (LTE<sub>4</sub>), eosinophil cationic protein (ECP), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin (IL)-8. Sputum eosinophils, LTE<sub>4</sub>, ECP and RANTES levels (but not IL-8) were significantly higher in patients with poorly controlled asthma as compared to patients with controlled asthma. By contrast, sputum cells and sputum inflammatory markers were not different among groups of patients with different severity of asthma. These results suggest that sputum eosinophilia is associated with poorly controlled asthma rather than with the severity of asthma.
Tumor Cell Death and ATP Release Prime Dendritic Cells and Efficient Anticancer Immunity
Authors: Laetitia Aymeric, Lionel Apetoh, François Ghiringhelli, Antoine Tesniere, Isabelle Martins, Guido Kroemer, Mark J. Smyth, Laurence Zitvogel
Journal: Cancer Research (2010)

Abstract By destroying tumor cells, conventional anticancer therapies may stimulate the host immune system to eliminate residual disease. Anthracyclines, oxaliplatin, and ionizing irradiation activate a type of tumor cell death that elicits efficient anticancer immune responses depending on interferon γ (IFNγ) and the IFNγ receptor. Thus, dying tumor cells emit danger signals that are perceived by dendritic cells (DC), which link innate and cognate immune responses. Recently, we observed that ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1β (IL-1β). IL-1β then is required for the adequate polarization of IFNγ-producing CD8+ T cells. These results imply a novel danger signal, ATP, and a novel receptor, P2RX7, in the chemotherapy-elicited anticancer immune response. Cancer Res; 70(3); 855–8
Sniff nasal inspiratory pressure as a marker of respiratory function in motor neuron disease
Authors: M.B. Chaudri, C. Liu, L. Watson, D. Jefferson, W.J. Kinnear
Journal: European Respiratory Journal (2000)

Vital capacity (VC) and maximum mouth pressures are often used to monitor respiratory function in motor neuron disease (MND), but require the use of a mouthpiece. Sniff nasal inspiratory pressure (SNIP) is a simple and reliable means of measuring inspiratory muscle strength; it does not involve the use of a mouthpiece and might therefore be better than VC or mouth pressures for assessing patients with bulbar disease. SNIP, maximum inspiratory (MIP) and expiratory mouth pressure (MEP), VC and arterial carbon dioxide tension (Pa,CO2) were measured in 59 consecutive patients attending a specialist MND clinic. Thirty-one had bulbar involvement on clinical grounds. Both SNIP and VC were inversely related to Pa,CO2 in nonbulbar patients only. Neither MIP nor MEP were related to Pa,CO2. The 10 patients with an elevated Pa,CO2 (&gt;6 kPa) had significantly lower SNIP and VC than normocapnic patients. Sniff nasal inspiratory pressure can be used to monitor respiratory function in motor neuron disease. It is quick and easy for patients to perform, but otherwise appears to offer little advantage over vital capacity measurement. Patients with bulbar disease are often poor at performing sniff nasal inspiratory pressure manoeuvres, possibly because of upper airway collapse or inability to close the mouth completely during the manoeuvre.
Syncytia Induction Enhances the Oncolytic Potential of Vesicular Stomatitis Virus in Virotherapy for Cancer
Authors: Oliver Ebert, Katsunori Shinozaki, Chryssanthi Kournioti, Man-Seong Park, Adolfo García-Sastre, Savio L. C. Woo
Journal: Cancer Research (2004)

