tbuckley/cabot-search huggingface dataset:
Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure.
Authors: M C Subauste, D B Jacoby, S M Richards, D Proud
Journal: Journal of Clinical Investigation (1995)

Rhinovirus infections cause over one third of all colds and are a contributing factor to exacerbations of asthma. To gain insights into the early biochemical events that occur in infected epithelial cells, we develop, for the first time, a model in which a pure respiratory epithelial cell population can be routinely infected by rhinovirus. Viral infection was confirmed by demonstrating that viral titers of supernatants and lysates from infected cell increased with time and by PCR. Infection by rhinovirus 14 was inhibited by homotypic antiserum and by antibodies to intercellular adhesion molecule-1 (ICAM-1), the receptor for this virus. Susceptibility of epithelial cells to infection by rhinovirus 14 (but not rhinovirus 2, an ICAM-1 independent strain) can be increased by preexposure of cells to TNF alpha, whereas IFN gamma reduces susceptibility to infection by both rhinovirus strains. Rhinovirus infection per se does not markedly alter ICAM-1 expression on epithelial cells. Finally, we demonstrate that rhinovirus infection induced increased production of IL-8, IL-6, and GM-CSF from epithelial cells. Production of IL-8 correlated with viral replication during the first 24 h after infection. This model should provide useful insights into the pathogenesis of rhinovirus infections.
Nix-Mediated Apoptosis Links Myocardial Fibrosis, Cardiac Remodeling, and Hypertrophy Decompensation
Authors: Abhinav Diwan, Janaka Wansapura, Faisal M. Syed, Scot J. Matkovich, John N. Lorenz, Gerald W. Dorn
Journal: Circulation (2008)

Background— Pathological cardiac hypertrophy inevitably remodels, leading to functional decompensation. Although modulation of apoptosis-regulating genes occurs in cardiac hypertrophy, a causal role for programmed cardiomyocyte death in left ventricular (LV) remodeling has not been established. Methods and Results— We targeted the gene for proapoptotic Nix, which is transcriptionally upregulated in pressure overload and Gq-dependent hypertrophies, in the mouse germ line or specifically in cardiomyocytes (knockout [KO]) and conditionally overexpressed it in the heart (transgenic [TG]). Conditional forced Nix expression acted synergistically with the prohypertrophic Gq transgene to increase cardiomyocyte apoptosis (0.8±0.1% in GqTG versus 7.8±0.6% in GqTG+NixTG; P &lt;0.001), causing lethal cardiomyopathy with LV dilation and depressed systolic function (percent fractional shortening, 39±4 versus 23±4; P =0.042). In the reciprocal experiment, germ-line Nix ablation significantly reduced cardiomyocyte apoptosis (4.8±0.2% in GqTG+ Nix KO versus 8.4±0.5% in GqTG; P =0.001), which improved percent fractional shortening (43±3% versus 27±3%; P =0.017), attenuated LV remodeling, and largely prevented lethality in the Gq peripartum model of apoptotic cardiomyopathy. Cardiac-specific (Nkx2.5-Cre) Nix KO mice subjected to transverse aortic constriction developed significantly less LV dilation by echocardiography and magnetic resonance imaging, maintained concentric remodeling, and exhibited preserved LV ejection fraction (61±2% in transverse aortic constriction cardiac Nix KO versus 36±6% in transverse aortic constriction wild-type mice; P =0.003) at 9 weeks, with reduced cardiomyocyte apoptosis at day 4 (1.70±0.21% versus 2.73±0.35%; P =0.032). Conclusions— Nix-induced cardiomyocyte apoptosis is a major determinant of adverse remodeling in pathological hypertrophies, a finding that suggests therapeutic value for apoptosis inhibition to prevent cardiomyopathic decompensation.
Pathologists Enter Debate on Consent for Genetic Research on Stored Tissue
Authors: Joan Stephenson
Journal: JAMA (1996)

