tbuckley/cabot-search huggingface dataset:
Abstract 4919: Multiplexed EGFR signaling pathway analysis in FFPE tissue using quantitative mass spectrometry
Authors: Todd Hembrough, Sheeno Thyparambil, David Krizman, Marlene Darfler, Yuhong Wei, Paul Taylor, Jiefei Tong, Nhu-An Pham, Bharat Jasani, Richard Adams, Ming-Sound Tsao, Michael Moran, Jon Burrows
Journal: Cancer Research (2011)

Abstract The epidermal growth factor receptor (EGFR) is a drug target for both small molecule and antibody therapeutics and has been approved in non small-cell lung carcinoma (NSCLC) and colorectal carcinoma (CRC) among other indications. These drugs block receptor signaling though blockade of the tyrosine kinase domain, or through inhibition of ligand binding. Current genomic tests measure receptor amplification, RNA levels, the mutation status of receptor or pathway molecules (EGFR or kRAS mutations) but no current assay can directly assess the activation state of the EGFR or its downstream signaling pathway components. Indeed, the EGFR mutation positive NSCLC tumors (thought to be constitutively active) show a high response rate to TKI therapy, but the many non responders (50% or more) demonstrate the limitation of genomic analysis. Since activation of EGFR is necessary for the response to these targeted agents, it is critical to measure what levels of receptor activation and downstream signaling determines tumor responsiveness to EGFR targeted therapies in these patients. For this reason, we have developed a panel of new diagnostic assays which measure the activation of the EGFR and key downstream signaling proteins through quantitation of the phosphorylation state of these proteins. These assays are based on the Liquid Tissue®-SRM technology platform. This approach enables relative and absolute quantification of proteins and their phosphorylation status directly in formalin fixed paraffin embedded (FFPE) tissue. We preclinically validated the multiplexed Liquid Tissue® phospho-SRM assay on formalin fixed EGF stimulated A431 cells. We followed up these in vitro studies with phospho-SRM analysis of FFPE NSCLC xenograft explants where extensive independent histopathologic and molecular characterization had been performed, allowing us to benchmark our phospho-SRM analysis with standard diagnostic analyses. We have now extended these quantitation studies by measuring the expression of EGFR and phospho-EGFR in FFPE tissues obtained from relevant human clinical trial cohorts – Gefitinib treated NSCLC and Cetuximab treated CRC. It is hoped that we will be able to correlate EGFR expression, activation and signaling in these tumors with responsiveness to EGFR targeted therapy, and to validate this assay for use as a companion diagnostic to guide therapy in both NSCLC and CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4919. doi:10.1158/1538-7445.AM2011-4919
IMPACT OF CIGARETTE SMOKING ON P2Y12 RECEPTOR BINDING ACTIVITY BEFORE AND AFTER CLOPIDOGREL THERAPY IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Jung Rae Cho, Bhaloo Desai, Michael J Haas, Fabiana Rollini, Francesco Franchi, Elisabetta Ferrante, Christopher DeGroat, Mona Bhatti, Ana Muñiz-Lozano, Antonio Tello-Montoliu, Luis A Guzman, Theodore A Bass, Dominick Angiolillo
Journal: Journal of the American College of Cardiology (2014)
Absence of nuclear factor κB inhibition by NSAIDs in hepatocytes
Authors: Nuria A. Callejas, Marta Casado, Lisardo Boscá, Paloma Martín-Sanz
Journal: Hepatology (2002)

