tbuckley/cabot-search huggingface dataset:
A common type of the spectrin alpha I 46-50a-kD peptide abnormality in hereditary elliptocytosis and pyropoikilocytosis is associated with a mutation distant from the proteolytic cleavage site. Evidence for the functional importance of the triple helical model of spectrin.
Authors: P G Gallagher, W T Tse, T Coetzer, M C Lecomte, M Garbarz, H S Zarkowsky, A Baruchel, S K Ballas, D Dhermy, J Palek
Journal: Journal of Clinical Investigation (1992)

We studied nine individuals from five unrelated families with alpha I/46-50a hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP), including one of the original HHP probands first reported by Zarkowsky and colleagues (1975. Br. J. Haematol. 29:537-543). Biochemical analysis of erythrocyte membrane proteins from these patients revealed, as a common abnormality, the presence of the alpha I/46-50a peptide after limited tryptic digestion of spectrin. The polymerase chain reaction was utilized to study the structure of the DNA encoding the alpha I domain of spectrin in the affected individuals. The DNA sequence of the alpha-spectrin gene encoding the region of the alpha-spectrin chain surrounding the abnormal proteolytic cleavage site was normal. We identified a point mutation causing the replacement of a highly conserved leucine residue by proline at position 207 in the alpha-spectrin chain, a site 51 residues to the amino-terminal side of the abnormal proteolytic cleavage site. Analysis of the proposed triple helical model of spectrin repeats reveals that the mutation occurs in helix 2 at a position directly opposite the abnormal proteolytic cleavage site in helix 3, making this the first report of a mutation occurring in helix 2 of a repeat in the alpha I domain of spectrin. These results add to the molecular heterogeneity of mutations associated with HE/HPP and provide further support for the proposed triple helical model of spectrin. Disruption of this proposed alpha-helical structure by helix-breaking proline substitutions may result in a functionally defective spectrin chain.
Urinary Polycyclic Aromatic Hydrocarbons and Childhood Obesity: NHANES (2001–2006)
Authors: Franco Scinicariello, Melanie C. Buser
Journal: Environmental Health Perspectives (2014)

Polycyclic aromatic hydrocarbons (PAHs) are known carcinogens and suspected endocrine disruptors. Prenatal exposure to PAHs has been associated with obesity in early childhood.We examined the association of urinary PAH metabolites with adiposity outcomes [body mass index (BMI) z-score, waist circumference (WC), and rate of obesity] in children and adolescents.We performed whole-sample analyses of 3,189 individuals 6-19 years of age who participated in the 2001-2006 National Health and Nutrition Examination Survey. We performed multivariate linear and logistic regression to analyze the association of BMI z-score, WC, and obesity with concentrations of single urinary PAH compounds and the sum of PAHs. Furthermore, the analyses were stratified by developmental stage [i.e., children (6-11 years) and adolescents (12-19 years)].BMI z-score, WC, and obesity were positively associated with the molecular mass sum of the PAHs and the total sum of naphthalene metabolites. Most associations increased monotonically with increasing quartiles of exposure among children 6-11 years of age, whereas dose-response trends were less consistent for adolescents (12-19 years of age). Neither total PAHs nor total naphthalene metabolites were associated with overweight in either age group, and there was little evidence of associations between the outcomes and individual PAHs.Total urinary PAH metabolites and naphthalene metabolites were associated with higher BMI, WC, and obesity in children 6-11 years of age, with positive but less consistent associations among adolescents.Scinicariello F, Buser MC. 2014. Urinary polycyclic aromatic hydrocarbons and childhood obesity: NHANES (2001-2006). Environ Health Perspect 122:299-303; http://dx.doi.org/10.1289/ehp.1307234.
Response to Letter Regarding Article, “Cardiac Biomarkers Are Associated With an Increased Risk of Stroke and Death in Patients With Atrial Fibrillation: A Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Substudy”
Authors: Ziad Hijazi, Jonas Oldgren, Lars Wallentin, Ulrika Andersson, Stuart J. Connolly, Salim Yusuf, Michael D. Ezekowitz, Stefan H. Hohnloser, Paul A. Reilly, Dragos Vinereanu, Agneta Siegbahn
Journal: Circulation (2013)
A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival
Authors: Christine P. Hans, Dennis D. Weisenburger, Julie M. Vose, Lynette M. Hock, James C. Lynch, Patricia Aoun, Timothy C. Greiner, Wing C. Chan, Robert G. Bociek, Philip J. Bierman, James O. Armitage
Journal: Blood (2003)
Orai1-Mediated <i> I <sub>CRAC</sub> </i> Is Essential for Neointima Formation After Vascular Injury
Authors: Wei Zhang, Katharine E. Halligan, Xuexin Zhang, Jonathan M. Bisaillon, José C. Gonzalez-Cobos, Rajender K. Motiani, Guoqing Hu, Peter A. Vincent, Jiliang Zhou, Margarida Barroso, Harold A. Singer, Khalid Matrougui, Mohamed Trebak
Journal: Circulation Research (2011)

