tbuckley/cabot-search huggingface dataset:
Mercury-induced renal autoimmunity: changes in RT6+ T-lymphocytes of susceptible and resistant rats.
Authors: L L Kosuda, D L Greiner, P E Bigazzi
Journal: Environmental Health Perspectives (1993)

The repeated administration of mercury to rats of the Brown Norway (BN) inbred strain results in a self-limiting production of autoantibodies to renal antigens (e.g., laminin) and autoimmune glomerulonephritis. In contrast, rats of the Lewis (LEW) strain do not develop renal autoimmunity after mercury treatment. Suppressor T-cells and/or the idiotype-anti-idiotype network have been implicated in the control of autoimmunity in susceptible (BN) rats as well as the "resistant" state of nonsusceptible (LEW) animals. In our investigations of the immune regulation of mercury-induced autoimmune glomerulonephritis, we have performed a phenotypic analysis of lymphocyte subpopulation in the spleens and lymph nodes of mercury-treated and control LEW, BN, and (BN x LEW) F1 hybrid rats. Of particular interest were RT6+ T-cells, a subpopulation of lymphocytes that may have immunoregulatory properties and show a relative decrease in mercury-treated BN rats concomitantly with the development of autoimmune responses to renal autoantigens. LEW rats did not develop renal autoimmunity after mercury treatment and had no significant change in the ratio of RT6+ to RT6- T-lymphocytes. Interestingly, the administration of mercury to (BN x LEW) F1 hybrid rats caused effects similar to those observed in the BN strain. Auto-immune responses to antigens of the kidney coincided with a change in the balance within the RT6 cell population, which was altered in favor of T-lymphocytes that do not express the RT6 phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
When Life Support Is Questioned Early in the Care of Patients with Cervical-Level Quadriplegia
Authors: D R Patterson, C Miller-Perrin, T R McCormick, L D Hudson
Journal: New England Journal of Medicine (1993)

Some patients with cervical spinal cord injuries ask to die. It is generally held that a competent, informed adult has the right to forgo medical treatment, even life-sustaining therapy1. Furthermore, respect for patients' autonomy is not only a fundamental ethical principle, but is also sanctioned by law2,3. In particular, there are a number of published accounts of patients with high-level cervical injuries who have been granted permission by the courts to discontinue life support48. In all these cases, the patients were beyond the acute phase of their injury when they made their decisions.In this . . .
Cardiac Small Conductance Ca <sup>2+</sup> -Activated K <sup>+</sup> Channel Subunits Form Heteromultimers via the Coiled-Coil Domains in the C Termini of the Channels
Authors: Dipika Tuteja, Sassan Rafizadeh, Valeriy Timofeyev, Shuyun Wang, Zheng Zhang, Ning Li, Robertino K. Mateo, Anil Singapuri, J. Nilas Young, Anne A. Knowlton, Nipavan Chiamvimonvat
Journal: Circulation Research (2010)

Ca(2+)-activated K(+) channels are present in a wide variety of cells. We have previously reported the presence of small conductance Ca(2+)-activated K(+) (SK or K(Ca)) channels in human and mouse cardiac myocytes that contribute functionally toward the shape and duration of cardiac action potentials. Three isoforms of SK channel subunits (SK1, SK2, and SK3) are found to be expressed. Moreover, there is differential expression with more abundant SK channels in the atria and pacemaking tissues compared with the ventricles. SK channels are proposed to be assembled as tetramers similar to other K(+) channels, but the molecular determinants driving their subunit interaction and assembly are not defined in cardiac tissues.To investigate the heteromultimeric formation and the domain necessary for the assembly of 3 SK channel subunits (SK1, SK2, and SK3) into complexes in human and mouse hearts.Here, we provide evidence to support the formation of heteromultimeric complexes among different SK channel subunits in native cardiac tissues. SK1, SK2, and SK3 subunits contain coiled-coil domains (CCDs) in the C termini. In vitro interaction assay supports the direct interaction between CCDs of the channel subunits. Moreover, specific inhibitory peptides derived from CCDs block the Ca(2+)-activated K(+) current in atrial myocytes, which is important for cardiac repolarization.The data provide evidence for the formation of heteromultimeric complexes among different SK channel subunits in atrial myocytes. Because SK channels are predominantly expressed in atrial myocytes, specific ligands of the different isoforms of SK channel subunits may offer a unique therapeutic opportunity to directly modify atrial cells without interfering with ventricular myocytes.
Why do people seek treatment by alternative medicine?
Authors: J Moore, K Phipps, D Marcer, G Lewith
Journal: BMJ (1985)