Stimulation of fetal hepatocytes with proinflammatory cytokines and lipopolysaccharide promotes the expression of cyclooxygenase-2 (COX-2) and nitric oxide synthase-2 (NOS-2), whereas the hepatoma cell line HepG2 exhibits a behavior similar to that described for adult hepatocytes and only expresses NOS-2. The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the inflammatory onset was analyzed in these cells since in addition to the inhibition of cyclooxygenase activity, these drugs interfere with other signaling pathways related with the inflammatory response. Inhibition of nuclear factor kappaB (NF-kappaB) activation by aspirin and salicylate has been described in many cells. However, incubation of hepatic cells with salicylate, aspirin, indomethacin, ibuprofen, or 5,5-dimethyl-3(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone (DFU), a fluorinated derivative of rofecoxib, failed to impair IkappaB kinase activity, the processing of NF-kappaB, and the expression of NF-kappaB-dependent genes, such as NOS-2. Moreover, selective COX-2 inhibitors did not promote apoptosis in hepatocytes under inflammatory conditions, suggesting that prostaglandins are not required to maintain cell viability. In conclusion, these data indicate that hepatocytes are not sensitive to NF-kappaB inhibition by NSAIDs and that these drugs, especially the COX-2 selective inhibitors, do not alter cell viability.
RELATIONSHIP BETWEEN BIOMARKERS AND SUBSEQUENT ADVERSE ISCHEMIC AND BLEEDING EVENTS AFTER ST-ELEVATION MYOCARDIAL INFARCTION: A HORIZONS-AMI SUBSTUDY
Authors: Bimmer E. Claessen, Gregg W. Stone, Roxana Mehran, Bernhard Witzenbichler, Bruce R. Brodie, Witold Ruzyllo, Krzysztof Zmudka, Giulio Guagliumi, Jochen Wöhrle, Kurt Huber, Janusz Kochman, George Syros, Franz Hartmann, Irene Apostolidou, Selene Leon, George D. Dangas
Journal: Journal of the American College of Cardiology (2011)
Partial clinical response to anakinra in severe palmoplantar pustular psoriasis
Authors: M. Tauber, M. Viguier, E. Alimova, A. Petit, F. Lioté, A. Smahi, H. Bachelez
Journal: British Journal of Dermatology (2014)

Palmoplantar pustular psoriasis is a clinical psoriasis variant characterised by a high impact on quality of life and poor response to biologics approved for plaque type psoriasis.The recombinant interleukin‐1 (IL‐1) receptor antagonist anakinra has been recently used for the treatment of isolated refractory cases of generalised pustular psoriasis with contrasted results. To report the clinical response in two patients treated with anakinra as salvage therapy in two patients with severe palmoplantar pustular psoriasis refractory to currently available antipsoriatic systemic therapies. Anakinra was given subcutaneously at the daily dose of 100 mg, and clinical response was evaluated using the palmoplantar psoriasis area and severity index (PPPASI). Only partial and transient responses were observed in both patients, who had to stop anakinra due to lack of efficacy and to side effects. Anakinra appears to provide only partial clinical improvement in refractory palmoplantar pustular psoriasis. Prospective clinical studies on larger populations are warranted to investigate more accurately both efficacy and safety of IL‐1‐inhibiting strategies in pustular psoriasis.
Pathogenesis of thrombocytopenia in chronic hepatitis (CH): hepatic fibrosis plays a central role
Authors: L.E. Adinolfi, A. Andreana, M. Giordano, E.Durante Mangoni, G. Cesaro, M. Tripodi, R. Utili, E. Ragone, G. Ruggiero
Journal: Journal of Hepatology (2001)
GPs should have to take financial responsibility
Authors: D. Ruta
Journal: BMJ (2010)

What is the real aim of this white paper, Equity and Excellence: Liberating the NHS , this mother of all policy interventions? For me its ultimate purpose is almost surreptitiously inserted in just one terse bullet point on page 45, perhaps in the hope that it will pass unnoticed all the way to the statute books. It states, “GP consortia will align clinical decisions in general practice with the financial consequences of those decisions.” These reforms will fail unless GPs are legally obliged to take financial responsibility for practice budgets.

There it is: to force doctors, once and for all, to consider the opportunity costs of their day to day clinical decisions. I believe that this has been the unstated aim of every major health policy initiative since the mid-1970s. Why? Because only by getting doctors to acknowledge that NHS resources are scarce, that every clinical decision has an opportunity cost, and that they should take financial responsibility …
New Users of Metformin Are at Low Risk of Incident Cancer
Authors: Gillian Libby, Louise A. Donnelly, Peter T. Donnan, Dario R. Alessi, Andrew D. Morris, Josie M.M. Evans
Journal: Diabetes Care (2009)

OBJECTIVE The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase (AMPK). Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels. We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes. RESEARCH DESIGN AND METHODS In an observational cohort study using record-linkage databases and based in Tayside, Scotland, U.K., we identified people with type 2 diabetes who were new users of metformin in 1994–2003. We also identified a set of diabetic comparators, individually matched to the metformin users by year of diabetes diagnosis, who had never used metformin. In a survival analysis we calculated hazard ratios for diagnosis of cancer, adjusted for baseline characteristics of the two groups using Cox regression. RESULTS Cancer was diagnosed among 7.3% of 4,085 metformin users compared with 11.6% of 4,085 comparators, with median times to cancer of 3.5 and 2.6 years, respectively (P &amp;lt; 0.001). The unadjusted hazard ratio (95% CI) for cancer was 0.46 (0.40–0.53). After adjusting for sex, age, BMI, A1C, deprivation, smoking, and other drug use, there was still a significantly reduced risk of cancer associated with metformin: 0.63 (0.53–0.75). CONCLUSIONS These results suggest that metformin use may be associated with a reduced risk of cancer. A randomized trial is needed to assess whether metformin is protective in a population at high risk for cancer.
Augmentation of macrophage complement receptor function in vitro. III. C3b receptors that promote phagocytosis migrate within the plane of the macrophage plasma membrane.
Authors: F M Griffin, P J Mullinax
Journal: The Journal of Experimental Medicine (1981)

