tbuckley/cabot-search huggingface dataset:
Loss of NAPRT1 Expression by Tumor-Specific Promoter Methylation Provides a Novel Predictive Biomarker for NAMPT Inhibitors
Authors: David S. Shames, Kristi Elkins, Kimberly Walter, Thomas Holcomb, Pan Du, Dane Mohl, Yang Xiao, Thinh Pham, Peter M. Haverty, Bianca Liederer, Xiaorong Liang, Robert L. Yauch, Thomas O'Brien, Richard Bourgon, Hartmut Koeppen, Lisa D. Belmont
Journal: Clinical Cancer Research (2013)

We sought to identify predictive biomarkers for a novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitor.We use a NAMPT inhibitor, GNE-617, to evaluate nicotinic acid rescue status in a panel of more than 400 cancer cell lines. Using correlative analysis and RNA interference (RNAi), we identify a specific biomarker for nicotinic acid rescue status. We next determine the mechanism of regulation of expression of the biomarker. Finally, we develop immunohistochemical (IHC) and DNA methylation assays and evaluate cancer tissue for prevalence of the biomarker across indications.Nicotinate phosphoribosyltransferase (NAPRT1) is necessary for nicotinic acid rescue and its expression is the major determinant of rescue status. We demonstrate that NAPRT1 promoter methylation accounts for NAPRT1 deficiency in cancer cells, and NAPRT1 methylation is predictive of rescue status in cancer cell lines. Bisulfite next-generation sequencing mapping of the NAPRT1 promoter identified tumor-specific sites of NAPRT1 DNA methylation and enabled the development of a quantitative methylation-specific PCR (QMSP) assay suitable for use on archival formalin-fixed paraffin-embedded tumor tissue.Tumor-specific promoter hypermethylation of NAPRT1 inactivates one of two NAD salvage pathways, resulting in synthetic lethality with the coadministration of a NAMPT inhibitor. NAPRT1 expression is lost due to promoter hypermethylation in most cancer types evaluated at frequencies ranging from 5% to 65%. NAPRT1-specific immunohistochemical or DNA methylation assays can be used on archival formalin paraffin-embedded cancer tissue to identify patients likely to benefit from coadministration of a Nampt inhibitor and nicotinic acid.
RAPID DIAGNOSIS OF MALARIA BY ACRIDINE ORANGE STAINING OF CENTRIFUGED PARASITES
Authors: LelandS. Rickman, Richard Oberst, Ruperto Sangalang, JeffreyD. Chulay, GaryW. Long, Arturo Cabanban, JosephI. Smith, StephenL. Hoffman
Journal: The Lancet (1989)
Effect of Weight Loss on Cardiac Synchronization and Proinflammatory Cytokines in Premenopausal Obese Women
Authors: Raffaele Marfella, Katherine Esposito, Mario Siniscalchi, Federico Cacciapuoti, Francesco Giugliano, Domenico Labriola, Myriam Ciotola, Carmen Di Palo, Lucio Misso, Dario Giugliano
Journal: Diabetes Care (2004)

Obesity is an important risk factor for heart failure in both women and men. Dyssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of heart failure. We examined the relationship of ventricular synchronization abnormalities with the concentration of proinflammatory cytokines in obese women at baseline and after sustained weight loss.Echocardiographic parameters of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women.Compared with nonobese women, obese women had increased concentrations of CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01), and IL-18 (P < 0.01). Moreover, obese women had a higher myocardial performance index (P < 0.02) and lower transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02), and ejection fraction (P < 0.05), indicating ventricular dyssynchrony. Concentrations of CRP, TNF-alpha, and IL-6 were related to anthropometric indexes of obesity and to echocardiographic parameters of ventricular dyssynchrony. After 1 year of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. This was associated with reduction of cytokine (P < 0.01) and CRP (P < 0.02) concentrations and with improvement of echocardiographic parameters of ventricular dyssynchrony, which correlated with changes in adiposity, particularly visceral adiposity.In obese women, ventricular dyssynchrony correlates with body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating cardiac function in obese women.
COMMON CHARACTERISTICS OF EPILEPSY AND SCHIZOPHRENIA: CLINICAL OBSERVATION AND DEPTH ELECTRODE STUDIES
Authors: ROBERT G. HEATH
Journal: American Journal of Psychiatry (1962)

