tbuckley/cabot-search huggingface dataset:
DEOXYRIBONUCLEIC ACID (DNA) AND PROTEIN ALTERATIONS IN H<scp>E</scp>L<scp>A</scp> CELLS INFECTED WITH TYPE 4 ADENOVIRUS
Authors: Harold S. Ginsberg, Mary K. Dixon
Journal: The Journal of Experimental Medicine (1959)

During a single cycle of multiplication of type 4 adenovirus in HeLa cells an average 2-fold increase in total DNA occurred over that measured in uninfected cells. Of the total DNA from infected cells about 23 per cent was extractable into 0.15 M NaCl, a quantity approximately four and a half times greater than that of the DNA obtained from normal cells in 0.15 M NaCl. Ninety to 99 per cent of infectious virus was also extracted into the 0.15 M NaCl fraction. Concurrently with the accumulation of DNA in virus-infected cells there occurred a 2-fold increase in total protein. The proportionate increases in protein were approximately equal in 0.15 M NaCl and water extracts of infected cells. High speed centrifugation indicated that the bulk of the DNA and protein was not directly associated with infectious viral particles. Although in virus-infected cells a markedly increased synthesis occurred of a DNA which had solubility properties different from the major portion of normal host DNA, nucleotide analysis did not reveal any other qualitative differences. However, a marked change in nucleotide molar ratios was observed in the 0.15 M NaCl-soluble DNA from virus-infected cells. It seems apparent from the findings that the biochemical alterations found in HeLa cells infected with type 4 adenovirus are intimately related to the infectious process.
Long term treatment of rheumatoid arthritis with high doses of intravenous immunoglobulins: effects on disease activity and serum cytokines.
Authors: C Muscat, A Bertotto, R Ercolani, O Bistoni, E Agea, M Cesarotti, G Fiorucci, F Spinozzi, R Gerli
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To evaluate the effects of long term treatment of rheumatoid arthritis (RA) with high doses of intravenous immunoglobulins (IVIg). METHODS--Ten patients with active RA and prior unsuccessful treatment with at least one slow acting antirheumatic drug were treated with 400 mg/kg of IVIg for the first three days and then once a month for 12 months. Clinical evaluation and laboratory analysis were performed every month. Serum levels of tumour necrosis factor alpha (TNF alpha), soluble interleukin-2 receptor (sIL-2R), IL-1 alpha, IL-1 beta, IL-6 and interferon gamma (IFN gamma) were measured at baseline and at three monthly intervals for 15 months. RESULTS--Although laboratory parameters were not influenced by the treatment, a late but significant clinical improvement was observed after six months. Serial measurement of cytokines revealed a rapid and persistent decrease in serum TNF alpha and a late and significant reduction in sIL-2R concentrations. CONCLUSION--This study suggests that IVIg can ameliorate the symptoms and improve the functional capability of RA patients. This effect is associated with a partial modulation of serum concentrations of inflammatory cytokines and, more interestingly, with a late decrease in sIL-2R which correlated with the late reduction in disease activity.
Coronary Artery Wall Shear Stress Is Associated With Progression and Transformation of Atherosclerotic Plaque and Arterial Remodeling in Patients With Coronary Artery Disease
Authors: Habib Samady, Parham Eshtehardi, Michael C. McDaniel, Jin Suo, Saurabh S. Dhawan, Charles Maynard, Lucas H. Timmins, Arshed A. Quyyumi, Don P. Giddens
Journal: Circulation (2011)

Background Experimental studies suggest that low wall shear stress (WSS) promotes plaque development and high WSS is associated with plaque destabilization. We hypothesized that low-WSS segments in patients with coronary artery disease develop plaque progression and high-WSS segments develop necrotic core progression with fibrous tissue regression. Methods and Results Twenty patients with coronary artery disease underwent baseline and 6-month radiofrequency intravascular ultrasound (virtual histology intravascular ultrasound) and computational fluid dynamics modeling for WSS calculation. For each virtual histology intravascular ultrasound segment (n=2249), changes in plaque area, virtual histology intravascular ultrasound–derived plaque composition, and remodeling were compared in low-, intermediate-, and high-WSS categories. Compared with intermediate-WSS segments, low-WSS segments developed progression of plaque area ( P =0.027) and necrotic core ( P &lt;0.001), whereas high-WSS segments had progression of necrotic core ( P &lt;0.001) and dense calcium ( P &lt;0.001) and regression of fibrous ( P &lt;0.001) and fibrofatty ( P &lt;0.001) tissue. Compared with intermediate-WSS segments, low-WSS segments demonstrated greater reduction in vessel ( P &lt;0.001) and lumen area ( P &lt;0.001), and high-WSS segments demonstrated an increase in vessel ( P &lt;0.001) and lumen ( P &lt;0.001) area. These changes resulted in a trend toward more constrictive remodeling in low- compared with high-WSS segments (73% versus 30%; P =0.06) and more excessive expansive remodeling in high- compared with low-WSS segments (42% versus 15%; P =0.16). Conclusions Compared with intermediate-WSS coronary segments, low-WSS segments develop greater plaque and necrotic core progression and constrictive remodeling, and high-WSS segments develop greater necrotic core and calcium progression, regression of fibrous and fibrofatty tissue, and excessive expansive remodeling, suggestive of transformation to a more vulnerable phenotype. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00576576.
European Working Time Directive may contribute to fatigue
Authors: C. J. A. Cowie
Journal: BMJ (2013)