The molecular correlate of the calcium release-activated calcium current (I(CRAC)), the channel protein Orai1, is upregulated in proliferative vascular smooth muscle cells (VSMC). However, the role of Orai1 in vascular disease remains largely unknown.The goal of this study was to determine the role of Orai1 in neointima formation after balloon injury of rat carotid arteries and its potential upregulation in a mouse model of VSMC remodeling.Lentiviral particles encoding short-hairpin RNA (shRNA) targeting either Orai1 (shOrai1) or STIM1 (shSTIM1) caused knockdown of their respective target mRNA and proteins and abrogated store-operated calcium entry and I(CRAC) in VSMC; control shRNA was targeted to luciferase (shLuciferase). Balloon injury of rat carotid arteries upregulated protein expression of Orai1, STIM1, and calcium-calmodulin kinase IIdelta2 (CamKIIδ2); increased proliferation assessed by Ki67 and PCNA and decreased protein expression of myosin heavy chain in medial and neointimal VSMC. Incubation of the injured vessel with shOrai1 prevented Orai1, STIM1, and CamKIIδ2 upregulation in the media and neointima; inhibited cell proliferation and markedly reduced neointima formation 14 days post injury; similar results were obtained with shSTIM1. VSMC Orai1 and STIM1 knockdown inhibited nuclear factor for activated T-cell (NFAT) nuclear translocation and activity. Furthermore, Orai1 and STIM1 were upregulated in mice carotid arteries subjected to ligation.Orai1 is upregulated in VSMC during vascular injury and is required for NFAT activity, VSMC proliferation, and neointima formation following balloon injury of rat carotids. Orai1 provides a novel target for control of VSMC remodeling during vascular injury or disease.
BCL6 is regulated by p53 through a response element frequently disrupted in B-cell non-Hodgkin lymphoma
Authors: Ofer Margalit, Hila Amram, Ninette Amariglio, Amos J. Simon, Sigal Shaklai, Galit Granot, Neri Minsky, Avichai Shimoni, Alon Harmelin, David Givol, Mordechai Shohat, Moshe Oren, Gideon Rechavi
Journal: Blood (2005)
Radiofrequency Ablation Combined with KS-IL2 Immunocytokine (EMD 273066) Results in an Enhanced Antitumor Effect against Murine Colon Adenocarcinoma
Authors: Erik E. Johnson, Brett H. Yamane, Ilia N. Buhtoiarov, Hillary D. Lum, Alexander L. Rakhmilevich, David M. Mahvi, Stephen D. Gillies, Paul M. Sondel
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Radiofrequency ablation (RFA) is a common treatment modality for surgically unresectable tumors. However, there is a high rate of both local and systemic recurrence. Experimental Design: In this preclinical study, we sought to enhance the antitumor effect of RFA by combining it with huKS-IL2 immunocytokine [tumor-specific monoclonal antibody fused to interleukin-2 (IL2)] in mice bearing CT26-KS colon adenocarcinoma. Mice were treated with RFA, huKS-IL2 via intratumoral injection, or combination therapy. Results: Treatment of mice bearing s.c. tumors with RFA and huKS-IL2 resulted in significantly greater tumor growth suppression and enhanced survival compared with mice treated with RFA or huKS-IL2 alone. When subtherapeutic regimens of RFA or huKS-IL2 were used, tumors progressed in all treated mice. In contrast, the combination of RFA and immunocytokine resulted in complete tumor resolution in 50% of mice. Treatment of a tumor with RFA and intratumoral huKS-IL2 also showed antitumor effects against a distant untreated tumor. Tumor-free mice after treatment with RFA and huKS-IL2 showed immunologic memory based on their ability to reject subsequent challenges of CT26-KS and the more aggressive parental CT26 tumors. Flow cytometry analysis of tumor-reactive T cells from mice with complete tumor resolution showed that treatment with RFA and huKS-IL2 resulted in a greater proportion of cytokine-producing CD4 T cells and CD8 T cells compared with mice treated with RFA or huKS-IL2 alone. Conclusions: These results show that the addition of huKS-IL2 to RFA significantly enhances the antitumor response in this murine model, resulting in complete tumor resolution and induction of immunologic memory.
Genetic Variants In Cep68 In Patients With Hypersensitivity Reactions To Nsaids
Authors: J.A. Cornejo-Garcia, M.C. Plaza-Seron, C. Flores, I. Dona, N. Blanca-Lopez, L.R. Jagemann, J.J. Laguna, J. Fernandez, G. Canto, M. Blanca
Journal: Journal of Allergy and Clinical Immunology (2012)
Positive Charge Loading at Protein Termini Is Due to Membrane Protein Topology, Not a Translational Ramp
Authors: Catherine A. Charneski, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2013)

