tbuckley/cabot-search huggingface dataset:
Delay in Right Ventricular Activation Contributes to Brugada Syndrome
Authors: Raymond Tukkie, Peter Sogaard, Jim Vleugels, Irma K.L.M. de Groot, Arthur A.M. Wilde, Hanno L. Tan
Journal: Circulation (2004)

Background— Although Brugada syndrome revolves around reduced net depolarizing force, the electrophysiological mechanisms of its defining features (right precordial ST-segment elevation and ventricular tachyarrhythmias) remain unresolved. Two proposed mechanisms are (1) right ventricular (RV) conduction delay and (2) selective and significant RV subepicardial action potential shortening. Both mechanisms must cause disparate contractile changes: delay in RV contraction and reduction of contractile force, respectively. We aimed to establish the electrophysiological mechanism of Brugada syndrome by studying the timing and force of RV contraction. Methods and Results— Using tissue Doppler echocardiography, we studied how these contractile variables change on induction of the characteristic ST-segment changes of Brugada syndrome by flecainide challenge. Accordingly, we studied patients in whom flecainide induced these changes (inducible) and those in whom these changes were not induced (control). We found that (1) the occurrence of a positive response (coved-type ST elevation) after flecainide coincides with delay in the onset of contraction between the RV and left ventricle (LV); (2) the extent of contraction delay between RV and LV correlates with the magnitude of ST elevation; and (3) RV ejection time (duration of RV ejection phase) shortens as the Brugada ECG pattern emerges. Conclusions— These results indicate that both proposed mechanisms of Brugada syndrome may be operative.
DCCP and DICP: Construction and Analyses of Databases for Copper- and Iron-Chelating Proteins
Authors: Hao Wu, Yan Yang, Sheng-Juan Jiang, Ling-Ling Chen, Hai-Xia Gao, Qing-Shan Fu, Feng Li, Bin-Guang Ma, Hong-Yu Zhang
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract Copper and iron play important roles in a variety of biological processes, especially when being chelated with proteins. The proteins involved in the metal binding, transporting and metabolism have aroused much interest. To facilitate the study on this topic, we constructed two databases (DCCP and DICP) containing the known copper- and iron-chelating proteins, which are freely available from the website http://sdbi.sdut.edu.cn/en. Users can conveniently search and browse all of the entries in the databases. Based on the two databases, bioinformatic analyses were performed, which provided some novel insights into metalloproteins.
CORRELATION OF PRODUCTION OF INFECTIOUS VIRUS WITH SEQUENTIAL STAGES OF CYTOLOGIC ALTERATION IN H<scp>E</scp>L<scp>A</scp> CELLS INFECTED WITH ADENOVIRUSES TYPES 5 AND 7
Authors: Georgianna S. Boyer, Floyd W. Denny, Irving Miller, Harold S. Ginsberg
Journal: The Journal of Experimental Medicine (1960)

Studies correlating the production of infectious adenovirus (types 5 and 7) and the progression of the stages of virus-induced cytologic change in HeLa cells are presented. The results reveal a close relationship between the development of the characteristic nuclear changes and adenovirus synthesis. They suggest that cells manifesting the first stages of nuclear change, characterized by the appearance of eosinophilic, Feulgen-negative inclusions, contain little or no mature infectious virus, whereas cells in the later stages, with Feulgen-positive and basophilic inclusions, contain relatively large amounts.
BI-02 * FUNCTIONAL CHARACTERIZATION OF NOVEL BIOMARKERS IN SELECTING FOR SUBTYPE SPECIFIC MEDULLOBLASTOMA PHENOTYPES
Authors: C. Aiken, L. Liang, L. Morrison, M. Del Bigio, M. Remke, M. Taylor, T. Werbowetski-Ogilvie
Journal: Neuro-Oncology (2014)