Sokol highlights the serious problems caused by exhaustion in doctors and indicates that one of the reasons why medical staff are overtired is non-compliance with the European Working Time Directive (EWTD).1 The two issues are inextricably linked, but compliance with the EWTD may also contribute to fatigue.

Redesigning rotas to comply with the EWTD means …
Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2
Authors: A V Purandare, T M McDevitt, H Wan, D You, B Penhallow, X Han, R Vuppugalla, Y Zhang, S U Ruepp, G L Trainor, L Lombardo, D Pedicord, M M Gottardis, P Ross-Macdonald, H de Silva, J Hosbach, S L Emanuel, Y Blat, E Fitzpatrick, T L Taylor, K W McIntyre, E Michaud, C Mulligan, F Y Lee, A Woolfson, T L Lasho, A Pardanani, A Tefferi, M V Lorenzi
Journal: Leukemia (2011)
Isometrics in Lowering Blood Pressure
Authors: Broino Kiveloff
Journal: JAMA (1973)

<h3>To the Editor.—</h3> The EDITORIAL "Hypertension: A "Neglected Phenomenon" (222:579,1972), based on the report by Schoenberger et al states that "these findings indicate that the control of hypertension is an unsolved problem in the United States. There is an urgent need for implementing improved and effective approaches to this major health problem." In the SPECIAL COMMUNICATION "Current Status of Hypertension Control in an Industrial Population," in the same issue by the same author (p 559), attention was given only to the use of hypertension drugs in treating persons with hypertension. Evidence for an effective physical method for treating hypertension, by brief, maximal, extensive isometric exercise has been published in the<i>Journal of the American Geriatrics Society</i>(December 1971). It was demonstrated that blood pressure was reduced in four to eight weeks after the initiation of a regimen of isometric exercises. In further investigation of the reason for the reduction, it
Co-delivery of paclitaxel and gemcitabine via CD44-targeting nanocarriers as a prodrug with synergistic antitumor activity against human biliary cancer
Authors: Ilkoo Noh, Hyun-Ouk Kim, Jihye Choi, Yuna Choi, Dong Ki Lee, Yong-Min Huh, Seungjoo Haam
Journal: Biomaterials (2015)
Developmental Lead Exposure Induces Tactile Defensiveness in Rhesus Monkeys ( <i>Macaca Mulatta</i> )
Authors: Colleen F. Moore, Lisa L. Gajewski, Nellie K. Laughlin, Melissa L. Luck, Julie A. Larson, Mary L. Schneider
Journal: Environmental Health Perspectives (2008)

Tactile defensiveness in children is associated with difficult social relations, emotional dysregulation, and inattention. However, there are no studies of lead exposure and tactile defensiveness in children or animals in spite of the fact that lead exposure is also associated with inattention and emotional dysregulation.In this study we tested whether lead exposure induces tactile defensiveness in rhesus monkeys.We tested 61 monkeys from a 3 (no lead, 1-year lead, 2-year lead) x 2 (succimer chelation or not) factorial experiment for tactile defensiveness at 4 years of age. Lead-treated monkeys had been orally administered lead in a daily milk solution from 8 days of life to either 1 or 2 years of age to produce blood lead levels of 35-40 mg/dL. Succimer chelation therapy or placebo was administered at 1 year of age. We measured tactile defensiveness using six repeated trials of each of three textures as a swipe to the cheek and neck.Lead-exposed monkeys showed higher negative responses to repeated tactile stimulation compared with controls. Blood lead during the first 3 months of life was positively correlated with the negative response on the tactile defensiveness test. There was an interaction of lead exposure x succimer chelation x trials, but it is not clear that succimer chelation was beneficial with respect to tactile defensiveness.This is the first report to implicate lead as a potential cause of tactile defensiveness. Research should examine whether lead exposure is associated with tactile defensiveness in children.
Professionalism Reborn: Theory, Prophecy, and Policy
Authors: J P Bunker
Journal: BMJ (1994)

