tbuckley/cabot-search huggingface dataset:
The Relationship Between Physicians’ Self-Reported Target Fasting Blood Glucose Levels and Metabolic Control in Type 2 Diabetes
Authors: Maurizio Belfiglio, Giorgia De Berardis, Monica Franciosi, Donatella Cavaliere, Barbara Di Nardo, Sheldon Greenfield, Sherrie H. Kaplan, Fabio Pellegrini, Michele Sacco, Gianni Tognoni, Miriam Valentini, Antonio Nicolucci, Vittorio Caimi, Fabio Capani, Andrea Corsi, Roberto Della Vedova, Massimo Massi Benedetti, Antonio Nicolucci, Claudio Taboga, Massimo Tombesi, Giacomo Vespasiani
Journal: Diabetes Care (2001)

To investigate the relationship between beliefs of physicians relative to intensive metabolic control in type 2 diabetes and levels of HbA1c obtained in a sample of their patients.Physicians' beliefs were investigated through a questionnaire sent to a sample of self-selected clinicians participating in a nationwide initiative aimed at assessing the relationship between the quality of care delivered to patients with type 2 diabetes and their outcomes. At the same time, physicians were asked to collect clinical data on a random sample of their patients, stratified by age (<65 vs. > or = 65 years). Mean HbA1c levels in the study population were thus evaluated according to target fasting blood glucose (FBG) used by their physicians.Of 456 physicians, 342 (75%) returned the questionnaire. Among the responders, 200 diabetologists and 99 general practitioners (GPs) recruited 3,297 patients; 2,003 of whom were always followed by the same physician and 1,294 of whom were seen by different physicians in the same structure on different occasions. Only 14% of the respondents used target FBG levels < or = 6.1 mmol/l, whereas 38% pursued values >7.8 mmol/l, with no statistically significant difference between diabetologists and GPs. The analysis of the relationship between FBG targets and metabolic control, restricted to those patients always seen by the same physician, showed a strong linear association, with mean HbA1c values of 7.0 +/- 1.6 for patients in the charge of physicians pursuing FBG levels < or = 6.1 mmol/l and 7.8 +/- 1.8 for those followed by physicians who used target values >7.8 mmol/l. After adjusting for patients' and physicians' characteristics, the risk of having HbA1c values > 7.0% was highly correlated with physicians' beliefs. Patients followed by different physicians in the same unit showed a risk of inadequate metabolic control similar to that of patients followed by physicians adopting a nonaggressive policy.Doctors adopt extremely heterogeneous target FBG levels in patients with type 2 diabetes, which in turn represent an important independent predictor of metabolic control. To improve patient outcomes, physicians-centered educational activities aimed at increasing the awareness of the potential benefits of a tight metabolic control in patients with type 2 diabetes are urgently needed.
Adiponectin Mediates the Metabolic Effects of FGF21 on Glucose Homeostasis and Insulin Sensitivity in Mice
Authors: Zhuofeng Lin, Haishan Tian, Karen S.L. Lam, Shaoqiang Lin, Ruby C.L. Hoo, Morichika Konishi, Nobuyuki Itoh, Yu Wang, Stefan R. Bornstein, Aimin Xu, Xiaokun Li
Journal: Cell Metabolism (2013)
The effect of nedocromil sodium on human airway epithelial cell-induced eosinophil chemotaxis and adherence to human endothelial cell in vitro
Authors: MM Abdelaziz, JL Devalia, OA Khair, C Rusznak, M Calderon, RJ Sapsford, H Bayram, RJ Davies
Journal: European Respiratory Journal (1997)

