tbuckley/cabot-search huggingface dataset:
Epigenetic Inactivation of the Potential Tumor Suppressor Gene <i>FOXF1</i> in Breast Cancer
Authors: Pang-Kuo Lo, Ji Shin Lee, Xiaohui Liang, Liangfeng Han, Tsuyoshi Mori, Mary Jo Fackler, Helen Sadik, Pedram Argani, Tej K. Pandita, Saraswati Sukumar
Journal: Cancer Research (2010)

Abstract The expression of several members of the FOX gene family is known to be altered in a variety of cancers. We show that in breast cancer, FOXF1 gene is a target of epigenetic inactivation and that its gene product exhibits tumor-suppressive properties. Loss or downregulation of FOXF1 expression is associated with FOXF1 promoter hypermethylation in breast cancer cell lines and in invasive ductal carcinomas. Methylation of FOXF1 in invasive ductal carcinoma (37.6% of 117 cases) correlated with high tumor grade. Pharmacologic unmasking of epigenetic silencing in breast cancer cells restored FOXF1 expression. Re-expression of FOXF1 in breast cancer cells with epigenetically silenced FOXF1 genes led to G1 arrest concurrent with or without apoptosis to suppress both in vitro cell growth and in vivo tumor formation. FOXF1-induced G1 arrest resulted from a blockage at G1-S transition of the cell cycle through inhibition of the CDK2-RB-E2F cascade. Small interfering RNA–mediated depletion of FOXF1 in breast cancer cells led to increased DNA re-replication, suggesting that FOXF1 is required for maintaining the stringency of DNA replication and genomic stability. Furthermore, expression profiling of cell cycle regulatory genes showed that abrogation of FOXF1 function resulted in increased expression of E2F-induced genes involved in promoting the progression of S and G2 phases. Therefore, our studies have identified FOXF1 as a potential tumor suppressor gene that is epigenetically silenced in breast cancer, which plays an essential role in regulating cell cycle progression to maintain genomic stability. Cancer Res; 70(14); 6047–58. ©2010 AACR.
Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing
Authors: David M. Kurtz, Michael R. Green, Scott V. Bratman, Florian Scherer, Chih Long Liu, Christian A. Kunder, Kazuhiro Takahashi, Cynthia Glover, Colm Keane, Shingo Kihira, Brendan Visser, Jason Callahan, Katherine A. Kong, Malek Faham, Karen S. Corbelli, David Miklos, Ranjana H. Advani, Ronald Levy, Rodney J. Hicks, Mark Hertzberg, Robert S. Ohgami, Maher K. Gandhi, Maximilian Diehn, Ash A. Alizadeh
Journal: Blood (2015)
(39) Epidermolysis bullosa simplex. Mental and physical handicap
Authors: C.I. Harrington
Journal: British Journal of Dermatology (1986)

Journal Article (39) Epidermolysis bullosa simplex. Mental and physical handicap Get access C.I. Harrington, Dr C.I. Harrington, Dr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 84–85, https://doi.org/10.1111/j.1365-2133.1986.tb07734.x Published: 01 July 1986
Increased Circulation of Galectin-3 in Cancer Induces Secretion of Metastasis-Promoting Cytokines from Blood Vascular Endothelium
Authors: Chen Chen, Carrie A. Duckworth, Qicheng Zhao, David Mark Pritchard, Jonathan M. Rhodes, Lu-Gang Yu
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Cytokines such as interleukin (IL)-6 and granulocyte colony-stimulating factor (G-CSF) are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in patients with cancer and in particular those with metastasis, on cytokine secretion from the blood vascular endothelium in cancer. Experimental Design: The effects of galectin-3 on secretion of cytokines from human microvascular lung endothelial cells were assessed in vitro by cytokine array and in vivo in mice. The consequences of galectin-3–induced cytokine secretion on endothelial cell behaviors were determined, and the relationship between the levels of circulating galectin-3 and cytokines in patients with colorectal cancer with and without metastasis was investigated. Results: Galectin-3 at pathologic concentrations found in patients with cancer induces secretion of IL-6, G-CSF, sICAM-1, and granulocyte macrophage colony-stimulating factor from blood vascular endothelial cells in vitro and in mice. These cytokines autocrinely/paracrinely interact with the vascular endothelium to increase the expressions of endothelial cell surface adhesion molecules integrinαvβ1, E-selectin, ICAM-1, and VCAM-1, resulting in increased cancer cell–endothelial adhesion and increased endothelial cell migration and tubule formation. In patients with metastatic colon cancer, higher serum galectin-3 levels correlated significantly with increased serum G-CSF, IL-6, and sICAM1 concentrations. Conclusion: The increased circulation of galectin-3 in patients with cancer induces secretion of several metastasis-promoting cytokines from the blood vascular endothelium that enhances endothelial cell activities in metastasis. Targeting the actions of circulating galectin-3 in patients with cancer therefore represents a promising therapeutic strategy to reduce metastasis and improve survival. Clin Cancer Res; 19(7); 1693–704. ©2013 AACR.
Diabetes and Risk of Hospitalized Fall Injury Among Older Adults
Authors: Rebecca K. Yau, Elsa S. Strotmeyer, Helaine E. Resnick, Deborah E. Sellmeyer, Kenneth R. Feingold, Jane A. Cauley, Eric Vittinghoff, Nathalie De Rekeneire, Tamara B. Harris, Michael C. Nevitt, Steven R. Cummings, Ronald I. Shorr, Ann V. Schwartz
Journal: Diabetes Care (2013)

