tbuckley/cabot-search huggingface dataset:
Crucial Role of Transient Receptor Potential Ankyrin 1 and Mast Cells in Induction of Nonallergic Airway Hyperreactivity in Mice
Authors: Valérie Hox, Jeroen A. Vanoirbeek, Yeranddy A. Alpizar, Sabrina Voedisch, Ina Callebaut, Sonja Bobic, Ali Sharify, Vanessa De Vooght, Laura Van Gerven, Fien Devos, Adrian Liston, Thomas Voets, Rudi Vennekens, Dominique M. A. Bullens, Annick De Vries, Peter Hoet, Armin Braun, Jan L. Ceuppens, Karel Talavera, Benoit Nemery, Peter W. Hellings
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Airway hyperreactivity (AHR) is a key feature of bronchial asthma, and inhalation of irritants may facilitate development of nonallergic AHR. Swimmers exposed to hypochlorite (ClO(-))-containing water show a higher risk of developing AHR. We developed a mouse model in which instillation of ClO(-) before ovalbumin (OVA) induces AHR without bronchial inflammatory cells.To investigate the mechanisms of ClO(-)-OVA-induced nonallergic AHR.The involvement of the transient receptor potential ankyrin (TRPA)1 channel was checked in vivo by the use of TRPA1(-/-) mice and in vitro by Ca(2+) imaging experiments. The role of substance P (SP) was investigated by pretreating animals with the receptor antagonist RP67580, by replacing ClO(-) with SP in vivo, and by immunofluorescent staining of large airways of exposed mice. The role of mast cells was evaluated by exposing mast cell-deficient Kit(Wh)/Kit(Wsh) mice to ClO(-)-OVA with or without mast cell reconstitution.ClO(-)-OVA did not induce AHR in TRPA1(-/-) mice, and ClO(-) generates a Ca(2+) influx in TRPA1-transfected cells. Pretreatment with RP67580 reduces ClO(-)-OVA-induced AHR, although no increased SP expression was shown in the airways. SP-OVA exposure resulted in the same AHR as induced by ClO(-)-OVA. Kit(Wsh)/Kit(Wsh) mice did not develop AHR in response to ClO(-)-OVA unless they were reconstituted with bone marrow-derived mast cells.Induction of AHR by exposure to ClO(-)-OVA depends on a neuroimmune interaction that involves TRPA1-dependent stimulation of sensory neurons and mast cell activation.
Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration
Authors: Hikaru Nagahara, Adamina M. Vocero-Akbani, Eric L. Snyder, Alan Ho, Dawn G. Latham, Natalie A. Lissy, Michelle Becker-Hapak, Sergei A. Ezhevsky, Steven F. Dowdy
Journal: Nature Medicine (1998)
Low-dose aspirin improves in vivo hemodynamics in conscious, chronically infarcted rats
Authors: Regien G Schoemaker, Pramod R Saxena, Ed A.J Kalkman
Journal: Cardiovascular Research (1998)

The equivalent of the clinically used low (= antiplatelet)-dose aspirin, inhibited collagen deposition in the non-infarcted myocardium in rats with myocardial infarction. In the present study, the in vivo hemodynamic consequences of this daily low-dose aspirin were investigated in conscious, chronically instrumented, infarcted rats.Rats, treated with 25 mg/kg aspirin daily from 2 days before to 3 weeks after coronary artery ligation, were chronically instrumented with an electromagnetic flow-probe and arterial and venous catheters, to record cardiac output, and arterial and venous blood pressure, respectively, in the conscious freely moving animal. In parallel, isolated hearts were studied with regard to left ventricular stiffness (pressure/volume relationships), maximal cardiac perfusion (adenosine), and in vitro heart rate and beta-adrenergic responsiveness. Plasma catecholamine levels were measured.Aspirin normalized the increased heart rate after infarction, at a preserved cardiac output. This was accompanied by a (non-significant) increase in stroke volume, at unchanged cardiac loading conditions. The lower heart rate after aspirin was due to reduced intrinsic heart rate rather than to lower sympathetic activation of the heart, since similar effects were observed in isolated perfused hearts, while circulating levels of catecholamines and beta-adrenergic responsiveness were not influenced. The improved stroke volume was not explained by reduced left ventricular stiffness or increased maximal perfusion after aspirin.In addition to the antithrombotic action, effects of low-dose aspirin on cardiac remodeling could be associated with favorable hemodynamic effects, as reflected by a lower heart rate for the same cardiac output. Although the underlying mechanisms are still unknown, it suggests a clinically relevant beneficial effect which deserves further investigation.
Alternative tests: carcinogenesis as an example.
Authors: B Schwetz, D Gaylor
Journal: Environmental Health Perspectives (1998)