Although some studies have shown that long-term treatment of asthmatics with nedocromil sodium can reduce airway hyperresponsiveness and improve symptoms and lung function, the mechanisms underlying its effects are not well understood. We have investigated the effect of nedocromil sodium on eosinophil chemotaxis, eosinophil adherence to human endothelial cells and release of soluble intercellular adhesion molecule-1 (sICAM-1) from endothelial cells, induced by conditioned medium collected from cultured human bronchial epithelial cells. Conditioned medium significantly increased eosinophil chemotaxis from a baseline median value of 2.1 (range 1.9-4.5) cells-high power field(-1) (HPF) to 10.5 (range 7.8-12.3) cells-HPF(-1) (p<0.05). Similarly, conditioned medium significantly increased eosinophil adherence to endothelial cells from a baseline value of 9 (range 8-12)% to 23 (range 21-30)% (p<0.05). Nedocromil sodium, at 10(-5) M concentration, significantly attenuated the eosinophil chemotaxis and adherence induced by conditioned medium. Conditioned medium also significantly increased the release of sICAM-1 from endothelial cells, from a baseline value of 11.5 (range 8.1-15.4) pg x microg(-1) protein to 67.6 (range 55.6-73.5) pg x microg(-1) protein (p<0.05). This was significantly attenuated by anti-tumour necrosis factor-alpha (TNF-alpha), anti-interleukin-1beta (IL-1beta) and 10(-5) M nedocromil sodium. These findings suggest that human bronchial epithelial cell-derived mediators may potentiate eosinophil activity, and that this can be modulated by nedocromil sodium, suggesting a possible mechanism underlying its anti-inflammatory effect.
Antisense RNA Down-Regulation of bcl-2 Expression in DU145 Prostate Cancer Cells Does Not Diminish the Cytostatic Effects of G3139 (Oblimersen)
Authors: Anthony Raffo, Johnathan C. Lai, C. A. Stein, Paul Miller, Steven Scaringe, Anastasia Khvorova, Luba Benimetskaya
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Inhibition of the function of the bcl-2 protein has been postulated to sensitize cells to cytotoxic chemotherapy, and thus provides an attractive target for investigative therapies. G3139, a phosphorothioate antisense oligonucleotide targeted to the initiation codon region of the bcl-2 mRNA, is currently being evaluated in several Phase II and Phase III clinical trials. However, the mechanism of action of this molecule appears to depend on a combination of antisense plus nonantisense events. Indeed, the very idea that bcl-2 is a critical target is, at least in part, an extrapolation from experiments in which intracellular bcl-2 protein concentrations have been dramatically increased, yielding chemoresistant cells. Experimental Design: In this work, we down-regulated the expression of bcl-2 protein by 80–90% by two different antisense RNA strategies (antisense RNA and small interfering RNA) in DU145 prostate cancer cells. Results: Even after down-regulation of bcl-2 protein expression by either one of these strategies, the cellular phenotype induced by subsequent G3139 treatment (inhibition of cellular growth and the generation of reactive oxygen species) was essentially identical to that induced in mock-infected or wild-type DU145 cells in which bcl-2 protein expression had not been down-regulated previously. Conclusions: These results strongly suggest that bcl-2 expression in DU145 cells is not strongly associated with the prolife phenotype and that the mechanism by which G3139 produces its cytostatic effects in this cell line is bcl-2 independent.
Influence of Temperature on the Mechanical Properties of Cardiac Muscle
Authors: GORDON H. TEMPLETON, KERN WILDENTHAL, JAMES T. WILLERSON, WILLIAM C. REARDON
Journal: Circulation Research (1974)

The influence of temperature on contractile performance, total myocardial stiffness, and the elastic and viscous components of stiffness was studied in intact hearts (dog) and isolated cardiac muscle (cat). In 12 dogs on whole-heart bypass, stiffness (Δ P /Δ V ) was determined by inducing sinusoidal 0.5-ml volume changes in paced, isovolumically contracting left ventricles and measuring the resultant pressure changes (Δ P ). In eight cat papillary muscles contracting isometrically at Lmax, stiffness (Δ T /Δ L ) was similarly determined from the changes in tension and length during sinusoidal length changes of 0.25% L max. Total stiffness was linearly related to ventricular pressure or muscular tension during both contraction and rest. As the temperature rose from 33° to 40°C in vivo and from 22° to 40°C in vitro, the slopes of the stiffness-pressure and stiffness-tension relationships and the intercept of the latter declined; therefore, stiffness is inversely related to temperature. Since both preparations responded as linear second-order systems, stiffness could be separated into its elastic and viscous components. The moduli of both components varied in the same direction as total stiffness during temperature changes; however, the viscous component was more sensitive to the influence of temperature.
Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease
Authors: J. Tuomilehto, G. Vidgren, L. Toivanen, E. Tuomilehto-Wolf, K. Kohtamaki, J. Stengård, P. Zimmet, I.R. Mackay, Mj Rowley, P. Koskela
Journal: The Lancet (1994)
COMPARISON OF THE REDUCING POWER OF SOME TYPICAL TRANSPLANTABLE TUMORS AND OF TUMORS PRODUCED BY FILTERABLE VIRUSES
Authors: E. S. Guzman Barron
Journal: The Journal of Experimental Medicine (1932)

