tbuckley/cabot-search huggingface dataset:
Nerve growth factor (NGF) regulates the proliferative activities of the intraphepatic biliary epithelium through the modulation of ERK and PI-3-kinase pathways
Authors: A. Gigliozzi, G. Alpini, G. Svegliati-Baroni, L. Marucci, B. Barbaro, V. Drudi Metalli, A.F. Attili, A. Benedetti, D. Alvaro
Journal: Journal of Hepatology (2003)
Hemagglutination during photopheresis
Authors: Lisa Mask-Bull, Sunaina B. Likhari, John A. Zic, John P. Greer
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Cold agglutinin disease (CAD) is an uncommon form of autoimmune hemolytic anemia that results from complement fixation to IgM agglutinated red blood cells (RBCs).1 These IgM antibodies are known as cold agglutinins (CAs) because they react at cold temperatures with RBC surface antigens.2,3 Although hemagglutination has been reported during cardiopulmonary bypass, there are no reports of this complication with extracorporeal photopheresis (ECP).4,5 We present a case of hemagglutination that occurred in a patient with CAD receiving ECP.
INDIUM-111 LABELLED MONOCLONAL ANTIBODY TO PLACENTAL ALKALINE PHOSPHATASE IN THE DETECTION OF NEOPLASMS OF TESTIS, OVARY, AND CERVIX
Authors: A.A. Epenetos, G. Hooker, H. Durbin, W.F. Bodmer, D. Snook, R. Begent, R.T.D. Oliver, J.P. Lavender
Journal: The Lancet (1985)
Phase I and Pharmacokinetic Study of Sunitinib in Pediatric Patients with Refractory Solid Tumors: A Children's Oncology Group Study
Authors: Steven G. DuBois, Suzanne Shusterman, Ashish M. Ingle, Charlotte H. Ahern, Joel M. Reid, Bing Wu, Sylvain Baruchel, Julia Glade-Bender, Percy Ivy, Holcombe E. Grier, Peter C. Adamson, Susan M. Blaney
Journal: Clinical Cancer Research (2011)

Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor. The purpose of this study was to determine the recommended phase 2 dose, pharmacokinetics, pharmacodynamic effects, and preliminary antitumor activity of sunitinib in a pediatric population.Patients who were 2 to 21 years of age with refractory solid tumors were eligible if they had measurable or evaluable disease and met baseline organ function requirements. Patients received sunitinib once daily for 28 days followed by a 14-day break between each cycle. Dose levels of 15 and 20 mg/m(2)/d were evaluated, with dose escalation based on a 3 + 3 design. Sunitinib pharmacokinetics and biomarkers of angiogenesis were also evaluated during the first cycle.Twenty-three patients were treated (median age 13.9 years; range, 3.9-20.6 years). The most common toxicities were neutropenia, thrombocytopenia, elevated liver transaminases, gastrointestinal symptoms, and fatigue. Two patients developed dose-limiting reductions in cardiac ejection fraction prompting a protocol amendment to exclude patients with previous exposure to anthracyclines or cardiac radiation. In patients without these cardiac risk factors, the maximum tolerated dose (MTD) was 15 mg/m(2)/d. Steady-state plasma concentrations were reached by day 7. No objective responses were observed. Four patients with sarcoma and glioma had stable disease for 2 to 9 cycles.Cardiac toxicity precluded determination of a recommended dose for pediatric patients with previous anthracycline or cardiac radiation exposure. The MTD of sunitinib for patients without risk factors for cardiac toxicity is 15 mg/m(2)/d for 28 days followed by a 14-day break.
Remodeling associated expression of matrix metalloproteinase 9 but not tissue inhibitor of metalloproteinase 1 in airway epithelium: Modulation by immunostimulatory DNA
Authors: Jae Youn Cho, Marina Miller, Kirsti McElwain, Shauna McElwain, Jung Yeon Shim, Eyal Raz, David H. Broide
Journal: Journal of Allergy and Clinical Immunology (2006)
Randomized, Controlled Trial of the Safety and Effectiveness of a Contact Force–Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial Fibrillation
Authors: Vivek Y. Reddy, Srinivas R. Dukkipati, Petr Neuzil, Andrea Natale, Jean-Paul Albenque, Josef Kautzner, Dipen Shah, Gregory Michaud, Marcus Wharton, David Harari, Srijoy Mahapatra, Hendrik Lambert, Moussa Mansour
Journal: Circulation (2015)