We have previously reported that treatment with a unique lymphokine enables resident mouse peritoneal macrophages to phagocytize via their complement receptors and we have presented evidence that the lymphokine act by enabling complement receptor engagement by C3b ligands to generate a phagocytic signal, thereby linking the cell surface binding event with the intracellular phagocytic machinery. In the present experiments, we used immobilized immune complexes to study the topography of C3b receptors of resident mouse peritoneal macrophages treated with the lymphokine. Our results indicate that lymphokine treatment enables the macrophages' C3b receptors to migrate within the plane of the cells' plasma membrane and that manipulations of macrophages that abrogate one response to the lymphokine, complement receptor mobility, also abrogate the other response, complement receptor-mediated phagocytosis. These findings strongly suggest that lateral mobility of a ligand-bound receptor within the macrophage plasma membrane is an essential component of the phagocytic signal. Moreover, our results indicate that the difference in complement receptor function among various populations of macrophages is not due to the expression of different types of complement receptors by the different macrophage populations but rather to a difference in the relationship of the C3b receptor with other plasma membrane or intracellular components.
"Choking Death" Booklet
Authors: Frederick J. Newirth
Journal: JAMA (1974)

To the Editor.—  The article in MEDICAL NEWS (229:746, 1974) that describes the Heimlich method of treating cafe coronary is excellent because it brings additional attention to an unnecessary and preventable fatal emergency and points out that the layman can successfully apply this rescue technique.  The article's first paragraph, however, gives the impression that this method is effective in all food inhalation emergencies. This is incorrect and unfortunate, because it tends to dispel interest in learning other methods of emergency treatment that many doctors think to be more effective, or have a long history of success in application.  There is the method developed by Drs. Eller and Haugen of Ft. Lauderdale, Fla, in which the bolus is removed by pulling the victim's tongue forward so that it can be grasped, tweezer-like, between the index and middle finger of the rescuer. This has proved effective in many emergencies. However, even this
THE SURGERY OF THE ABDOMEN, WITH SOME OF ITS RESPONSIBILITIES.Read in the Section of Medical Jurisprudence, at the Forty-first Annual Meeting of the American Medical Association, Nashville, Tenn., May, 1890.
Authors: THOMAS H. MANLEY
Journal: JAMA (1890)

(Concluded from page 625.) THE SURGICAL MANAGEMENT OF TRAUMATIC PERITONITIS. Acting on the good old maxim that "an ounce of prevention is worth a pound of cure" we have endeavored to dispense with therapeutic measures formerly in vogue, in the treatment of peritonitis, by resorting to operative interference in wounds within the abdomen, and have generally succeeded, but unfortunately, lost most of our patients. Septic infection can be absolutely prevented by flushing with antiseptic fluids, and by drainage. But reliable antiseptics are all irritants, unhappily, and leave everything they come in contact with, more prone to adhesive inflam mation than ever. Further, antiseptic flushing has been so often followed by mortal collapse, that now, many distinguished operators, have discarded it altogether. The means taken to save, then, will often destroy the patient's slender chance of recovery. Hence we must regard laparotomy under those circumstances, like a hipjoint amputation, always as
REPORT OF THE COMMITTEE ON MEDICINE OF THE KANSAS MEDICAL SOCIETY FOR 1882-83, READ AT THE MEETING IN TOPEKA MAY 15, 1883.
Authors: W. L. SCHENCK
Journal: JAMA (1883)

