tbuckley/cabot-search huggingface dataset:
Cellular and Ionic Basis of Arrhythmias in Postinfarction Remodeled Ventricular Myocardium
Authors: Dayi Qin, Zhi-Hao Zhang, Edward B. Caref, Mohamed Boutjdir, Praveer Jain, Nabil El-Sherif
Journal: Circulation Research (1996)

After myocardial infarction (MI), the noninfarcted myocardium undergoes significant hypertrophy as part of the post-MI structural remodeling. Electrophysiological changes associated with the hypertrophied remodeled myocardium may play a key role in arrhythmia generation in the post-MI heart. We investigated the cellular and ionic basis of arrhythmias in remodeled left ventricular (LV) myocardium 3 to 4 weeks after MI in the rat. We analyzed (1) the incidence of induced ventricular tachyarrhythmias (VTs) in the in vivo heart, (2) action potential characteristics and arrhythmia mechanisms in multicellular preparations and isolated remodeled LV myocytes, and (3) the density and kinetics of the L-type Ca2+ current (ICa-L) and the fast and slow components of transient outward K+ currents (Ito-f and Ito-s, respectively). The results were compared with those from sham-operated rats. In vivo, programmed stimulation induced sustained VT in 80% of post-MI rats but not in sham-operated rats. The capacitance of post-MI hypertrophied myocytes was significantly increased compared with myocytes from sham-operated rats. Post-MI myocytes had prolonged action potential duration (APD) with marked heterogeneity of the time course of repolarization. The prolongation of APD could be explained by the significant decrease of the density of both Ito-f and Ito-s. There was no change in the kinetics of both currents compared with control. Both the density and kinetics of ICa-L were not significantly different in post-MI remodeled myocytes compared with control. The cellular studies showed that reentrant excitation secondary to dispersion of repolarization and triggered activity from both early and delayed afterdepolarizations are potential mechanisms for VT in the post-MI remodeled heart.
Simulator Designed for Advanced Traffic Research
Authors: Phil Gunby
Journal: JAMA (1992)

IN THE MID-1990s, some of the most sophisticated equipment yet devised to study the problem of traffic-associated violence is expected to be in operation at the University of Iowa, Iowa City.  It will be called the National Advanced Driving Simulator. Faculty members who study traffic problems are working with the Army and the National Aeronautics and Space Administration to develop graphics that—like those for simulators used to train and test aircraft pilots—will give subjects the impression of potential dangers; in this case such situations as skidding, appearance of an animal or child on the road, fog, or another vehicle approaching head-on.  $32 Million Price Tag  The US Department of Transportation, Washington, DC, says it will provide about two thirds of the expected $32 million cost of the simulator. The state, university, and other sources are expected to provide $11 million.  Besides studying how motorists cope with potentially dangerous traffic situations
Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4
Authors: Wahid Doss, Gamal Shiha, Mohamed Hassany, Reham Soliman, Rabab Fouad, Marwa Khairy, Waleed Samir, Radi Hammad, Kathryn Kersey, Deyuan Jiang, Brian Doehle, Steven J. Knox, Benedetta Massetto, John G. McHutchison, Gamal Esmat
Journal: Journal of Hepatology (2015)
E is for equivocal in EBM
Authors: Matthew R Kiln
Journal: BMJ (2004)