Eliot Freidson Polity Press, £39.50, pp 238 ISBN 0–7456–1280–6

As doctors in the NHS find themselves increasingly forced to defend their professional status, Professionalism Reborn provides a welcome framework for debate. With the stated intention of exploring the general phenomenon of professionalism, the author draws heavily from his long term studies of medicine. The issues he discusses and the messages and advice he offers are generic ones as relevant to the NHS as to his native America.

Professor Freidson postulates that “professionalism is being reborn in a hierarchical form in which everyday practitioners become subject to …
An Appraisal of the Double Indicator-Dilution Method for the Estimation of Mitral Regurgitation in Human Subjects
Authors: WILLIAM S. WILSON, RALPH L. BRANDT, RICHARD D. JUDGE, JOE D. MORRIS, MARY E. CLIFFORD
Journal: Circulation (1961)

The amount of mitral regurgitation was estimated in 50 patients by an indicator-dilution technic and by the usual clinical, catheterization, operative, and autopsy criteria. There was a good correlation between the two estimates. Patients with significant mitral regurgitation (grade 2 or grade 3) had, with one exception, Q R / Q F ratios above 0.41. There were at least two instances where the calculated Q R / Q F was almost certainly falsely high. It seems likely that these discrepancies are related to the presence of an unusually large volume between the pulmonary artery and the femoral artery.
Abstract C60: The integrative genomics viewer
Authors: James Robinson, Helga Thorvaldsdottir, Marc-Danie Nazaire, Wendy Winckler, Michael Reich, Gad Getz, Jill Mesirov
Journal: Cancer Research (2009)

Abstract Rapid improvements in next generation sequencing and array-based profiling methods have created a paradigm shift in how scientists approach the study of the cancer genome. Projects such as The Cancer Genome Atlas (TCGA) are harnessing these advances to probe the cancer genome at unprecedented resolution, generating comprehensively catalogs of the genetic alterations of hundreds of tumors. Visualization plays an important role in assimilating the large, muti-modal datasets produced by TCGA and similar projects. To be maximally effective tools must flexibly integrate genomic, functional, and phenotypic data from a variety of platforms, and efficiently handle large datasets. To address these critical challenges we developed the Integrative Genomics Viewer (IGV), a flexible, scalable, high-performance tool for the concurrent visualization of multiple large scale datasets. The IGV supports integrated views of any data type that can be mapped to genomic coordinates, including, but not limited to, next generation sequence data, copy number, gene expression, RNAi, ChIP-seq, RNA-seq, and genome annotations. Data can be annotated, filtered, grouped, and sorted according to clinical and phenotypic attributes. A particular strength of IGV is its ability to handle very large datasets, for example deep coverage sequence data from whole genome scans, or highresolution copy number data from thousands of samples, on standard desktop computers. IGV permits the user to move seamlessly across these datasets at any level of detail, and quickly zoom out to whole genome or drill down to base pair resolution. The ability to dynamically and flexibly integrate multiple data modalities and view them at any scale allows the user to elucidate complex biological relationships that would not otherwise be apparent. The IGV is freely available without restriction. It is currently under active development and use in The Cancer Genome Atlas, 1000 Genomes Project, and other large genomic projects. Citation Information: Cancer Res 2009;69(23 Suppl):C60.
Experimental Asthma Induced By Tropomyosins from Cockroach and Shrimp: Insights into in Vivo Cross-Reactivity
Authors: Thalita Freitas Martins, Marina M. Dias, Rafael Q. Prado, Thamires Milani, Adriana S. Moreno, Luana Delcaro, Vânia Bonato, Simone Ramos, Marcos Borges, Luisa Karla P. Arruda
Journal: Journal of Allergy and Clinical Immunology (2015)
Fatal Haemorrhage from Ulceration of the Internal Jugular and Branch of Subclavian Veins, in a Case of Scarlatina
Authors: R. J. Hale
Journal: BMJ (1850)

laborious.An emetic of tartarized antimony with ipecacuanha was given; this produced slight vomiting, which was followed by profuse purging.Calomel with ipecacuanha, followed by a saline draught, were adminis- tered duriing the rest of the day; leeches were applied to the throat.$8p.mThe throat was relieved, and he could breathe more freely.
Atypical Secondary or Symptomatic Thrombocytopenic Purpura Developing with the Use of Quinidine Sulfate
Authors: DONALD C. COLLINS
Journal: Circulation (1950)