[Published in advance of the Transactions of the Society.] Your committee are not aware of any special progress in medicine during the year that has just closed, though the labors of many eminent men of the profession have doubtless resulted in healthful growth. Philosophers entertain different views of growth. One school believes in a continuous development resulting from natural and fixed laws; another that all great, time-enduring monuments are the result of special inspiration. Spencer says God in Nature, before all things, in all things, bringing forth by immutable law order, progress, growth. Carlyle beheld Him above Nature, inspiring anew the human soul, and thus promoting progress. To the one the event made the man; to the other, man the event. Both are in a measure correct. The perception of truth, the conception of a great event, by an earnest soul gives the seeming super-natural power that enables one man
Double-blinded, Placebo-controlled Plasmid GHRH Trial for Cancer-associated Anemia in Dogs
Authors: Angela M Bodles-Brakhop, Patricia A Brown, Melissa A Pope, Ruxandra Draghia-Akli
Journal: Molecular Therapy (2008)

The use of growth hormone releasing hormone (GHRH) plasmid-based therapy to treat companion dogs with spontaneous malignancies and anemia receiving a cancer-specific treatment was examined in a double-blinded, placebo-controlled trial. The dogs (age 10.5 +/- 2.5 years, weight 24.9 +/- 12.9 kg) received a single 0.35 mg dose of plasmid or placebo intramuscularly (i.m.), followed by electroporation (EP), and were analyzed for up to 120 days. The response rate was defined as > or = 5% increase above the nadir in the red blood cell (RBC), hemoglobin (Hb), and hematocrit (Ht) levels. Plasmid-treated dogs had at least a 7% increase in all three parameters. The initial response rates for the plasmid-treated dogs were 40.6 and 35.5%, respectively on days 40 and 60, which increased to 54.2% on day 90. Although the response rate reduced to 47.1% by day 120, it was still 22.1% higher than in the control dogs. Post-hoc analysis of the GHRH-treated group showed that responder dogs survived 84% longer, 178 +/- 26 days post-treatment, while nonresponders and controls survived for 95 +/- 16 and 97 +/- 31 days post-treatment, respectively. The quality of life, defined by 10 different parameters, dramatically improved with treatment. Overall, the possibility of a GHRH plasmid-based therapy for anemia in cancer-afflicted subjects is important enough to deserve further investigation.
Brain Abscess and Head Trauma
Authors: Arthur Winter
Journal: JAMA (1961)

TWO RECENT articles have called attention to the fact that minor head injuries can result in brain abscesses or recurrent meningitides.<sup>1, 2</sup>The interval until the onset of symptoms after the trauma may not be determined during the life of the patient and may, at first, even be designated as an "idiopathic brain abscess."<sup>3</sup> We present the following case because the type of sequence described, a minor head injury followed shortly by the onset of symptoms of a brain abscess, took place. <h3>Report of a Case</h3> A 39-year-old married woman who had previously been in good health was admitted to Newark Beth Israel Hospital on Aug. 16, 1960. While at work on Aug. 8, she had tripped, fallen, and struck the right side of her head. There was no immediate or delayed loss of consciousness following this injury. However, 24 hours after this she complained of a severe
ANTERIOR POLIOMYELITIS.REPORT OF CASE IN THE PRESENT EPIDEMIC.
Authors: J. M. WARD
Journal: JAMA (1907)

<h3>Patient.</h3> —Oct. 26, 1907, I was called to see J. L. A., a school boy, aged 9. He was a healthy child, having escaped the usual diseases of childhood. His parents are living and well; the family history is good. <h3>Present Illness.</h3> —Tuesday, October 22, at bed time, he complained of slight pain in his right ankle, which his mother attributed to a probable slight sprain acquired while gathering chestnuts with the other children after school. The next morning, Wednesday, he was rather feverish, vomited, wanted nothing to eat, but was thirsty and complained of pain in both arms, both legs and especially in his back. His mother gave him a dose of castor oil and kept him in bed. As there was no improvement, she sent for me Saturday morning. <h3>Examination.</h3> —I found him with temperature 102, pulse 96, respirations 24. He was lying with his back to the
Scavenger Receptor BI Prevents Nitric Oxide–Induced Cytotoxicity and Endotoxin-Induced Death
Authors: Xiang-An Li, Ling Guo, Reto Asmis, Mariana Nikolova-Karakashian, Eric J. Smart
Journal: Circulation Research (2006)

