tbuckley/cabot-search huggingface dataset:
Contribution of anti-cyclic citrullinated peptide antibody and rheumatoid factor to the diagnosis of arthropathy in haemochromatosis
Authors: E Aigner, I Schmid, C H Osterreicher, J Zwerina, G Schett, M Strasser, F Niksic, F Hohla, T Ramsauer, U Dorn, W Patsch, C Datz
Journal: Annals of the Rheumatic Diseases (2007)

To investigate the prevalence of antibodies to cyclic citrullinated peptide (anti-CCP) and rheumatoid factor in patients with hereditary haemochromatosis (HHC) and to evaluate their diagnostic reliability in distinguishing HHC-associated arthropathy from rheumatoid arthritis.Anti-CCP antibodies and rheumatoid factor levels were determined by ELISA in sera from 87 patients with HHC homozygous for the C282Y mutation of the HFE gene, 31 patients with rheumatoid arthritis and 162 healthy controls.Of the 87 patients with HHC, 32 (36.8%) had joint involvement. Anti-CCP antibodies were detected in only 1 patient (1.1%) with HHC, who had no joint disease, and in (1.2%) healthy controls. In total, 18 (58.1%) patients with rheumatoid arthritis displayed anti-CCP reactivity (p<0.001). Rheumatoid factor was detected in 10 (11.5%) patients with HHC compared with 7 (4.3%) healthy control subjects (p = 0.03) and 21 of 31 (65.6%) patients with rheumatoid arthritis.Testing for anti-CCP antibodies discriminates HHC arthropathy from rheumatoid arthritis, as these patients were consistently anti-CCP negative. Thus, HHC arthropathy should be considered in the differential diagnosis of CCP-negative arthritis.
The genome of the mesopolyploid crop species Brassica rapa
Authors: Xiaowu Wang, Hanzhong Wang, Jun Wang, Rifei Sun, Jian Wu, Shengyi Liu, Yinqi Bai, Jeong-Hwan Mun, Ian Bancroft, Feng Cheng, Sanwen Huang, Xixiang Li, Wei Hua, Junyi Wang, Xiyin Wang, Michael Freeling, J Chris Pires, Andrew H Paterson, Boulos Chalhoub, Bo Wang, Alice Hayward, Andrew G Sharpe, Beom-Seok Park, Bernd Weisshaar, Binghang Liu, Bo Li, Bo Liu, Chaobo Tong, Chi Song, Christopher Duran, Chunfang Peng, Chunyu Geng, Chushin Koh, Chuyu Lin, David Edwards, Desheng Mu, Di Shen, Eleni Soumpourou, Fei Li, Fiona Fraser, Gavin Conant, Gilles Lassalle, Graham J King, Guusje Bonnema, Haibao Tang, Haiping Wang, Harry Belcram, Heling Zhou, Hideki Hirakawa, Hiroshi Abe, Hui Guo, Hui Wang, Huizhe Jin, Isobel A P Parkin, Jacqueline Batley, Jeong-Sun Kim, Jérémy Just, Jianwen Li, Jiaohui Xu, Jie Deng, Jin A Kim, Jingping Li, Jingyin Yu, Jinling Meng, Jinpeng Wang, Jiumeng Min, Julie Poulain, Jun Wang, Katsunori Hatakeyama, Kui Wu, Li Wang, Lu Fang, Martin Trick, Matthew G Links, Meixia Zhao, Mina Jin, Nirala Ramchiary, Nizar Drou, Paul J Berkman, Qingle Cai, Quanfei Huang, Ruiqiang Li, Satoshi Tabata, Shifeng Cheng, Shu Zhang, Shujiang Zhang, Shunmou Huang, Shusei Sato, Silong Sun, Soo-Jin Kwon, Su-Ryun Choi, Tae-Ho Lee, Wei Fan, Xiang Zhao, Xu Tan, Xun Xu, Yan Wang, Yang Qiu, Ye Yin, Yingrui Li, Yongchen Du, Yongcui Liao, Yongpyo Lim, Yoshihiro Narusaka, Yupeng Wang, Zhenyi Wang, Zhenyu Li, Zhiwen Wang, Zhiyong Xiong, Zhonghua Zhang
Journal: Nature Genetics (2011)
A re-evaluation of three putative functional single nucleotide polymorphisms in rheumatoid arthritis
Authors: D Plant, A Barton, W Thomson, X Ke, S Eyre, A Hinks, J Bowes, L J Gibbons, A G Wilson, I Marinou, A W Morgan, S Steer, L J Hocking, D M Reid, P Wordsworth, P Harrison, J Worthington
Journal: Annals of the Rheumatic Diseases (2009)