Data presented, gathered by special techniques, add some clarification to the nature of the seemingly similar and related disease processes of schizophrenia and epilepsy. These data indicate that schizophrenia and epilepsy probably are different entities.
LOX-1 is a novel marker for peripheral artery disease in patients with type 2 diabetes
Authors: Michiaki Fukui, Muhei Tanaka, Takafumi Senmaru, Mamoru Nakanishi, Jun Mukai, Makoto Ohki, Mai Asano, Masahiro Yamazaki, Goji Hasegawa, Naoto Nakamura
Journal: Metabolism (2013)
Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial
Authors: Colin P Derdeyn, Marc I Chimowitz, Michael J Lynn, David Fiorella, Tanya N Turan, L Scott Janis, Jean Montgomery, Azhar Nizam, Bethany F Lane, Helmi L Lutsep, Stanley L Barnwell, Michael F Waters, Brian L Hoh, J Maurice Hourihane, Elad I Levy, Andrei V Alexandrov, Mark R Harrigan, David Chiu, Richard P Klucznik, Joni M Clark, Cameron G McDougall, Mark D Johnson, G Lee Pride, John R Lynch, Osama O Zaidat, Zoran Rumboldt, Harry J Cloft
Journal: The Lancet (2013)
Effect of low-dose ciclesonide on allergen-induced responses in subjects with mild allergic asthma
Authors: Gail M. Gauvreau, Louis Philippe Boulet, Dirkje S. Postma, Tomotaka Kawayama, Richard M. Watson, MyLinh Duong, Francine Deschesnes, Jan G.R. De Monchy, Paul M. O'Byrne
Journal: Journal of Allergy and Clinical Immunology (2005)
SPECIFIC IMMUNE RESPONSE GENES OF THE GUINEA PIG
Authors: Harry G. Bluestein, Ira Green, Paul H. Maurer, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1972)

The ability of guinea pigs to make immune responses to the random linear copolymer of L-glutamic acid and L-alanine, GA, and to L-glutamic acid and L-tyrosine, GT, is each controlled by a different immune response gene. On the other hand, the random linear terpolymer of L-glutamic acid, L-alanine, and L-tyrosine, GAT, which contains both GA and GT antigenic determinants, is immunogenic in all guinea pigs. After GAT immunization, all animals develop delayed hvpersensitivity and serum antibody specific for GAT. However, only those guinea pigs possessing the GA immune response gene demonstrate cross-reactive delayed hypersensitivity when challenged with GA. In addition, the anti-GAT antisera produced by those animals having the GA gene contain cross-reacting anti-GA antibodies. The sera from guinea pigs lacking the GA gene have no anti-GA antibody activity. Thus, we have demonstrated that a specific immune response gene controlling responsiveness to a "simple" antigen can determine the specificity of both cellular and humoral immune responses to a more complex antigen.
Corrigendum to “Percutaneous drainage and sclerosis of mesenteric cysts: Literature overview and report of an innovative approach” [Int. J. Surg. 12 (2014) S90–S93]
Authors: Giada Pozzi, Alessia Ferrarese, Marco Busso, Alessandro Borello, Silvia Catalano, Alessandra Surace, Silvia Marola, Valentina Gentile, Valter Martino, Mario Solej, Mario Nano
Journal: International Journal of Surgery (2015)
The immunoglobulin-like modules Cε3 and α2 are the minimal units necessary for human IgE-FcεRI interaction
Authors: Luca Vangelista, Sylvia Laffer, Robert Turek, Hans Grönlund, Wolfgang R. Sperr, Peter Valent, Annalisa Pastore, Rudolf Valenta
Journal: Journal of Clinical Investigation (1999)

Atopic allergy is a genetically determined immunodisorder that affects almost 20% of the population worldwide. Immediate symptoms of type I allergy are caused by the release of biologic mediators from effector cells induced by IgE-allergen complexes that cross-link the high-affinity receptor for IgE (FcεRI). Chronic disease manifestations result from allergen-specific T-cell activation, a process that is enhanced when allergens are presented via FcεRI-bound IgE. We report the baculovirus expression, as soluble recombinant proteins, of the minimal units required for human IgE and FcεRI interaction: Cε3 represents the third constant domain of the IgE heavy chain, and α2 is the membrane-proximal Ig-like module from FcεRIα. Native overlay experiments showed binding of human FcεRIα to recombinant Cε3 and of natural or recombinant human IgE to recombinant α2. Moreover, recombinant Cε3 inhibited binding of natural IgE antibodies to α2, and preincubation of human IgE with α2 inhibited anti-IgE–triggered histamine release from human basophils. Isolated Cε3 and α2 can now be used for the molecular and structural analysis of the IgE-FcεRI interaction, as well as for diagnostic and therapeutic applications.
Aspirations and ideals in the Olympic games
Authors: A. de Merode
Journal: JAMA (1996)

