tbuckley/cabot-search huggingface dataset:
High levels of type VII collagen expression in recessive dystrophic epidermolysis bullosa cutaneous squamous cell carcinoma keratinocytes increases PI3K and MAPK signalling, cell migration and invasion
Authors: C. Pourreyron, M. Chen, J.A. McGrath, J.C. Salas-Alanis, A.P. South, I.M. Leigh
Journal: British Journal of Dermatology (2013)

Journal Article High levels of type VII collagen expression in recessive dystrophic epidermolysis bullosa cutaneous squamous cell carcinoma keratinocytes increases PI3K and MAPK signalling, cell migration and invasion Get access C. Pourreyron, C. Pourreyron Division of Cancer Research Ninewells Hospital and Medical School University of Dundee Dundee DD1 9SY U.K Search for other works by this author on: Oxford Academic Google Scholar M. Chen, M. Chen Department of Dermatology Keck School of Medicine University of Southern California Los Angeles CA U.S.A Search for other works by this author on: Oxford Academic Google Scholar J.A. McGrath, J.A. McGrath St John's Institute of Dermatology King's College London (Guy's Campus) London U.K Search for other works by this author on: Oxford Academic Google Scholar J.C. Salas‐Alanis, J.C. Salas‐Alanis Universidad Autonoma de Nuevo Leon Monterrey Mexico Search for other works by this author on: Oxford Academic Google Scholar A.P. South, A.P. South Division of Cancer Research Ninewells Hospital and Medical School University of Dundee Dundee DD1 9SY U.K Correspondence Andrew South. E‐mail: a.p.south@dundee.ac.uk Search for other works by this author on: Oxford Academic Google Scholar I.M. Leigh I.M. Leigh Division of Cancer Research Ninewells Hospital and Medical School University of Dundee Dundee DD1 9SY U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 170, Issue 6, 1 June 2014, Pages 1256–1265, https://doi.org/10.1111/bjd.12715 Published: 01 June 2014
The 1,4,5-inositol trisphosphate pathway is a key component in Fas-mediated hypertrophy in neonatal rat ventricular myocytes
Authors: Y BARAC, N ZEEVILEVIN, G YANIV, I REITER, F MILMAN, M SHILKRUT, R COLEMAN, Z ABASSI, O BINAH
Journal: Cardiovascular Research (2005)

Cardiac hypertrophy is a compensatory response to increased mechanical load. Since Fas receptor activation is an important component in hypertrophy induced by pressure- and volume-overload, deciphering the underlying signaling pathways is of prime importance. Based on our previous work showing that in mice and rats ventricular myocytes the electrophysiological disturbances and diastolic [Ca2+]i-rise caused by 3 h of Fas activation are dependent on the Fas-->phospholipase C (PLC)-->1,4,5-inositol trisphosphate (1,4,5-IP3)-->sarcoplasmic reticulum (SR) [Ca2+]i release pathway, we tested the hypothesis that this pathway is also critical for Fas-mediated hypertrophy.The effects of 24 h Fas activation in cultured neonatal rat ventricular myocytes (NRVM) were analyzed by means of RT-PCR, Western blot, immunofluorescence and fura-2 fluorescence.Fas activation increased nuclei surface area, atrial natriuretic peptide and connexin43 (Cx43) mRNA, the protein levels of total Cx43 and non-phosphorylated Cx43, and sarcomeric actin, all indicating hypertrophy. Concomitantly, Fas activation decreased mRNA of SERCA2a, the ryanodine receptor (RyR) and nuclear IP3R3. Further, Fas activation caused NFAT nuclear translocation. The hypertrophy was abolished by U73122, xestospongin C (blockers of the 1,4,5-IP3 pathway), genistein and by the PI3K blocker LY294002.Fas-mediated hypertrophy is dependent on the 1,4,5-IP3 pathway, which is functionally inter-connected to the PI3K/AKT/GSK3beta pathway. Both pathways act in concert to cause NFAT nuclear translocation and subsequent hypertrophy.
Anencephalic Infants as Organ Donors
Authors: Michael P. McQuillen
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The authors of the article on the use of anencephalic neonates as organ donors<sup>1</sup>have taken a most unethical and injudicious step in proposing a violation of the dead donor rule. The very language they use—"anencephalic neonates" as opposed to "the infant with anencephaly"<sup>2</sup>-bespeaks a degrading value judgment with which the mother of Baby K<sup>3</sup>and, indeed, the mothers of most such infants vehemently disagree. Infants with this horrific anomaly remain human beings in the same sense that infants with severe spinal muscular atrophy are human beings, even though neither can articulate the consciousness that we "know" is present in the latter condition (because infants with severe spinal muscular atrophy have cerebral hemispheres) and "know" is absent in the former (because infants with anencephaly do not). What evidence can the authors adduce to defend their knowledge that infants with anencephaly lack consciousness? In
Cyclophosphamide in the Management of Advanced Graves' Ophthalmopathy
Authors: S. THOMAS BIGOS
Journal: Annals of Internal Medicine (1979)

