tbuckley/cabot-search huggingface dataset:
A Monoclonal Antibody that Binds Anionic Phospholipids on Tumor Blood Vessels Enhances the Antitumor Effect of Docetaxel on Human Breast Tumors in Mice
Authors: Xianming Huang, Mary Bennett, Philip E. Thorpe
Journal: Cancer Research (2005)

Abstract Anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of viable vascular endothelial cells in tumors, providing an excellent marker for tumor vascular targeting. We recently raised an IgG monoclonal antibody, 3G4, which binds to anionic phospholipids in a β2-glycoprotein I–dependent manner. It inhibited tumor growth in a variety of rodent tumor models by stimulating antibody-dependent cellular cytotoxicity toward tumor vessels. In the present study, we tested the hypothesis that docetaxel, which is known to have antivascular effects on tumors, might induce exposure of anionic phospholipids on tumor vasculature and, thus, enhance the antitumor activity of 3G4. Treatment of human umbilical vascular endothelial cells with subtoxic concentrations of docetaxel (20 pmol/L) in vitro caused anionic phospholipids to be externalized without inducing apoptosis. Docetaxel treatment of mice increased the percentage of tumor vessels that expose anionic phospholipids from 35% to 60%. No induction of phosphatidylserine was observed on vessels in normal tissues even after systemic treatment with docetaxel. Treatment of mice bearing orthotopic MDA-MB-435 human breast tumors with 3G4 plus docetaxel inhibited tumor growth by 93%. Treatment of mice bearing disseminated MDA-MB-435 tumors with 3G4 plus docetaxel reduced the average number of tumor colonies in the lungs by 93% and half the animals did not develop tumors. In both tumor models, the antitumor effect of the combination was statistically superior (P &amp;lt; 0.01) to that of docetaxel or 3G4 alone. Combination therapy reduced the tumor vessel density and plasma volume in tumors to a greater extent than did the individual drugs. The combination therapy was no more toxic to the mice than was docetaxel alone. These results indicate that, as an adjuvant therapy, 3G4 could enhance the therapeutic efficacy of docetaxel in breast cancer patients.
H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. The H-2K structure involved is coded by a single cistron defined by H-2Kb mutant mice.
Authors: R M Zinkernagel
Journal: The Journal of Experimental Medicine (1976)

Lymphocytic choriomeningitis or vaccinia virus-immune spleen cells of H-2 mutant mice carrying a point mutation in the K region (B6 H-2ba, B6 H-2bf) cannot lyse infected wild-type H-2Kb targets and vice versa. Yet, cytotoxic T cells specific for infected H-2Kba or H-2Kbf targets are generated during virus infections as shown by cold target competition experiments. The critical structure for the apparent restriction by the K or D regions of the H-2 gene complex of cytolytic interactions between T cells and virus-infected target cells are therefore each coded, at least as shown for the K region, by a single cistron. This finding is most readily accommodated within the altered self concept (postulating that T cells are specific for virus-modified self structures) but cannot exclude the possibility of a physiological interaction mechanism being responsible for the apparent H-2 restriction of virus-specific cytotoxic T cells.
Increased Risk for Depression After Breast Cancer: A Nationwide Population-Based Cohort Study of Associated Factors in Denmark, 1998-2011
Authors: Nis P. Suppli, Christoffer Johansen, Jane Christensen, Lars V. Kessing, Niels Kroman, Susanne O. Dalton
Journal: Journal of Clinical Oncology (2014)

To investigate the risk for first depression, assessed as incident hospital contacts for depression and incident use of antidepressants, among women with breast cancer.Danish national registries were used to identify 1,997,669 women with no diagnosis of cancer or a major psychiatric disorder. This cohort was followed from 1998 to 2011 for a diagnosis of breast cancer and for the two outcomes, hospital contact for depression and redeemed prescriptions for antidepressants. Rate ratios for incident hospital contacts for depression and incident use of antidepressants were estimated with Poisson regression models. Multivariable Cox regression was used to evaluate factors associated with the two outcomes among patients with breast cancer.We identified 44,494 women with breast cancer. In the first year after diagnosis, the rate ratio for a hospital contact for depression was 1.70 (95% CI 1.41 to 2.05) and that for use of antidepressants was 3.09 (95% CI 2.95 to 3.22); these rate ratios were significantly increased after 3 and 8 years, respectively. Comorbidity, node-positive disease, older age, basic and vocational educational levels, and living alone were associated with use of antidepressants.Women with breast cancer are at long-term increased risk for first depression, including both severe episodes leading to hospital contact and use of antidepressants. Clinicians should be aware that the risk is highest in women with comorbid conditions, node-positive disease, and age of 70 years or more. We found no clear association between type of surgery or adjuvant treatment and risk for depression.
A randomized, double-blind, phase II study of erlotinib with or without sunitinib for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC)
Authors: H.J.M. Groen, M.A. Socinski, F. Grossi, E. Juhasz, C. Gridelli, P. Baas, C.A. Butts, E. Chmielowska, T. Usari, P. Selaru, C. Harmon, J.A. Williams, F. Gao, L. Tye, R.C. Chao, G.R. Blumenschein
Journal: Annals of Oncology (2013)
Guidelines on the management of ascites in cirrhosis
Authors: Guruprasad P Aithal, Naaventhan Palaniyappan, Louise China, Suvi Härmälä, Lucia Macken, Jennifer M Ryan, Emilie A Wilkes, Kevin Moore, Joanna A Leithead, Peter C Hayes, Alastair J O"Brien, Sumita Verma
Journal: Gut (2020)