LAST FALL, a number of academic pathologists began to realize that an ongoing debate about informed consent and privacy issues prompted by the Human Genome Project had important implications for them as well as for geneticists. Rumors abounded, faxes flew, and editorials and newsletters warned that some of the ideas being floated in drafts of proposals could impose unprecedented costs and administrative burdens on biomedical researchers. The investigators feared that some documents developed to address informed consent for genetic research—one of which has been offered as a guideline for state and federal legislation aimed at protecting "genetic privacy"—could lead to research-crippling restrictions on the collection and oversight of tissue samples, and perhaps even interfere with patient care. "Pathologists are concerned about this because we are generally the legal custodians of tissue banks and of stored tissue specimens remaining from diagnostic evaluation," says Joe W. Grisham, MD, chair of the Department
LATE POISONING WITH CHLOROFORM AND OTHER ALKYL HALIDES IN RELATIONSHIP TO THE HALOGEN ACIDS FORMED BY THEIR CHEMICAL DISSOCIATION
Authors: Evarts A. Graham
Journal: The Journal of Experimental Medicine (1915)

The central lobular necrosis in the liver, which has been regarded by some writers as characteristic of late chloroform poisoning, has been produced experimentally with a number of other drugs. It is, therefore, in no sense peculiar to chloroform poisoning. Substances which have been shown to produce a morphological picture indistinguishable from that of late chloroform poisoning are: (a) dichlor- and tetrachlormethane, (b) tribrom- and triiodomethane, (c) monochlor-, monobrom-, and monoiodoethane, also the dibromethane; that is, in general, the halogen substituted aliphatic hydrocarbons containing one or two carbon atoms. Presumably similar results might be obtained with the higher members of the same series. The mechanism by which chloroform produces its characteristic tissue changes must accordingly be considered as a group reaction. Outside the body the similarities between the chemical behavior of different members of this group have been correlated by Nef on the basis of the type of dissociation which these substances undergo and the differences in their behavior on the basis of the differences of the degree to which such dissociations occur. According to the work of Nef, the group of substances under discussion has the property of dissociating to yield a halogen acid and an unsaturated alkylidene rest. Thus with chloroform the type of dissociation may be expressed thus: See PDF for Equation In this paper the view is developed that the changes characteristic of late poisonings with the above named group, namely edema, multiple hemorrhages, fat infiltration, and necrosis are ascribable (1) to acids and (2) to the fact that the amount of acid formed parallels the chemical dissociability of the drug outside of the body. Favoring the view that acid is responsible for the changes are the following observations. 1. All the characteristic features of late chloroform poisoning have been produced merely by the administration of hydrochloric acid, except, however, for a different distribution of the liver necrosis. 2. The areas of central necrosis produced in the liver by the various substances under discussion give an acid reaction to neutral red. 3. Sodium carbonate in a hypertonic sodium chloride solution markedly inhibits the production of the lesions.
Alcoholic liver disease in women
Authors: G Nicholson
Journal: BMJ (1977)

observers have noted, that night visiting rates are higher in the north of England and in Scotland.2 -4 Finally, while congratulating Mr Buxton and his colleagues on their excellent paper, I consider their last paragraph to be mistaken.Each doctor must decide, and then take responsibility for, any action following a request for a night call.This will depend on his knowledge of the patient and the circum- stances, and not on any 'consensus' of explicit criteria.
Tetanus — Still Here?
Authors: Johannes Ipsen
Journal: New England Journal of Medicine (1969)

The current status of prevention of lockjaw is a glaring illustration of how things can go awry generally and, specifically, of the discrepancy between highly developed medical knowledge and tools and the distribution of medical care and prevention in the population.Tetanus ought not to exist by now. It is one of the few diseases for which there is an almost infallible preventive agent. Tetanus toxoid was developed almost 50 years ago by Glenny, and its usefulness was shown experimentally in the next 15 years. It was officially standardized for human use in 1935 in Germany — and disregarded by . . .
Can Guideline Adherence Be Improved by Letter Outreach?
Authors: Mongthuong T. Tran, Sarah J. Billups
Journal: Diabetes Care (2008)

The Heart Protection Study established that statins are beneficial for most patients with diabetes regardless of baseline LDL cholesterol (1–2). Kaiser Permanente Colorado, a group-model, nonprofit health-maintenance organization in the Denver/Boulder metropolitan area, developed a letter-based population management strategy to improve statin utilization in patients with diabetes.