Three patients with advanced Graves' ophthalmopathy were treated with cyclophosphamide. All had proptosis and diplopia. One patient had disabling iatrogenic Cushing's syndrome from steroid treatment of the ophthalmopathy and had undergone bilateral orbital decompression before cyclophosphamide therapy; steroids could not subsequently be withdrawn. When cyclophosphamide was administered to the cushingoid patient, withdrawal of glucocorticoid therapy was then possible. Diplopia completely resolved in two patients and improved in the third coincident with administration of cyclophosphamide. Deteriorating visual acuity resolved in one patient. Chemosis improved in the two affected patients. Proptosis was unchanged in all three patients. Cyclophosphamide deserves further study as a therapeutic agent in Graves' disease.
Specific inhibition of nonsense-mediated mRNA decay components, SMG-1 or Upf1, rescues the phenotype of ullrich disease fibroblasts
Authors: Fusako Usuki, Akio Yamashita, Isao Kashima, Itsuro Higuchi, Mitsuhiro Osame, Shigeo Ohno
Journal: Molecular Therapy (2006)

Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that degrades aberrant mRNAs containing premature translation termination codons (PTCs). The essential proteins for NMD include SMG-1, a protein kinase, and Upf1, a substrate of SMG-1 with RNA helicase activity. In this study, we evaluated the effects of NMD inhibition by siRNA-mediated knockdown of SMG-1 or Upf1 on the phenotype of Ullrich disease, an autosomal recessive congenital muscular dystrophy. The patient studied showed a homozygous frameshift mutation with a PTC in the collagen VI α2 gene, which encodes a truncated but partially functional protein. The patient's fibroblasts showed a nearly complete loss of the triple-helical collagen VI protein and functional defects in the extracellular matrix (ECM) due to the crucial deficiency of the collagen VI α2 protein. We have shown that siRNA-mediated knockdown of SMG-1 or Upf1 causes the up-regulation of the mutant triple-helical collagen VI, resulting in the formation of partially functional ECM. We suggest that the inhibition of NMD may be useful as a therapeutic approach to treat some human genetic diseases exacerbated by NMD.
Profits of Science: The American Marriage of Business and Technology
Authors: George Ross Fisher
Journal: JAMA (1994)

This is a superb book; it can be recommended without reservation. After reading it, this reviewer imagined someone had plunged a stick in his skull and stirred vigorously. Robert Teitelman is senior editor of<i>Institutional Investor</i>, here primarly writing about the drug industry from the viewpoint of managers of huge pools of the public's capital in mutual funds and pension funds. Such managers want to know whether to invest in the pharmaceutical industry in these politically trying times, and, if so, in what type of company. And why. Physician investors, waxing euphoric whenever a new drug revolutionizes therapy, would be well advised to ponder the cooler assessment by this den-mother of big investors: biotechnology (the human genome and all that) is "a business, like any other." Physician idealists, denouncing encroachment on medical science by a medical-industrial complex, might listen to a more measured cadence: "the role of the public— particularly
Yellow Fever Eradication
Authors: Richard J. Wagman
Journal: JAMA (1962)