Abstract Vesicular stomatitis virus (VSV) selectively replicates in tumor but not in normal cells and is being developed as an oncolytic agent for cancer therapy. Here we report the construction of a recombinant VSV capable of inducing syncytia formation between tumor cells through membrane fusion at neutral pH, which led to enhanced oncolytic properties against multifocal hepatocellular carcinoma (HCC) in the livers of immunocompetent rats. Recombinant VSV vectors were constructed by insertion into their genome a transcription unit expressing a control or fusion protein derived from Newcastle disease virus. In vitro characterization of the recombinant fusogenic VSV vector on human and rat HCC cells showed extensive syncytia formation and significantly enhanced cytotoxic effects. In vivo, administration of fusogenic VSV into the hepatic artery of Buffalo rats bearing syngeneic multifocal HCC lesions in their livers resulted in syncytia formation exclusively within the tumors, and there was no collateral damage to the neighboring hepatic parenchyma. The fusogenic VSV also conferred a significant survival advantage over a nonfusogenic control virus in the treated animals (P = 0.0078, log-rank test). The results suggest that fusogenic VSV can be developed into an effective and safe therapeutic agent for cancer treatment in patients, including those with multifocal HCC in the liver.
BRCA1 and BRCA2 Mutation Frequency in Women Evaluated in a Breast Cancer Risk Evaluation Clinic
Authors: Helen A. Shih, Fergus J. Couch, Katherine L. Nathanson, M. Anne Blackwood, Timothy R. Rebbeck, Katrina A. Armstrong, Kathleen Calzone, Jill Stopfer, Sheila Seal, Michael R. Stratton, Barbara L. Weber
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine the prevalence of BRCA1 and BRCA2 mutations in families identified in a breast cancer risk evaluation clinic. PATIENTS AND METHODS: One hundred sixty-four families seeking breast cancer risk evaluation were screened for coding region mutations in BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis and DNA sequencing. RESULTS: Mutations were identified in 37 families (22.6%); 28 (17.1%) had BRCA1 mutations and nine (5.5%) had BRCA2 mutations. The Ashkenazi Jewish founder mutations 185delAG and 5382insC (BRCA1) were found in 10 families (6.1%). However, 6174delT (BRCA2) was found in only one family (0.6%) despite estimates of equal frequency in the Ashkenazi population. In contrast to other series, the average age of breast cancer diagnosis was earlier in BRCA2 mutation carriers (32.1 years) than in women with BRCA1 mutations (37.6 years, P = .028). BRCA1 mutations were detected in 20 (45.5%) of 44 families with ovarian cancer and 12 (75%) of 16 families with both breast and ovarian cancer in a single individual. Significantly fewer BRCA2 mutations (two [4.5%] of 44) were detected in families with ovarian cancer (P = .01). Eight families had male breast cancer; one had a BRCA1 mutation and three had BRCA2 mutations. CONCLUSION: BRCA1 mutations were three times more prevalent than BRCA2 mutations. Breast cancer diagnosis before 50 years of age, ovarian cancer, breast and ovarian cancer in a single individual, and male breast cancer were all significantly more common in families with BRCA1 and BRCA2 mutations, but none of these factors distinguished between BRCA1 and BRCA2 mutations. Evidence for reduced breast cancer penetrance associated with the BRCA2 mutation 6174delT was noted.
Human hepatic stellate cells are resistant to apoptosis: implications for human fibrogenic liver disease
Authors: N Kawada
Journal: Gut (2005)

IL-12 receptor b1 (IL12Rb1) subunit.IL-23 promotes the development of a pathogenic T lymphocyte population described as T H -17, distinct from T H 1 and T H 2, which is characterized by and TNF production.23 Therefore, it is possible that antagonism of IFN-c signalling may have a more restricted effect compared with antagonism of IL-12p40 (antagonising both IL-12 and IL-23) and antagonism of TNF (fig 2).In addition, blockade of IFN-c may enhance the development of T H 17 effector cells.Chronic inflammation is a nexus of pathways, and multipoint blockade may be necessary to increase clinical efficacy. Futher clinical trial experience with anti-IL-12p40 and anti-IFN-c is necessary to determine which one of these monoclonal antibodies prove to be more effective in the treatment of inflammatory bowel disease, including CD and UC.
P19. Immunomodulation of blasts in AML-patients (pts) with clinically approved response modifiers to improve anti leukaemic T-cell reactivity: an ex vivo simulation of the clinical situation
Authors: H Schmetzer, Z Stankova, D Deen, A Hirn, Y Vokac, T Kroell, R Buhmann, A Hausmann, C Schmid, J Tischer
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Allogenic SCT/DLI are promising T-cell based therapies to cure AML-pts. Antileukaemic T-cell-reactivity has to be improved/re-established in pts in vivo. Ex vivo leukaemia-derived DC (DCleu) are the most effective antileukaemic T-cell-stimulators. We generated DCleu ex vivo from
Matrix metalloproteinase genetic polymorphisms in premature coronary artery disease
Authors: Samuele Nanni, Giovanni Melandri, Roeland Hanemaaijer, Vittorio Cervi, Luciana Tomasi, Annalisa Altimari, Pierluigi Tricoci, Chiara Melloni, Angelo Branzi
Journal: Journal of the American College of Cardiology (2003)
Serum Xylosyltransferase Activity in Diabetic Patients as a Possible Marker of Reduced Proteoglycan Biosynthesis
Authors: Christian Götting, Joachim Kuhn, Knut Kleesiek
Journal: Diabetes Care (2008)

Proteoglycan metabolism is altered in diabetic patients. The xylosyltransferases (XTs) are the initial and rate-limiting enzymes in the biosynthesis of the glycosaminoglycan chains in proteoglycans. Here, we analyzed whether the changed proteoglycan metabolism leads to altered serum XT levels in diabetic patients.Serum XT activity was determined in 100 diabetic patients and 100 blood donors using a novel high-performance liquid chromatography electrospray ionization tandem mass spectrometry assay.Serum XT activities in male and female diabetic patients were significantly decreased compared with those in the corresponding normoglycemic control subjects (mean +/- SD: male patients, 19.3 +/- 4.44 mU/l; male nondiabetic control subjects, 26.6 +/- 2.79 mU/l; female patients, 18.9 +/- 3.14 mU/l; female nondiabetic control subjects, 21.8 +/- 3.74 mU/l; P < 0.0001). No significant differences were detected between patients with type 1 and type 2 diabetes.Our data show decreased XT activity in patients with diabetes, a disease that is accompanied by an altered proteoglycan biosynthesis.