1. The tissues of Rous chicken sarcoma and of the infectious myxoma of the rabbit do not possess the oxidation-reduction enzyme succinodehydrogenase, which is present in normal tissues and in transplantable tumors. 2. Filterable virus diseases (rabbit Virus III, rabbit neurovaccine, rabbit herpes, fowl-pox) produce in the tissues affected by them a partial inhibition of succinodehydrogenase.
Urinary excretion of free noradrenaline and adrenaline in trained and untrained men.
Authors: B. Davies, B. H. Massey, T. G. Lohman, B. T. Williams
Journal: British Journal of Sports Medicine (1977)

Measurements of free noradrenaline and adrenaline were made in the urine of 28 men sampled after rest and exercise prior to, and following six and twelve weeks of an excercise programme. The training consisted of thirty minutes of running and walking four times per week at an intensity estimated at 75% of the age-predicted maximum heart rate. A fifteen minute standardized cycle ergometer work test was conducted on all subjects prior to the training and following six and twelve weeks of training. Noradrenaline and adrenaline excretions in the urine were measured before and after the work test.
The FTA-ABS Test in Dark-Field-Positive Primary Syphilis
Authors: W. Christopher Duncan
Journal: JAMA (1974)

The fluorescent treponemal antibody absorption (FTA-ABS) test was performed in 77 consecutive patients with dark-field-positive primary syphilis. The test was reactive in 70 of the 77 patients (91%). These results make this serologic test extremely valuable in the diagnosis of syphilis at a time when this disease is on the increase, and the number of well-trained darkfield technicians is on the wane. (<i>JAMA</i>228:859-860, 1974)
Relation of Inflammation and Benefit of Statins After Percutaneous Coronary Interventions
Authors: Albert W. Chan, Deepak L. Bhatt, Derek P. Chew, Joel Reginelli, Jakob P. Schneider, Eric J. Topol, Stephen G. Ellis
Journal: Circulation (2003)

Background— Beyond lipid lowering, statins are known to possess antiinflammatory and antithrombotic properties. Recent studies suggested an association between statins and early reduction in death or myocardial infarction (MI) after percutaneous coronary interventions (PCIs). We sought to examine the interrelationship between inflammation, statin use, and PCI outcomes. Methods and Results— In the year 2000, 1552 consecutive United States residents underwent elective or urgent PCI at the Cleveland Clinic and were prospectively followed for 1 year. Preprocedural serum high-sensitivity C-reactive protein (hsCRP) levels were routinely measured. Patients who had statins initiated before the procedure (39.6%) had a lower median hsCRP level (0.40 versus 0.50 mg/dL, P =0.012) independent of the baseline cholesterol levels and had less frequent periprocedural MI (defined by CKMB ≥3×upper limit of normal, 5.7% versus 8.1%, P =0.038). At 1 year, statin pretreatment was predictive of survival predominantly among patients within the highest hsCRP quartile (mortality rate with statin pretreatment versus no pretreatment when hsCRP ≥1.11 mg/dL, 5.7% versus 14.8%, P =0.009). Using multivariate analysis, preprocedural hsCRP level remained an independent predictor for 1-year death or MI only in patients without statin therapy (hazard ratio, 1.32/quartile; P =0.001). After adjusting for the propensity of receiving statins, statin pretreatment was an independent predictor for 1-year survival within the highest hsCRP quartile (hazard ratio, 0.44; P =0.039). Conclusions— Statin therapy before PCI is associated with a marked reduction in mortality among patients with high hsCRP levels. A hsCRP-guided strategy may improve targeting of statin therapy and clinical outcome among patients undergoing PCI.
Quantification of Obstructive and Nonobstructive Coronary Lesions by 64-Slice Computed Tomography
Authors: Alexander W. Leber, Andreas Knez, Franz von Ziegler, Alexander Becker, Konstantin Nikolaou, Stephan Paul, Bernd Wintersperger, Maximilian Reiser, Christoph R. Becker, Gerhard Steinbeck, Peter Boekstegers
Journal: Journal of the American College of Cardiology (2005)
39-kD protein inhibits tissue-type plasminogen activator clearance in vivo.
Authors: I Warshawsky, G Bu, A L Schwartz
Journal: Journal of Clinical Investigation (1993)