In European rheumatoid arthritis (RA) patients, the strongest genetic effects are conferred by the HLA-DRB1 locus1 and the protein tyrosine phosphatase 22 gene ( PTPN22 ).2 A further three susceptibility loci ( OLIG3 / TNFAIP3 , TRAF1 / C5 and STAT4 ) have been confirmed.3 4 All five loci associate with RA in UK patients.5

Functional variants of the Fc receptor-like 3 gene ( FCRL3 ), the solute carrier 22 member 4 gene ( SLC22A4 ) and the major histocompatibility complex, class II, transactivator gene ( MHC2TA ) associate with RA in some but not all populations.

We have previously investigated polymorphisms in FCRL3 , MHC2TA and SLC22A4 in moderately sized UK studies and not detected evidence of association.6–8 Here we revisit these putative RA …
EXPERIENCES IN THE MANAGEMENT OF GERIATRIC PATIENTS WITH CHRONIC BRAIN SYNDROME
Authors: ISADORE GREEN
Journal: American Journal of Psychiatry (1965)

Hospitalized patients with chronic brain syndrome, whether associated with senile brain disease or cerebral arteriosclerosis, are especially subject to adverse side effects from phenothiazine derivatives. Previous favorable experiences with deanol acetamidobenzoate suggested a trial in managing the functional overlay of these disorders in patients presenting difficult ward problems. Fourteen subjects were treated over an average period of 2 weeks, most of them receiving oral doses of 100 mg. q.i.d.; several highly agitated patients were given intramuscular injections (60 mg. q.i.d.). A gratifying rate of success was achieved in spite of the generally unfavorable prognosis in cases of severe brain damage. More than half (53.8%) of the patients responded to deanol acetamidobenzoate with increased alertness and greater cooperation, thus requiring less nursing care. Side effects were minimal. The most outstanding successes were in agitated patients with suicidal tendencies. Until further investigations point the way to selecting patients predisposed to respond to treatment, an indiscriminate trial in all cases of chronic brain syndrome is eminently worthwhile.
<i>Fra-1</i> Promotes Breast Cancer Chemosensitivity by Driving Cancer Stem Cells from Dormancy
Authors: Dan Lu, Si Chen, Xiaoyue Tan, Na Li, Chenghu Liu, Zongjin Li, Ze Liu, Dwayne G. Stupack, Ralph A. Reisfeld, Rong Xiang
Journal: Cancer Research (2012)

Fra-1 is a member of the Fos transcription factor family that is highly expressed in multiple cancers, playing important roles in transformation, proliferation, and metastasis. In this study, we observed an inverse correlation between the expression of Fra-1 in human stage II breast cancer tissues and the corresponding level of clinical chemoresistance. Extending these findings in vitro, we found that knockdown of Fra-1 in breast tumor cells was sufficient to confer resistance to doxorubicin and cyclophosphamide, whereas enhanced Fra-1 expression could render these cells chemosensitive. The tumor cell side population, which is enriched for cancer stem cells, was found to be associated with chemoresistance. Increased side population fractions were detected among tumor cell lines subjected to Fra-1 knockdown. In contrast, enhanced expression of Fra-1 was correlated with a decreased side population fraction, and significantly, this finding was recapitulated in vivo, where tumors with enhanced expression of Fra-1 were found to have blunted growth. Tumor cells subjected to Fra-1 knockdown grew faster and were larger in size. Taken together, our findings suggest that Fra-1 may be an important prognostic marker for breast cancer therapy.
Derepression of MicroRNA‐138 Contributes to Loss of the Human Articular Chondrocyte Phenotype
Authors: Christine I. Seidl, Aida Martinez‐Sanchez, Christopher L. Murphy
Journal: Arthritis & Rheumatology (2015)