Major research efforts have focused on the isolation and characterization of brain tumor stem cells, or propagating cells (BTPC) in a variety of brain cancers. Elucidating cell surface marker profiles that can be used to selectively isolate this cellular population is an imperative first step in the development of targeted therapies. Medulloblastoma (MB) is the most common form of pediatric brain cancer. MB is divided into 4 molecular subgroups; Wnt, Sonic Hedgehog (SHH), Group 3 and Group 4. Given the variable results obtained for currently utilized markers, as well as the cellular heterogeneity within and between MB sub-groups, it is likely there are additional surface marker profiles capable of selecting for sub-type specific MB BTPCs. We set out to identify novel surface marker combinations capable of selecting for TPCs in SHH MB. We employed the new BD Bioscience Lyoplate screening platform to compare 242 human cell surface marker levels across high and low self-renewing SHH MB sub-clones. The top 25 markers were refined by evaluating expression levels in Shh vs Group 3,4 and Wnt variants in transcriptome datasets representing 548 patient samples. Four markers, CD271, CD106/VCAM1, EGFR and CD171/NCAM-L1 showed consistent differential expression in the SHH subtype relative to the other variants. Flow cytometry validation in additional cell lines confirmed these findings. As a proof of principle, functional characterization of CD271 in SHH MB in vitro and in vivo was performed. Using fluorescence activated cell sorting and gain/loss of function studies, our results suggest that CD271 selects for MB progenitor cells. This work highlights a new approach to screening for differentially expressed surface markers across matched samples. We delineated a cell surface fingerprint for BTPC populations from MB molecular variants, however the utility can be seen in normal stem cell biology and across all forms of cancer.
SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival
Authors: Terra L. Lasho, Thitina Jimma, Christy M. Finke, Mrinal Patnaik, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Ayalew Tefferi
Journal: Blood (2012)
Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery
Authors: William R. Zhang, Amit X. Garg, Steven G. Coca, Philip J. Devereaux, John Eikelboom, Peter Kavsak, Eric McArthur, Heather Thiessen-Philbrook, Colleen Shortt, Michael Shlipak, Richard Whitlock, Chirag R. Parikh
Journal: Journal of the American Society of Nephrology (2015)

Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a ≥50% or ≥0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.
Receptor editing in self-reactive bone marrow B cells.
Authors: S L Tiegs, D M Russell, D Nemazee
Journal: The Journal of Experimental Medicine (1993)

A central paradigm of immunology is clonal selection: lymphocytes displaying clonally distributed antigen receptors are generated and subsequently selected by antigen for growth or elimination. Here we show that in mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Transgenic bone marrow B cells encountering membrane-bound Kb or Kk proteins modify their receptors by expressing the V(D)J recombinase activator genes and assembling endogenously encoded immunoglobulin light chain variable genes. This (auto)antigen-directed change in the specificity of newly generated lymphocytes is termed receptor editing.
Default is not in the female, but in the theory
Authors: Roslyn Holly Fitch, Victor H. Denenberg
Journal: Behavioral and Brain Sciences (1998)