45 days, above it on 51, and below it on 84.Patients received heparin for a median of four days, and the kaolin cephalin clotting time was within the therapeutic range for a median of one day in each patient (though never in 13 patients) (table).Interestingly, there was no trend towards improved control with duration of treatment.Day by day analysis of anticoagulant state of patients receiving heparin infusion (figures are numbers (%O) of patients) Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 (n=45) (n=45) (n=41) (n=36) (n=12) (n = 1) Within therapeutic range 10 ( 22) 10 ( 22) 14 (34) 7 ( 20) 4 (33) Above therapeutic range 12 (27) 8 ( 18) 12 ( 29) 17 ( 47) 5 ( 42) 1 (100) Below therapeutic range 23 (51) 27 ( 60) 15 (37) 12 (33) 3 (25)
Endarterectomy for Asymptomatic Carotid Artery Stenosis
Authors: Marc R. Mayberg
Journal: JAMA (1995)

Since its inception in the 1950s, carotid endarterectomy has been widely applied as a means to prevent cerebral infarction. The removal of stenotic or ulcerated lesions at the cervical carotid bifurcation appeared to be a logical and practical approach to stroke prevention. However, the appropriateness of this operation became a matter of controversy in the mid 1980s,<sup>1,2</sup>in part because of the lack of objective data demonstrating the efficacy of carotid endarterectomy in preventing stroke. Subsequent to that time, six prospective, randomized trials for endarterectomy have been reported,<sup>3-8</sup>five of which have shown benefit for surgery in preventing cerebral ischemia. Three trials<sup>4-6</sup>randomized patients with symptomatic carotid stenosis (ie, transient ischemic attack, amaurosis fugax, or small completed stroke ipsilateral to the carotid narrowing). Several notable features were common to all three trials of symptomatic carotid stenosis. First, carotid endarterectomy provided significant protection against subsequent ipsilateral stroke in
Bystander Chronic Infection Negatively Impacts Development of CD8+ T Cell Memory
Authors: Erietta Stelekati, Haina Shin, Travis A. Doering, Douglas V. Dolfi, Carly G. Ziegler, Daniel P. Beiting, Lucas Dawson, Jennifer Liboon, David Wolski, Mohammed-Alkhatim A. Ali, Peter D. Katsikis, Hao Shen, David S. Roos, W. Nicholas Haining, Georg M. Lauer, E. John Wherry
Journal: Immunity (2014)
Neurotensin is a proinflammatory neuropeptide in colonic inflammation
Authors: Ignazio Castagliuolo, Chi-Chung Wang, Leyla Valenick, Asiya Pasha, Sigfus Nikulasson, Robert E. Carraway, Charalabos Pothoulakis
Journal: Journal of Clinical Investigation (1999)

The neuropeptide neurotensin mediates several intestinal functions, including chloride secretion, motility, and cellular growth. However, whether this peptide participates in intestinal inflammation is not known. Toxin A, an enterotoxin from Clostridium difficile, mediates pseudomembranous colitis in humans. In animal models, toxin A causes an acute inflammatory response characterized by activation of sensory neurons and intestinal nerves and immune cells of the lamina propria. Here we show that neurotensin and its receptor are elevated in the rat colonic mucosa following toxin A administration. Pretreatment of rats with the neurotensin receptor antagonist SR-48,692 inhibits toxin A–induced changes in colonic secretion, mucosal permeability, and histologic damage. Exposure of colonic explants to toxin A or neurotensin causes mast cell degranulation, which is inhibited by SR-48,692. Because substance P was previously shown to mediate mast cell activation, we examined whether substance P is involved in neurotensin-induced mast cell degranulation. Our results show that neurotensin-induced mast cell degranulation in colonic explants is inhibited by the substance P (neurokinin-1) receptor antagonist CP-96,345, indicating that colonic mast activation in response to neurotensin involves release of substance P. We conclude that neurotensin plays a key role in the pathogenesis of C. difficile–induced colonic inflammation and mast cell activation.
Abstract 1122: UVB-induced PTEN down-regulation and its association with skin carcinogenesis
Authors: Mei Ming, Weinong Han, Christopher R. Shea, Keyoumars Soltani, Jessica Maddox, Diane M. Freeman, Yu-Ying He
Journal: Cancer Research (2010)