To determine whether older adults with diabetes are at increased risk of an injurious fall requiring hospitalization.The longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged 70-79 years at baseline. Hospitalizations that included ICD-9-Clinical Modification codes for a fall and an injury were identified. The effect of diabetes with and without insulin use on the rate of first fall-related injury hospitalization was assessed using proportional hazards models.At baseline, 719 participants had diabetes, and 117 of them were using insulin. Of the 293 participants who were hospitalized for a fall-related injury, 71 had diabetes, and 16 were using insulin. Diabetes was associated with a higher rate of injurious fall requiring hospitalization (hazard ratio [HR] 1.48 [95% CI 1.12-1.95]) in models adjusted for age, race, sex, BMI, and education. In those participants using insulin, compared with participants without diabetes, the HR was 3.00 (1.78-5.07). Additional adjustment for potential intermediaries, such as fainting in the past year, standing balance score, cystatin C level, and number of prescription medications, accounted for some of the increased risk associated with diabetes (1.41 [1.05-1.88]) and insulin-treated diabetes (2.24 [1.24-4.03]). Among participants with diabetes, a history of falling, poor standing balance score, and A1C level ≥8% were risk factors for an injurious fall requiring hospitalization.Older adults with diabetes, in particular those using insulin, are at greater risk of an injurious fall requiring hospitalization than those without diabetes. Among those with diabetes, poor glycemic control may increase the risk of an injurious fall.
Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): a phase 3, randomised controlled trial
Authors: P David Adelson, Stephen R Wisniewski, John Beca, S Danielle Brown, Michael Bell, J Paul Muizelaar, Pamela Okada, Sue R Beers, Goundappa K Balasubramani, Deborah Hirtz
Journal: The Lancet Neurology (2013)

On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48-72 h with slow rewarming improved mortality in children after brain injury.In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6-15 years, 16-17 years]) to either hypothermia (rapidly cooled to 32-33°C for 48-72 h, then rewarmed by 0·5-1·0°C every 12-24 h) or normothermia (maintained at 36·5-37·5°C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GOS-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742.The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1, 2007, and Feb 28, 2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0·15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events.Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury.National Institute of Neurological Disorders and Stroke and National Institutes of Health.
The Genetic Architecture of Schizophrenia: New Mutations and Emerging Paradigms
Authors: Laura Rodriguez-Murillo, Joseph A. Gogos, Maria Karayiorgou
Journal: Annual Review of Medicine (2011)

Although a genetic component of schizophrenia has been acknowledged for a long time, the underlying architecture of the genetic risk remains a contentious issue. Early linkage and candidate association studies led to largely inconclusive results. More recently, the availability of powerful technologies, samples of sufficient sizes, and genome-wide panels of genetic markers facilitated systematic and agnostic scans throughout the genome for either common or rare disease risk variants of small or large effect size, respectively. Although the former had limited success, the role of rare genetic events, such as copy-number variants (CNVs) or rare point mutations, has become increasingly important in gene discovery for schizophrenia. Importantly, recent research building upon earlier findings of de novo recurrent CNVs at the 22q11.2 locus, has highlighted a de novo mutational paradigm as a major component of the genetic architecture of schizophrenia. Recent progress is bringing us closer to earlier intervention and new therapeutic targets.
Bee venom processes human skin lipids for presentation by CD1a
Authors: Elvire A. Bourgeois, Sumithra Subramaniam, Tan-Yun Cheng, Annemieke De Jong, Emilie Layre, Dalam Ly, Maryam Salimi, Annaliza Legaspi, Robert L. Modlin, Mariolina Salio, Vincenzo Cerundolo, D. Branch Moody, Graham Ogg
Journal: The Journal of Experimental Medicine (2015)

Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom–derived phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2. These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases. The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease.
A prospective longitudinal study to assess psychological changes following anterior cruciate ligament reconstruction surgery
Authors: J L Langford, K E Webster, J A Feller
Journal: British Journal of Sports Medicine (2008)