A number of commentators agree that the evidence reviewed in the target article supports a previously unrecognized role for ovarian hormones in feminization of the brain. Others question this view, suggesting that the traditional model of sexual differentiation already accounts for ovarian influence. This position is supported by various reinterpretations of the data presented (e.g., ovarian effects are secondary to the presence/absence of androgen, ovarian effects are smaller than testicular effects, ovarian effects are not organizational). We discuss these issues, and reiterate our position that evidence of neurobehavioral ovarian effects is incompatible with the currently accepted model of sexual differentiation. Other points regarding species generalizations, the direct versus indirect action of estrogen, and nonhormonal mechanisms of sexual differentiation are also discussed. Finally, we address the controversial issue of using ratio scores in the assessment of the human corpus callosum (where CC scores are divided by an index of brain size). Future applications to human research are also discussed.
Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
Authors: Johannes R Lemke, Dennis Lal, Eva M Reinthaler, Isabelle Steiner, Michael Nothnagel, Michael Alber, Kirsten Geider, Bodo Laube, Michael Schwake, Katrin Finsterwalder, Andre Franke, Markus Schilhabel, Johanna A Jähn, Hiltrud Muhle, Rainer Boor, Wim Van Paesschen, Roberto Caraballo, Natalio Fejerman, Sarah Weckhuysen, Peter De Jonghe, Jan Larsen, Rikke S Møller, Helle Hjalgrim, Laura Addis, Shan Tang, Elaine Hughes, Deb K Pal, Kadi Veri, Ulvi Vaher, Tiina Talvik, Petia Dimova, Rosa Guerrero López, José M Serratosa, Tarja Linnankivi, Anna-Elina Lehesjoki, Susanne Ruf, Markus Wolff, Sarah Buerki, Gabriele Wohlrab, Judith Kroell, Alexandre N Datta, Barbara Fiedler, Gerhard Kurlemann, Gerhard Kluger, Andreas Hahn, D Edda Haberlandt, Christina Kutzer, Jürgen Sperner, Felicitas Becker, Yvonne G Weber, Martha Feucht, Hannelore Steinböck, Birgit Neophythou, Gabriel M Ronen, Ursula Gruber-Sedlmayr, Julia Geldner, Robert J Harvey, Per Hoffmann, Stefan Herms, Janine Altmüller, Mohammad R Toliat, Holger Thiele, Peter Nürnberg, Christian Wilhelm, Ulrich Stephani, Ingo Helbig, Holger Lerche, Fritz Zimprich, Bernd A Neubauer, Saskia Biskup, Sarah von Spiczak
Journal: Nature Genetics (2013)
Clinical validation of an autoantibody test for lung cancer
Authors: P. Boyle, C.J. Chapman, S. Holdenrieder, A. Murray, C. Robertson, W.C. Wood, P. Maddison, G. Healey, G.H. Fairley, A.C. Barnes, J.F.R. Robertson
Journal: Annals of Oncology (2010)

BackgroundAutoantibodies may be present in a variety of underlying cancers several years before tumours can be detected and testing for their presence may allow earlier diagnosis. We report the clinical validation of an autoantibody panel in newly diagnosed patients with lung cancer (LC).Patients and methodsThree cohorts of patients with newly diagnosed LC were identified: group 1 (n = 145), group 2 (n = 241) and group 3 (n = 269). Patients were individually matched by gender, age and smoking history to a control individual with no history of malignant disease. Serum samples were obtained after diagnosis but before any anticancer treatment. Autoantibody levels were measured against a panel of six tumour-related antigens (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2). Assay sensitivity was tested in relation to demographic variables and cancer type/stage.ResultsThe autoantibody panel demonstrated a sensitivity/specificity of 36%/91%, 39%/89% and 37%/90% in groups 1, 2 and 3, respectively, with good reproducibility. There was no significant difference between different LC stages, indicating that the antigens included covered the different types of LC well.ConclusionThis assay confirms the value of an autoantibody panel as a diagnostic tool and offers a potential system for monitoring patients at high risk of LC.
Interstitial granulomatous drug reaction presenting as erythroderma: remission after discontinuation of enalapril maleate
Authors: Y-C. Chen, C-H. Hsiao, T-F. Tsai
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, Interstitial granulomatous drug reaction (IGDR) is a recently described drug‐induced eruption.1 Most patients present with erythematous to violaceous plaques on the axillary folds and groin areas.1 We describe a Chinese man with hypertension in whom erythroderma developed during enalapril maleate treatment; histopathological findings showed typical interstitial granulomatous dermatitis. A 66‐year‐old man presented with a mildly pruritic skin rash since November 2006. He had a history of medically controlled hypertension and benign prostate hyperplasia. He denied any previous skin disorder. Medications included enalapril maleate (since December 2004), tamsulosin HCl (June–November 2006) and terazosin HCl (November–December 2006). Under the suspicion of drug‐induced skin eruption, tamsulosin HCl and terazosin HCl were discontinued sequentially. However, the eruption persisted and progressed from the abdomen and upper chest to erythroderma within 3 months. He was referred to our clinic for further evaluation in January 2007. Physical examination showed diffuse erythematous changes over the whole body (Fig. 1) with redundant skin folds on the axillae and bilateral palpable inguinal lymph nodes. A full blood count revealed eosinophilia (13·3%) and atypical lymphocytes (3·1%). Other biochemistry examinations were all within normal range, including hepatic and renal function, except for elevated alkaline phosphatase (232 U L−1, normal < 220) and uric acid (8·3 mg dL−1, normal < 7·5). Antinuclear antibodies, rheumatoid factor, complement and tumour markers were all either negative or normal. Serum protein electrophoresis showed increased α2 globulins and polyclonal gammopathy. Skin biopsies from the left axilla and upper left arm showed diffuse interstitial granulomatous infiltrates in the dermis. The infiltrate was composed of mainly small histiocytes and lymphocytes with palisading around partially degenerated collagen. There were numerous eosinophils and scattered multinucleated giant cells. Focal vacuolar interface dermatitis was also observed (Fig. 2). Neither dermal mucin nor neutrophilia was prominent. No vasculitis was observed, nor was there subcutaneous tissue involvement. Most infiltrating cells were CD3+ and partially CD8+. Sparse CD56+ cells were also identified. The CD20 staining revealed scattered reactive B cells. No medication was prescribed and the cutaneous lesions resolved within 2 months after discontinuation of enalapril maleate. The blood tests showed no more atypical lymphocytes after discontinuation of the implicated drug for 9 months.
Human myeloma IgG half-molecules. Catabolism and biological properties.
Authors: H L Spiegelberg
Journal: Journal of Clinical Investigation (1975)