Objective To investigate the function of microRNA‐138 (miR‐138) in human articular chondrocytes (HACs). Methods The expression of miR‐138 in intact cartilage and cultured chondrocytes and the effects of miR‐138 overexpression on chondrocyte marker genes were investigated. Targets of miR‐138 relevant to chondrocytes were identified and verified by overexpression of synthetic miRNA mimics and inhibitors, luciferase assays, chromatin immunoprecipitation, and RNA immunoprecipitation of native argonaute 2, using quantitative polymerase chain reaction, Western blotting, and luciferase assays. Results Expression levels of miR‐138 were maintained at relatively low levels in intact human cartilage but were greatly increased upon loss of the differentiated phenotype in culture, with a concomitant decrease in the major cartilage extracellular matrix component COL2A1. We showed that miR‐138 is able to repress the expression of COL2A1 by directly targeting Sp‐1 and hypoxia‐inducible factor 2α (HIF‐2α), 2 transcription factors that are essential for COL2A1 transcription. We further demonstrated a direct association of these targets with miR‐138 in the RNA‐induced silencing complex and confirmed binding of Sp‐1 to the COL2A1 promoter region in HACs. Conclusion We propose that an evolutionary pressure helps to suppress expression levels of miR‐138 in human cartilage, thus enabling expression of appropriate tissue‐specific matrix genes. Inhibition of miR‐138 may serve as a potential therapeutic strategy to maintain the chondrocyte phenotype or reduce the progression of dedifferentiation in cultured HACs.
Loss of PTEN Expression by Blocking Nuclear Translocation of EGR1 in Gefitinib-Resistant Lung Cancer Cells Harboring Epidermal Growth Factor Receptor–Activating Mutations
Authors: Chizuko Yamamoto, Yuji Basaki, Akihiko Kawahara, Kazutaka Nakashima, Masayoshi Kage, Hiroto Izumi, Kimitoshi Kohno, Hidetaka Uramoto, Kosei Yasumoto, Michihiko Kuwano, Mayumi Ono
Journal: Cancer Research (2010)

Abstract Gefitinib (Iressa) and erlotinib (Tarceva), which target the epidermal growth factor receptor (EGFR), are approved for treatment of patients with advanced non–small cell lung cancer (NSCLC). Patients whose tumors harbor mutations in the EGFR gene, including delE746-A750 in exon 19 and L858R in exon 21, may benefit in particular from gefitinib treatment. However, acquired resistance to gefitinib has been a serious clinical problem, and further optimization is needed for application of EGFR-targeted drugs in lung cancer patients. In this study, we established gefitinib-resistant NSCLC cells from PC-9 cell line, which harbors the delE746-A750 mutation, by exposing the cell line to gefitinib for over 7 months. Gefitinib-resistant PC-9/GEFs cell lines showed a marked downregulation of PTEN expression and increased Akt phosphorylation. In revertant, gefitinib-sensitive clones (PC-9/Rev) derived from PC-9/GEF1-1 and PC-9/GEF2-1, PTEN expression, as well as sensitivity to gefitinib and erlotinib, was restored. Knockdown of PTEN expression using small interfering RNA specific for PTEN in PC-9 cells resulted in drug resistance to gefitinib and erlotinib. Nuclear translocation of the EGR1 transcription factor, which regulates PTEN expression, was shown to be suppressed in resistant clones and restored in their revertant clones. Reduced PTEN expression was also seen in tumor samples from a patient with gefitinib-refractory NSCLC. This study thus strongly suggests that loss of PTEN expression contributes to gefitinib and erlotinib resistance in NSCLC. Our findings reinforce the therapeutic importance of PTEN expression in the treatment of NSCLC with EGFR-targeted drugs. Cancer Res; 70(21); 8715–25. ©2010 AACR.
Clinical outcome in patients undergoing stenting of saphenous vein grafts using the TriActiv™ balloon-protection system: initial U.S. and European experience
Authors: Joseph P. Carrozza, Bernard Lancelin, Christophe Caussin, Peter Braun, William Kussmaul, Barry George, Barry Uretsky, Gregory Braden
Journal: Journal of the American College of Cardiology (2002)
3D ESOPHAGEAL RECONSTRUCTION WITH MULTI SLICE 64 COMPUTED TOMOGRAPHY AND PASSIVE FUSION WITH ESOPHAGUS SHELL. A NOVEL APPROACH TO GUIDE PULMONARY VEIN ISOLATION.
Authors: Fernando Scazzuso, Santiago Rivera, Gastón Albina, Ruben Laiño, Victoria Sammartino, Matias Kamlofsky, Alberto Giniger
Journal: Journal of the American College of Cardiology (2011)
The political determinants of health--10 years on
Authors: I. Kickbusch
Journal: BMJ (2015)

