tbuckley/cabot-search huggingface dataset:
Determining the Absolute Requirement of G Protein–Coupled Receptor Kinase 5 for Pathological Cardiac Hypertrophy
Authors: Jessica I. Gold, Erhe Gao, Xiying Shang, Richard T. Premont, Walter J. Koch
Journal: Circulation Research (2012)

Rationale: Heart failure (HF) is often the end phase of maladaptive cardiac hypertrophy. A contributing factor is activation of a hypertrophic gene expression program controlled by decreased class II histone deacetylase (HDAC) transcriptional repression via HDAC phosphorylation. Cardiac-specific overexpression of G proteinen–coupled receptor kinase-5 (GRK5) has previously been shown to possess nuclear activity as a HDAC5 kinase, promoting an intolerance to in vivo ventricular pressure overload; however, its endogenous requirement in adaptive and maladaptive hypertrophy remains unknown. Objective: We used mouse models with global or cardiomyocyte-specific GRK5 gene deletion to determine the absolute requirement of endogenous GRK5 for cardiac hypertrophy and HF development after chronic hypertrophic stimuli. Methods and Results: Mice with global deletion of GRK5 were subjected to transverse aortic constriction. At 12 weeks, these mice showed attenuated hypertrophy, remodeling, and hypertrophic gene transcription along with preserved cardiac function. Global GRK5 deletion also diminished hypertrophy and related gene expression due to chronic phenylephrine infusion. We then generated mice with conditional, cardiac-specific deletion of GRK5 that also demonstrated similar protection from pathological cardiac hypertrophy and HF after transverse aortic constriction. Conclusions: These results define myocyte GRK5 as a critical regulator of pathological cardiac growth after ventricular pressure overload, supporting its role as an endogenous (patho)-physiological HDAC kinase. Further, these results define GRK5 as a potential therapeutic target to limit HF development after hypertrophic stress.
Trichlorethylene – Relationship of Metabolite Levels to Atmospheric Concentrations: Preliminary Communication
Authors: G F Smith
Journal: Journal of the Royal Society of Medicine (1978)

The search for a practical index of trichlorethylene exposure must take into account its degree of narcotic activity in turn related to air concentration. Trichloracetic acid level in urine provides a useful means of assessing exposure and it can be related to trichlorethylene in air. A small investigation of this relationship has been carried out on two continuously exposed subjects.
Twenty top papers—the ones that got away and the results of the top six poll
Authors: David Payne
Journal: BMJ (2015)

Many thanks to all our readers, authors, friends, and colleagues past and present who nominated their most memorable paper for this article.1

Sadly we couldn’t include everybody because of the “20” theme, but I wanted to mention this nomination by Utah medical librarian Mike Nielson. Mike is great at giving us constructive feedback about the website (he often notices when things aren’t working before we do).

Mike’s nomination is about feedback. After GP Craig Brown’s wife died of a secondary brain tumour, he and his family had concerns about her care and decided to complain. At first his children had mixed feelings about this. They feared it would remind them of a bad experience and have no effect. Brown wanted to make a “compassionate complaint” and to avoid projecting his family’s …
Reduced Prevalence of the Lucké Renal Adenocarcinoma in Populations of Rana pipiens in Minnesota2
Authors: Robert G. McKinnell, Eville Gorham, Frank B. Martin, John W. Schaad
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Reduced Prevalence of the Lucké Renal Adenocarcinoma in Populations of Rana pipiens in Minnesota Get access Robert G. McKinnell, Robert G. McKinnell 3Department of Genetics and Cell Biology, University of Minnesota, St. Paul, Minn. 55108. Search for other works by this author on: Oxford Academic PubMed Google Scholar Eville Gorham, Eville Gorham 4Department of Ecology and Behavioral Biology, University of Minnesota. Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank B. Martin, Frank B. Martin 5Statistical Center, University of Minnesota. Search for other works by this author on: Oxford Academic PubMed Google Scholar John W. Schaad, IV John W. Schaad, IV 3Department of Genetics and Cell Biology, University of Minnesota, St. Paul, Minn. 55108. 6We thank Mr. Floyd A. Hennagir and Mr. Phil Economon, Minnesota Department of Natural Resources, St. Paul Minn., for information about frog abundance. Mr. Gib Hedstrom, Alexandria, Minn., gave us valuable advice concerning collecting sites. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 3, September 1979, Pages 821–824, https://doi.org/10.1093/jnci/63.3.821 Published: 01 September 1979 Article history Received: 16 November 1978 Accepted: 07 February 1979 Published: 01 September 1979
Infliximab efficiency and failure
Authors: A P Rozin
Journal: Annals of the Rheumatic Diseases (2004)