A human IgG1 myeloma protein that has a delection in the third constant domain of the heavy chain (Cgamma3) and forms two-chain half-molecules was studied for its in vivo turnover and its ability to fix C1q and hemolytic complement, to bind to human lymphocytes, neutrophils, and monocytes, and to induce a passive cutaneous reaction in guinea pigs. In both man and monkeys, the half-molecule was rapidly catabolized and in part excreted into the urine. The half-life in man was 4.3 days and the fractional turnover 165% per day; 7.6% of the intravascular pool was excreted into the urine per day. Although the 7S four-chain myeloma protein could not be obtained in a pure form, the elimination from the serum of a partially purified preparation suggested that it was also rapidly catabolized. The unaggregated half-molecule neither formed complexes with C1q, cound to human lymphocytes, neutrophils, and monocytes, nor elicited a reverse passive cutaneous reaction in guinea pigs. In contrast, the aggregated half-molecule fixed hemolytic complement and bound to the human white cells similarly to an intact IgG1 myeloma protein. In order to explain the biological activities of this half-moleculr, it is postulated that IgG1 may have several (at least two) submolecular sites for a given biological activity that are localized on both the Cgamma2 and Cgamma3 domains. Proteins having both sites would be capable of binding to C1q and Fc cell receptors in unaggregated in order to obtain half-molecule, must be aggregated in order to obtain this binding.
Effect of leukotriene receptor antagonist on expression and variation of TGF-beta in T lymphocyte for mild persistent asthma in children
Authors: Wenfang Dong, Xiaojian Zhou, Jianguo Hong
Journal: European Respiratory Journal (2011)