<h3>To the Editor:—</h3> I wish to draw your attention to an error inThe Journal(<b>178</b>:32 [Nov. 25] 1961), in the article entitled "PAHO Tallies Smallpox, Urges<i>Aedes aegypti</i>Eradication." It states that "Eight U.S. States Are Still On List Of Infested Areas." In the most recent edition of the International Sanitary Regulations, Geneva, 1961, page 98, under the heading of "Yellow Fever Receptive Areas on 1 May 1961," 10 states are listed under the United States of America. These are: Alabama, Arkansas, Florida, Georgia, Louisiana, Mississippi, South Carolina, Tennessee, Hawaii, and that part of Texas east of a line extending from Del Rio through Wichita Falls and including those cities.
Ombudsman criticises GP for striking patients off without warning
Authors: L. Eaton
Journal: BMJ (2002)

England's health service ombudsman, Sir Michael Buckley, has criticised five GPs for unreasonably striking off patients without giving them proper warning.

The latest summary of investigations, completed by his office for the quarter August-November 2001, indicate an upward trend in the number of complaints. For the whole of the previous year (April 2000 to April 2001) only nine such complaints were made, of which seven were upheld.

The …
Abstract 3056: miR-125b suppresses p14ARF and modulates p53-dependent and p53-independent apoptosis in prostate cancer cells.
Authors: Xu-Bao Shi, Sumaira Amir, Ai-Hong Ma, Lingru Xue, Ralph W. deVere White
Journal: Cancer Research (2013)

Abstract Increasing evidence has revealed that miR-125b functions as a potential oncogene in different types of human cancer. Our previous studies demonstrated that miR-125b directly targets p53, Puma and Bak1 in human prostate cancer (CaP). To further elucidate the role of miR-125b in modulating the p53 network, we utilized a bioinformatics approach to identify miR-125b-regulated, CaP-relevant tumor suppressor gene, and identified p14ARF gene as a miR-125b target. We first evaluated the effect of miR-125b on the regulation of p14ARF expression, and found that miR-125b treatment induced reduction of p14ARF by 80% in LNCaP CaP cells and 60% in 22Rv1 CaP cells. Conversely, anti-miR-125b increased the p14ARF level by 40% in LNCaP and 30% in 22Rv1. We then performed luciferase assay to validate that the miR-125b binding site in the 3’UTR of p14ARF mRNA is responsible for the regulation of p14ARF by miR-125b. Since p14ARF accelerates Mdm2 degradation, resulting in p53 up-regulation, we thus assessed the effect of miR-125b on the expression of Mdm2 and p53. Compared with miRNA control, miR-125b treatment induced a dramatic increase in Mdm2 and a significant reduction of p53 in CaP cell lines, as well as in miR-125b-overexpressed xenograft tumor. Additionally, miR-125b treatment resulted in a reduction of interaction between p14ARF and Mdm2. Next, we examined the effect of miR-125b on CaP cell proliferation. Both LNCaP and 22Rv1 cells were transfected with miR-125b and cell proliferation was determined by clone formation assay. When compared with the control, miR-125b treatment increased clonogenic survival of CaP cells, while anti-miR-125b caused a dramatic reduction in the number of colonies. We evaluated the effect of downregulation of miR-125b on apoptosis in p53-positive 22Rv1 CaP cells. Data from TUNEL assay demonstrated that anti-miR-125 caused 63% of cells to undergo apoptosis. Similarly, in p53-negative PC3 CaP cells, miR-125b treatment induced a 2-fold increase in survival, while anti-miR-125b caused 50% of cells to undergo apoptosis. In summary, we observed that overexpression of miR-125b negatively regulates the expression of p14ARF, resulting in promotion of cell proliferation and inhibition of apoptosis. Inactivation of miR-125b using anti-miR-125b affects apoptosis involving both p53-dependent and p53-independent pathways. Therefore, our data suggest that miR-125b has a great potential to be used as a therapeutic target for CaP treatment. Citation Format: Xu-Bao Shi, Sumaira Amir, Ai-Hong Ma, Lingru Xue, Ralph W. deVere White. miR-125b suppresses p14ARF and modulates p53-dependent and p53-independent apoptosis in prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3056. doi:10.1158/1538-7445.AM2013-3056
Conflict of Interest Reporting by Authors Involved in Promotion of Off-Label Drug Use: An Analysis of Journal Disclosures
Authors: Aaron S. Kesselheim, Bo Wang, David M. Studdert, Jerry Avorn
Journal: PLoS Medicine (2012)