Abstract Non-melanoma skin cancer including squamous cell carcinoma (SCC) is the most common cancer in the United States and ultraviolet (UV) radiation in sunlight is a major environmental trigger for skin carcinogenesis. PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a proven critical tumor suppressor. We found that UVB down-regulates PTEN in primary human keratinocytes, human HaCaT keratinocytes and mouse skin, and the ERK/AKT/PTEN axis may form a positive feedback loop following UVB irradiation. We also examined PTEN levels in different types of skin cancer that are associated with chronic sun exposure, including actinic keratoses (AK, premalignant lesion), keratocanthoma (KA), squamous cell carcinoma (SCC) in situ (SCC is), SCC invasive (SCC iv). As compared with normal skin, PTEN expression is significantly down-regulated in human skin cancer with these different diagnoses. In addition, PTEN down-regulation is significantly associated with solar UV damage and age of patients. Our findings indicate that UVB radiation suppresses PTEN expression in human skin cancer and this down-regulation may play critical roles in the development and progression of human skin cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1122.
Abstract 4296: Ultrasmall gadolinium-loaded polymer nanoparticles for imaging in glioblastoma
Authors: Benjamin Himes, Jiangbing Zhou, Toral Patel, Daniel Coman, Fahmeed Hyder, Mark Saltzman
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) is a devastating disease for which prognosis remains exceptionally poor even with maximal intervention. A central challenge in the treatment of GBM is realizing effective drug delivery to the tumor and surrounding brain tissue, due to the inability of many drugs to cross the blood-brain barrier (BBB). The use of nanoparticles comprised of biodegradeable polymer as vehicles for intracranial drug delivery circumvents the BBB and allows for sustained, controlled release of drug in a targeted area. Nanoparticle encapsulation also protects therapeutic payloads from premature degradation in the microenvironment. However, effective distribution of nanoparticles in brain tissue has emerged as a potential hurdle to therapeutic efficacy. To this end we have synthesized ultrasmall poly(lactic-co-glycolic acid) (PLGA) nanoparticles 60-80nm in size, which demonstrate pronounced improvement in volume of distribution relative to larger particles. This enables particle diffusion into normal brain tissue, where the pore size of the extracellular matrix is limited to 38-64nm, allowing for drug delivery to the infiltrative edge to the tumor. Further, as the utility of these nanoparticles lies in their ability to deliver drug in a clinically relevant area, it is vital to develop a translatable means of imaging intracranial particle delivery to ensure adequate distribution. To address this issue we have developed gadolinium-loaded ultrasmall PLGA nanoparticles. These particles are detectable by MRI and distribute over a wide area when administered with the aid of convection-enhanced delivery (CED). These particles, composed entirely of FDA-approved materials, provide a diagnostic means to visualize distribution of nanoparticles in a clinically applicable capacity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4296. doi:1538-7445.AM2012-4296
A randomised controlled trial of surgery for glue ear.
Authors: N A Black, C F Sanderson, A P Freeland, M P Vessey
Journal: BMJ (1990)

To assess the effect of five different surgical treatments for glue ear (secretory otitis media) on improvement in hearing and, assuming one or more treatments to be effective, to identify the appropriate indications for surgery.Randomised controlled trial of children receiving (a) adenoidectomy, bilateral myringotomy, and insertion of a unilateral grommet; (b) adenoidectomy, unilateral myringotomy, and insertion of a unilateral grommet; (c) bilateral myringotomy and insertion of a unilateral grommet; and (d) unilateral myringotomy and insertion of a grommet. Children were followed up at seven weeks, six months, 12 months, and 24 months by symptom history and clinical investigations.Otolaryngology department in an urban hospital.149 Children aged 4-9 years who were admitted for surgery for glue ear and who had no history of previous operations on tonsils, adenoids, or ears and no evidence of sensorineural deafness. Inadequate follow up information on levels of hearing and on middle ear function was obtained from 22.Mean hearing loss (dB) of the three worst heard frequencies between 250 and 4000 Hz, results of impedance tympanometry, and parental views on their child's progress.In the 127 children for whom adequate information was available ears in which a grommet had been inserted performed better in the short term (for at least six months) than those in which no grommet had been inserted, irrespective of any accompanying procedure. Most of the benefit had disappeared by 12 months. Adenoidectomy produced a slight improvement that was not significant, though was sustained for at least two years. The ears of children who had had an adenoidectomy with myringotomy and grommet insertion, however, continued to improve so that two years after surgery about 50% had abnormal tympanometry compared with 83% of those who had had only myringotomy and grommet insertion, and 93% of the group that had had no treatment. Logistic regression analyses identified preoperative hearing level as the single best predictor of good outcome from surgery. Other variables contributed little additional predictive power.If the principal objective of surgery for glue ear is to restore hearing then our study shows that insertion of grommets is the treatment of choice. The addition of an adenoidectomy will increase the likelihood of restoration of normal function of the middle ear but will not improve hearing. When deciding appropriate indications for surgery, a balance has to be made between performing unnecessary operations and failing to treat patients who might benefit from surgical intervention. Preoperative audiometry scores might be the best predictor in helping to make this decision.
Diffusion of Carbon Monoxide Through Gypsum Wallboard
Authors: Neil B. Hampson, Todd G. Courtney, James R. Holm
Journal: JAMA (2013)