Nitric oxide (NO)-induced oxidative stress contributes to a variety of diseases. Although numerous mechanisms have been described controlling the production of NO, the mechanisms to prevent NO-induced cytotoxicity after NO synthesis are largely unknown. Here we report that scavenger receptor BI (SR-BI) prevents NO-induced cytotoxicity. Using CHO cell lines expressing wild-type and single-site mutant SR-BI protein, we demonstrate that SR-BI prevents NO-induced cytotoxicity and that a highly conserved CXXS redox motif is required for the anti-NO cytotoxicity activity of SR-BI. Using genetically manipulated mice, we demonstrate that SR-BI–null mice have a 3- to 4-fold increase in tyrosine nitrated proteins in aorta and liver compared with wild-type littermates, indicating that expression of SR-BI prevents peroxynitrite formation in vivo. Using lipopolysacharide (LPS)-challenged mice as an in vivo model of NO-induced cytotoxicity, we found that a single dose of LPS (120 000 U/g IP) induced 90% fatality of SR-BI–null mice within 3 days, whereas all of the wild-type littermates survived (n=20), demonstrating that SR-BI is highly protective against NO cytotoxicity in vivo. Importantly, SR-BI prevents LPS-induced death without eliminating NO production, suggesting that SR-BI prevents NO-induced cytotoxicity post-NO synthesis. Our study describes a novel observation that may shed new light on the treatment of nitric oxidative stress–associated diseases, such as septic shock.
North-South twinning in paediatric haemato-oncology: the La Mascota programme, Nicaragua
Authors: G Masera, F Baez, A Biondi, F Cavalli, V Conter, A Flores, G Fontana, F Fossati Bellani, P Lanfranco, A Malta, G Mendez, E Ocampo, C Pacheco, L Riva, A Sala, F Silva, C Sessa, G Tognoni
Journal: The Lancet (1998)
Theories in health care and research: Theories and studying the care of dying people
Authors: C. Seale
Journal: BMJ (1998)

This is the last in a series of six articles on the importance of theories and values in health research

The quality of care for dying people is often investigated by interviews with dying people, or with carers before or after the death. Conventionally the respondent's account is treated as a resource for learning about previous events. Analysis is concerned with veracity, bias, and the validity of such data. This article describes a project in which the initial analysis of interviews took this approach. Subsequently, the analysis shifted towards a view of the interview as a topic, primarily concerned with events during the interview. This article also shows how theories of language and self identity led the researchers to a questioning of accepted views about the needs of dying people and their carers.

#### Summary points

The study concerned events in the final year of life of a nationally representative sample of 639 adults who died in 1987. 1 2 Surviving relatives and others who knew the people who died were interviewed to discover their perceptions of the quality of health care. To investigate bias, relatives' accounts were compared with those of healthcare staff about the symptoms of the people who died, the number of admissions to hospital, the incidence of various procedures, the effectiveness of pain …
Platelet NAD(P)H-oxidase–generated ROS production regulates αIIbβ3-integrin activation independent of the NO/cGMP pathway
Authors: Antonija Jurak Begonja, Stepan Gambaryan, Jörg Geiger, Barsom Aktas, Miroslava Pozgajova, Bernhard Nieswandt, Ulrich Walter
Journal: Blood (2005)
Intestinal obstruction and hypothyroidism.
Authors: P. Cole, J. C. Petrie, P. D. Bewsher
Journal: BMJ (1969)

DITAiJ5OURNALis likely to be nearer the upper than the lower of these limits."The comparable ratio between affected and control patients in our original study was 3 to 1, which again suggests a bias of 2-3 to 1.
535 HIGH BILIRUBIN REDUCES CELL SURVIVAL AND DIFFERENTIATION OF PRIMARY HUMAN OSTEOBLASTS. IS THIS EFFECT APPLICABLE TO THE SERUM OF CHRONIC CHOLESTATIC PATIENTS?
Authors: S. Ruiz-Gaspà, A. Martinez-Ferrer, A. Enjuanes, P. Peris, M.J. Mertinez de Osaba, L. Alvarez, A. Monegal, A. Combalia, N. Guañnabens, A. Parés
Journal: Journal of Hepatology (2010)
New cancer society study of 1 million people to begin
Authors: Phil Gunby
Journal: JAMA (1981)

The American life-style and environment have changed dramatically in the last two decades. Have these changes had any effects, good or bad, on the incidence of various cancers and possibly some other diseases? The American Cancer Society (ACS) will try to find out by questioning 1 million women and men over the next six years. The first step is to test a basic questionnaire in Tampa, Fla, to see if it produces enough of the desired information. It was in 1959 that 68,000 ACS volunteers, directed by E. Cuyler Hammond, PhD, began the first such study of a comparable number of Americans. Data from that study, say ACS officials, suggested the following: dangers in cigarette smoking, added risk of uterine or ovarian cancer among obese women, beneficial effects of moderate exercise in cardiovascular disease prevention, and the association of sexual intercourse at an early age with increased risk of cervical