Acceptance of new tests that are alternatives to currently used toxicology tests is a topic of considerable importance in the field of toxicology. Carcinogenicity testing today normally includes 2-year studies in rats and mice of both sexes, following widely accepted procedures for husbandry; selection of dose levels; pathology and toxicity observations; and statistical interpretation of tumor data. These studies are usually preceded by tests for genetic toxicity and subchronic toxicity studies to select dose levels for the 2-year studies. Although these data are used for quantitative risk assessment, the mechanistic basis for effects is usually unknown. The series of studies is very expensive and requires 5 years or more to conduct. Alternative approaches are being developed that would provide more mechanistic information and hopefully would permit decisions to be made about carcinogenic potential without the need to conduct 2-year studies in rats and mice of both sexes. Decisions could be based on a profile of data rather than on the result of one test. Procedures for regulatory acceptance of new approaches for carcinogenicity testing are critical to future progress.
Sequential Molecular Changes during Multistage Pathogenesis of Small Peripheral Adenocarcinomas of the Lung
Authors: Junichi Soh, Shinichi Toyooka, Shuji Ichihara, Hiroaki Asano, Naruyuki Kobayashi, Hiroshi Suehisa, Hiroki Otani, Hiromasa Yamamoto, Kouichi Ichimura, Katsuyuki Kiura, Adi F. Gazdar, Hiroshi Date
Journal: Journal of Thoracic Oncology (2008)
Abstract 4247: Comparison of two-dimensional verses three-dimensional breast cancer models in drug discovery
Authors: Carrie J. Lovitt, Vicky M. Avery
Journal: Cancer Research (2012)

Abstract Two-dimensional (2D) monolayer cancer cell culture is generally used in most drug discovery screening programmes to identify novel anti-cancer compounds. However, three-dimensional (3D) cell culture more closely represents the in vivo tumor environment thus providing a more accurate measure of compound activity. Development of an automated, reproducible and miniaturised 3D culture model for drug discovery in breast cancer would be highly advantageous. Thus we have developed and optimised a miniaturised in vitro 3D culture model in which breast cancer cells interact with reconstituted basement membrane from MatrigelTM. To determine the effectiveness of our 3D breast cancer model for use in future drug discovery, chemotherapeutic drugs commonly used in breast cancer therapy were tested and differences in drug activity were compared to 2D cell culture models. Once validated, this 3D culture model will be used to evaluate and further characterise novel compounds. The results presented describe the development and reproducibility of our 3D culture model and its 2D culture model counterpart. This includes the linear relationship between fluorescence intensity and cell number for measurement of metabolic activity as an indicator of cell viability when using the indicator dye Resazurin; determination of an adequate signal window and the reproducible average mean sizes of spheroids present under assay conditions. We report that there is significantly more drug resistance in our 3D cell culture model compared to our 2D culture model. This is particularly evident in the presence of taxanes and anthracyclines. Results from this study also show that the degree of drug resistance in 3D is breast cancer cell line dependent for each of the chemotherapeutic drugs studied and not necessarily correlated to the profile observed in 2D. Image based analysis demonstrated a distinct correlation of 3D cell culture morphology to drug dose, where disassociation of spheroids indicates drug effectiveness and intact spheroids indicates ineffectiveness of drug activity. Further research is underway to determine the mechanism for the drug resistance in 3D culture, which may be important in providing information on resistance mechanisms and potential drug targets. Miniaturisation of 3D culture for breast cancer cell lines allows a higher throughput of novel compound testing in a more cost effective, biologically relevant model. Our work highlights the importance of using 3D cell culture in the early stages of drug discovery in evaluating compound activity. 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 4247. doi:1538-7445.AM2012-4247
Syndrome of Suprarenal Haemorrhage in the Adult
Authors: C. J. Dewhurst
Journal: BMJ (1951)