In the great majority of genomes, the use of positive charge increases, on average, approaching protein N-termini. Such charged residues slow ribosomes by interacting with the negatively charged exit tunnel. This has been proposed to be selectively advantageous as it provides an elongation speed ramp at translational starts. Positive charges, however, are known to orientate proteins in membranes by the positive-inside rule whereby excess charge lies on the cytoplasmic side of the membrane. Which of these two models better explains the N-terminal loading of positively charged amino acids? We find strong evidence that the tendency for average positive charge use to increase at termini is exclusively due to membrane protein topology: 1) increasing N-terminal positive charge is not found in cytosolic proteins, but in transmembrane ones with cytosolic N-termini, with signal sequences contributing additional charge; 2) positive charge density at N-termini corresponds to the length of cytoplasmically exposed transmembrane tails, its usage increasing just up until the membrane; 3) membrane-related patterns are repeated at C-termini, where no ramp is expected; and 4) N-terminal positive charge patterns are no different from those seen internally in proteins in membrane-associated domains. The overall apparent increase in positive charge across all N-termini results from membrane proteins using positive charge adjacent to the cytosolic leaflet, combined with a skewed distribution of where N-termini cross the plasma membrane; 5) while Escherichia coli was predicted to have a 5′ ribosomal occupancy ramp of at least 31 codons, in contrast to what is seen in yeast, we find in ribosomal footprinting data no evidence for such a ramp. In sum, we find no need to invoke a translational ramp to explain the rising positive charge densities at N-termini. The membrane orientation model makes a full account of the trend.
TCT-66 Impact of Residual Chronic Total Occlusion of Right Coronary Artery on the Long Term Outcome in Patients treated for Unprotected Left Main Disease: The MIlan and New-TOkyo (MITO) Registry
Authors: Kensuke Takagi, Alfonso Ielasi, Alaide Chieffo, Sandeep Basavarajaiah, Azeem Latib, Cosmo Godino, Santo Ferrarello, Ahmed Rezq, Tasuku Hasegawa, Chiara Bernelli, Filippo Figini, Koji Hozawa, Naoyuki Kurita, Satoko Tahara, Mauro Carlino, Matteo Montorfano, Shotoro Nakamura, Sunao Nakamura, Antonio Colombo
Journal: Journal of the American College of Cardiology (2012)
11C-Choline Positron Emission Tomography/Computerized Tomography for Preoperative Lymph-Node Staging in Intermediate-Risk and High-Risk Prostate Cancer: Comparison with Clinical Staging Nomograms
Authors: Riccardo Schiavina, Vincenzo Scattoni, Paolo Castellucci, Maria Picchio, Barbara Corti, Alberto Briganti, Alessandro Franceschelli, Francesco Sanguedolce, Alessandro Bertaccini, Moshen Farsad, Giampiero Giovacchini, Stefano Fanti, Walter Franco Grigioni, Ferruccio Fazio, Francesco Montorsi, Patrizio Rigatti, Giuseppe Martorana
Journal: European Urology (2008)
Coronary Microcirculation in Health and Disease
Authors: William M. Chilian
Journal: Circulation (1997)