I would like to comment on an interesting letter in the Annals about anti-tumour necrosis factor (TNF) monotherapy for giant cell arteritis (GCA).1 The suggestion that vasculitis may be cured by anti-TNF treatment may seem to be reasonable. The factors sustaining autoimmune inflammation may include new target antigen production, immune system activation, and a vicious cycle of lymphocyte cascade activation. This mechanism has been recently suggested2 after a report of long term remission (6–24 months) of Wegener’s granulomatosis as a result of infliximab treatment,3 but unfortunately, it is not relevant in this case.

The authors considered overcoming infliximab failure with an increased dose and frequency,1 but “such an approach is by no means cost effective and should not be attempted”. There is another way of dealing with a loss of infliximab efficiency, which may be explained by examining the generation of human antichimeric antibodies (HACA). The following information should be considered:
İlk Basamak Palyatif Kemoterapi ile Tedavi Edilen İleri Küçük Hücreli Dışı Akciğer Kanserli Hastalarda C-Reaktif Protein ve Sigaranın Prognostik Önemi
Authors: Andrea Koch, em> Helena Fohlin, em, Sverre Sörenson
Journal: Journal of Thoracic Oncology (2009)
Exploring the association betwen active hormonal life and the presence of emphysema/airway obstruction in female smokers
Authors: Juan Berto Botella, Juan Pablo De Torres, Javier Zulueta, Arantzazu Campo, Ana Belén Alcaide, Jorge Zagaceta, Pablo Sánchez, Pilar Rivero, Esmeralda Lopez Zalduendo
Journal: European Respiratory Journal (2013)

Introduction  Data suggest that women are more susceptible to the harmful effects of tobacco on the respiratory sistem. Little is known about the potential impact that active hormonal life could have on the presence of emphysema/airway obstruction.  Material and methods  From January 2011 untill November 2012 we recruided former and current female smokers which we performed a chest CT, lung function tests and a questionaire asking their age at menarche, age at menopause, contraceptive/hormone replacement therapy comsumption and age of initiation of smoking.  Results  Conclusions  Our data does not show an association betwen active hormonal life and emphysema/airway obstruction presence in female smokers. Larger studies should confirm our findings.
Independent development of lymphoid and histiocytic malignancies from a shared early precursor
Authors: E Waanders, K M Hebeda, E J Kamping, P J T A Groenen, A Simons, A Hoischen, M C J Jongmans, P M Hoogerbrugge, F N van Leeuwen, R P Kuiper, D M W M te Loo
Journal: Leukemia (2015)
Relationship of Hypoglycemia to Tumor Necrosis Factor Production and Antitumor Activity: Role of Glucose, Insulin, and Macrophages&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N Satomi, A Sakurai, K Haranaka
Journal: JNCI Journal of the National Cancer Institute (1985)

The role of hypoglycemia in tumor necrosis factor (TNF) production was examined. TNF was produced from sera of animals presensitized with reticuloendothelial system stimulants after lipopolysaccharide (LPS) challenge. Blood glucose was strongly reduced during TNF production. Glucose administration to presensitized mice (before LPS challenge) caused inhibition of TNF production. Exogenous insulin injection inhibited TNF production in a dose-related manner. Peritoneal exudate cells (PEC) from Propionibacterium acnes-primed mice revealed increased glucose consumption during in vitro TNF production but showed no relationship between the degree of glucose consumption and the ability to produce TNF. Insulin addition to the culture medium caused inhibition of TNF production from PEC, which indicated that insulin may block TNF production from macrophages. Administration of highly purified TNF (without concomitant LPS) induced extensive tumor necrosis but did not induce hypoglycemia; LPS induced moderate necrosis with accompanying hypoglycemia; insulin induced hypoglycemia but did not induce tumor necrosis. It is concluded that hypoglycemia does not accompany the action of TNF.
Comparison between individual- and area-level measures of socioeconomic status (SES) among French elderly women
Authors: Sofia Temam, Raphaelle Varraso, Carole Pornet, Benedicte Jacquemin, Margaux Sanchez, Françoise Clavel-Chapelon, Gregoire Rey, Stephane Rican, Nicole Le Moual
Journal: European Respiratory Journal (2014)

Associations between SES and asthma are not always consistent, partly due to the complexity of the SES assessment at individual- or area-level. A first step to better understand this point is to examine consistency between SES measures.