Background— Contact force (CF) is a major determinant of lesion size and transmurality and has the potential to improve efficacy of atrial fibrillation ablation. This study sought to evaluate the safety and effectiveness of a novel irrigated radiofrequency ablation catheter that measures real-time CF in the treatment of patients with paroxysmal atrial fibrillation. Methods and Results— A total of 300 patients with symptomatic, drug-refractory, paroxysmal atrial fibrillation were enrolled in a prospective, multicenter, randomized, controlled trial and randomized to radiofrequency ablation with either a novel CF-sensing catheter or a non-CF catheter (control). The primary effectiveness end point consisted of acute electrical isolation of all pulmonary veins and freedom from recurrent symptomatic atrial arrhythmia off all antiarrhythmic drugs at 12 months. The primary safety end point included device-related serious adverse events. End points were powered to show noninferiority. All pulmonary veins were isolated in both groups. Effectiveness was achieved in 67.8% and 69.4% of subjects in the CF and control arms, respectively (absolute difference, −1.6%; lower limit of 1-sided 95% confidence interval, −10.7%; P =0.0073 for noninferiority). When the CF arm was stratified into optimal CF (≥90% ablations with ≥10 g) and nonoptimal CF groups, effectiveness was achieved in 75.9% versus 58.1%, respectively ( P =0.018). The primary safety end point occurred in 1.97% and 1.40% of CF patients and control subjects, respectively (absolute difference, 0.57%; upper limit of 1-sided 95% confidence interval, 3.61%; P =0.0004 for noninferiority). Conclusions— The CF ablation catheter met the primary safety and effectiveness end points. Additionally, optimal CF was associated with improved effectiveness. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT01278953.
MicroRNAs in Cancer
Authors: Gianpiero Di Leva, Michela Garofalo, Carlo M. Croce
Journal: Annual Review of Pathology Mechanisms of Disease (2013)

MicroRNAs (miRNAs) are small noncoding RNAs that typically inhibit the translation and stability of messenger RNAs (mRNAs), controlling genes involved in cellular processes such as inflammation, cell-cycle regulation, stress response, differentiation, apoptosis, and migration. Thus, miRNAs have been implicated in the regulation of virtually all signaling circuits within a cell, and their dysregulation has been shown to play an essential role in the development and progression of cancer. Here, after a brief description of miRNA genomics, biogenesis, and function, we discuss the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies.
Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study
Authors: Frank W Roemer, Ali Guermazi, David T Felson, Jingbo Niu, Michael C Nevitt, Michel D Crema, John A Lynch, Cora E Lewis, James Torner, Yuqing Zhang
Journal: Annals of the Rheumatic Diseases (2011)

Objective To evaluate if two different measures of synovial activation, baseline Hoffa synovitis and effusion synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis of the knee. Methods Non-contrast-enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a short tau inversion recovery sequence in the coronal plane. Hoffa synovitis, effusion synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic osteoarthritis nor MRI-detected tibiofemoral cartilage damage at the baseline visit. The presence of Hoffa synovitis was defined as any grade ≥2 (range 0–3) and effusion synovitis as any grade ≥2 (range 0–3). Logistic regression was performed to examine the relation of the presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders. Results Of 514 knees included in the analysis, the prevalence of Hoffa synovitis and effusion synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion synovitis was associated with an increased risk of cartilage loss. No such association was observed for baseline Hoffa synovitis. Conclusions Baseline effusion synovitis, but not Hoffa synovitis, predicted cartilage loss. The findings suggest that effusion synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in the future development of cartilage lesions in knees without osteoarthritis.
Activation of the Unfolded Protein Response in Infarcted Mouse Heart and Hypoxic Cultured Cardiac Myocytes
Authors: Donna J. Thuerauf, Marie Marcinko, Natalie Gude, Marta Rubio, Mark A. Sussman, Christopher C. Glembotski
Journal: Circulation Research (2006)