Thirty years ago, although sports medicine certainly existed, it was still on the sidelines of medical activity. The leaders of the sports world, less than receptive to this kind of activity, happily affirmed that sports teams needed nothing more than a  doctor. A costly figure who often got in the way, the team physician fought against the empiricism of coaches and ruined their credibility with his scientific theories, the value of which none of the sports leaders could understand. Sport was governed by the rules of a romantic amateurism that frowned on the professional strictness of a new generation of scientists. Sports medicine was regarded as a costly and pointless activity.  The extraordinary improvement in human performance reflected in a fabulous number of records, the increasing media focus on sports events, and the medical problems that have accompanied the sporting expansion of recent years have led sports leaders to
Weight Loss Strategies Associated With BMI in Overweight Adults With Type 2 Diabetes at Entry Into the Look AHEAD (Action for Health in Diabetes) Trial
Authors: Hollie A. Raynor, Robert W. Jeffery, Andrea M. Ruggiero, Jeanne M. Clark, Linda M. Delahanty
Journal: Diabetes Care (2008)

OBJECTIVE—Intentional weight loss is recommended for those with type 2 diabetes, but the strategies patients attempt and their effectiveness for weight management are unknown. In this investigation we describe intentional weight loss strategies used and those related to BMI in a diverse sample of overweight participants with type 2 diabetes at enrollment in the Look AHEAD (Action for Health in Diabetes) clinical trial. RESEARCH DESIGN AND METHODS—This was a cross-sectional study of baseline weight loss strategies, including self-weighing frequency, eating patterns, and weight control practices, reported in 3,063 women and 2,082 men aged 45–74 years with BMI ≥25 kg/m2. RESULTS—Less than half (41.4%) of participants self-weighed ≥1/week. Participants ate breakfast 6.0 ± 1.8 days/week, ate 5.0 ± 3.1 meals/snacks per day, and ate 1.9 ± 2.7 fast food meals/week. The three most common weight control practices (increasing fruits and vegetables, cutting out sweets, and eating less high-carbohydrate foods) were reported by ∼60% of participants for ≥20 weeks over the previous year. Adjusted models showed that self-weighing less than once per week (B = 0.83), more fast food meals consumed per week (B = 0.14), and fewer breakfast meals consumed per week (B = −0.19) were associated (P &amp;lt; 0.05) with a higher BMI (R2 = 0.24). CONCLUSIONS—Regular self-weighing and breakfast consumption, along with infrequent consumption of fast food, were related to lower BMI in the Look AHEAD study population.
Bilateral Wilms' tumor: long-term survival and some epidemiological features.
Authors: M J Coppes, J de Kraker, P J van Dijken, H J Perry, J F Delemarre, M F Tournade, J Lemerle, P A Voûte
Journal: Journal of Clinical Oncology (1989)

Sixty-seven children with a bilateral Wilms' tumor (BWT) who were registered to the International Society of Pediatric Oncology (SIOP) nephroblastoma trial and studies 1, 2, and 5, conducted between 1971 and 1980, were analyzed. The overall 10-year survival was 64%. While most deaths due to tumor occurred within 3 years after diagnosis of bilateral disease, five patients died after 3 years (20%), three with synchronous and two with metachronous BWT. The survival rates for the 42 children with synchronous BWT (follow-up time, 6 1/2 to 14 years) and the 25 children with metachronous BWT (follow-up time, 5 to 13 years) were 69% and 56%, respectively. Due to an improvement in the synchronous group, overall survival improved over the years: 47%, 72%, and 70%, in SIOP 1, 2, and 5, respectively. Age at diagnosis and most advanced tumor stage affected prognosis. Children presenting a tumor manifestation before the age of 2 years had better prognosis than older children. This difference is significant in synchronous BWT. Prognosis for children with local stage 1 or 2 was better than for those with local stage 3. Median age at initial presentation in BWT was lower than in unilateral nephroblastoma and lower in metachronous BWT than in synchronous BWT. Young children presenting with unilateral nephroblastoma should have a careful follow-up of the contralateral kidney for at least the next 3 1/2 years, as most contralateral tumors will develop during this period.
Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial
Authors: Michael Schiff, Michael E Weinblatt, Robert Valente, Désirée van der Heijde, Gustavo Citera, Ayanbola Elegbe, Michael Maldonado, Roy Fleischmann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To compare over 2 years the safety, efficacy and radiographic outcomes of subcutaneous abatacept versus adalimumab, in combination with methotrexate (MTX), in patients with rheumatoid arthritis (RA). <h3>Methods</h3> AMPLE is a phase IIIb, 2-year, randomised, investigator-blinded study with a 1-year primary endpoint. Biologic-naive patients with active RA and an inadequate response to MTX were randomised to 125 mg abatacept weekly or 40 mg adalimumab bi-weekly, both with a stable dose of MTX. <h3>Results</h3> Of 646 patients randomised, 79.2% abatacept and 74.7% adalimumab patients completed year 2. At year 2, efficacy outcomes, including radiographic, remained comparable between groups and with year 1 results. The American College Rheumatology 20, 50 and 70 responses at year 2 were 59.7%, 44.7% and 31.1% for abatacept and 60.1%, 46.6% and 29.3% for adalimumab. There were similar rates of adverse events (AEs) and serious adverse events (SAEs). More serious infections occurred with adalimumab (3.8% vs 5.8%) including two cases of tuberculosis with adalimumab. There were fewer discontinuations due to AEs (3.8% vs 9.5%), SAEs (1.6% vs 4.9%) and serious infections (0/12 vs 9/19 patients) in the abatacept group. Injection site reactions (ISRs) occurred less frequently with abatacept (4.1% vs 10.4%). <h3>Conclusions</h3> Through 2 years of blinded treatment in this first head-to-head study between biologic disease-modifying antirheumatic drugs in RA patients with an inadequate response to MTX, subcutaneous abatacept and adalimumab were similarly efficacious based on clinical, functional and radiographic outcomes. Overall, AE frequency was similar in both groups but there were less discontinuations due to AEs, SAEs, serious infections and fewer local ISRs with abatacept. <h3>ClinicalTrials.gov Identifier</h3> NCT00929864.
Longitudinal changes in gastro-oesophageal reflux from 3 months to 6 months after lung transplantation
Authors: A G N Robertson, C Ward, J P Pearson, T Small, J Lordan, A J Fisher, A J Bredenoord, J Dark, S M Griffin, P A Corris
Journal: Thorax (2009)