The aim was to define the most appropriate area-level SES in the French context by 1) measuring agreement between area-level SES 2) testing the well-known hypothesis that French elderly women with low SES have lowest probability to smoke than those with high SES.

Analyses were performed in Asthma-E3N (nested case-control study on asthma; n=19,346; mean age=70 yrs; 72% never smokers, 12% low education level (number of school years (NSY) ≤12)). Two individual (education & occupation) and 3 area-level Deprivation Index (DI) (Townsend, French European Deprivation Index (FEDI), French Deprivation Index (Fdep) defined at the smallest French area-level and classified in quintiles) were used.

According to Townsend, FEDI, Fdep, 23%, 20% and 12% of the women lived in most deprived areas, respectively. Agreement between Townsend and the 2 French DIs was slight (weighted kappa: 0.21 and 0.06, respectively) and moderate between FEDI & Fdep ( k =0.54). As expected, using individual measures, elderly women with low SES were significantly less often smokers than those with high SES (NSY ≤12 vs. >17: OR adjusted for age [CI95%]=0.40[0.35-0.46]). At area-level, significant associations were only found for the Fdep (most vs. least deprived area: 0.81[0.72-0.91]).

Fdep seems to be adapted for E3N elderly women, mostly teachers living in urban areas. Analyses will be pursued by studying associations between body mass index, alcohol intake, asthma and SES.
A review of 241 subjects who were patch tested twice: could fragrance mix I cause active sensitization?
Authors: J.M.L. White, J.P. McFadden, I.R. White
Journal: British Journal of Dermatology (2008)

Journal Article A review of 241 subjects who were patch tested twice: could fragrance mix I cause active sensitization? Get access J.M.L. White, J.M.L. White Department of Cutaneous Allergy, St John’s Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. Correspondence: Jonathan White. E‐mail: jonathanmlwhite@hotmail.com; jonathan.white@gstt.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar J.P. McFadden, J.P. McFadden Department of Cutaneous Allergy, St John’s Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar I.R. White I.R. White Department of Cutaneous Allergy, St John’s Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 3, 1 March 2008, Pages 518–521, https://doi.org/10.1111/j.1365-2133.2007.08391.x Published: 01 March 2008
Effects of Allopurinol on Gouty and Non-Gouty Uric Acid Nephropathy
Authors: M. A. Ogryzlo, M. B. Urowitz, H. M. Weber, J. B. Houpt
Journal: Annals of the Rheumatic Diseases (1966)

The kidneys are probably the only vital organs that are commonly affected by the precipitation of uric acid in patients with gout.Microscopic crystals of uric acid can sometimes be demonstrated in the collecting tubules, along with macros^opic concre- tions or calculi in the medulla and pelvis (Lichten- stein, Scott, and Levin, 1956; Talbott and Terplan, 1960; Gonick, Rubini, Gleason, and Sommers, 1965).Deposits of urate in the renal parenchyma may lead to a granulomatous reaction with foreign body giant cells and accumulations of chronic inflammatory cells, comparable to tophaceous lesions in other sites and obliterating the normal architecture.These are the more specific lesions of gouty nephropathy.Less specific, but perhaps more common, are the secondary changes affecting the renal parenchyma, generally regarded as indis- tinguishable from chronic nephritis, nephrosclerosis, or pyelonephritis.Progressive impairment of renal function with proteinuria and hypertension may reach an incidence of 25 per cent.or more.How- ever, it is the vascular complications of atherosclero- sis rather than renal insufficiency that account for the greatest mortality in gout.More dramatic than these chronic renal changes is the acute uric acid nephropathy which frequently complicates myeloproliferative disorders during oncolytic therapy (Kritzler, 1958; Greenbaum and Stone, 1959; Frei, Bentzel, Reiselbach, and Block, 1963).Such cases are usually accompanied by an acute hyperuricaemia, resulting in the flooding of the urinary tract with excessive amounts of uric acid and giving rise to varying degrees of renal tubular ob- struction or even complete urinary suppression, sometimes requiring haemodialysis (R.eiselbach, Bentzel, Cotlove, Frei, and Freireich, 1964).The present report concerns observations on
Evaluation of real time polymerase chain reaction, adenosine deaminase and interferon gamma in tubercular pleural effusions
Authors: Charanjeet Kaur, Balakrishnan Menon
Journal: European Respiratory Journal (2012)