<h3>Abstract</h3> Particle tracking is a ubiquitous task in the study of dynamic molecular and cellular processes by live microscopy. Light-sheet microscopy has recently opened a path to acquiring complete cell volumes for investigation in 3-dimensions (3D). However, hypothesis formulation and quantitative analysis have remained difficult due to fundamental challenges in the visualization and the verification of large sets of 3D particle trajectories. Here we describe u-track 3D, a software package that addresses these two challenges with three algorithmic innovations. Building on the established framework of globally optimal particle association in space and time implemented in the u-track package and recent advances in gaining association robustness in the case of erratic motion, we first report a complete and versatile pipeline for particle tracking. We then present the concept of dynamic region of interest (dynROI), which allows an experimenter to interact with dynamic 3D processes in 2D views amenable to visual inspection. Third, we present an estimator of trackability, which provides for every trajectory a confidence score, thereby overcoming the challenges of visual validation of trajectories in dense particle fields. With these combined strategies, u-track 3D provides a framework for the unbiased study of molecular processes in complex volumetric sequences.
Mammographic Breast Density and Subsequent Risk of Breast Cancer in Postmenopausal Women According to Tumor Characteristics
Authors: L. Yaghjyan, G. A. Colditz, L. C. Collins, S. J. Schnitt, B. Rosner, C. Vachon, R. M. Tamimi
Journal: JNCI Journal of the National Cancer Institute (2011)

Few studies that investigated the associations between breast density and subsequent breast cancer according to tumor characteristics have produced inconclusive findings. We aimed to determine whether the associations between breast density and subsequent breast cancer varied by tumor characteristics. We included 1042 postmenopausal women diagnosed with breast cancer between June 1, 1989, and June 30, 2004, and 1794 matched control subjects from the Nurses' Health Study, an ongoing prospective cohort study of 121 701 registered female nurses across the United States. Breast density was estimated from digitized images using computerized techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires before the date of cancer diagnosis for case subjects and matched control subjects. Polychotomous logistic regression was used to assess associations of breast density with tumor subtypes based on invasiveness, histology, size, grade, receptor status, and involvement of lymph nodes. All tests of statistical significance were two-sided. The risk of breast cancer increased progressively with increase in percent breast density ( Ptrend < .001). Women with higher breast density (≥50%) showed a 3.39-fold (odds ratio = 3.39, 95% confidence interval = 2.46 to 4.68) increased risk of breast cancer compared with women with lower breast density (<10%). The associations between breast density and breast cancer risk were stronger for in situ compared with invasive tumors ( Pheterogeneity < .01), high-grade compared with low-grade tumors ( Pheterogeneity = .02), larger (>2 cm) compared with smaller (≤2 cm) tumors ( Pheterogeneity < .01), and estrogen receptor–negative compared with estrogen receptor–positive tumors ( Pheterogeneity = .04). There were no differences in associations by tumor histology, involvement of lymph nodes, and progesterone receptor and HER2 status ( Pheterogeneity > .05). The findings suggest that higher mammographic density is associated with more aggressive tumor characteristics and also with in situ tumors.
De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells
Authors: Yuko Tadokoro, Hideo Ema, Masaki Okano, En Li, Hiromitsu Nakauchi
Journal: The Journal of Experimental Medicine (2007)

