tbuckley/cabot-search huggingface dataset:
Cross-Talk Between the Toll-Like Receptor 4 and Notch1 Pathways Augments the Inflammatory Response in the Interstitial Cells of Stenotic Human Aortic Valves
Authors: Qingchun Zeng, Chunhua Jin, Lihua Ao, Joseph C. Cleveland, Rui Song, Dingli Xu, David A. Fullerton, Xianzhong Meng
Journal: Circulation (2012)

Calcific aortic stenosis is a chronic inflammatory disease, and aortic valve interstitial cells (AVIC) play an important role in valvular inflammation. Whereas AVIC from stenotic aortic valves exhibit an augmented response to Toll-like receptor 4 (TLR4) stimulation, the underlying mechanism is unclear. This study tested the hypothesis that an excessive cross-talk between the TLR4 and Notch1 pathways is responsible for augmentation of the inflammatory response to lipopolysaccharide (LPS) in AVIC of stenotic valves.Human AVIC were isolated from normal and stenotic leaflets. Nuclear factor kappa-B (NF-κB) activation and production of interleukin-8, monocyte chemoattactrant protein-1, and intercellular adhesion molecule-1 were analyzed after treatment with LPS. The role of Notch1 in the inflammatory response was determined using inhibitor, siRNA, and specific ligand. Cells from diseased valves produced greater levels of chemokines and intercellular adhesion molecule-1 that are associated with enhanced NF-κB activation. Interestingly, diseased cells exhibited augmented Jagged1 release and Notch1 activation after TLR4 stimulation. Inhibition and silencing of Notch1 each resulted in greater suppression of the TLR4-induced inflammatory response in diseased cells. Conversely, activation of Notch1 with a specific ligand, Jagged1, enhanced the LPS-induced inflammatory response in normal AVIC. Further, Notch1 intracellular domain was coimmunoprecipited with the inhibitor of NF-κB kinase after LPS stimulation, and inhibition of Notch1 abrogated the difference in the level of NF-κB activation between diseased and normal cells.Notch1 enhances the inflammatory response to TLR4 stimulation in human AVIC through modulating NF-κB activation. Excessive cross-talk between the TLR4 and Notch1 pathways is responsible for augmentation of the TLR4 response in AVIC of stenotic valves.
A Nonphysician Looks at Medical Utopia
Authors: Joseph D. Cooper
Journal: JAMA (1966)

The medical welfare state, should it become fact in the United States, would find little to guide it in the experiences of Sweden, Saskatchewan, Britain, Czechoslovakia, or any other land that has nationalized its health services. State medical systems in operation have made use of organizational systems and insurance plans to provide free access to medical service, regardless of ability to pay. Otherwise, they have embraced no radical technological advances in the nature and delivery of medical services.  In the United States, a medical welfare state would be a mammoth systems laboratory, integrating medical research, medical education, patient care, medical-records-center management, systems-information feedback (such as medical audits and drug-effects reporting), communicable-disease-control centers, mass-screening programs, coordinated progressive referral systems (essential in an age of specialization), community organization, epidemiological surveys, and other components of the ultimate medical program in a systems society.  Applied science and technology would be maximally exploited in diagnosis,
Simvastatin, Fenofibrate, and Rhabdomyolysis
Authors: Sindhu S. Jacob, Sony Jacob, Craig Williams, Mark A. Deeg
Journal: Diabetes Care (2005)