To determine whether the psychological characteristics of athletes who have undergone an anterior cruciate ligament (ACL) reconstruction change during rehabilitation are related to returning to competitive sport.Prospective longitudinal study.87 athletes completed the Emotional Response of Athletes to Injury Questionnaire (ERAIQ) and the ACL Return to Sport after Injury scale (ACL-RSI) at 3, 6 and 12 months following ACL reconstruction surgery. Physical outcome measures were also taken at each time point.At 12 months 44 (51%) participants had returned to competitive sport and 43 (49%) participants had not returned. There were no differences in physical recovery or scores on the ERAIQ between the two groups. Participants who had returned to competitive sport at 12 months, however, scored significantly higher on the ACL-RSI scale (reflecting a more positive psychological response about sport participation) at both 6 and 12 months than participants who had not returned to competitive sport.During rehabilitation there are significant psychological differences regarding sport resumption between athletes who do, and do not, resume competitive sport 12 months following ACL reconstruction. These differences occur as early as 6 months postoperatively and highlight the importance of addressing all aspects of an athlete's recovery in order to help facilitate the athlete returning to sport.
MECHANISM OF PROTEINURIA
Authors: Richard W. Lippman, Helen J. Ureen, Jean Oliver
Journal: The Journal of Experimental Medicine (1951)

Intraperitoneal administration of bovine albumin sharply increases glomerular permeability to hemoglobin in the rat kidney. In addition, bovine albumin "saturates" the tubular absorption mechanism and inhibits the tubular absorption of subsequently administered hemoglobin. Egg white, ovalbumin, and ovomucoid, in contrast, do not produce significant changes in glomerular permeability to hemoglobin or in the tubular absorption of hemoglobin. These effects have been demonstrated both by physiologic measurements and by the morphologic demonstration of the absorbed proteins.
The Global Threat of Counterfeit Drugs: Why Industry and Governments Must Communicate the Dangers
Authors: Robert Cockburn, Paul N Newton, E. Kyeremateng Agyarko, Dora Akunyili, Nicholas J White
Journal: PLoS Medicine (2005)

The production of substandard and fake drugs is a vast and underreported problem, particularly affecting poorer countries. Cockburn and colleagues argue that the pharmaceutical industry and governments must both take action.
Competing endogenous RNA networks: tying the essential knots for cancer biology and therapeutics
Authors: Avencia Sanchez-Mejias, Yvonne Tay
Journal: Journal of Hematology & Oncology (2015)

A recently discovered dimension of post-transcriptional gene regulation involves co-regulatory crosstalk between RNA transcripts, which compete for common pools of microRNA (miRNA) molecules. These competing endogenous RNAs (ceRNAs), or natural miRNA sponges, have an active role in regulating miRNA availability within the cell and form intertwined regulatory networks. Recent reports have implicated diverse RNA species including protein-coding messenger RNAs and non-coding RNAs as ceRNAs in human development and diseases including human cancer. In this review, we discuss the most recent discoveries that implicate natural miRNA decoys in human cancer biology, as well as exciting advances in the study of ceRNA networks and dynamics. The structure and topology of intricate genome-scale ceRNA networks can be predicted computationally, and their dynamic response to fluctuations in ceRNA and miRNA levels can be studied via mathematical modeling. Additionally, the development of new methods to quantitatively determine absolute expression levels of miRNA and ceRNA molecules have expanded the capacity to accurately study the efficiency of ceRNA crosstalk in diverse biological models. These major milestones are of critical importance to identify key components of ceRNA regulatory networks that could aid the development of new approaches to cancer diagnostics and oligonucleotide-based therapeutics.
Characterization of A1 adenosine receptors in atrial and ventricular myocardium from diseased human hearts.
Authors: M Böhm, B Pieske, M Ungerer, E Erdmann
Journal: Circulation Research (1989)