Kaiser Permanente Colorado maintains a disease state registry of patient-specific data for members with validated diagnoses, which serves as an ideal tool for patient tracking, quality improvement, and population management. Although letters have previously been employed for population education purposes (3–5), no published literature describes their effectiveness at …
Electrosurgical Devices-Reply
Authors: Stephen L. Corson
Journal: JAMA (1976)

Electrosurgical generators that depend on spark-gap circuitry show great variations between individual machines at similar dial settings. This can be of importance in operating suites where one does not always use the same generator. Moreover, spark-gap units are affected by conditions such as humidity, and in general, vary tremendously from calibrated settings soon after being serviced. Probably the most demanding electrosurgical procedure with respect to the output of the generator is a transurethral resection. We have measured voltages and current for various surgical procedures.<sup>1</sup>Whatever the procedure, the larger solid state units have sufficient capacity and, like other solid state electronic components, demonstrate little fluctuation in performance over a long period of time. This is not to say that a poorly designed solid-state generator is better than a well-designed tubed model. Spark-gap units, however, are notoriously unreliable, and I know of no clinical circumstance in which they
Co-proxamol and suicide: Availability of co-proxamol has been successfully reduced in Doncaster
Authors: P. T Fryers
Journal: BMJ (2003)

EDITOR—In 1998 an audit of suicides in Doncaster identified the alarming rate of co-proxamol overdose as a method of suicide: of the 44 suicides with prescribed drugs between 1995 and 1998, 18 were with co-proxamol (41%).1 That this is much higher than the national figure of 18% quoted by Hawton et al2 may be because the rates of prescribing of co-proxamol …
Prevalence and prognostic significance of portal blood flow reversionin severe steroid-treated alcoholic hepatitis
Authors: F. Maille, C. Duvoux, J.P. Richardet, C. Radier, I. Rosa, S. Hospitel, V. Sitruk, O. Seror, H. Blondon, E.S. Zafrani, I. Abd-Alsamad, M. Ziol, F. Roudot-Thoraval, D. Dhumeaux
Journal: Journal of Hepatology (2000)
Periodic Examination of Supposedly Well Persons
Authors: Maurice Fremont-Smith
Journal: New England Journal of Medicine (1953)

A REALLY sick person in this country is assured of probably the best medical attention in the world. But the so-called "well" person seeking to avoid future illness, or to discover early evidence of trouble already present, usually receives but superficial attention from the busy physician. It is upon these two aspects of medicine — prevention of disease and early diagnosis — that the state and federal governments are now encroaching, and will continue to encroach (in spite of outcries from the American Medical Association and in spite of national propaganda drives and legislative lobbying) unless the medical profession can . . .
Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy
Authors: Qiao-ling Zhu, Yi Zhou, Min Guan, Xiao-feng Zhou, Shu-di Yang, Yang Liu, Wei-liang Chen, Chun-ge Zhang, Zhi-qiang Yuan, Chun Liu, Ai-jun Zhu, Xue-nong Zhang
Journal: Biomaterials (2014)
Abstract 1630: Critical role of Shp2 protein tyrosine phosphatase in tumorigenesis of carcinoma
Authors: Yuan Ren, Zhengming Chen, Liwei Chen, Hla WinPiazza, Steven Enkemann, Eric Haura, Jie Wu
Journal: Cancer Research (2010)

Abstract Increasing evidence suggests that tumorigenic function requires coordinated action of both protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Certain PTPs, similar to PTKs, may play positive roles in the initiation and maintenance of human cancer. Shp2 is a non-receptor PTP encoded by the human PTPN11 gene. Gain-of-function Shp2 mutants have been linked to hematologic malignancies. While the role of Shp2 in carcinoma is less clear, Shp2 is a positive regulator of signaling by receptor tyrosine kinases such as EGFR, MET, and ALK that are involved in pathogenesis of carcinomas. To determine if Shp2 is required for tumor growth of carcinoma, we suppressed Shp2 expression and PTP activity using shRNAs and a PTP-inactive mutant in breast, prostate, and lung carcinoma cells. Shp2 knockdown and inactivation prevented tumor xenograft growth of these carcinoma cells. Biochemical analyses indicated that Shp2 inhibition suppressed Src, Erk1/2, and c-Myc activities, whereas it elevated p27 (CDKN1B) both in cell cultures and in tumors. These results suggest that Shp2 is a non-oncogene addiction gene critically involved in malignant growth of carcinoma and a potential target for development of a novel PTP-targeted therapy. 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 1630.
Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect.
Authors: A Raouf, N Parker, D Iddon, S Ryder, B Langdon-Brown, J D Milton, R Walker, J M Rhodes
Journal: Gut (1991)