TREATMENT OF ACUTELY BLEEDING PEPTIC ULCER BDIBGJOHRNAL however, not have changed the prognosis in these cases, as they all died).Thus Bohn's procedure is worthy of recommendation as the criteria are simple, easy to evaluate, and seem to be reliable.SummaryAmong the 17,254 patients treated during a seven-year period, 87 had macroscopic melaena (without haematemesis) and 127 haematemesis with or without melaena.Only one of the 87 melaena patients died (from cancer) therefore in this group surgery was not indicated.The 127 patients who had haematemesis were treated with light diet, rest in bed, iron, and vitamin medication, and, as the period investigated advanced, to an increasing degree with blood transfusions.The diagnostic distribution is seen in Table I.In 115 cases the haemorrhage was caused by peptic ulcer (21 of these patients died); in 12 cases tIe haemorrhage was due to other affections (6 died).Two of the patients with peptic ulcer died from other affections, while 19 died from their haemorrhage-that is, a mortality rate of 16.5%.J0rgen Pedersen's criteria for surgical intervention (age over 50 years; haematemesis at hospital; recognized ulcer) were fulfilled in eight patients, four of whom died (Table II).Bohn's criteria, which apply to patients over 40 years and which indicate surgery when two or more are fulfilled (severe haemorrhage; good evidence of a chronic peptic ulcer, particularly corpus ulcer; haematemesis at hospital) designated 47 patients, including 18 of the 19 that died from haemorrhage in peptic ulcer (Table III).The group includes three cases in which the haemorrhage was not caused by peptic ulcer.In this group the mortality from haematemesis due to peptic ulcer amounts to 40%'.It is concluded that Bohn's criteria must be regarded as suitable for determining which patients are to be subjected to immediate surgery.
Hepatobiliary Scan Appearance of Heterotopic Liver Transplantation
Authors: CHARLES INTENZO, SANTIAGO MUNOZ, MICHAEL MORITZ, CHAN PARK, SUNG KIM, BRUCE JARRELL
Journal: Clinical Nuclear Medicine (1991)

Radionuclide studies of the liver with Tc-99m iminodiacetic acid (IDA) compounds are often utilized for postoperative evaluation of liver transplant recipients. Both structural and functional complications are identified, namely graft rejection, vascular compromise, infection, cholestasis, biliary obstruction, and biliary leakage. In most instances, orthotopic transplantations are performed in which the patients' native liver is replaced by the donor liver. Recently, heterotopic liver transplantations, in which the patients' native liver is left in place while a portion of a donor liver is simply added, has been used in high-risk candidates. We report the hepatobiliary scan findings of a recent heterotopic liver transplantation on a patient with fulminant hepatitis complicated by hepatic encephalopathy, who is thus far leading a normal lifestyle.
Lack of interferon-g modulates systolic but not diastolic function during the acute phase of murine autoimmune myocarditis
Authors: Marina Afanasyeva, Dimitrios Georgakopolous, DeLisa Fairweather, Yan Wang, Ziya Kaya, Patrizio Caturegli, David A. Kass, Noel R. Rose
Journal: Journal of the American College of Cardiology (2002)
The Mechanistic Classification of Addictive Drugs
Authors: Christian Lüscher, Mark A Ungless
Journal: PLoS Medicine (2006)

Research in Translation discusses health interventions in the context of translation from basic to clinical research, or from clinical evidence to practice. Some of the Key Papers on the Cellular Effects of Addictive DrugsJohnson and North, 1992 [11]: A classic paper demonstrating the disinhibitory effect of opioids on dopamine neurons.et al., 2004 [17]: A current model explaining how the popular club drug GHB activates VTA neurons via its action on the GABA B receptor.[21]: An elegant study showing that in knockout mice lacking the β2 subunit of the acetylcholine receptor, the rewarding properties of nicotine can be restored by selective re-expression in VTA neurons. Cruz Maskos et al., 2005 Chen et al., 2006[39]: A recent paper demonstrating that the rewarding properties of cocaine are absent in mice that express a cocaine-insensitive dopamine transporter . Ungless et al., 2001 [56]:The fi rst in a series of papers to observe a form of long-term synaptic plasticity of glutamatergic synapses in the VTA in response to addictive drugs.This and other adaptive changes common to several addictive drugs downstream of the dopamine increase are the focus of much current research.et al., 2003 [57]: In this paper the authors observe a form of long-term synaptic plasticity of glutamatergic synapses in the VTA in response to several addictive drugs.This and other adaptive changes downstream of the dopamine increase are the focus of much current research. Saal
THE "NORMAL" CARBON MONOXIDE CONTENT OF THE BLOOD
Authors: ALEXANDER O. GETTLER
Journal: JAMA (1933)