Endoplasmic reticulum (ER) stresses that reduce ER protein folding activate the unfolded protein response (UPR). One effector of the UPR is the transcription factor X-box binding protein-1 (XBP1), which is expressed on ER stress-mediated splicing of the XBP1 mRNA. XBP1 induces certain ER-targeted proteins, eg, glucose-regulated protein 78 (GRP78), that help resolve the ER stress and foster cell survival. In this study, we determined whether hypoxia can activate the UPR in the cardiac context. Neonatal rat ventricular myocyte cultures subjected to hypoxia (16 hours) exhibited increased XBP1 mRNA splicing, XBP1 protein expression, GRP78 promoter activation, and GRP78 protein levels; however, the levels of these UPR markers declined during reoxygenation, suggesting that the UPR is activated during hypoxia but not during reoxygenation. When cells were infected with a recombinant adenovirus (AdV) encoding dominant-negative XBP1 (AdV-XBP1dn), UPR markers were reduced; however, hypoxia/reoxygenation-induced apoptosis increased. Confocal immunocytofluorescence demonstrated that hypoxia induced GRP78 in neonatal rat and isolated adult mouse ventricular myocytes. Moreover, mouse hearts subjected to in vivo myocardial infarction exhibited increased GRP78 expression in cardiac myocytes near the infarct, but not in healthy cells distal to the infarct. These results indicate that hypoxia activates the UPR in cardiac myocytes and that XBP1-inducible proteins may contribute to protecting the myocardium during hypoxic stress.
The paradoxes of genetically modified foods
Authors: E. Plugge
Journal: BMJ (1999)

Editor—In his editorial on genetically modified foods Dixon eschews certain important issues.1

Firstly, he does not point out that, although scientists claim this technology will help to feed the world’s burgeoning population, food production is not the problem. There are enough natural resources for us all to be fed: inequity of food distribution results in the starvation of millions in poorer nations.

Secondly, he dismisses the campaigners who draw parallels between bovine spongiform encephalopathy and genetically modified foods. The connection between the two in the public’s mind has little to do with genetic manipulation and everything to do with a lack of faith in policy makers. Not so long ago the government reassured the public that beef was safe. We now know that there was a risk of bovine spongiform encephalopathy, albeit very small. The public is right to be cynical and mistrustful.

We must ask why we need these foods when there are no obvious benefits to the population from their immediate introduction. The driving force behind genetically modified foods is neither need nor demand but certain multinational corporations. Thus, it is important to ensure that a desire to protect the public health—not the profits of multinational organisations—underpins all decisions on the introduction of genetically modified foods.
Synthesis of arachidonate cyclo-oxygenase products by rheumatoid and nonrheumatoid synovial lining in nonproliferative organ culture
Authors: J.A. Salmon, G.A. Higgs, J.R. Vane, Lucille Bitensky, J. Chayen, B. Henderson, B. Cashman
Journal: Annals of the Rheumatic Diseases (1983)

Specimens of human rheumatoid and nonrheumatoid synovial lining were maintained in nonproliferative organ culture for 20 hours. The culture fluids were then assayed for prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)) by specific radioimmunoassay. The presence of each of these substances was confirmed by gas chromatography and mass spectrometry. Rheumatoid tissue produced significantly more of each cyclo-oxygenase product than nonrheumatoid tissue.
Na <sup>+</sup> -Ca <sup>2+</sup> Exchange Current and Submembrane [Ca <sup>2+</sup> ] During the Cardiac Action Potential
Authors: Christopher R. Weber, Valentino Piacentino, Kenneth S. Ginsburg, Steven R. Houser, Donald M. Bers
Journal: Circulation Research (2002)

Na + -Ca 2+ exchange (NCX) is crucial in the regulation of [Ca 2+ ] i and cardiac contractility, but key details of its dynamic function during the heartbeat are not known. In the present study, we assess how NCX current ( I NCX ) varies during a rabbit ventricular action potential (AP). First, we measured the steady-state voltage and [Ca 2+ ] i dependence of I NCX under conditions when [Ca 2+ ] i was heavily buffered. We then used this relationship to infer the submembrane [Ca 2+ ] i ([Ca 2+ ] sm ) sensed by NCX during a normal AP and [Ca 2+ ] i transient (when the AP was interrupted to produce an I NCX tail current). The [Ca 2+ ] i dependence of I NCX at −90 mV allowed us to convert the peak inward I NCX tail currents to [Ca 2+ ] sm . Peak [Ca 2+ ] sm measured via this technique was &gt;3.2 μmol/L within &lt;32 ms of the AP upstroke (versus peak [Ca 2+ ] i of 1.1 μmol/L at 81 ms measured with the global Ca 2+ indicator indo-1). The voltage and [Ca 2+ ] sm dependence of I NCX allowed us to infer I NCX during the normal AP and Ca 2+ transient. The early rise in [Ca 2+ ] sm causes I NCX to be inward for the majority of the AP. Thus, little Ca 2+ influx via NCX is expected under physiological conditions, but this can differ among species and in pathophysiological conditions.
On the Genesis of the Absolute Ventricular Arrhythmia Associated with Atrial Fibrillation
Authors: KAZUO YAMADO, MITSUHARU OKAJIMA, KAZUHIKO HORI, TETSURO FUJINO, HIROSHIGE MURAKI, HITOSHI HISHIDA, TOSIJI KOBAYASHI
Journal: Circulation Research (1968)