Litigation documents reveal that pharmaceutical companies have paid physicians to promote off-label uses of their products through a number of different avenues. It is unknown whether physicians and scientists who have such conflicts of interest adequately disclose such relationships in the scientific publications they author.We collected whistleblower complaints alleging illegal off-label marketing from the US Department of Justice and other publicly available sources (date range: 1996-2010). We identified physicians and scientists described in the complaints as having financial relationships with defendant manufacturers, then searched Medline for articles they authored in the subsequent three years. We assessed disclosures made in articles related to the off-label use in question, determined the frequency of adequate disclosure statements, and analyzed characteristics of the authors (specialty, author position) and articles (type, connection to off-label use, journal impact factor, citation count/year). We identified 39 conflicted individuals in whistleblower complaints. They published 404 articles related to the drugs at issue in the whistleblower complaints, only 62 (15%) of which contained an adequate disclosure statement. Most articles had no disclosure (43%) or did not mention the pharmaceutical company (40%). Adequate disclosure rates varied significantly by article type, with commentaries less likely to have adequate disclosure compared to articles reporting original studies or trials (adjusted odds ratio [OR] = 0.10, 95%CI = 0.02-0.67, p = 0.02). Over half of the authors (22/39, 56%) made no adequate disclosures in their articles. However, four of six authors with ≥ 25 articles disclosed in about one-third of articles (range: 10/36-8/25 [28%-32%]).One in seven authors identified in whistleblower complaints as involved in off-label marketing activities adequately disclosed their conflict of interest in subsequent journal publications. This is a much lower rate of adequate disclosure than has been identified in previous studies. The non-disclosure patterns suggest shortcomings with authors and the rigor of journal practices. Please see later in the article for the Editors' Summary.
The Changing Electrocardiogram in Wilson Block
Authors: CORNELIO PAPP, K. SHIRLEY SMITH
Journal: Circulation (1955)

The significance of the Wilson variety of right bundle-branch block was investigated on the basis of serial electrocardiographic changes seen in almost half of the series. Wilson block may originate from both anteroseptal and posterior infarction; in the former it may form a solitary relic without prognostic significance; in the latter it denotes extensive septal involvement. It may modify the injury pattern of anterior infarction and may abolish the signs of posterior infarction; cardiac infarction may approximate it to the classic form of right bundle-branch block. Except in two patients, less than 4 per cent of the series, it was related to pathologic causes; it should therefore be regarded as a sign of organic heart disease.
A Patient-Reported Symptom-Based Predictor Of Objective Sinus Inflammation
Authors: Alcina K. Lidder, Rakesh Chandra, David Conley, Stephanie Shintani-Smith, Anju T. Peters, Leslie C. Grammer, Robert C. Kern, Brian Schwartz, Bruce K. Tan
Journal: Journal of Allergy and Clinical Immunology (2014)
Reproduction and development.
Authors: H Spielmann
Journal: Environmental Health Perspectives (1998)

The currently developed and validated in vitro tests for female and male fertility and also for developmental toxicity are described and evaluated according to their potential use as screening or replacement alternatives to the established in vivo tests in reproductive and developmental toxicology. Alternative methods today can only be used to evaluate a few specific components of the integrated reproductive functions in both females and males. However, in the field of developmental toxicity testing there is a strong theoretical and empirical basis for the predictive power of in vitro screens using mammalian embryos as well as embryonic cells and tissues. Several of these assays have been validated or are currently undergoing validation in several laboratories and are > 80% concordant with in vivo results. Failure to achieve 100% accuracy reflects the inherent limitations of these systems, which are manageable, as the concordance rates are still good. The level of concordance suggests that these assays are adequate for screening purposes to complement traditional in vivo testing. The use of these assays as screens will save valuable in vivo testing resources for those compounds most likely to enter the market and to which people will be exposed.
Confusing Correlates of Chlamydial Infection
Authors: Paul J. Wiesner
Journal: JAMA (1982)