Diffusion of Carbon Monoxide Through Gypsum WallboardCarbon monoxide (CO) poisoning is a significant US health problem, responsible for approximately 500 accidental deaths annually, 1 and a risk of 18% to 35% for cognitive brain injury 1 year after poisoning. 2Most morbidity and mortality from CO poisoning is believed to be preventable through public education and CO alarm use.States have been enacting legislation mandating residential CO alarm installation. 3However, as of December 2012, 10 of the 25 states with statutes mandating CO alarms exempted homes without fuel-burning appliances or attached garages, believing that without an internal CO source, risk is eliminated.This may not be true if CO diffuses directly through wallboard material.Methods | A Plexiglas chamber divided by various configurations of gypsum wallboard was used to determine whether CO diffuses across drywall.Single-layer 0.25-and 0.5-inch thick wallboard, double-layer 0.5-inch thick wallboard, and double-layer 0.5-inch thick wallboard painted on 1 side were tested.Carbon monoxide test gas (3000 ppm) was infused into 1 chamber at 15 L per minute to a concentration of 500 to 600 ppm and then CO concentrations were measured once per minute in each chamber for 24 hours with monitors having a resolution of 1 ppm and range of 0 to 999 ppm (Biosystems Toxipro Single-Sensor Gas Monitor, Honeywell Inc).Six trials for each of the plain wallboard configurations were performed (3 in each direction) and 3 trials with the painted double-layer wallboard, infusing CO on the unpainted side.Experiments were performed from March 22, 2012, through November 28, 2012.We sought to determine how rapidly a concentration of CO toxic to humans (100 ppm) would be reached in the noninfused chamber and whether diffusion would then continue, measuring the time until the chambers reached less than 5% of their initial concentration difference.Mean and standard deviation results were calculated using GraphPad statistical software (GraphPad Software Inc).
Points from Letters: Tired Doctors
Authors: S. Stowe
Journal: BMJ (1971)

gastroenteritis and other toxic conditions in infants there was extreme hyperuricaemia-20 mg/100 ml was often recorded.With such levels precipitation of urate in the kid- ney had to be considered.To investigate this possibility experimen- tal production of the syndrome was, effected in rats by blocking the uricase activity with oxonic acid.3By application of sublethal tourniquet shock in these animals we regularly found hyperuricaemia and massive uric acid precipitation in the renal tubules.4It is possible that "shock" kidney is provoked by this mechanism, and the par- ticular purine metabolism of man may also be the explanation of his special proneness to kidney damage in shock.-Weare, etc.,
Tissue kallikrein deficiency aggravates cardiac remodelling and decreases survival after myocardial infarction in mice
Authors: Sandrine Pons, Violaine Griol‐Charhbili, Christophe Heymes, Paul Fornes, Didier Heudes, Albert Hagege, Xavier Loyer, Pierre Meneton, Jean‐François Giudicelli, Jane‐Lise Samuel, François Alhenc‐Gelas, Christine Richer
Journal: European Journal of Heart Failure (2008)
Stinging insect hypersensitivity: A practice parameter update 2011
Authors: David B.K. Golden, John Moffitt, Richard A. Nicklas, Theodore Freeman, David F. Graft, Robert E. Reisman, James M. Tracy, David Bernstein, Joann Blessing-Moore, Linda Cox, David A. Khan, David M. Lang, John Oppenheimer, Jay M. Portnoy, Christopher Randolph, Diane E. Schuller, Sheldon L. Spector, Steven A. Tilles, Dana Wallace
Journal: Journal of Allergy and Clinical Immunology (2011)
Morpholino Oligomer–Mediated Exon Skipping Averts the Onset of Dystrophic Pathology in the mdx Mouse
Authors: Sue Fletcher, Kaite Honeyman, Abbie M Fall, Penny L Harding, Russell D Johnsen, Joshua P Steinhaus, Hong M Moulton, Patrick L Iversen, Stephen D Wilton
Journal: Molecular Therapy (2007)