Tissue-type plasminogen activator (t-PA) is a plasma serine protease that catalyzes the initial and rate-limiting step in the fibrinolytic cascade. t-PA is widely used as a thrombolytic agent in the treatment of acute myocardial infarction. However, its use has been impaired by its rapid hepatic clearance from the circulation following intravenous administration. Studies with both rat hepatoma MH1C1 cells (G. Bu, S. Williams, D. K. Strickland, and A. L. Schwartz, 1992. Proc. Natl. Acad. Sci. USA. 89:7427-7431) and human hepatoma HepG2 cells (G. Bu, E. A. Maksymovitch, and A. L. Schwartz. 1993. J. Biol. Chem. 28:13002-13009) have shown that binding of t-PA to its clearance receptor, the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor, is inhibited by a 39-kD protein that copurifies with this receptor. Herein we investigated whether administration of purified recombinant 39-kD protein would alter t-PA clearance in vivo. We found that intravenous administration of purified 39-kD protein to rats prolonged the plasma half-life of 125I-t-PA from 1 min to approximately 5-6 min. The plasma half-life of t-PA enzymatic activity was similarly prolonged following intravenous administration of purified 39-kD protein. In addition we found that the 39-kD protein itself was rapidly cleared from the circulation in vivo. Clearance of 125I-39-kD protein was a biphasic process with half-lives of 30 s and 9 min and the liver was the primary organ of clearance. Preadministration of excess unlabeled 39-kD protein slowed 125I-39-kD protein clearance in rats in a dose-dependent manner, suggesting that specific clearance receptors were responsible for this process. Administration of increasing doses of unlabeled 39-kD protein along with labeled 39-kD protein resulted in a decrease in the amount of labeled 39-kD protein associating with the liver and a concomitant increase in the amount of labeled 39-kD protein associating with the kidneys, indicating two clearance mechanisms exist for the 39-kD protein.
Serum Fibroblast Growth Factor 19 Levels Are Decreased in Chinese Subjects With Impaired Fasting Glucose and Inversely Associated With Fasting Plasma Glucose Levels
Authors: Qichen Fang, Huating Li, Qianqian Song, Wenjing Yang, Xuhong Hou, Xiaojing Ma, Junxi Lu, Aimin Xu, Weiping Jia
Journal: Diabetes Care (2013)

OBJECTIVE Fibroblast growth factor 19 (FGF19), a hormone secreted from the small intestine, has recently been shown to stimulate glycogen synthesis and inhibit gluconeogenesis through insulin-independent pathways. This study investigated the change of FGF19 in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM) and explored the association of serum FGF19 levels with parameters of glucose metabolism in Chinese subjects. RESEARCH DESIGN AND METHODS Fasting serum FGF19 levels were determined by ELISA in 81 normal glucose tolerance (NGT), 91 impaired fasting glucose (IFG), 93 impaired glucose tolerance (IGT), and 104 newly diagnosed T2DM subjects, and their association with parameters of glucose metabolism was studied. An ordinal logistic regression analysis was performed in subjects with NGT, IFG, and T2DM. Serum FGF19 levels at 2 h after a 75-g oral glucose tolerance test in the different glucose tolerance categories were studied in a subgroup. RESULTS Fasting serum FGF19 levels in subjects with IFG (210 pg/mL [142–327]) (median [interquartile range]) and T2DM (196 pg/mL [137–280]) were significantly lower than those in NGT subjects (289 pg/mL [224–393]) (both P &amp;lt; 0.001). However, no significant difference in fasting FGF19 levels was observed between IGT (246 pg/mL [138–379]) and NGT subjects. Fasting serum FGF19 levels were negatively associated with fasting plasma glucose and independently associated with the deterioration of glucometabolic status from NGT to IFG and T2DM. CONCLUSIONS Fasting serum FGF19 levels were decreased in Chinese subjects with IFG and inversely associated with fasting glucose levels.
FDA Approval: Ceritinib for the Treatment of Metastatic Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung Cancer
Authors: Sean Khozin, Gideon M. Blumenthal, Lijun Zhang, Shenghui Tang, Margaret Brower, Emily Fox, Whitney Helms, Ruby Leong, Pengfei Song, Yuzhuo Pan, Qi Liu, Ping Zhao, Hong Zhao, Donghao Lu, Zhe Tang, Ali Al Hakim, Karen Boyd, Patricia Keegan, Robert Justice, Richard Pazdur
Journal: Clinical Cancer Research (2015)