Gastro-oesophageal reflux (GOR) and microaspiration are implicated in the pathophysiology of asthma, chronic obstructive pulmonary disease, interstitial lung disease and chronic lung allograft dysfunction.1 2 Aspiration, which is often asymptomatic, has been identified as a treatable allograft injury that may affect mortality.1 2

The potential for thoracic mechanical changes caused by advanced lung disease to predispose to reflux has been highlighted.2 Although aspiration could cause lung damage, alternatively reflux might represent a secondary event. Longitudinal data are lacking,2 so we have undertaken a prospective study of reflux in lung transplantation. This allowed investigations in patients where thoracic mechanical changes associated with advanced lung disease had improved. We hypothesised that reflux was prevalent and could develop at different times following transplantation in patients with good allograft function.

### Methods

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Psychiatric Screening Through Multiphasic Health Testing
Authors: RICHARD E. GORDON
Journal: American Journal of Psychiatry (1971)

The author discusses automated multiphasic health testing (AMHT) and its potential value to psychiatry. He describes screening instruments and techniques being developed and tested at the University of Florida for specific use in AMHT centers. These include psychophysiological measures, blood chemical indicators of psychological state, and paper-and-pencil psychological instruments that measure psychosocial history, psychiatric symptoms, and critical social readjustments.
The sigma ligand, igmesine, inhibits cholera toxin and Escherichia coli enterotoxin induced jejunal secretion in the rat
Authors: J L Turvill, P Kasapidis, M J G Farthing
Journal: Gut (1999)

<h3>BACKGROUND</h3> Cholera toxin, and<i>Escherichia coli</i> heat labile (LT) and heat stable (STa) enterotoxins induce small intestinal secretion in part by activating enteric nerves. Igmesine is a novel sigma receptor ligand that inhibits neurally mediated secretion. <h3>AIMS</h3> To assess the antisecretory potential of igmesine in cholera toxin, LT, and STa induced water and electrolyte secretion using an in vivo rat model of jejunal perfusion. <h3>METHODS</h3> After pretreatment with igmesine, 0.03–10 mg/kg intravenously, jejunal segments of anaesthetised, adult male Wistar rats were incubated with cholera toxin (25 μg), LT (25 μg), or saline. Jejunal perfusion with a plasma electrolyte solution containing a non-absorbable marker was undertaken. In some cases 200 μg/l STa was added to the perfusate. After equilibration, net water and electrolyte movement was determined. In additional experiments rats received igmesine, intravenously or intrajejunally, after exposure to cholera toxin. <h3>RESULTS</h3> Cholera toxin induced net water secretion was inhibited by 1 mg/kg igmesine (median −120 versus −31 μl/min/g, p&lt;0.001). LT and STa induced secretion were also inhibited by 1 mg/kg igmesine (−90 versus −56, p&lt;0.03; and −76 versus −29, p&lt;0.01, respectively). Igmesine reduced established cholera toxin induced secretion. <h3>CONCLUSION</h3> The sigma ligand, igmesine, inhibits neurally mediated enterotoxigenic secretion. Its ability to inhibit established secretion makes it an agent with therapeutic potential.
Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study
Authors: Chanaki Amaratunga, Sokunthea Sreng, Seila Suon, Erika S Phelps, Kasia Stepniewska, Pharath Lim, Chongjun Zhou, Sivanna Mao, Jennifer M Anderson, Niklas Lindegardh, Hongying Jiang, Jianping Song, Xin-zhuan Su, Nicholas J White, Arjen M Dondorp, Tim JC Anderson, Michael P Fay, Jianbing Mu, Socheat Duong, Rick M Fairhurst
Journal: The Lancet Infectious Diseases (2012)
Is there a role for revascularisation in asymptomatic carotid stenosis? No
Authors: J David Spence
Journal: BMJ (2010)