The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)' system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years' time.
Non-proteinuric pathways in loss of renal function in patients with type 2 diabetes
Authors: Esteban Porrini, Piero Ruggenenti, Carl Erik Mogensen, Drazenka Pongrac Barlovic, Manuel Praga, Josep M Cruzado, Radovan Hojs, Manuela Abbate, Aiko P J de Vries
Journal: The Lancet Diabetes & Endocrinology (2015)
Planning the diffusion of a neck-injury prevention programme among community rugby union coaches
Authors: Alex Donaldson, Roslyn G Poulos
Journal: British Journal of Sports Medicine (2012)

This paper describes the development of a theory-informed and evidence-informed, context-specific diffusion plan for the Mayday Safety Procedure (MSP) among community rugby coaches in regional New South Wales, Australia.Step 5 of Intervention Mapping was used to plan strategies to enhance MSP adoption and implementation.Coaches were identified as the primary MSP adopters and implementers within a system including administrators, players and referees. A local advisory group was established to ensure context relevance. Performance objectives (eg, attend MSP training for coaches) and determinants of adoption and implementation behaviour (eg, knowledge, beliefs, skills and environment) were identified, informed by Social Cognitive Theory. Adoption and implementation matrices were developed and change-objectives for coaches were identified (eg, skills to deliver MSP training to players). Finally, intervention methods and specific strategies (eg, coach education, social marketing and policy and by-law development) were identified based on advisory group member experience, evidence of effective coach safety behaviour-change interventions and Diffusion of Innovations theory.This is the first published example of a systematic approach to plan injury prevention programme diffusion in community sports. The key strengths of this approach were an effective researcher-practitioner partnership; actively engaging local sports administrators; targeting specific behaviour determinants, informed by theory and evidence; and taking context-related practical strengths and constraints into consideration. The major challenges were the time involved in using a systematic diffusion planning approach for the first time; and finding a planning language that was acceptable and meaningful to researchers and practitioners.
Response to Mtb Rv2628 latency antigen associates with bacterial containment
Authors: Linda Petrone, Valentina Vanini, Elisa Petruccioli, Teresa Chiacchio, Gilda Cuzzi, Kees L. M. C. Franken, Francesco Nicola Lauria, Enrico Girardi, Tom H.M. Ottenhoff, Delia Goletti
Journal: European Respiratory Journal (2012)

Introduction: Interferon(IFN)γ response to Mtb Rv2628 latency antigen is associated with latent tuberculosis infection (LTBI). Immune response against Rv2628 may contribute to evaluate Mtb infection control.  Aims: To compare the Rv2628 specific response in recent contacts of patients with active TB before, during and after isoniazid prophylaxis.  Methods: In this cross-sectional study we evaluated 139 QuantiFERON TB-Gold In-Tube (QFT-IT) positive contacts: 37 enrolled at baseline, 32 during prophylaxis, 17 at the end of prophylaxis, 53 after 1 year of prophylaxis completion. Whole blood IFNγ response to Rv2628 and QFT-IT (early phase antigens) at day 1 post-culture was evaluated. Controls unexposed to Mtb were also included.  Results: IFNγ levels in response to Rv2628 antigen were significantly higher at baseline than after 1 year prophylaxis completion (p  Conclusions: Whole blood IFNγ response to Rv2628 antigen is significantly reduced in QFT-IT-positive contacts after 1 year prophylaxis completion. Rv2628 is considered a latency antigen therefore it is unclear at the moment if the decreasing response is due to the fact that prophylaxis allows Mtb eradication and a consequent decrease in latency responses, or whether prophylaxis inhibits Mtb to remain in a latent stage. These results may be helpful to better characterize LTBI immune response and to generate tools to monitor prophylaxis efficacy.
Reaping the Benefits of Biomedical Research: Partnerships Required
Authors: Lili M. Portilla, Barbara Alving
Journal: Science Translational Medicine (2010)