Response to radiation incidents and radionuclear threatsMedical treatment should be given only when safe to do so Editor-Turai et al reviewed the medical response to radiation incidents and radionuclear threats. 1 Puzzlingly, they say that providing care for a patient in a life threatening condition always has priority over decontamination from radioactive materials or those actions required for the safety of others involved (medical staff, emergency rescue teams) or related to the wider public and environment. 1I disagree.This statement will encourage inexperienced staff to disregard the safety of themselves and others in a "heroic" attempt to treat those ill and injured.The latest edition of the Major Incident Medical Management and Support Course rightly emphasises self and scene safety over that of survivors. 2Experience has shown again and again that well meaning but poorly trained or equipped rescue and medical staff are highly likely to become further victims. 3As an example, the article points out that some of the 28 radiation deaths from the Chernobyl disaster of 1986 were among fire fighters.Medical treatment should be given only when it is safe to do so: poorly considered and risky actions will simply lengthen the list of casualties.
Immunohistochemical Separation of Follicular Variant of Papillary Thyroid Carcinoma from Follicular Adenoma
Authors: Nobuki Nakamura, Lori A. Erickson, Long Jin, Sabine Kajita, Heyu Zhang, Xiang Qian, Kandelaria Rumilla, Ricardo V. Lloyd
Journal: Endocrine Pathology (2006)
Phototoxic Reaction With Nalidixic Acid
Authors: Alvin S. Zelickson
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Photosensitizing agents may reach the skin by contact, injection, or ingestion. Among those ingested are the following: sulfonamides and related drugs, the barbiturates, quinine, phenothiazines,<i>Rauwolfia</i>alkaloids and several of the antibiotics. The purpose of this paper is to add a new photosensitizer to the above list. A 22-year-old white female, in general good health, presented with a history of recurrent urinary tract infections. In July, 1963, she complained of increased frequency of urination and discomfort on urination. Catheterized urine contained 20-30 white blood cells and 40-50 red blood cells per high-power field. Urine culture was negative. The patient took tetracycline, 250 mg four times daily for one week, and three weeks later was asymptomatic. In November, 1963, increased frequency and dysuria again developed, and again urine culture was negative, although there was an increased number of WBC in the urine. Treatment consisted of sulfisoxazole (Gantrisin), 4
Lessons in Conflict of Interest: The Construction of the Martyrdom of David Healy and The Dilemma of Bioethics
Authors: James Coyne
Journal: The American Journal of Bioethics (2005)

Bioethics journals have lagged behind medical and science journals in exploring the threat of conflict of interest (COI) to the integrity of publications. Some recent discussions of COI that have occurred in the bioethics literature are reviewed. Discussions of what has been termed the “Healy affair” unintentionally demonstrate that the direct and indirect influence of undisclosed COI may come from those who call for protection from the undue influence of industry. Paradoxically, the nature and tone of current discussions may serve to dull sensitivities to what is indeed a serious set of issues facing bioethics. Some proposals are presented to address COI and other challenges to the integrity of bioethics and its journals. COI is too important a topic to be left to ideologues, and there is no substitute for readers' caution and skepticism as tools in dealing with the full range of biases that exist in published papers.
Traumatic haemorrhage into the thyroid simulating major vessel damage from deceleration injury
Authors: G. Lawton
Journal: Thorax (1974)

<b>Lawton, G. (1974).</b><i>Thorax</i>, <b>29</b>, 607-608. <b>Traumatic haemorrhage into the thyroid simulating major vessel damage from deceleration injury.</b> Haemorrhage into the thyroid gland is a well recognized condition but there are few cases in the literature of severe haemorrhage associated with trauma. A case is described of a patient involved in a road traffic accident where the clinical features strongly suggested a diagnosis of great vessel rupture associated with deceleration injury. The importance of considering the possibility of haemorrhage into a retrosternal thyroid gland in a closed chest injury is stressed, as is the importance of arch aortography in management.
Cancer Survival-Reply
Authors: John M. Merrill
Journal: JAMA (1984)