Abstract This article summarizes a 2-day workshop on the coronary microcirculation held in Bethesda, Md, in September 1994 and sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health. The workshop explored a variety of topics pertaining to coronary microvascular physiology and pathophysiology. The latest methodologies that are being used to investigate the coronary microvasculature, including endoscopic microscopy of the intramural coronary microvasculature and micro–x-ray computerized tomography, were discussed. The most recent advances in the regulation of the coronary microcirculation—for example, myogenic and flow-dependent responses, K ATP channels, and regional heterogeneity—were reported. The workshop touched on the relation of the microcirculation to clinically important conditions and offered recommendations for future research in this important area. Comparisons are made to recent advances in the peripheral circulation and current gaps in our knowledge concerning the coronary microcirculation. In recent years, research on the coronary microcirculation has made substantial advances, in part as a result of investigations in the peripheral microcirculation but also because of the application of unique methodologies. This research is providing new ways to investigate abnormalities of myocardial perfusion, an area of inquiry that until recently has been limited to examination of coronary pressure-flow relationships.
Association of population and practice factors with potentially avoidable admission rates for chronic diseases in London: cross sectional analysis
Authors: S. Saxena
Journal: Journal of the Royal Society of Medicine (2006)

Objectives:To examine the association between underlying ill health, material deprivation and primary care supply factors and hospital admission rates for potentially avoidable admissions in primary care trusts in London. Design:Cross sectional analysis at primary care trusts level using routine data from multiple sources. Main outcome measures:Age-standardized hospital admission rates for asthma, diabetes, heart failure, hypertension and chronic obstructive pulmonary disease. Results:Admission rates varied widely for the conditions examined across the 31 primary care trusts. In 2001, age adjusted admission rates for asthma varied from 76 to 189 per 100 000 and for diabetes from 38 to 183 per 100 000. There was a significant association between higher admission rates and measures of underlying ill health and material deprivation but not quantitative measures of primary care service provision. Provision of specialist chronic disease services in primary care for diabetes but not for asthma were significantly associated with reduced admission rates. There was no association of prescribing levels in primary care trusts with admission rates for any of the conditions examined. Conclusions:Although hospital admission for some chronic diseases is potentially avoidable and rates of hospital admission for these conditions are possible indicators of the quality of care, they should be interpreted in conjunction with measures of population composition and deprivation. Failure to do this may result in primary care trusts and general practitioners being criticized for aspects of health care utilization that are not under their direct control.
Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation
Authors: T A Seldon, R Pryor, A Palkova, M L Jones, N D Verma, M Findova, K Braet, Y Sheng, Y Fan, E Y Zhou, J D Marks, T Munro, S M Mahler, R T Barnard, P D Fromm, P A Silveira, Z Elgundi, X Ju, G J Clark, K F Bradstock, D J Munster, D N J Hart
Journal: Leukemia (2015)
miRNA-130a Targets <i>ATG2B</i> and <i>DICER1</i> to Inhibit Autophagy and Trigger Killing of Chronic Lymphocytic Leukemia Cells
Authors: Valentina Kovaleva, Rodrigo Mora, Yoon Jung Park, Christoph Plass, Abhilash I. Chiramel, Ralf Bartenschlager, Hartmut Döhner, Stephan Stilgenbauer, Armin Pscherer, Peter Lichter, Martina Seiffert
Journal: Cancer Research (2012)