Reaping the benefits of investments in biomedical research can be achieved most efficiently through active collaboration among industry, academia, government, and nonprofit organizations. The National Institutes of Health (NIH) are exploring multiple ways in which to increase the efficiency of the translational process. Investigators involved in the NIH-funded Clinical and Translational Science Awards are developing public-private partnerships, addressing the barriers to collaboration, training the next generation of interdisciplinary team-oriented researchers, and producing open-source tools for collaboration. NIH is engaging with industry through the Foundation for the NIH and the Small Business Innovation Research Awards.
Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase
Authors: Olivier Feron, Chantal Dessy, Stephane Moniotte, Jean-Pierre Desager, Jean-Luc Balligand
Journal: Journal of Clinical Investigation (1999)

Hypercholesterolemia is a central pathogenic factor of endothelial dysfunction caused in part by an impairment of endothelial nitric oxide (NO) production through mechanisms that remain poorly characterized. The activity of the endothelial isoform of NO synthase (eNOS) was recently shown to be modulated by its reciprocal interactions with the stimulatory Ca2+–calmodulin complex and the inhibitory protein caveolin. We examined whether hypercholesterolemia may reduce NO production through alteration of this regulatory equilibrium. Bovine aortic endothelial cells were cultured in the presence of serum obtained from normocholesterolemic (NC) or hypercholesterolemic (HC) human volunteers. Exposure of endothelial cells to the HC serum upregulated caveolin abundance without any measurable effect on eNOS protein levels. This effect of HC serum was associated with an impairment of basal NO release paralleled by an increase in inhibitory caveolin–eNOS complex formation. Similar treatment with HC serum significantly attenuated the NO production stimulated by the calcium ionophore A23187. Accordingly, higher calmodulin levels were required to disrupt the enhanced caveolin–eNOS heterocomplex from HC serum–treated cells. Finally, cell exposure to the low-density lipoprotein (LDL) fraction alone dose-dependently reproduced the inhibition of basal and stimulated NO release, as well as the upregulation of caveolin expression and its heterocomplex formation with eNOS, which were unaffected by cotreatment with antioxidants. Together, our data establish a new mechanism for the cholesterol-induced impairment of NO production through the modulation of caveolin abundance in endothelial cells, a mechanism that may participate in the pathogenesis of endothelial dysfunction and the proatherogenic effects of hypercholesterolemia.
The stomach in health and disease
Authors: R H Hunt, M Camilleri, S E Crowe, E M El-Omar, J G Fox, E J Kuipers, P Malfertheiner, K E L McColl, D M Pritchard, M Rugge, A Sonnenberg, K Sugano, J Tack
Journal: Gut (2015)

The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by <i>Helicobacter pylori</i> infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. <i>H. pylori</i>-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that <i>a healthy stomach is the gateway to a healthy and balanced host</i>. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.
LSC 2012 abstract - Systemic inflammation and vascular disorders in patients with combined flow of chronic obstructive pulmonary disease and arterial hypertension
Authors: Vitaliy Krivenko
Journal: European Respiratory Journal (2012)

Objective: To study systemic inflammation and vascular disorders in patients with combined flow and chronic obstructive pulmonary disease (COPD) and arterial hypertension (AH).  Design and method: 92 patients with COPD and combined flow of COPD and AH were examined. The first group was formed by patients with combined flow of COPD and AH (n=51), the second was formed by patients with COPD (n=41). All patients underwent general clinical examination, biochemical analysis of blood, measurement of lipid fractions, levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), ultrasound examination of common right and left carotid artery.  Results: Patients with COPD and AH had higher levels of plasma IL-6 (5.3 pg/ml; CI 95%, 3.51–8.14; p
Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application
Authors: Vindhya Koppaka, David C. Thompson, Ying Chen, Manuel Ellermann, Kyriacos C. Nicolaou, Risto O. Juvonen, Dennis Petersen, Richard A. Deitrich, Thomas D. Hurley, Vasilis Vasiliou
Journal: Pharmacological Reviews (2012)