Objective:  To investigate the role of TGF-β 1  and action of montelukast (MT) in the pathogenesis of asthma in children.   Methods:  A single-blind, placebo-controlled trail was conducted in 60 mild persistent asthma children (5-14 y). Patients were randomly assigned to receive 5mg MT or placebo for 12 weeks. 30 healthy children (5-14 y) were as control. Clinical and pulmonary function were assessed before and after treatment. The mRNA expression of TGF-β 1  in PBMC cells, subtypes of FoxP 3  + CD 4  +  T cells and TGF-β 1  in plasma were measured.   Result:  After treatment, symptomes were improved with signigicant increase in pulmonary function in asthmatic, MT superior to placebo (p 1  and TGF-β 1  level in asthmatic were lower than that in control (0.312±0.07 vs 0.607±0.2, p 3  + CD 4  +  cell and CD 45 RA + Foxp 3  lo  were higher in asthmatic (8.3%±1.3% vs 6.05%±1.8%, p=0.007 and 4.60%±1.04% vs 3.27%±1.03%, p=0.011, respectively). CD 45 RA - Foxp 3  hi  was lower (0.75%±0.13% vs 0.93%±0.26%, p=0.021). After treatment, CD 45 RA - Foxp 3  hi  was increased in MT compared to placebo group (1.16%±0.24% vs 0.89%±0.22%, p=0.01). TGF-β 1  levels had no correlation with those levels of pulmonary function.   Conclusion:  The expression of TGF-β 1  was low in asthmatic children. Insufficient secretion of TGF-β 1  and the defection in activating FoxP 3  + CD 4  +  Treg cells might play an important role in pathogenesis of asthma. Up-regulation of expression of TGF-β 1  and induction of expression of CD 45 RA - Foxp 3  hi  in Foxp 3  + CD 4  + Treg cells by MT may be one of the mechanisms by which airway inflammation is inhibited in asthma.
Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response
Authors: T Jonsdottir, I Gunnarsson, A Risselada, E W Henriksson, L Klareskog, R F van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To evaluate efficacy, serological responses, and predictors of response in patients with severe and refractory systemic lupus erythematosus (SLE) treated with rituximab plus cyclophosphamide. <h3>Methods:</h3> 16 patients entered a treatment protocol using rituximab plus cyclophosphamide. Disease activity was assessed by the SLE disease activity index (SLEDAI) and by the British Isles Lupus Assessment Group (BILAG) index. <h3>Results:</h3> At six months follow up, mean SLEDAI values decreased significantly from (mean (SD)) 12.1 (2.2) to 4.7 (1.1). Clinical improvement (50% reduction in SLEDAI) occurred in all but three patients. All but one patient responded according to BILAG. Remission defined as SLEDAI &lt;3 was achieved in nine of 16 patients. Isotype analysis of anti-dsDNA antibodies revealed preferential decreases of IgG and IgA, but not IgM. Higher absolute numbers of CD19+ cells at baseline were correlated with shorter depletion time (<i>r</i> = −0.6). <h3>Conclusions:</h3> The majority of patients improved following rituximab plus cyclophosphamide. The differential downregulation of anti-DNA of the IgG and IgA but not the IgM isotypes supports the hypothesis that cells producing pathogenic autoantibodies are preferentially targeted by the treatment. The fact that greater absolute numbers of CD19+ cells at baseline predict a less impressive clinical and serological response suggests that more flexible dosing could be advantageous.
Epigenetic Repression of miR-31 Disrupts Androgen Receptor Homeostasis and Contributes to Prostate Cancer Progression
Authors: Pei-Chun Lin, Ya-Lin Chiu, Samprit Banerjee, Kyung Park, Juan Miguel Mosquera, Eugenia Giannopoulou, Pedro Alves, Ashutosh K. Tewari, Mark B. Gerstein, Himisha Beltran, Ari M. Melnick, Olivier Elemento, Francesca Demichelis, Mark A. Rubin
Journal: Cancer Research (2012)

Abstract Androgen receptor signaling plays a critical role in prostate cancer pathogenesis. Yet, the regulation of androgen receptor signaling remains elusive. Even with stringent androgen deprivation therapy, androgen receptor signaling persists. Here, our data suggest that there is a complex interaction between the expression of the tumor suppressor miRNA, miR-31, and androgen receptor signaling. We examined primary and metastatic prostate cancer and found that miR-31 expression was reduced as a result of promoter hypermethylation, and importantly, the levels of miR-31 expression were inversely correlated with the aggressiveness of the disease. As the expression of androgen receptor and miR-31 was inversely correlated in the cell lines, our study further suggested that miR-31 and androgen receptor could mutually repress each other. Upregulation of miR-31 effectively suppressed androgen receptor expression through multiple mechanisms and inhibited prostate cancer growth in vivo. Notably, we found that miR-31 targeted androgen receptor directly at a site located in the coding region, which was commonly mutated in prostate cancer. In addition, miR-31 suppressed cell-cycle regulators including E2F1, E2F2, EXO1, FOXM1, and MCM2. Together, our findings suggest a novel androgen receptor regulatory mechanism mediated through miR-31 expression. The downregulation of miR-31 may disrupt cellular homeostasis and contribute to the evolution and progression of prostate cancer. We provide implications for epigenetic treatment and support clinical development of detecting miR-31 promoter methylation as a novel biomarker. Cancer Res; 73(3); 1232–44. ©2012 AACR.