The ideal normal individual should have no carbon monoxide in his blood, but the average person under ordinary conditions is exposed so frequently to it that it is not possible to regard him as being carbon monoxide free unless procedures are employed which are suitable only for the detection of amounts known to be toxic. It is our purpose to determine to what extent carboxyhemoglobin exists in the blood of presumably normal persons as shown by a precise and delicate method. The literature reveals no record of such analyses. <h3>CARBON MONOXIDE POISONING</h3> An able review of carbon monoxide poisoning has been compiled by Sayers and Davenport.<sup>1</sup>This review traces the knowledge of "vapor" poisoning from ancient times, lists the sources of carbon monoxide in industry, discusses public and private hazards, portrays the symptoms of poisoning, describes aids to diagnosis and laboratory methods, depicts the pathology of carbon monoxide poisoning,
Selective cardiac sympathetic blockade as an adjunct to bronchodilator therapy
Authors: R. Powles, E. Shinebourne, J. Hamer
Journal: Thorax (1969)

It has been shown in nine asthmatic patients that practolol, a selective cardiac beta-adrenergic antagonist, successfully blocks the unwanted tachycardia and palpitation following isoprenaline inhalation without hindering the beneficial bronchodilator action of the drug. Practolol is a useful adjunct to bronchodilator therapy in the management of bronchial asthma.
Group B streptococci in pooled human milk.
Authors: A Lucas, C D Roberts
Journal: BMJ (1978)

and invited confirmation, though the mech- anism of action was unknown.We gave 5 g of cholestyramine or methyl- celluose twice daily in a double-blind crossover trial to five patients receiving chronic haemo- dialysis, using the same grading of pruritus.The daily pruritus score was calculated and the mean scores before, during four weeks of cholestyramine, and during four weeks of placebo treatment were compared.The results are shown in the accompanying table.Mean pruritus scores before and during treatment with placebo and cholestyramine
European Consensus for Gynecologycal and Obstetric Management of Women with Hereditary Angioedema due to C1-Inhibitor Deficiency (HAE): PREHAEAT
Authors: T. Caballero, L. Bouillet, K. Bork, C. Bucher, A. Bygum, C. De Carolis, H. Farkas, H. Longhurst, E. Nielsen, R. Perricone, N. Prior, M. Cicardi
Journal: Journal of Allergy and Clinical Immunology (2007)
Crohn's disease--a permeability disorder of the tight junction?
Authors: D Hollander
Journal: Gut (1988)

Leading articleCrohn's disease -a permeability disorder of the tight junction?Despite extensive efforts the aetiology of Crohn's disease has yet to be established.Studies have concentrated on possible infectious or immuno- logical causes, but have not provided a clear explanation of the pathogenesis of this disease.Many infectious agents such as bacteria, viruses, myco- plasma, and mycobacteria have been considered as possibly causing Crohn's disease.1-3 So far none of the infectious agents have fulfilled Koch's postulates or been consistently confirmed as a causative agent of this disease.Possible immunological abnormalities have also been studied.4Numerous investigators have looked for either primary immunological abnormalities5 or abnormalities of immune response.6Again, none of these efforts have consistently identified immunological abnormalities as the cause of Crohn's disease.78Prostanoid metabolism has recently received extensive scrutiny in the search for the aetiology of Crohn's disease.Numerous investigators have been able to show increased PGE2 concentrations in inflamed colonic mucosa9 '°or colonic lumenal contents from patients with Crohn's disease.'1Increased elaboration of other prostanoids9 1213 and leucotrienes"`has also been reported in patients with Crohn's disease.The consensus of opinion is that changes in prostanoid metabolism in Crohn's disease are probably secondary to the inflammatory process itself and not an underlying aetio- logical factor. 14While the aetiology and pathogenesis of Crohn's disease is complex, I propose that increased intestinal permeability through abnormal tight junctions could play a role.I am not proposing that increased intestinal permeability is the only aetiological factor in the development of Crohn's disease; rather, I am proposing that increased intestinal permeability could allow the penetration of antigenic or infectious agents into the intestinal wall and thus start the process which in susceptible individuals culminates in Crohn's disease.The proposal that increased intestinal permeability could be important is not new.'5Recent new clinical and experimental evidence,'"2' however, is sufficient to suggest serious consideration of this proposal as a working hypothesis.The term permeability needs clarification and definition.Normally the intestinal epithelium is able to act as a selective entry gate into the body.The intestinal epithelium which absorbs needed nutrients, fluids, and electro- lytes with a very high degree of efficiency can also selectively prevent the absorption of water soluble compounds larger than 0.4 nm in diameter.22Such size considerations do not apply to lipid soluble molecules, because they penetrate the absorptive cell membrane directly.23Strictly speaking, small water soluble charged molecules can also be absorbed by a process which is also sometimes referred to as permeability.24The penetration of the intestinal epithelium by sodium ions is an example for such a process.
Investigators seek shared virus antigens
Authors: Chris Anne Raymond
Journal: JAMA (1986)