Quinidine sulfate, which has a very similar chemical structural formula to that of quinine bisulfate, may on a rare occasion be the etiologic causative agent of an atypical secondary or symptomatic thrombocytopenic purpura of serious degree. Fortunately, the withdrawal of the drug results in a rapid return to normal of the hematologic picture. A case report of such an occurrence is presented. Three additional case reports have been collected from the literature since 1941.
Successful prophylaxis against febrile convulsions with valproic acid or phenobarbitone.
Authors: S J Wallace, J A Smith
Journal: BMJ (1980)

A total of 184 six-month periods were analysed during which feverish illnesses occurred in children aged 6-42 months with a history of a febrile convulsion. Fits occurred in 34 out of 100 such periods when no treatment was being given, in six out of 45 periods when the serum phenobarbitone concentration was 69.0 mumol/l (1.6 mg/100 ml) or more, and in five out of 39 periods when the plasma valproic acid concentration was 416.4 mumol/l (6.0 mg/100 ml) or more. Thus in adequate dosage both phenobarbitone and valproic acid were significantly better than no treatment in preventing febrile convulsions (p less than 0.02). The two drugs were of comparable efficacy. It is concluded that with improved compliance valproic acid, which is relatively free from side effects, might be an effective prophylactic agent against febrile convulsions.
IL-1 receptor–associated kinase 3 gene (IRAK3) variants associate with asthma in a replication study in the Spanish population
Authors: María Pino-Yanes, Inmaculada Sánchez-Machín, José Cumplido, Javier Figueroa, María José Torres-Galván, Ruperto González, Almudena Corrales, Orlando Acosta-Fernández, José Carlos García-Robaina, Teresa Carrillo, Anselmo Sánchez-Palacios, Jesús Villar, Mariano Hernández, Carlos Flores
Journal: Journal of Allergy and Clinical Immunology (2011)
Abstract 3499: Nanoparticle formulation of SN-38 by the IVECT method results in a safer, more effective treatment for colorectal cancer
Authors: Adam E. Carie, Jonathan Rios-Doria, Gregoire Cardoen, Tara Lee Costich, Kevin Sill
Journal: Cancer Research (2010)

Abstract Polymeric micelles represent an emerging class of nano-scale vehicles with unmatched potential for delivering potent, targeted chemotherapy. Intezyne's advanced tri-block copolymer system, the IVECT(TM) Method, has been proven to encapsulate a wide variety of therapeutic and diagnostic agents into a proprietary micelle with unique physiochemical properties. Conventional micelles become destabilized rapidly upon dilution into the bloodstream and release a significant portion of their drug payload systemically, harming healthy tissues and limiting therapeutic effects. Intezyne's IVECT Method utilizes a unique cross-linked stabilizer block that maintains micellar structure for a longer period of time post administration and is designed such that a downshift in pH at the tumor activates drug release by destroying the zinc cross-link, allowing for focused drug exposure. The IVECT Method's unmatched plasma stability allows for longer circulation times while protecting healthy tissues, and it maximizes tumor retention and efficacy through the enhanced permeability and retention (EPR) effect and pH-responsive cross-linker. Intezyne's lead product IT-141 encapsulates the extremely potent active metabolite of irinotecan, SN-38. Recently, IT-141 has demonstrated 14-fold greater plasma exposure and 8-fold greater tumor accumulation vs. irinotecan. This superior pharmacokinetic profile confers 500% greater anti-tumor activity at half the dose (30mg/kg, 3X Q4D, vs. 60mg/kg irinotecan). In xenograft models, IT-141 has demonstrated tumor regression of up to 88%, with 60% of tumors regressing completely. The IVECT copolymer is safe and well tolerated at up to 6 times the therapeutic doses, with no sick mouse syndrome, and can be lyophilized for long-term storage (&amp;gt;1 year). Intezyne is preparing its IND for IT-141. The Company has additional programs in development that focus on delivering best-in-class chemotherapies. 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 3499.
THE PREVENTION AND CONTROL OF TUBERCULOSIS AS IT CONCERNS THE MEDICAL PROFESSION
Authors: HENRY BOSWELL
Journal: JAMA (1923)