The National Cholesterol Education Program (NCEP) guidelines recommend use of statin-fibrate combinations to treat combined dyslipidemia. Myopathy and rhabdomyolysis are reported side effects, especially with gemfibrozil-statin combinations (1). This risk is recognized to result from both pharmacodynamic and pharmacokinetic interactions. In vitro studies in human hepatocytes have shown that unlike gemfibrozil, fenofibrate has no pharmacokinetic interaction with simvastatin at concentrations achieved with clinical dosing (2). The acid form of simvastatin is partly eliminated by glucuronidation and lactonization, both of which are inhibited by gemfibrozil but not fenofibrate (2). This lack of a pharmacokinetic interaction between simvastatin and fenofibrate relaxed the recommendation in the package insert for simvastatin, …
Anti-tumor characteristics of radiation-induced tumor-infiltrating neutrophils
Authors: Tsuguhide Takeshima, Ellen Vitetta, Raquibul Hannan
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts It is now evident that interactions between tumor cells and host tissue stoma play a key role in tumor progression. Understanding the composition of the stromal cells in the tumor microenvironment immediately after tumor irradiation might be an important first step in
Altered biologic activities of commercial polychlorinated biphenyl mixtures after microbial reductive dechlorination.
Authors: M A Mousa, P E Ganey, J F Quensen, B V Madhukar, K Chou, J P Giesy, L J Fischer, S A Boyd
Journal: Environmental Health Perspectives (1998)

The reductive dechlorination of polychlorinated biphenyls (PCBs) by anaerobic bacteria has recently been established as an important environmental fate of these compounds. This process removes chlorines directly from the biphenyl ring with replacement by hydrogen, resulting in a product mixture in which the average number of chlorines per biphenyl is reduced. In this study, dechlorination of commercial PCB mixtures (Aroclors 1242 and 1254) by microorganisms eluted from PCB-contaminated sediments of the River Raisin (Michigan) and Silver Lake (Massachusetts) caused a depletion in the proportion of highly chlorinated PCB congeners and an accumulation of lesser-chlorinated congeners. Dechlorination occurred primarily at the meta and, to a much lesser extent, para positions of biphenyl. The concentrations of the coplanar congeners including 3,3',4,4',5-pentachlorobiphenyl, the most potent dioxinlike congener, were significantly lowered by reductive dechlorination. Microbial reductive dechlorination of commercial PCB mixtures caused a substantial reduction in biologic activities in several instances. It significantly lowered or eliminated the inhibitory effects of Aroclors on fertilization of mouse gametes in vitro. Similarly, the dechlorinated product mixtures had substantially lower ethoxyresorufin-O-deethylase induction potencies and showed less ability to induce activating protein 1 transcription factor activity as compared to the unaltered Aroclors. In other assays the same dechlorinated product mixtures demonstrated biologic activities similar to the nondechlorinated Aroclors, including the ability of PCB mixtures to stimulate insulin secretion and cause neutrophil activation. The data presented here establish that the biologic activities of commercial PCB mixtures are altered by microbial reductive dechlorination and that an assessment of their toxic potential requires an array of tests that include the different mechanisms associated with PCBs.
Constitutive activation of Stat5 promotes its cytoplasmic localization and association with PI3-kinase in myeloid leukemias
Authors: Noria Harir, Christian Pecquet, Marc Kerenyi, Karoline Sonneck, Boris Kovacic, Remy Nyga, Marie Brevet, Isabelle Dhennin, Valerie Gouilleux-Gruart, Hartmut Beug, Peter Valent, Kaiss Lassoued, Richard Moriggl, Fabrice Gouilleux
Journal: Blood (2006)
Antibody to Endotoxin in the Treatment of Gram-negative Sepsis-Reply
Authors: Richard L. Greenman
Journal: JAMA (1992)