Previous reports of a selective mucin subclass defect in ulcerative colitis have been reassessed using high performance chromatography (Superose 6 and Mono Q) for mucin purification and fractionation coupled with analysis of the fractions obtained using a combination of enzyme linked lectin and mucin antibody assays. Mucin samples purified from snap frozen rectal biopsy specimens obtained from patients with ulcerative colitis (n = 12), Crohn9s disease (n = 5), and non-inflammatory bowel disease control subjects (n = 9) were subject to ion exchange chromatography using a continuous 0-0.35 mol/l NaCl salt gradient with a final 2.5 mol/l NaCl step. In all samples the major proportion (mean (SD) 86.7 (8.9)%) of the mucin detectable by wheat germ agglutinin binding eluted between 0.15 and 0.35 mol/l NaCl with no significant difference in elution profile between ulcerative colitis and control subjects. Significant elution of glycoprotein at less than 0.15 mol/l NaCl did occur, however, when a lower molecular weight mucin containing fraction which contained concanavalin A positive (glucose or mannose containing) material was analysed similarly. Similar ion exchange profiles were obtained when (3H)N-acetylglucosamine labelled mucins were studied after tissue culture of rectal biopsy specimens. No significant alteration in the ion exchange profile of purified mucins in ulcerative colitis has been shown in these studies. It is possible that the previously reported relative depletion of mucin subclass IV (eluting with 0.20 mol/l NaCl) may simply have reflected mucin depletion.
Myocardial Perfusion Patterns Related to Thrombolysis in Myocardial Infarction Perfusion Grades After Coronary Angioplasty in Patients With Acute Anterior Wall Myocardial Infarction
Authors: Hiroshi Ito, Atsunori Okamura, Katsuomi Iwakura, Tohru Masuyama, Masatsugu Hori, Shin Takiuchi, Shinji Negoro, Yoshiaki Nakatsuchi, Yoshiaki Taniyama, Yorihiko Higashino, Kenshi Fujii, Takazo Minamino
Journal: Circulation (1996)

Background Epicardial coronary flow is occasionally reduced even after coronary intervention despite the absence of vessel obstruction in patients with acute myocardial infarction. Our aim was to clarify the cause and outcomes of radiocontrast slow filling in patients with reperfused acute anterior myocardial infarction by assessing microvascular damage with the use of myocardial contrast echocardiography (MCE) and functional outcomes. Methods and Results We carefully reviewed the cineangiograms of 86 patients who achieved coronary revascularization within 12 hours of the onset and underwent MCE before and soon after recanalization with the intracoronary injection of sonicated microbubbles. Antegrade coronary flow after recanalization was graded by two observers based on Thrombolysis in Myocardial Infarction (TIMI) trial flow grades. Left ventricular ejection fraction was measured on the day of infarction and 1 month later. TIMI grade 2 was observed in 18 patients (21%), and the other 68 patients manifested TIMI grade 3 after recanalization. All patients with TIMI 2 showed substantial MCE no reflow, whereas only 11 patients (16%) with TIMI 3 showed MCE no reflow. Functional improvement was worse in patients with TIMI 2 than in those with TIMI 3 (TIMI 2, 38±8% versus 40±8%, P =NS [acute versus late]; TIMI 3, 44±13% versus 55±13%, P &lt;.001). Among patients with TIMI 3, significant functional improvement was observed only in patients with MCE reflow (MCE reflow, 46±13% versus 57±12%, P &lt;.001; MCE no reflow, 35±11% versus 45±12%, P =NS). Conclusions Despite no obstructive lesion of the vessel, TIMI 2 is caused by advanced microvascular damage and is a highly specific, although not sensitive, predictor of poor functional outcomes in patients with acute myocardial infarction. TIMI 3 does not necessarily indicate myocardial salvage, and detection of MCE no reflow in these patients is particularly useful for the prediction of functional outcome.
The Great-toe Jerk
Authors: G. A. Ransome
Journal: BMJ (1958)