The prevention and control of any disease is dependent on two factors: (1) The high ideals of the medical profession having for its object the saving and prolongation of the span of human life, and (2) the demand of the people for protection. The medical profession for centuries, out of altruistic motives and love of service, endeavored to find a ray of light in the impenetrable darkness and unfathomed mysteries surrounding tuberculosis which would prevent or ameliorate the ravages on the human family, but not until Villemin, about 1870, proved it transmissible from animal to animal was the faintest hope discerned. Immediately following this, in 1882, Robert Koch succeeded in isolating the causative agent. Thus, hope became an attained fact. To this point only the profession had been concerned in the attainment of ambition. Beginning now, the suffering public, which had groped with fear in ignorance, demanded the practical application
Countries face "hidden problem" of prescription drug misuse
Authors: J. Zarocostas
Journal: BMJ (2010)

The number of people addicted to prescription drugs has risen sharply in many countries, with many people combining this misuse with that of heroin, cocaine, and MDMA (ecstasy), warns a report from the International Narcotics Control Board, the independent body that monitors implementation of the United Nations’ drug control conventions.

The board says that national authorities need to give more attention to this “hidden problem” when formulating public health policies.

It is estimated that about 15 million people in the United States misused prescription drugs in 2008. Most of those (about 12 million people) misused pain relievers. Similarly, in …
New Hampshire Medical Society
Authors: George C. Wilkins, James W. Jameson
Journal: New England Journal of Medicine (1951)

THIS annual meeting was unique — at least in New England — as it was held jointly with the Vermont State Medical Society and the New Hampshire Surgical Club. Better attendance, more enthusiastic speakers, larger exhibits and furtherance of friendly relations with the physicians of our sister state were direct results.The general session was opened at the Mount Washington Hotel, Bretton Woods, New Hampshire, at 9:20 a.m., with Dr. Francis M. Appleton, of Gorham, presiding and welcoming the societies to his county. Dr. John P. Bowler, President of the New Hampshire Medical Society, and Dr. Hiram E. Upton, President . . .
Differential Effect of Urotensin II on Vascular Tone in Normal Subjects and Patients With Chronic Heart Failure
Authors: Melissa Lim, Suzy Honisett, Christopher D. Sparkes, Paul Komesaroff, Andrew Kompa, Henry Krum
Journal: Circulation (2004)

Urotensin II (U-II) is a novel vasoactive peptide that also has direct hypertrophic and profibrotic effects on the myocardium. Upregulation of U-II and its receptor has been observed within the heart of patients with chronic heart failure (CHF). Furthermore, plasma levels of U-II have been found to be elevated in some but not all studies in such patients. However, the functional consequences of activation of the U-II system in patients with CHF, assessed by direct administration of exogenous U-II, have not been previously determined.We compared the effect of iontophoresed U-II on skin microvascular tone in normal subjects and patients with CHF, assessed with the use of laser Doppler velocimetry. U-II mediated a dose-dependent vasodilator response in normal subjects (baseline, 137.9+/-52; U-II, 10(-12) mol/L, 145+/-134; U-II, 10(-9) mol/L, 712+/-179; U-II, 10(-7) mol/L, 943+/-139 arbitrary flux units [AFUs], P<0.0001). In contrast, a dose-dependent vasoconstrictor response was observed in patients with CHF (baseline, 336.1+/-129; U-II, 10(-12) mol/L, 317+/-131; U-II, 10(-9) mol/L, 129+/-137; U-II, 10(-7) mol/L, 22.4+/-130 AFUs, P<0.05). Differences in flow between normal subjects and patients with CHF were significant overall (P<0.001, 2-way ANOVA) and at the U-II 10(-9) mol/L and U-II 10(-7) mol/L dose level by Student's unpaired t test (P<0.05, P<0.0001, respectively). In contrast, there was no significant difference between baseline blood flux and any dose of U-II in either group (or between groups) when the opposite polarity was applied.In addition to direct effects on the myocardium, U-II may contribute to the increased peripheral vascular tone that is characteristic of human CHF. The present observations support the contention that the U-II system may be a potentially important target for pharmacological blockade in the treatment of this condition.
Shear stress-induced activation of the AMP-activated protein kinase regulates FoxO1a and angiopoietin-2 in endothelial cells
Authors: M. Dixit, E. Bess, B. Fisslthaler, F. V. Hartel, T. Noll, R. Busse, I. Fleming
Journal: Cardiovascular Research (2007)

AimsPhosphorylation of forkhead box O (FoxO) transcription factors induces their nuclear exclusion and proteosomal degradation. Here, we investigated the effect of fluid shear stress on FoxO1a in primary cultures of human endothelial cells and the kinases that regulate its phosphorylation.