The purpose of the present study was to characterize adenosine receptors in human atrial and ventricular myocardium. In isolated electrically driven preparations, adenosine produced "direct" negative inotropic effects in atrial myocardium (AT). In ventricular myocardium (VE), it only had negative inotropic properties when force of contraction had been stimulated with isoprenaline ("indirect" effect), but it has no inotropic effect alone. The adenosine receptor antagonist 8-phenyltheophylline antagonized the "direct" and "indirect" effects; these findings indicated that both effects were mediated by adenosine receptors. In cardiac membranes from human AT and VE, adenosine receptors were characterized with [3H]-8-cyclopentyl-1,3-dipropylxanthine (DPCPX) binding. The effects of agonists R-(-)-N6-phenylisopropyladenosine (R-PIA), S-(+)-N6-phenylisopropyladenosine (S-PIA), and 5'-(N-ethylcarboxamido) adenosine (NECA) and the effects of guanine nucleotides [Gpp(NH)p] were studied also. The antagonist affinities as judged from the apparent affinity, Kd, of [3H]DPCPX were similar in AT (2.2 nmol/l; 95% confidence limits, 1.4-3.7) and VE (1.8 nmol/l; 95% confidence limits, 1.0-3.0). The number of adenosine receptors was 1.7 times greater in AT (26.9 +/- 2.33 fmol/mg protein; n = 5) than in VE (16.2 +/- 2.3 fmol/mg protein; n = 5). High and low affinity states of adenosine receptors evaluated with the influence of Gpp(NH)p on agonist competition with R-PIA were similar in AT or VE. The rank orders of potency for agonists (R-PIA greater than S-PIA greater than NECA) and antagonists (DPCPX greater than 8-phenyltheophylline greater than theophylline) were characteristic for the A1 receptor subtype. It is concluded that A1 adenosine receptors exist in the human myocardium. Since binding properties were similar in AT and VE, the same A1 adenosine receptor probably couples to different effectors in a similar guanine nucleotide-dependent way. [3H]DPCPX is the first radiolabeled antagonist ligand that allows detection of A1 adenosine receptors and their coupling in the human myocardium.
Learning vaccinology from viral infections
Authors: Rafi Ahmed, Bali Pulendran
Journal: The Journal of Experimental Medicine (2011)

This issue of the Journal of Experimental Medicine celebrates and honors the life of Ralph Steinman (1943-2011), winner of the 2011 Nobel Prize in Physiology or Medicine. Ralph's science was rooted in fundamental discovery with the goal of translating these findings into clinical medicine. He recognized the power of immunology in treating human disease and passionately championed studies on vaccine design, immune therapy, and human immunology. One particular collaborative effort between the Steinman and Sekaly laboratories resulted in a paper published in this issue of the journal.
Arguments for interleukin 1 as a target in chronic arthritis
Authors: W. B van den Berg
Journal: Annals of the Rheumatic Diseases (2000)

Tumour necrosis factor (TNF) and interleukin 1 (IL1) are considered as master cytokines in chronic, destructive arthritis. Therapeutic approaches in rheumatic arthritis (RA) patients so far mainly focused on TNF. Although TNF is a major inflammatory mediator in RA and a potent inducer of IL1, anti-TNF treatment is not effective in all patients, nor does it fully control the arthritic process in affected joints of good responders. Analysis of cytokine patterns in early synovial biopsy specimens of RA patients reveals prominent TNF staining in 50% of the patients, whereas IL1b staining was evident in 100%. This argues that TNF independent IL1 production occurs in some of the patients. Studies in a range of experimental arthritis models in mice make it clear that TNF is involved in early joint swelling. However, TNF alone is not arthritogenic nor destructive and exerts its arthritogenic potential through IL1 induction. Intriguingly, TNF independent IL1 production is found in many models. Its relevance is further underlined by the greater efficacy of anti-IL1 treatment as compared with anti-TNF treatment and the total lack of chronic, erosive arthritis in IL1b deficient mice. IL1b is not necessarily involved in early joint swelling, but is a crucial mediator in chronic arthritis and cartilage erosion in all models studied so far. This makes ILb an attractive target in chronic, destructive arthritis.
Inferring Species Trees Directly from Biallelic Genetic Markers: Bypassing Gene Trees in a Full Coalescent Analysis
Authors: David Bryant, Remco Bouckaert, Joseph Felsenstein, Noah A. Rosenberg, Arindam RoyChoudhury
Journal: Molecular Biology and Evolution (2012)

The multispecies coalescent provides an elegant theoretical framework for estimating species trees and species demographics from genetic markers. However, practical applications of the multispecies coalescent model are limited by the need to integrate or sample over all gene trees possible for each genetic marker. Here we describe a polynomial-time algorithm that computes the likelihood of a species tree directly from the markers under a finite-sites model of mutation effectively integrating over all possible gene trees. The method applies to independent (unlinked) biallelic markers such as well-spaced single nucleotide polymorphisms, and we have implemented it in SNAPP, a Markov chain Monte Carlo sampler for inferring species trees, divergence dates, and population sizes. We report results from simulation experiments and from an analysis of 1997 amplified fragment length polymorphism loci in 69 individuals sampled from six species of Ourisia (New Zealand native foxglove).
Association of mitochondrial polymorphism m.709G&gt;A with Behcet's disease
Authors: J. M. Xavier, N. M. Shafiee, F. Ghaderi, A. Rosa, B. S. Abdollahi, A. Nadji, F. Shahram, F. Davatchi, S. A. Oliveira
Journal: Annals of the Rheumatic Diseases (2011)

further validation and investigation in BD and in other rheumatic diseases.