Introduction:    Pleural effusions are a common manifestation of tuberculosis. Real Time Polymerase Chain Reaction (RT-PCR), Adenosine Deaminase (ADA) and Interferon gamma release assay (INF) provide faster results than Ziehl Neelsen (ZN) staining and Culture on LJ medium. RT-PCR is superior to conventional PCR in sensitivity, specificity with lower contamination and reduction in time to result.    Aims and Objectives:    To evaluate the sensitivity of RT-PCR, ADA and INF in cases of pleural effusions due to tuberculosis.    Methods:    RT-PCR was performed in 168 patients of tubercular pleural effusions. All patients had positive Mantoux test with high protein and lymphocyte predominance in effusion.  RT-PCR was performed by detecting amplification reaction for the insert element IS6110 of the  Mycobacterium tuberculosis  complex (Biotub-QT, Biotools Labs, Spain) using a real-time centrifugal amplifcation system (Rotor-Gene 3000, Corbett Research, Australia).  ADA was estimated by enzymatic method (BQ Kits, San Diego, USA) and INF was measured using Quantiferon TB Gold kit from Cellestis Ltd, USA on Automated ELISA Reader (TECAN, Minilyzer)    Results:    RT-PCR was positive in 154 of the 168 cases of tubercular pleural effusions (Sensitivity 91.67%). ADA showed high positivity in 162 of 168 cases (sensitivity 96.42%). INF showed sensitivity of 69.64% (positive in 117 of 168 cases).  The sensitivity of ZN staining in tubercular pleural effusion was 13.10%, Culture for AFB by LJ medium was 31.55% and BACTEC was 57.14%.    Conclusion:    Real time PCR provides rapid diagnosis of tubercular pleural effusions. The diagnostic efficiency could be increased by combining RT-PCR with ADA.
Particulate matter induces the expression of procoagulant microparticles by human monocytic cells
Authors: Tommaso Neri, Federica Rota, Silvia Petrini, Yuri Carmazzi, Cristina Balia, Valentina Scalise, Roberto Pedrinelli, Valentina Bollati, Alessandro Celi
Journal: European Respiratory Journal (2014)

Background:  Cell derived microparticles (MP), ranging in size between 0.05 and 1 μm, are phospholipid vesicles involved in blood coagulation and inflammation. Cell activation and apoptosis can lead to MP formation; while the mechanisms that lead to MP formation are not completely elucidated, intracellular calcium mobilization is known to be involved. Particulate matter (PM) is a mixture of solid and liquid particles suspended in the air, originated from a variety of sources. Exposure to PM has been associated with increased cardiopulmonary morbidity and mortality. The observation that PM induces cytosolic calcium mobilization is consistent with the hypothesis that PM induces the generation of MP.   Aim:  To investigate whether PM induces the generation of procoagulant MP by the human monocytic cell line,THP-1.   Methods:  THP-1 were incubated with PM. PM treatments were performed using SRM1648a (Standard Reference Material,  National Institute of Standards and Technology).The presence of MP was evaluated through a prothrombinase assay; MP-associated tissue factor activity was assessed by a onestage clotting assay.   Resuts:  1h PM treatment induces a dose-dependent increase in MP generation and 4h treatment induces an increase of MP-associated tissue factor activity (fig 1 a,b)  .   Conclusions: PM-mediated generation of procoagulant MP might help to understand the possible correlation between PM exposure and cardiopulmonary diseases.
Phenotypes of asthma seen in secondary care clinics of the Welsh Valleys
Authors: Ahsan Mughal, Alexandra Cormack, Faye Sheel, Kirsty Hett, Samantha Cahill, Sadiyah Hand, John Geen
Journal: European Respiratory Journal (2013)