Genetic factors in the formation of the long R-R interval in ventricular arrhythmia associated with atrial fibrillation were investigated in the isolated rabbit heart which was perfused using Langendorff's technique. The trans-membrane action potentials recorded from a single cell within the A-V node or within its vicinity were analyzed, and contiguous bipolar-lead electrograms simultaneously recorded from the right atrium and ventricle. Atrial fibrillation was induced by the combined application of acetylcholine solution and electrical stimulation. Atrial excitation was mainly blocked in the right atrium and in the anterior half of the A-V node. To clarify further the time-correlation between the right atrial electrogram and the A-V nodal responses, the pattern of atrio-ventricular conduction was studied by applying only the electrical stimulation at high frequency without acetylcholine. The conduction was mainly blocked in the same sites as in the above experiment and the pattern of the conduction block in Wenckebach rhythm was observed. The conduction block within the anterior half of the A-V node may be the most important factor in producing the long R-R interval in atrial fibrillation. It was shown that the pattern of the conduction block can be explained by the Wenckebach rhythm.
Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8
Authors: Jörg Vollmer, Sibylle Tluk, Claudia Schmitz, Svetlana Hamm, Marion Jurk, Alexandra Forsbach, Shizuo Akira, Kindra M. Kelly, Westley H. Reeves, Stefan Bauer, Arthur M. Krieg
Journal: The Journal of Experimental Medicine (2005)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies to certain cellular macromolecules, such as the small nuclear ribonucleoprotein particles (snRNPs), which had been considered to be passive targets of the autoimmune response. SLE is also characterized by the increased expression of type I interferon (IFN), which appears to be associated with the development and severity of disease. Here, we show that specific, highly conserved RNA sequences within snRNPs can stimulate Toll-like receptors (TLRs) 7 and 8 as well as activate innate immune cells, such as plasmacytoid dendritic cells (pDCs), which respond by secreting high levels of type I IFN. SLE patient sera containing autoantibodies to snRNPs form immune complexes that are taken up through the Fc receptor gammaRII and efficiently stimulate pDCs to secrete type I IFNs. These results demonstrate that a prototype autoantigen, the snRNP, can directly stimulate innate immunity and suggest that autoantibodies against snRNP may initiate SLE by stimulating TLR7/8.
Right axis deviation is a strong indicator of pulmonary hypertension in a risk population
Authors: Gabor Kovacs, Xhylsime Kqiku, Vasile Foris, Maria Tscherner, Natascha Troester, Stefan Scheidl, Christian Hesse, Horst Olschewski
Journal: European Respiratory Journal (2011)

Pulmonary hypertension (PH) is diagnosed by right heart catheterization (RHC), but non-invasive methods play an important role in screening and follow-up. ECG is routinely performed in the clinical work-up but its clinical value has not been defined. We hypothesized that a simple parameter, such as the presence of right axis deviation (RAD) in standard ECG might be useful in the diagnosis and follow up of PH.  We retrospectively analysed all patients who received a RHC and an ECG in our department between 2005 and 2010. The indication for RHC was heterogeneous, the pretest probability of PH was about 50%. We determined the ratio of the S and R waves in lead I in each patient, a value ≥1 (≥90°) was considered as RAD. The investigator was blinded to the RHC results. The sensitivity and specificity of RAD to predict PH (mean PAP≥25mmHg) was determined.  N=317 patients were included. RAD was present in n=71 patients. Within these, PH was detected in n=65 patients, and was missing in n=6 subjects (p  Our retrospective analysis on a large, heterogenous cohort of subjects including patients with and without PH suggests that the presence of RAD in the ECG has a high specificity but a low sensitivity for PH. This simple method may help to recognize PH patients within a population at risk for PH. In order to determine its appropriate role in a diagnostic algorithm, prospective, population based studies are needed.
A Randomized Controlled Trial Comparing Telemedical and Standard Outpatient Monitoring of Diabetic Foot Ulcers
Authors: Benjamin S.B. Rasmussen, Johnny Froekjaer, Mads R. Bjerregaard, Jens Lauritsen, Joergen Hangaard, Claus W. Henriksen, Ulrich Halekoh, Knud B. Yderstraede
Journal: Diabetes Care (2015)