<h3>In Reply.—</h3> Ms Glassman makes an error often committed by "alternative therapy" advocates. She takes a putative element of cancer prevention and assumes it not only to be true but also to be an element of therapy for cancer. Her comments about skepticism of the public are ironic. Desperate persons may accept the unorthodox therapy just because it is outside the "establishment." I saw greater skepticism about Laetrile (<i>l</i>-mandelonitrile-β-glucuronic acid) after it was legalized in my state (Illinois) and was no longer so unorthodox. This diminished its use more than all the studies proving it without value.
RSV-infection induced enhancement of airway hyperresponsiveness in allergen sensitized and challenged mice can be prevented by inhibition of IL-13
Authors: J. Park, C. Taube, E. Yang, A. Joetham, A. Balhorn, K. Takeda, N. Miyahara, A. Dakhama, D. Donaldson, E.W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2003)
MicroRNA-132–mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis
Authors: Sudarshan Anand, Bharat K Majeti, Lisette M Acevedo, Eric A Murphy, Rajesh Mukthavaram, Lea Scheppke, Miller Huang, David J Shields, Jeffrey N Lindquist, Philip E Lapinski, Philip D King, Sara M Weis, David A Cheresh
Journal: Nature Medicine (2010)
The Thy-1-bearing cell of murine epidermis. A distinctive leukocyte perhaps related to natural killer cells.
Authors: N Romani, G Stingl, E Tschachler, M D Witmer, R M Steinman, E M Shevach, G Schuler
Journal: The Journal of Experimental Medicine (1985)

Bone marrow-derived leukocytes of murine epidermis can express two phenotypes: typical Langerhans cells, which are Ia+ and Thy-1-, and a recently discovered second population that is Thy-1+ and Ia-. To verify that these phenotypes are expressed by two different cell types, and to help understand their lineage and function, we have studied morphology and reactivity with a large panel of antibodies. Dual antibody immunofluorescence combined with electron microscopy showed that Thy-1+ and Ia+ cells were each distributed in a regular fashion and formed adjacent dendritic systems in or close to the basal layer. Double-labeling studies with anti-Ia and a second monoclonal antibody revealed that all Langerhans cells expressed F4/80 (macrophage), Mac-1 (C3bi receptor), and 2.4G2 (Fc receptor), as well as the thymus leukemia (TL) and heat-stable (M1.69/16) antigens. A large fraction expressed S100 and all exhibited membrane ATPase and nonspecific esterase. In contrast, Thy-1+ cells lacked all these features of Langerhans cells, except that a minority were strongly reactive with 2.4G2. Thy-1+ cells also lacked differentiation antigens of most other types of leukocytes, except they were rich in asialo GM1. By electron microscopy, Thy-1+ cells had cytoplasmic granules that were similar in structure and in their aryl sulfatase content to those previously described in natural killer cells. The granules were enlarged in beige mice, suggesting a lysosomal origin, and were present in mast cell-deficient W/Wv mice, indicating no relation to mast cells. We conclude that Thy-1+ epidermal cells are thoroughly distinct from Langerhans cells. On the basis of morphology and phenotype, they may represent a type of tissue natural killer cell. Thy-1+ natural killer cells are now being identified in several nonlymphoid sites, such as gut epithelium and the livers of mice given adjuvants. If Thy-1+ epidermal cells prove to be natural killer cells, it is noteworthy that they represent a resident population regularly distributed in the basal layer of all mouse strains. The notion that Thy-1+ epidermal cells are immature natural killer cells is intriguing in light of recent evidence that Ia+ Langerhans cells are also immature with respect to accessory cell function. The epidermis may not have the functional capacities of a lymphoid organ, but it could contribute immature cells important for both natural and acquired resistance.
Spasticity in children and young people with non-progressive brain disorders: summary of NICE guidance
Authors: M. A. Mugglestone, P. Eunson, M. S. Murphy
Journal: BMJ (2012)

Spasticity is a form of hypertonia1 and is associated with conditions such as cerebral palsy, which affects 110 000 people in the United Kingdom.2 More than 2000 children born this year in the UK will develop spasticity, which, if unmanaged, will cause pain, affect quality of life, and may lead to complications requiring major surgery. Children and young people with spasticity need early referral to local services that will meet their individual needs and allow them access to the range of interventions that will encourage their motor development. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the management of spasticity in children and young people with non-progressive brain disorders, including those with cerebral palsy.3 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Principles of care #### Delivering care [ Both points based on the experience and opinion of the Guideline Development Group (GDG) ] #### Management programmes
Current and Future Applications of Toxicogenomics: Results Summary of a Survey from the HESI Genomics State of Science Subcommittee
Authors: Syril Pettit, Shelley Ann des Etages, Louis Mylecraine, Ronald Snyder, Jennifer Fostel, Robert T. Dunn, Kenneth Haymes, Manuel Duval, James Stevens, Cynthia Afshari, Alison Vickers
Journal: Environmental Health Perspectives (2010)