DNA methylation is an epigenetic modification essential for development. The DNA methyltransferases Dnmt3a and Dnmt3b execute de novo DNA methylation in gastrulating embryos and differentiating germline cells. It has been assumed that these enzymes generally play a role in regulating cell differentiation. To test this hypothesis, we examined the role of Dnmt3a and Dnmt3b in adult stem cells. CD34−/low, c-Kit+, Sca-1+, lineage marker− (CD34− KSL) cells, a fraction of mouse bone marrow cells highly enriched in hematopoietic stem cells (HSCs), expressed both Dnmt3a and Dnmt3b. Using retroviral Cre gene transduction, we conditionally disrupted Dnmt3a, Dnmt3b, or both Dnmt3a and Dnmt3b (Dnmt3a/Dnmt3b) in CD34− KSL cells purified from mice in which the functional domains of these genes are flanked by two loxP sites. We found that Dnmt3a and Dnmt3b function as de novo DNA methyltransferases during differentiation of hematopoietic cells. Unexpectedly, in vitro colony assays and in vivo transplantation assays showed that both myeloid and lymphoid lineage differentiation potentials were maintained in Dnmt3a-, Dnmt3b-, and Dnmt3a/Dnmt3b-deficient HSCs. However, Dnmt3a/Dnmt3b-deficient HSCs, but not Dnmt3a- or Dnmt3b-deficient HSCs, were incapable of long-term reconstitution in transplantation assays. These findings establish a critical role for DNA methylation by Dnmt3a and Dnmt3b in HSC self-renewal.
Gastritis of the Herniated Stomach in Patients with Esophageal Hiatus Hernia
Authors: G G FORSTNER, A BOGOCH
Journal: JAMA (1963)

Seven illustrative cases of gastritis of the herniated stomach in patients with sliding esophageal hiatus hernia are reported. Five had superficial gastritis (three mild, one moderate and one severe); two had atrophic gastritis. Gastritis was present in two patients whose mucosa appeared normal at esophagoscopy. Interstitial hemorrhage into the lamina propria was present in four of the seven biopsy specimens. The possibility that interstitial hemorrhage may be related to the development of gastric erosions is considered. The pathogenesis of this form of gastritis is discussed.
Nonadaptive Amino Acid Convergence Rates Decrease over Time
Authors: Richard A. Goldstein, Stephen T. Pollard, Seena D. Shah, David D. Pollock
Journal: Molecular Biology and Evolution (2015)

Convergence is a central concept in evolutionary studies because it provides strong evidence for adaptation. It also provides information about the nature of the fitness landscape and the repeatability of evolution, and can mislead phylogenetic inference. To understand the role of adaptive convergence, we need to understand the patterns of nonadaptive convergence. Here, we consider the relationship between nonadaptive convergence and divergence in mitochondrial and model proteins. Surprisingly, nonadaptive convergence is much more common than expected in closely related organisms, falling off as organisms diverge. The extent of the convergent drop-off in mitochondrial proteins is well predicted by epistatic or coevolutionary effects in our "evolutionary Stokes shift" models and poorly predicted by conventional evolutionary models. Convergence probabilities decrease dramatically if the ancestral amino acids of branches being compared have diverged, but also drop slowly over evolutionary time even if the ancestral amino acids have not substituted. Convergence probabilities drop-off rapidly for quickly evolving sites, but much more slowly for slowly evolving sites. Furthermore, once sites have diverged their convergence probabilities are extremely low and indistinguishable from convergence levels at randomized sites. These results indicate that we cannot assume that excessive convergence early on is necessarily adaptive. This new understanding should help us to better discriminate adaptive from nonadaptive convergence and develop more relevant evolutionary models with improved validity for phylogenetic inference.
Hypoplasia of the Small Pulmonary Arteries in Hypoplastic Left Heart Syndrome With Restrictive Atrial Septal Defect
Authors: Katsuhide Maeda, Shigeo Yamaki, Hideaki Kado, Toshihide Asou, Arata Murakami, Shinichi Takamoto
Journal: Circulation (2004)