OBJECTIVE The role of telemedical monitoring in diabetic foot ulcer care is still uncertain. Our aim was to compare telemedical and standard outpatient monitoring in the care of patients with diabetic foot ulcers in a randomized controlled trial. RESEARCH DESIGN AND METHODS Of the 736 screened individuals with diabetic foot ulcers, 401 met the eligibility criteria and were randomized between October 2010 and November 2014. The per-protocol telemedical monitoring consisted of two consultations in the patient’s own home and one consultation at the outpatient clinic. Standard practice consisted of three outpatient clinic visits. The three-visit cycle was repeated until study end point. The study end points were defined as complete ulcer healing, amputation, or death. RESULTS One hundred ninety-three individuals were randomized to telemedical monitoring and 181 to standard care. Demographics were similar in both groups. A cause-specific Cox proportional hazards model showed no difference in individuals monitored through telemedicine regarding wound healing (hazard ratio 1.11 [95% CI 0.87, 1.42], P = 0.42) or amputation (0.87 [0.54, 1.42], P = 0.59). We found a higher mortality incidence in the telemedical monitoring group compared with the standard outpatient monitoring group (8.68 [6.93, 10.88], P = 0.0001). CONCLUSIONS The findings of no significant difference regarding amputation and healing between telemedical and standard outpatient monitoring seem promising; however, for telemedical monitoring, a higher mortality throws into question the role of telemedicine in monitoring diabetic foot ulcers. Further studies are needed to investigate effects of telemedicine on mortality and other clinical outcomes and to identify patient subgroups that may have a poorer outcome through telemedical monitoring.
Phase III Study of Adjuvant Chemotherapy and Radiation Therapy Compared With Chemotherapy Alone in the Surgical Adjuvant Treatment of Colon Cancer: Results of Intergroup Protocol 0130
Authors: James A. Martenson, Christopher G. Willett, Daniel J. Sargent, James A. Mailliard, John H. Donohue, Leonard L. Gunderson, Charles R. Thomas, Barbara Fisher, Al Bowen Benson, Robert Myerson, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2004)

Some patients with colon cancer have a high risk of local recurrence postoperatively. This trial was undertaken to determine whether radiation therapy added to an adjuvant chemotherapy regimen improves outcome in high-risk patients.Patients with resected colon cancer with tumor adherence or invasion of surrounding structures, or with T3N1 or T3N2 tumors of the ascending or descending colon were randomly assigned to receive fluorouracil and levamisole therapy with or without radiation therapy. Patients who received chemotherapy and radiation therapy (chemoRT) received 45 to 50.4 Gy in 25 to 28 fractions beginning 28 days after starting chemotherapy. Patient enrollment was terminated because of slow accrual after 222 patients enrolled (original goal was 700 patients); 187 patients were assessable.Overall 5-year survival was 62% for chemotherapy patients and 58% for chemoRT patients (P >.50); 5-year disease-free survival was 51% for both groups (P >.50). Toxicity (>/= grade 3) occurred in 42% of chemotherapy patients and 54% of chemoRT patients (P =.04). Leukopenia (>/= grade 3) occurred in 10% of chemotherapy patients and 22% of chemoRT patients (P =.02). No significant difference in nonhematologic toxicity (>/= grade 3) was observed between chemoRT and chemotherapy patients (35% v 44%; P =.26).Patients who received chemotherapy or chemoRT had similar overall survival and disease-free survival. Toxicity was higher among chemoRT patients. These results must be interpreted with caution because of the high number of ineligible patients and the limited power of the study to detect potentially meaningful differences.