INTRODUCTION  Asthma is a heterogeneous disease. A number of different asthma phenotypes have been described. Poor socio-economic status (SES) is associated with increased asthma severity. Poor SES may also be associated with specific asthma phenotypes.  AIM  The aim of this study is to ascertain different phenotypes of asthma managed in secondary care asthma clinics in a poor socio-economic area in South Wales UK.  METHODS  After obtaining ethical approval, consecutive patients seen in clinic with secondary care diagnosis of Asthma were consented and included into the study. Information was gathered on atopic status, exacerbations and BMI. Asthma severity was based on Global Initiative for Asthma (GINA) classification. Welsh index of multiple deprivation (WIMD) was used to assess SES. See  for definitions.  RESULTS  87 asthmatics (61 females 28 males) have been included into the study so far, 67% (58) were atopic and 33%( 29) were non-atopic. Male gender was associated with atopy OR 3.81 (95 % CI 1.17 to 12.44) p 0.02. Atopic asthmatics were likely to have severe GINA class OR 4.09 (95% CI 1.47-11.34) p 0.009 and exacerbation prone phenotype OR 3.00 (95% CI 1.17-7.75) p 0.02. Patients with BMI over 30 were found to have exacerbation prone asthma OR 2.59 (95% CI 1.04-6.47) p 0.03 but were not found to have severe GINA score OR 0.96 (95% CI 0.36-2.59) p 0.57  CONCLUSION  In our socially deprived cohort, atopy and obesity were associated with exacerbation prone asthma phenotypes. Atopy was also associated with severe GINA class.
Antibody-Dependent, Cell-Mediated Cytotoxicity With Autochthonous Lymphocytes and Sera After Infection With Moloney Sarcoma Virus2
Authors: E.W. Lamon, P. Hale, H.D. Whitten
Journal: JNCI Journal of the National Cancer Institute (1976)

Antibody-dependent, cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was analyzed in terms of the ability of autochthonous antibody to induce or potentiate cytotoxicity by lymphocytes from animals infected with MSV. As previously demonstrated in microcytotoxicity assays, the lymphocytes from regressor animals taken 30 days after virus infection were consistently more cytotoxic than those from tumor-bearing animals 15 days after infection. Antisera from the regressors potentiated the activity of regressor lymphocytes from the same animals. Also, antisera from tumor bearers, 15 days after virus injection, induced cytotoxicity by the animals' autochthonous lymphocytes which, by themselves, were not cytotoxic. In an independent assay for antibody, both groups of sera produced cytotoxicity by control nonimmune lymphocytes. Specificity controls indicated that both antibody and lymphocytes were required for the induction of cytotoxicity against the target cells in vitro. Normal sera placed on the target cells in the same concentrations induced no cytotoxicity by the immune lymphocytes, and immune sera alone placed on the target cells caused no cytotoxicity. The cooperative actiVity between antibody and lymphocytes may be a factor that accounts for the observed high incidence of spontaneous tumor regression.
Safety and efficacy of auto-titrating noninvasive ventilation in COPD and obstructive sleep apnoea overlap syndrome
Authors: Patrick B. Murphy, Gill Arbane, Michelle Ramsay, Eui-Sik Suh, Swapna Mandal, Deepak Jayaram, Susannah Leaver, Michael I. Polkey, Nick Hart
Journal: European Respiratory Journal (2015)

The deleterious effects of comorbid chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) have long been recognised and are frequently encountered as a clinical scenario [1, 2]. Although continuous positive airways pressure can be used in order to abolish upper airways obstruction in OSA, it can have adverse effects on pulmonary mechanics in patients with airways obstruction [3]. Auto-titrating modes of noninvasive ventilation (NIV) that monitor tidal volume, respiratory rate and upper airway patency and can vary back up rate, inspiratory and expiratory positive airway pressure (IPAP and EPAP, respectively) may have clinical benefits. However, these auto-titration modes and the software algorithms driving the ventilators are being engineered and modified at a rapid rate. The clinician, therefore, needs to be reassured that these novel modes have an established safety and efficacy profile. We hypothesised that auto-titrating NIV would enhance overnight gas exchange, sleep quality, and patient comfort when compared to standard fixed-level NIV in COPD-OSA patients with chronic respiratory failure. Auto-titrating NIV controls sleep disordered breathing and augments patient sleep comfort in COPD-OSA overlap http://ow.ly/NtL24
Durability of hematopoiesis following autografting with peripheral blood hematopoietic progenitors
Authors: S. Siena, M. Bregni, M. Di Nicola, F. Ravagnani, F. Peccatori, L. Gandola, F. Lombardi, C. Tarella, G. Bonadonna, A.M. Gianni
Journal: Annals of Oncology (1994)
A Survey of Psychiatrists in Boston and Their Work with Violent Patients
Authors: KENNETH J. TARDIFF
Journal: American Journal of Psychiatry (1974)

A survey indicated that fewer than half the psychiatrists in Boston evaluate or treat violent patients. Psychiatrists working with violent patients tended to be under 40 years of age and in residency training. Patterns of treatment, suggestions for prevention of violent episodes, types of patients, and sources of referral are described. The author suggests ways to encourage work with violent patients as well as future areas for research.