Background— Restrictive atrial septal defect (ASD) (including intact atrial septum [IAS]) has been reported to be a risk factor that negatively impacts survival in hypoplastic left heart syndrome (HLHS). Although lymphangiectasia and “arterialization” of the veins of the lung in HLHS with restrictive ASD have been reported, they cannot fully explain the high mortality. We have introduced a new method of evaluating the development of the pulmonary vasculature in histological sections and used it to assess patients’ lungs. We tested the hypothesis that the small pulmonary arteries (SPA), which are pulmonary arteries in a histological section whose radii are ≈25 μm to 250 μm, in HLHS with restrictive ASD are hypoplastic, but that the alveoli are not, to elucidate the mechanism underlying the poor outcome of these patients. Methods and Results— Fourteen HLHS patients between 1 day and 40 days of age were studied. In 8 cases, the ASD was restrictive [R(+) group], and in the other 6 cases it was not [R(−) group]. Specimens from 12 autopsies of cases with no congenital heart or pulmonary disease were examined as a control group (C group). As a novel histological parameter, we assessed the size of SPA in relation to the size of accompanying bronchioles to identify SPA underdevelopment. To evaluate the development of alveoli and interstitial tissue, radial alveolar counts (RAC), which reflect alveolar maturity and complexity, were also performed. Statistical comparisons between groups were made by analysis of covariance with age as a covariant factor. When the radius of the accompanying bronchiole was 100 μm, the radius of the SPA was 34.0±10.8 μm in the R(+) group, and significantly lower than the 46.6±8.5 μm in R(−) group ( P =0.0022) and 70.5±8.4 μm in the C group ( P &lt;0.0001). The RAC was in 3.5±0.9 in the R(+) group, 3.4±0.6 in the R(−) group, and 3.7±0.9 in the C group (no significant differences between groups). Conclusion— The SPA in HLHS with restrictive ASD were underdeveloped compared with the SPA in HLHS with nonrestrictive ASD and the controls, but their alveoli were not hypoplastic. Based on these results, it is speculated that SPA hypoplasia may be responsible for the poor outcome of HLHS with restrictive ASD.
Teaching of Human Anatomy
Authors: J. C. Brash, E. R. A. Cooper, D. V. Davies, J. Davies, W. L. H. Duckworth, D. A. W. Edwards, J. D. Green, H. L. H. Green, R. B. Green, W. C. O. Hill, G. W. Harris, H. A. Harris, R. G. Inkster, E. B. Jamieson, J. K. Jamieson, J. T. Jones, F. W. Jones, A. Keith, R. D. Lockhart, A. Low, M. A. MacConaill, J. W. Millen, W. R. M. Morton, E. L. Patterson, G. F. Romanes, J. H. Scott, D. Stewart, R. Walmsley, T. Walmsley, W. H. Wood
Journal: BMJ (1945)
The Current Status of Systematic Densitization
Authors: JOSEPH WOLPE, JOHN PAUL BRADY, MICHAEL SERBER, W. STEWART AGRAS, ROBERT PAUL LIBERMAN
Journal: American Journal of Psychiatry (1973)

Systematic desensitization is indicated for phobias, obsessions, compulsions, and anxiety reactions that are maintained by anxiety-reducing defense mechanisms. The technique involves instruction in deep muscle relaxation, construction of an anxiety hierarchy, and stepwise pairing of relaxation with imagined anxiety-provoking scenes. The basic principle is that relaxation is incompatible with anxiety. Relaxation can be induced by direct instruction, drugs, carbon dioxide, hypnosis, positive imagery, and a metronome-conditioned method. More than 100 outcome studies indicate that systematic desensitization produces significantly better results than a variety of comparison therapies.
Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis
Authors: Mary Eapen, Vanderson Rocha, Guillermo Sanz, Andromachi Scaradavou, Mei-Jie Zhang, William Arcese, Anne Sirvent, Richard E Champlin, Nelson Chao, Adrian P Gee, Luis Isola, Mary J Laughlin, David I Marks, Samir Nabhan, Annalisa Ruggeri, Robert Soiffer, Mary M Horowitz, Eliane Gluckman, John E Wagner
Journal: The Lancet Oncology (2010)