Aldehyde dehydrogenases (ALDHs) belong to a superfamily of enzymes that play a key role in the metabolism of aldehydes of both endogenous and exogenous derivation. The human ALDH superfamily comprises 19 isozymes that possess important physiological and toxicological functions. The ALDH1A subfamily plays a pivotal role in embryogenesis and development by mediating retinoic acid signaling. ALDH2, as a key enzyme that oxidizes acetaldehyde, is crucial for alcohol metabolism. ALDH1A1 and ALDH3A1 are lens and corneal crystallins, which are essential elements of the cellular defense mechanism against ultraviolet radiation-induced damage in ocular tissues. Many ALDH isozymes are important in oxidizing reactive aldehydes derived from lipid peroxidation and thereby help maintain cellular homeostasis. Increased expression and activity of ALDH isozymes have been reported in various human cancers and are associated with cancer relapse. As a direct consequence of their significant physiological and toxicological roles, inhibitors of the ALDH enzymes have been developed to treat human diseases. This review summarizes known ALDH inhibitors, their mechanisms of action, isozyme selectivity, potency, and clinical uses. The purpose of this review is to 1) establish the current status of pharmacological inhibition of the ALDHs, 2) provide a rationale for the continued development of ALDH isozyme-selective inhibitors, and 3) identify the challenges and potential therapeutic rewards associated with the creation of such agents.
FIFA’s future activities in the fight against doping
Authors: J Dvorak, P McCrory, M D’Hooghe
Journal: British Journal of Sports Medicine (2006)

The fight against doping in sport receives considerable media interest and results in much speculation regarding the ability of athletes to compete on a level playing field. Football was one of the sports that took early leadership in this fight when the Federation Internationale de Football Association (FIFA) introduced doping controls in football in 1970 as part of a wider strategy to ensure that the results of representative matches were a fair reflection of the ability of those taking part.

As a result of the collaborative effort between FIFA and regional confederations and their member associations in conjunction with national anti-doping organisations, more than 20 000 doping controls are performed annually on football players. The overall incidence of positive doping samples for prohibited substances accounts for 0.4% of all tests. Most of the positive drug tests are due to cannabis and cocaine, the so-called social drugs. Only a few individual cases (0.07% of the positive tests in 2004) were positive for anabolic steroids, such as nandrolone and testosterone.

The majority of doping controls have been carried out in competition. FIFA, the Union of European Football Associations (UEFA), and some of the national anti-doping organisations also perform unannounced, out-of-competition controls at training venues during the football season. Prior to the 2006 FIFA World Cup being held in Germany, unannounced doping controls have been performed in the friendly matches between nations. Doping controls have also been performed during the training camps prior to the opening match on 9 June 2006. All tests to date have proved negative. UEFA has also performed unannounced testing in the 2005–06 football season in all of the teams participating in the UEFA Champions League and UEFA Cup. Ten players were randomly selected from each of the 38 European top professional teams and were subjected to testing. No …
Hypotension Due to Meprobamate Overdose
Authors: A. E. Stevens
Journal: BMJ (1960)

MEDICAL MEMORANDA MBprmSH1029 had started to rise just before the transfusion.The effects on uric-acid excretion were certainly not the effects of the blood transfusion per se, since control observations were made on this same patient on the three days following his second transfusion (also of 2,500 ml. of fresh blood) in August, 1958.On this occasion the uric-acid excretion on the three days after transfusion was 573, 548, and 715 mg./24 hours-that is, a greatly increased amount, sharply contrasted with the abrupt fall after the first transfusion (illustrated in the Chart).Further work is needed, particularly since there may be fallacies in relying on the results of uric-acid studies.It is remotely possible, for example, that accelerated uricolysis (Bien et al., 1956) could entirely explain the observations made in this patient.However, this would entail a rate of uricolysis exceeding 60% of the normal daily production-a rate which has not yet been shown to occur in human beings.The simplest explanation is that acute reduction in the rate of normal white-cell destruction was the first event, which, by tilting the balance in favour of the normal cell population, produced a temporary clinical and haematological remission.
Trends in Length of Stay and Short-term Outcomes Among Medicare Patients Hospitalized for Heart Failure, 1993-2006
Authors: Héctor Bueno
Journal: JAMA (2010)

2][3][4][5][6] Advances in the care of patients with HF, including drugs such as angiotensin-converting enzyme inhibitors, ␤-blockers or aldosterone antagonists, and cardiac device-related therapies such as implantable defibrillators or resynchronization, accrue benefits to patients after months or years of therapy.No parallel progress in the acute drug or procedural treatment of patients with HF has occurred.The reduction in hospital length of stay could have reduced the risk of hospital-associated adverse events.Conversely, shortening the time in the hospital could have led to more adverse events in the period early after dis-
Drug points: Hypersensitivity reaction to balsalazide
Authors: V Adhiyaman, A Vaishnavi, S Froese
Journal: BMJ (2001)

Balsalazide is used in short term and maintenance treatment of ulcerative colitis. It is a prodrug in which 5-aminosalicylic acid is linked via a diazo bond to 4-aminobenzoyl-β-alanine, an inert and biologically inactive carrier molecule. We report a case of a hypersensitivity reaction to balsalazide, involving pericarditis, an abnormal liver biochemistry profile, and splinter haemorrhages.