On April 29, 2014, the FDA granted accelerated approval to ceritinib (ZYKADIA; Novartis Pharmaceuticals Corporation), a breakthrough therapy-designated drug, for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. The approval was based on a single-arm multicenter trial enrolling 163 patients with metastatic ALK-positive NSCLC who had disease progression on (91%) or intolerance to crizotinib. Patients received ceritinib at a starting dose of 750 mg orally once daily. The objective response rate (ORR) by a blinded independent review committee was 44% (95% CI, 36-52), and the median duration of response (DOR) was 7.1 months. The ORR by investigator assessment was similar. Safety was evaluated in 255 patients. The most common adverse reactions and laboratory abnormalities included diarrhea (86%), nausea (80%), increased alanine transaminase (80%), increased aspartate transaminase (75%), vomiting (60%), increased glucose (49%), and increased lipase (28%). Although 74% of patients required at least one dose reduction or interruption due to adverse reactions, the discontinuation rate due to adverse reactions was low (10%). With this safety profile, the benefit-risk analysis was considered favorable because of the clinically meaningful ORR and DOR.
HOW TO WRITE A MEDICAL ARTICLE.A PLEA FOR PLAGIARISM.
Authors: G. FRANK LYDSTON
Journal: JAMA (1903)

One of the most galling experiences of the middle period of one's professional career is the discovery that he has been wasting his energies in ambitions which might have been easily gratified by a very modest expenditure of force. How sad the experience of the man who has been for years desperately striving to attain by his pen a certain degree of fame to discover that he has not had discernment sufficient to point out to him the direction of least resistance. How selfish the man who, having learned, alas too late, the error of his ways, does not give his younger and more unsophisticated brethren the benefit of his experience. In endeavoring to aid my professional friends in securing the greatest amount of result from the least expenditure of time and the smallest possible wear and tear of gray matter, I feel that I am sowing seed that, beyond
Integrin Targeting for Tumor Optical Imaging
Authors: Yunpeng Ye, Xiaoyuan Chen
Journal: Theranostics (2011)

Optical imaging has emerged as a powerful modality for studying molecular recognitions and molecular imaging in a noninvasive, sensitive, and real-time way. Some advantages of optical imaging include cost-effectiveness, convenience, and non-ionization safety as well as complementation with other imaging modalities such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Over the past decade, considerable advances have been made in tumor optical imaging by targeting integrin receptors in preclinical studies. This review has emphasized the construction and evaluation of diverse integrin targeting agents for optical imaging of tumors in mouse models. They mainly include some near-infrared fluorescent dye-RGD peptide conjugates, their multivalent analogs, and nanoparticle conjugates for targeting integrin αvβ3. Some compounds targeting other integrin subtypes such as α4β1 and α3 for tumor optical imaging have also been included. Both in vitro and in vivo studies have revealed some promising integrin-targeting optical agents which have further enhanced our understanding of integrin expression and targeting in cancer biology as well as related anticancer drug discovery. Especially, some integrin-targeted multifunctional optical agents including nanoparticle-based optical agents can multiplex optical imaging with other imaging modalities and targeted therapy, serving as an attractive type of theranostics for simultaneous imaging and targeted therapy. Continued efforts to discover and develop novel, innovative integrin-based optical agents with improved targeting specificity and imaging sensitivity hold great promises for improving cancer early detection, diagnosis, and targeted therapy in clinic.
Autoantibody Signatures Involving Glycolysis and Splicesome Proteins Precede a Diagnosis of Breast Cancer among Postmenopausal Women
Authors: Jon J. Ladd, Timothy Chao, Melissa M. Johnson, Ji Qiu, Alice Chin, Rebecca Israel, Sharon J. Pitteri, Jianning Mao, Mei Wu, Lynn M. Amon, Martin McIntosh, Christopher Li, Ross Prentice, Nora Disis, Samir Hanash
Journal: Cancer Research (2012)

We assessed the autoantibody repertoire of a mouse model engineered to develop breast cancer and the repertoire of autoantibodies in human plasmas collected at a preclinical time point and at the time of clinical diagnosis of breast cancer. In seeking to identify common pathways, networks, and protein families associated with the humoral response, we elucidated the dynamic nature of tumor antigens and autoantibody interactions. Lysate proteins from an immortalized cell line from a MMTV-neu mouse model and from MCF7 human breast cancers were spotted onto nitrocellulose microarrays and hybridized with mouse and human plasma samples, respectively. Immunoglobulin-based plasma immunoreactivity against glycolysis and spliceosome proteins was a predominant feature observed both in tumor-bearing mice and in prediagnostic human samples. Interestingly, autoantibody reactivity was more pronounced further away than closer to diagnosis. We provide evidence for dynamic changes in autoantibody reactivity with tumor development and progression that may depend, in part, on the extent of antigen-antibody interactions.
Transapical Implantation of a Melody Valve in a Degenerated Low-Diameter Prosthetic Aortic Valve
Authors: Yanai Ben-Gal, Ariel Finkelstein, Elchanan Bruckheimer, Shmuel Banai, Gad Keren, Amir Kramer, Gideon Uretzky
Journal: Circulation (2013)