Duchenne and Becker muscular dystrophies are allelic disorders arising from mutations in the dystrophin gene. Duchenne muscular dystrophy is characterized by an absence of functional protein, whereas Becker muscular dystrophy, commonly caused by in-frame deletions, shows synthesis of partially functional protein. Anti-sense oligonucleotides can induce specific exon removal during processing of the dystrophin primary transcript, while maintaining or restoring the reading frame, and thereby overcome protein-truncating mutations. The mdx mouse has a non-sense mutation in exon 23 of the dystrophin gene that precludes functional dystrophin production, and this model has been used in the development of treatment strategies for dystrophinopathies. A phosphorodiamidate morpholino oligomer (PMO) has previously been shown to exclude exon 23 from the dystrophin gene transcript and induce dystrophin expression in the mdxmouse, in vivo and in vitro. In this report, a cell-penetrating peptide (CPP)-conjugated oligomer targeted to the mouse dystrophin exon 23 donor splice site was administered to mdxmice by intraperitoneal injection. We demonstrate dystrophin expression and near-normal muscle architecture in all muscles examined, except for cardiac muscle. The CPP greatly enhanced uptake of the PMO, resulting in widespread dystrophin expression. Duchenne and Becker muscular dystrophies are allelic disorders arising from mutations in the dystrophin gene. Duchenne muscular dystrophy is characterized by an absence of functional protein, whereas Becker muscular dystrophy, commonly caused by in-frame deletions, shows synthesis of partially functional protein. Anti-sense oligonucleotides can induce specific exon removal during processing of the dystrophin primary transcript, while maintaining or restoring the reading frame, and thereby overcome protein-truncating mutations. The mdx mouse has a non-sense mutation in exon 23 of the dystrophin gene that precludes functional dystrophin production, and this model has been used in the development of treatment strategies for dystrophinopathies. A phosphorodiamidate morpholino oligomer (PMO) has previously been shown to exclude exon 23 from the dystrophin gene transcript and induce dystrophin expression in the mdxmouse, in vivo and in vitro. In this report, a cell-penetrating peptide (CPP)-conjugated oligomer targeted to the mouse dystrophin exon 23 donor splice site was administered to mdxmice by intraperitoneal injection. We demonstrate dystrophin expression and near-normal muscle architecture in all muscles examined, except for cardiac muscle. The CPP greatly enhanced uptake of the PMO, resulting in widespread dystrophin expression.
Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia: a single institution's experience
Authors: JE Rubnitz, SC Raimondi, AR Halbert, X Tong, DK Srivastava, BI Razzouk, C-H Pui, JR Downing, RC Ribeiro, FG Behm
Journal: Leukemia (2002)
A “paper-less” study on optimal treatment strategies for hypertension and CAD: pilot phase data from the INternational VErapamil-trandolapril STudy (INVEST)
Authors: C.J. Pepine, M. Conlon, E. Handberg-Thurmond, R.G. Marks, R. Cooper-DeHoff, H.Robert Kolb
Journal: Journal of the American College of Cardiology (1998)
P404 IDENTIFICATION OF NEW BIOMARKERS IN HEPATITIS B RELATED HEPATOCELLULAR CARCINOMA PATIENTS USING THE MASS SPECTROMETRY AND WESTERN BLOT ANALYSIS
Authors: J.H. Lee, J.H. Shim, G.W. Song, M.J. Jun, Y.-S. Lim, S.W. Choi, D.J. Suh
Journal: Journal of Hepatology (2014)
Corticosteroid-Responsive Hypercalcemia with Elevated Serum 1-Alpha, 25 Dihydroxyvitamin D
Authors: Boy Frame, A. M. Parfitt
Journal: Annals of Internal Medicine (1980)

A 51-year-old man has had absorptive hypercalciuria and corticosteroid-responsive hypercalcemia for at least 12 years. There has been no clinical or laboratory proof of primary hyperparathyroidism, hypervitaminosis D, or other known causes of hypercalcemia and absorptive hypercalciuria. Hypercalciuria as well as the elevated serum level of calcium and 1 alpha, 25(OH)2D fell to normal during treatment with corticosteroids. The disturbed calcium metabolism in this patient is characteristic of that observed in sarcoidosis, but extensive studies have failed to uncover evidence of this condition.