The identification of a number of viruses associated with the common cold, and the belief that there were few common cross-types, led Dorland J. Davis, then director of the National Institute of Allergy and Infectious Diseases to tell a House Appropriations Committee in 1972 that the National Institutes of Health was giving up on developing a cold vaccine. According to William P. Allen, PhD, of the National Institute of Allergy and Infectious Diseases: "It is not feasible to approach colds from the point of view of a vaccine. There is too much antigenic variation." Robert M. Chanock, MD, director of the institute's infectious diseases laboratory, reports that during 1985, no intramural research on cold vaccines was being conducted at the National Institutes of Health. The institutes have continued to support extramural research at a number of medical centers. However, recent work elsewhere has renewed hope, at least among some researchers,
Comparison of Caspofungin and Amphotericin B for Invasive Candidiasis
Authors: Jorge Mora-Duarte, Robert Betts, Coleman Rotstein, Arnaldo Lopes Colombo, Luis Thompson-Moya, Juanita Smietana, Robert Lupinacci, Carole Sable, Nicholas Kartsonis, John Perfect
Journal: New England Journal of Medicine (2002)

Caspofungin is an echinocandin agent with fungicidal activity against candida species. We performed a double-blind trial to compare caspofungin with amphotericin B deoxycholate for the primary treatment of invasive candidiasis.We enrolled patients who had clinical evidence of infection and a positive culture for candida species from blood or another site. Patients were stratified according to the severity of disease, as indicated by the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the presence or absence of neutropenia and were randomly assigned to receive either caspofungin or amphotericin B. The study was designed to compare the efficacy of caspofungin with that of amphotericin B in patients with invasive candidiasis and in a subgroup with candidemia.Of the 239 patients enrolled, 224 were included in the modified intention-to-treat analysis. Base-line characteristics, including the percentage of patients with neutropenia and the mean APACHE II score, were similar in the two treatment groups. A modified intention-to-treat analysis showed that the efficacy of caspofungin was similar to that of amphotericin B, with successful outcomes in 73.4 percent of the patients treated with caspofungin and in 61.7 percent of those treated with amphotericin B (difference after adjustment for APACHE II score and neutropenic status, 12.7 percentage points; 95.6 percent confidence interval, -0.7 to 26.0). An analysis of patients who met prespecified criteria for evaluation showed that caspofungin was superior, with a favorable response in 80.7 percent of patients, as compared with 64.9 percent of those who received amphotericin B (difference, 15.4 percentage points; 95.6 percent confidence interval, 1.1 to 29.7). Caspofungin was as effective as amphotericin B in patients who had candidemia, with a favorable response in 71.7 percent and 62.8 percent of patients, respectively (difference, 10.0 percentage points; 95.0 percent confidence interval, -4.5 to 24.5). There were significantly fewer drug-related adverse events in the caspofungin group than in the amphotericin B group.Caspofungin is at least as effective as amphotericin B for the treatment of invasive candidiasis and, more specifically, candidemia.
In Vitro Effects of Estradiol on the Aorta of Chickens
Authors: MANUEL RENÉ MALINOW
Journal: Circulation Research (1960)

Aortas of chickens were incubated during 72 hours with 17α- or with 17β-estradiol and the alkaline phosphomonoesterase activity determined. Paired experiments demonstrated that both isomers are able to enhance the activity of the enzyme in vitro. The possible relation of these results with atherogenesis is discussed.