In spite of the application of toxicogenomic (TGx) data to the field of toxicology for the past 10 years, the broad implementation and full impact of TGx for chemical and drug evaluation to improve decision making within organizations and by policy makers has not been achieved.The goal of the Health and Environmental Sciences Institute (HESI) Committee on the Application of Genomics to Mechanism-based Risk Assessment was to construct and summarize a multisector survey, addressing key issues and perspectives on the current and future practical uses and challenges of implementing TGx data to facilitate discussions for decision making within organizations and by policy makers.An online survey to probe the current status and future challenges facing the field of TGx for drug and chemical evaluation in experimental and nonclinical models was taken by scientists and scientific decision/policy makers actively engaged in the field of TGx within industrial, academic, and regulatory sectors of the United States, Europe, and Japan. For this survey, TGx refers specifically to the analysis of gene expression responses to evaluate xenobiotic exposure in experimental and preclinical models.The survey results are summarized from questions covering broad areas including technology used, organizational capacity and resource allocation, experimental approaches, data storage and exchange, perceptions of benefits and hurdles, and future expectations.The survey findings provide valuable information on the current state of the science of TGx applications and identify key areas in which TGx will have an impact as well as the key hurdles in applying TGx data to address issues. The findings serve as a public resource to facilitate discussions on the focus of future TGx efforts to ensure that a maximal benefit can be obtained from toxicogenomic studies.
Activation of the FGFR–STAT3 Pathway in Breast Cancer Cells Induces a Hyaluronan-Rich Microenvironment That Licenses Tumor Formation
Authors: Laura R. Bohrer, Pavlina Chuntova, Lindsey K. Bade, Thomas C. Beadnell, Ronald P. Leon, Nicholas J. Brady, Yungil Ryu, Jodi E. Goldberg, Stephen C. Schmechel, Joseph S. Koopmeiners, James B. McCarthy, Kathryn L. Schwertfeger
Journal: Cancer Research (2013)

Aberrant activation of fibroblast growth factor receptors (FGFR) contributes to breast cancer growth, progression, and therapeutic resistance. Because of the complex nature of the FGF/FGFR axis, and the numerous effects of FGFR activation on tumor cells and the surrounding microenvironment, the specific mechanisms through which aberrant FGFR activity contributes to breast cancer are not completely understood. We show here that FGFR activation induces accumulation of hyaluronan within the extracellular matrix and that blocking hyaluronan synthesis decreases proliferation, migration, and therapeutic resistance. Furthermore, FGFR-mediated hyaluronan accumulation requires activation of the STAT3 pathway, which regulates expression of hyaluronan synthase 2 (HAS2) and subsequent hyaluronan synthesis. Using a novel in vivo model of FGFR-dependent tumor growth, we demonstrate that STAT3 inhibition decreases both FGFR-driven tumor growth and hyaluronan levels within the tumor. Finally, our results suggest that combinatorial therapies inhibiting both FGFR activity and hyaluronan synthesis is more effective than targeting either pathway alone and may be a relevant therapeutic approach for breast cancers associated with high levels of FGFR activity. In conclusion, these studies indicate a novel targetable mechanism through which FGFR activation in breast cancer cells induces a protumorigenic microenvironment.
Where is the NHS Macpherson?
Authors: M. W McNicol
Journal: BMJ (2009)

Macpherson found an institutional problem of racism in the Metropolitan Police. The NHS seems to have an institutional problem about safety. Surely the failure of all the safety mechanisms at local, regional, and national levels in Staffordshire demand wider investigation than the narrow focus on the trust by the select committee, and the anecdotal approach of a recent conference.1 2

That the responsible heads of the NHS suggest juniors should “make waves” seems superficial. Senior medical and nursing …
GYNECOLOGICAL OBSERVATIONS IN THE INSANE.
Authors: C. A. KIRKLEY
Journal: JAMA (1892)