Associating a tenfold increased risk of perinatal death with prenatal endocervical chlamydial infection, as Martin et al have described in this issue ofThe Journal(p 1585), is remarkable. The authors themselves caution against overinterpretation of their surprising findings. They point out several limitations  their study: the small numbers of women, unequal numbers of uninfected mothers matched  each infected mother, the absence of data on simultaneous infections, and the lack of detailed pathological examinations of the placentas and products of conception. Their prospective study divided pregnant women into groups defined by presence or absence of endocervical infection with Chlamydia trachomatis . Each group was followed up  determine the incidence of perinatal death. The two study groups differed in a number of ways that could have confounded the findings. The authors took this into account by attempting to find two matched uninfected controls for each of the Chlamydia -positive
A TRANSPARENT SHIELD FOR MONOCULAR ISOLATION IN GONORRHEAL OPHTHALMIA
Authors: James M. Patton
Journal: JAMA (1927)

All who have had experience in treating gonorrheal ophthalmia of one side realize the imperative necessity of isolating the noninfected eye. Of course, this can be done with an opaque shield but this prevents the use of the eye and must be removed at frequent intervals to permit inspection for evidence of beginning infection. Buller recognized this when he devised the "Buller shield," which consisted of a watch glass fastened before the healthy eye with collodion and cotton or adhesive tape. This procedure has saved innumerable eyes and is of the utmost value; but sufficiently large watch crystals are sometimes hard to get, do not fit the area to be covered, are not easy to fasten tightly to the nose, cheek and brow, and are often uncomfortable to wear. A few years ago I<sup>1</sup>reported the use of a shield which met these objections in that it fitted the
Myocardial ischemia-reperfusion injury: a neglected therapeutic target
Authors: Derek J. Hausenloy, Derek M. Yellon
Journal: Journal of Clinical Investigation (2013)

Acute myocardial infarction (MI) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PPCI). However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI.
Emergency Medicine Training
Authors: Rodney D. Edwards
Journal: JAMA (1977)

<h3>To the Editor.—</h3> In the article "Medical Care in the Streets" (237:43, 1977), Nancy L. Caroline, MD, perceptively pointed out that the "weakest link" in the development of emergency medical services (EMS) systems may very well be the physician. With the rapid advancement in the technology of communications, transportation, and rescue, the emergency physician must become familiar, indeed expert, in areas that are covered in medical school curricula or in the traditional residency or fellowship programs. Dr Caroline outlines nine areas of expertise that are required to provide medical direction of modern EMS systems that heretofore a limited number of physicians have mastered by self-education and trial and error. As a solution to this dilemma, Caroline proposes that a "course of instruction for doctors by radio is urgently needed." I would submit that, although such courses are desirable, an even greater effort is necessary to meet the specialized physician manpower
Antisense Oligonucleotide Inhibition of PDGFR-β Receptor Subunit Expression Directs Suppression of Intimal Thickening
Authors: Martin G. Sirois, Michael Simons, Elazer R. Edelman
Journal: Circulation (1997)

Background The elucidation of molecular mechanisms of vascular cell biology has markedly influenced our thinking on the pathophysiology of vascular disease. Antisense oligonucleotide gene therapy has helped identify proteins critical to cell-cycle progression and proliferation and possible therapeutic strategies to combat human disease. This approach, however, has not yet been used to examine the contribution of chemotactic proteins and/or their receptors. Platelet-derived growth factor-BB (PDGF-BB) released from activated platelets adherent to subendothelial connective tissue is a principal smooth muscle cell chemotactic factor. Methods and Results A series of experiments was performed to assess the capacity of antisense oligonucleotides to reduce PDGF-β receptor subunit (PDGFR-β) expression and the contribution of PDGFR-β in neointimal formation. Sustained, direct, and local perivascular administration of two different antisense oligonucleotide sequences complementary to PDGFR-β mRNA almost completely abolished the expression of PDGFR-β protein in the intima and media of injured carotid arteries and decreased neointimal formation by 80% and 60%, respectively. Furthermore, neointimal formation correlated precisely with PDGFR-β expression in an exponential fashion. Conclusions Thus, myointimal proliferation depends on both PDGFR-β overexpression and its activation by PDGF-BB. Removal of either of these two elements can suppress neointimal formation.