<b>Marco Roffi (</b>doi:10.1136/bmj.c4898) thinks revascularisation should be the strategy of choice for patients with asymptomatic carotid stenosis but <b>J David Spence</b> argues that all but a tiny minority would do better with medical management
THE PSYCHIATRIC HOME TREATMENT SERVICE: PRELIMINARY REPORT OF FIVE YEARS OF CLINICAL EXPERIENCE
Authors: TOBIAS T. FRIEDMAN, ALVIN BECKER, LEONARD WEINER
Journal: American Journal of Psychiatry (1964)

This paper is an overview of the 6 years of existence of the Psychiatric Home Treatment Service and of the 4 clinical programs it pursued. The goal of the service was to define a new community approach to the care of those suffering from serious mental illness. An attempt was made to use home treatment as an alternative to hospitalization wherever appropriate with these patients. Of the patients referred to us, 30% did not appear to be hospital-bound. Of the remaining 70%, more than one-half could be managed outside the hospital using home treatment and/or other alternatives to hospitalization. It would seem from our experiences that a home treatment service can be a valuable facility attached to a state hospital, but perhaps could be even more valuable as an integral part of every community mental health center.
Septic arthritis due to Pasteurella multocida complicating rheumatoid arthritis.
Authors: R A Williams, W J Fincham
Journal: Annals of the Rheumatic Diseases (1979)

A patient with rheumatoid arthritis treated with corticosteroids developed a septic arthritis of her right knee. She had been bitten on her right leg by her pet cat 2 weeks earlier. Pasteurella multocida, resistant to penicillin, was isolated from the septic joint and from the oropharynx of the cat. The arthritis was successfully treated with ampicillin. No attempt to eradicate the organism from the cat was made because of the expectation of early recolonisation.
The Antimetastatic Role of Thrombomodulin Expression in Islet Cell-Derived Tumors and Its Diagnostic Value
Authors: Satoshi Iino, Kazuhiro Abeyama, Ko-ichi Kawahara, Munekazu Yamakuchi, Teruto Hashiguchi, Sumika Matsukita, Suguru Yonezawa, Shotaro Taniguchi, Masanori Nakata, Sonshin Takao, Takashi Aikou, Ikuro Maruyama
Journal: Clinical Cancer Research (2004)

Abstract Islet cell tumors, endocrine neoplasm arising from pancreatic islets of Langerhans, are histologically difficult to diagnose as benign or malignant. Molecular markers are associated with the clinical characteristics that most of insulinoma are usually benign tumors, whereas other islet cell tumors are malignant but have not been identified. In this context, we newly found that an endothelial anticoagulant thrombomodulin was expressed in the normal islet β cells and insulinoma, but not of other islet components or noninsulinoma islet cell tumors. Clinically, all of the subjects (n = 15) of the insulinoma group showed no metastasis together with thrombomodulin expression in the lesions, whereas the other islet cell tumor groups showed a high incidence of metastasis (82%) and a low expression rate of thrombomodulin (6%). To examine the functional role of thrombomodulin, especially regarding the clinical characteristics of islet cell tumors, we tested the effect of exogenous thrombomodulin overexpression on cell adhesiveness and proliferation using MIN6 insulinoma cell line. In cell-based experiments, thrombomodulin overexpression reduced cell proliferation and enhanced Ca2+-independent cell aggregation, possibly through direct interaction with neural cell adhesion molecule. Taken together, these results are suggesting that thrombomodulin may act as antimetastatic molecule of insulinomas. In addition, thrombomodulin is a clinically useful molecular marker not only for identifying β-cell–origin islet cell tumors (i.e., insulinomas) but also for predicting disease prognosis of islet cell tumors.