The observations recorded in this paper were made at the Toledo Hospital for Insane during a part of 1890 and 1891, the opportunity being kindly given by Dr. H. A. Tobey, Supt. Owing to the vicissitudes of politics, Dr. Tobey was succeeded by Dr. C. E. Tupper who kindly permitted the work to go on. To these gentlemen and their assistants is due the credit of facilitating in every possible way the difficult work. Acknowledgement is due Dr. Faber, one of the assistant physicians who kept a clinical record of the cases reported. Investigation in each case has been difficult, and it has been impossible to obtain reliable histories in some of them. In some cases patients had regained their normal mental condition sufficiently to give something of a correct history, but that concerning the reproductive organs in the application for admission to the hospital has been of little value.
Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.
Authors: J Gaschet, A Lim, L Liem, R Vivien, M M Hallet, J L Harousseau, J Even, E Goulmy, M Bonneville, N Milpied, H Vié
Journal: Journal of Clinical Investigation (1996)

Analysis of a large number of unrelated bone marrow transplantations (BMT) has shown that HLA-DP incompatibility did not detectably influence the risk for acute graft-versus-host disease (aGVHD). Accordingly, it was proposed that HLA-DP determinants did not function as transplantation antigens in the same way as HLA-A, -B, or -DR. We have previously shown that HLA-DP (as well as HLA-A, -B, -DQ, or -DR)-specific T cells could be isolated from skin biopsies of patients who developed an aGVHD after semiallogeneic BMT. Nevertheless, whether a single HLA-DP mismatched allele could induce a detectable allo-specific reaction in vivo after BMT remained to be established. To directly address this issue we studied one patient who presented aGVHD after receiving purified CD34+ bone marrow (BM) cells from an unrelated donor with a single HLA-DP mismatch in the GVHD direction. To characterize the immunological events associated with GVHD, we analyzed the peripheral T cell repertoire, the T cell receptor Vbeta diversity, and the specificity of T cells invading a skin biopsy at the onset of GVHD. Our results demonstrated that a large fraction of skin-infiltrating lymphocytes, which expressed diverse T cell receptors, were reactive against this single HLA-DPB1 *0501 mismatch and consequently that a single HLA-DP mismatch between BM donor and recipient can activate a strong T cell response in vivo.
Sodium- and energy-dependent uptake of myo-inositol by rabbit peripheral nerve. Competitive inhibition by glucose and lack of an insulin effect.
Authors: D A Greene, S A Lattimer
Journal: Journal of Clinical Investigation (1982)

Experimental diabetes consistently reduces the concentration of free myo-inositol in peripheral nerve, which usually exceeds that of plasma by 90-100-fold. This phenomenon has been explicitly linked to the impairment of nerve conduction in the acutely diabetic streptozocin-treated rat. However, the mechanism by which acute experimental diabetes lowers nerve myo-inositol content and presumably alters nerve myo-inositol content and presumably alters nerve myo-inositol metabolism is unknown. Therefore, the effects of insulin and elevated medium glucose concentration of 2-[3H]myo-inositol uptake were studied in a metabolically-defined in vitro peripheral nerve tissue preparation derived from rabbit sciatic nerve, whose free myo-inositol content is reduced by experimental diabetes. The results demonstrate that myo-inositol uptake occurs by at least two distinct transport systems in the normal endoneurial preparation. A sodium- and energy-dependent saturable transport system is responsible for at least 94% of the measured uptake at medium myo-inositol concentrations approximating that present in plasma. This carrier-mediated transport system has a high affinity for myo-inositol (Kt = 63 microM), and is not influenced acutely by physiological concentrations of insulin; it is, however, inhibited by hyperglycemic concentrations of glucose added to the incubation medium in a primarily competitive fashion. Thus, competitive inhibition of peripheral nerve myo-inositol uptake by glucose may constitute a mechanism by which diabetes produces physiologically significant alterations in peripheral nerve myo-inositol metabolism.