Wartenburg (1945), in the introduction to his book on the examination of reflexes, gives a healthy warning on the fallibility of describing new reflexes without first inquiring deeply into the literature of the subject.He says many a reflex has been discovered by one author after another, often at intervals of several decades.The authors, anxious to attach their own names to new reflexes, have completely neglected the work of their predecessors.Foster Kennedy, in liis foreword to the same volume, whimsically describes the hunting of the reflex as though it might have been the Snark.Nearly every muscle in the body can be made to con- tract when it or its tendon is struck; so that the pheno- menon I am going to describe is in no way new, though
453 THE EFFECT OF HMG-COA REDUCTASE INHIBITORS (STATINS) ON PPAR AND ABCA1 EXPRESSION IN CULTURED GALLBLADDER EPITHELIAL CELLS
Authors: J. Lee, E.M. Hong, D.H. Koh, S.H. Park, M.H. Choi, H.J. Jang, S.H. Kae
Journal: Journal of Hepatology (2008)
Authors' reply to Harwood, McCarthy, and Franke
Authors: A. Singh-Manoux
Journal: BMJ (2012)

The over-riding concern about our paper is that it propagates the tradition of emphasising decline and ignoring gains that occur with ageing.1 2 3 4 This was not our intention. We wanted to answer an important research question of whether cognitive decline occurs before the age of 60, and we had the …
Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells<i>in vitro</i>and<i>in vivo</i>
Authors: Inge Mannaerts, Nele R. Nuytten, Vera Rogiers, Karin Vanderkerken, Leo A. van Grunsven, Albert Geerts
Journal: Hepatology (2009)

Hepatic stellate cell (HSC) activation is a pivotal step in the pathogenesis of liver fibrosis. The clarification of this transdifferentiation process is therefore important for the development of effective therapies for fibrosis. We analyzed the effect of a histone deacetylase inhibitor, valproic acid (VPA), on mouse HSC transdifferentiation in vitro and in vivo. The exposure of freshly isolated mouse HSCs to 2.5 mM VPA led to increased histone H4 acetylation and inhibited cell proliferation. Expression of stellate cell activation markers analyzed by quantitative polymerase chain reaction and western blotting revealed that treatment with VPA inhibited the induction of activation markers such as Acta2, Lox, Spp1, and Myh11. Treatment of mice with VPA decreased collagen deposition and in vivo activation of stellate cells in the livers of CCl(4)-treated mice. Class I histone deacetylase silencing through RNA interference in mouse HSCs only partially mimicked treatment with VPA.Chronic administration of VPA results in a marked decrease in stellate cell activation both in vitro and in vivo. We hypothesize that the VPA effect results partially from class I histone deacetylase inhibition, but that also non-histone deacetylase class I VPA targets are involved in the stellate cell activation process.
Pharmacology and Toxicology of Lithium
Authors: M Schou
Journal: The Annual Review of Pharmacology and Toxicology (1976)

Lithium is distinguished by its therapeutic action in mania and its prophylactic action in recurrent manic-depressive disorder of the bipolar and unipolar type. By prophylactic action is meant the ability to attenuate or prevent manic and depressive recurrences. Lithium has a relatively low therapeutic index, and knowledge of its pharmacology and toxicology is important for safe and effective usage.
Legal Aspects of Artificial Insemination
Authors: Arthur Harris Rosenberg
Journal: New England Journal of Medicine (1968)

OF recent medical advances, few have stirred greater public controversy and aroused more comment and more legal difficulty than birth control. Discussions of that issue have been confined generally to the negative aspect — birth prevention. However, birth control has a positive aspect, which includes the development of technics to encourage and promote childbirth that is otherwise not possible.One positive birth-control technic, developed to overcome male reproductive deficiency, is artificial insemination. Generally, the legal questions involved may be divided into two areas: those arising from the use of homologous artificial insemination (AIH) and those arising from the use of . . .
Euthanasia endorsed in Dutch patient with dementia
Authors: T. Sheldon
Journal: BMJ (1999)

A doctor in the Netherlands has not been prosecuted for helping an elderly patient with vascular dementia to die. The psychiatric patient was considered to have been competent to request assisted suicide and the procedure was judged to be medically and legally sound.

The facts were reported in a rare case history in a Dutch medical journal (Nederlands Tijdschrift Voor Geneeskunde 1999;143:17). Dutch law states that doctors can avoid prosecution for assisted suicide only if their patient has persistently made …