Abstract Toxicity and relapses from the immunochemotherapy used to treat chronic lymphocytic leukemia (CLL) prompt continued interest in gentle but effective targeted treatment options for the mainly elderly population suffering from this disease. Here, we report the definition of critical CLL cell survival pathways that can be targeted by ectopic reexpression of the miRNA genes miR-130a and miR-143 which are widely downregulated in CLL. Notably, miR-130a inhibited autophagy by reducing autophagosome formation, an effect mediated by downregulation of the genes ATG2B and DICER1, the latter of which is a major component of the miRNA silencing machinery. In support of the concept of a fundamental connection between miRNA disregulation and altered autophagic flux in this cancer, we showed that RNA interference–mediated knockdown of DICER1 expression was sufficient to reduce autophagy in primary or established cultures of CLL cells. Together, our findings show that miR-130a modulates cell survival programs by regulating autophagic flux, and they define roles for miR-130a and Dicer1 in a regulatory feedback loop that mediates CLL cell survival. Cancer Res; 72(7); 1763–72. ©2012 AACR.
Bone marrow-derived mononuclear cell therapy attenuates silica-induced lung fibrosis
Authors: T Maron-Gutierrez, R C Castiglione, D G Xisto, M G Oliveira, F F Cruz, R Peçanha, H Carreira-Junior, D S Ornellas, M O Moraes, C M Takiya, P R M Rocco, M M Morales
Journal: European Respiratory Journal (2010)

This study tests the hypothesis that bone marrow-derived mononuclear cell (BMDMC) therapy may reduce lung inflammation and fibrosis leading to an improvement in respiratory mechanics in a murine model of silicosis. 52 female C57BL/6 mice were randomly assigned into four groups. In the silica group (SIL), silica suspension (20 mg/50 μL in saline) was intratracheally instilled. In the control animals, 50 μL saline was administered intratracheally. At 1 h, the control and SIL groups were further randomised, receiving BMDMC (2×10 6 i.v. control–cell and SIL–cell) or saline (50 μL i.v. control and SIL). BMDMC were obtained from male donor mice. At day 15, lung mechanics, histology, and the presence of Y chromosome, interleukin (IL)-1β, IL-1α, IL-1 receptor antagonist (IL-1RN), IL-1 receptor type 1, transforming growth factor (TGF)-β and caspase-3 mRNA expressions in lung tissue were analysed. In the SIL–cell group, the fraction area of granuloma, the number of macrophages and the collagen fibre content were reduced, yielding improved lung mechanics. The presence of male donor cells in lung tissue was not confirmed using detection of Y chromosome DNA. Nevertheless, caspase-3, IL-1β, IL-1α, IL-1RN and TGF-β mRNA expression diminished after cell therapy. In conclusion, BMDMC acted on inflammatory and fibrogenic processes improving lung function through paracrine effects.
DNA Copy Numbers Profiles in Affinity-Purified Ovarian Clear Cell Carcinoma
Authors: Kuan-Ting Kuo, Tsui-Lien Mao, Xu Chen, Yuanjian Feng, Kentaro Nakayama, Yue Wang, Ruth Glas, M. Joe Ma, Robert J. Kurman, Ie-Ming Shih, Tian-Li Wang
Journal: Clinical Cancer Research (2010)

Advanced ovarian clear cell carcinoma (CCC) is one of the most aggressive ovarian malignancies, in part because it tends to be resistant to platinum-based chemotherapy. At present, little is known about the molecular genetic alterations in CCCs except that there are frequent activating mutations in PIK3CA. The purpose of this study is to comprehensively define the genomic changes in CCC based on DNA copy number alterations.We performed 250K high-density single nucleotide polymorphism array analysis in 12 affinity-purified CCCs and 10 CCC cell lines. Discrete regions of amplification and deletion were also analyzed in additional 21 affinity-purified CCCs using quantitative real-time PCR.The level of chromosomal instability in CCC as defined by the extent of DNA copy number changes is similar to those previously reported in low-grade ovarian serous carcinoma but much less than those in high-grade serous carcinoma. The most remarkable region with DNA copy number gain is at chr20, which harbors a potential oncogene, ZNF217. This discrete amplicon is observed in 36% of CCCs but rarely detected in serous carcinomas regardless of grade. In addition, homozygous deletions are detected at the CDKN2A/2B and LZTS1 loci. Interestingly, the DNA copy number changes observed in fresh CCC tissues are rarely detected in the established CCC cell lines.This study provides the first high resolution, genome-wide view of DNA copy number alterations in ovarian CCC. The findings provide a genomic landscape for future studies aimed at elucidating the pathogenesis and developing new target-based therapies for CCCs.