<h3>In Reply.</h3> —We agree with Dr Spalter's assertion about the cost of monoclonal antibody therapy. Both E5 and HA-1A need to be studied further to develop efficient and clinically useful guidelines for their usage. The statistical analysis that he offers deals with data from the study on HA-1A,<sup>1</sup>and we feel this point should be directed to the authors of that article. Dr McCabe correctly notes that there was a reduction in the mortality of patients with gram-negative sepsis without shock. His contention that this group is unlikely to have serious gram-negative bacillary infections is hardly supported by the 46% mortality in the placebo group. While 74 of the 137 patients in this group were bacteremic, we feel it is not justified to equate known endotoxemia and proven gram-negative bacteremia, as McCabe suggests. McCabe describes some of the difficulties in identifying a population of patients with gram-negative sepsis. These
Ventricular Phosphodiesterase-5 Expression Is Increased in Patients With Advanced Heart Failure and Contributes to Adverse Ventricular Remodeling After Myocardial Infarction in Mice
Authors: Peter Pokreisz, Sara Vandenwijngaert, Virginie Bito, An Van den Bergh, Ilse Lenaerts, Cornelius Busch, Glenn Marsboom, Olivier Gheysens, Pieter Vermeersch, Liesbeth Biesmans, Xiaoshun Liu, Hilde Gillijns, Marijke Pellens, Alfons Van Lommel, Emmanuel Buys, Luc Schoonjans, Johan Vanhaecke, Erik Verbeken, Karin Sipido, Paul Herijgers, Kenneth D. Bloch, Stefan P. Janssens
Journal: Circulation (2009)

Ventricular expression of phosphodiesterase-5 (PDE5), an enzyme responsible for cGMP catabolism, is increased in human right ventricular hypertrophy, but its role in left ventricular (LV) failure remains incompletely understood. We therefore measured LV PDE5 expression in patients with advanced systolic heart failure and characterized LV remodeling after myocardial infarction in transgenic mice with cardiomyocyte-specific overexpression of PDE5 (PDE5-TG).Immunoblot and immunohistochemistry techniques revealed that PDE5 expression was greater in explanted LVs from patients with dilated and ischemic cardiomyopathy than in control hearts. To evaluate the impact of increased ventricular PDE5 levels on cardiac function, PDE5-TG mice were generated. Confocal and immunoelectron microscopy revealed increased PDE5 expression in cardiomyocytes, predominantly localized to Z-bands. At baseline, myocardial cGMP levels, cell shortening, and calcium handling in isolated cardiomyocytes and LV hemodynamic measurements were similar in PDE5-TG and wild-type littermates. Ten days after myocardial infarction, LV cGMP levels had increased to a greater extent in wild-type mice than in PDE5-TG mice (P<0.05). Ten weeks after myocardial infarction, LV end-systolic and end-diastolic volumes were larger in PDE5-TG than in wild-type mice (57+/-5 versus 39+/-4 and 65+/-6 versus 48+/-4 muL, respectively; P<0.01 for both). LV systolic dysfunction and diastolic dysfunction were more marked in PDE5-TG than in wild-type mice, associated with enhanced hypertrophy and reduced contractile function in isolated cardiomyocytes from remote myocardium.Increased PDE5 expression predisposes mice to adverse LV remodeling after myocardial infarction. Increased myocardial PDE5 expression in patients with advanced cardiomyopathy may contribute to the development of heart failure and represents an important therapeutic target.
Negative influence of age on CD4+ cell recovery after highly active antiretroviral therapy in naïve HIV-1-infected patients with severe immunodeficiency
Authors: Dariela Micheloud, Juan Berenguer, Jose M.a Bellón, Pilar Miralles, Jaime Cosin, Juan Carlos Lopez-Bernaldo de Quiros, Matilde Sánchez Conde, M. Ángeles Muñoz-Fernández, Salvador Resino
Journal: Journal of Infection (2008)
P160 Increased cough intensity in patients with chronic cough: Abstract P160 Table 1
Authors: KK Lee, K Ward, E Raywood, J Moxham, GF Rafferty, SS Birring
Journal: Thorax (2012)

<h3>Introduction and objectives</h3> Cough frequency is increased in chronic cough (CC) compared to healthy subjects. It is not known if patients with CC cough more intensely. We investigated cough intensity in maximum voluntary cough (MVC) in patients with chronic cough and in healthy controls. <h3>Methods</h3> 28 subjects with chronic cough and 21 healthy subjects underwent measurement of oesophageal pressure (Poes), gastric pressure (Pga), peak abdominal electromyographic activity (EMGabd) and peak cough flow rate (PCFR) during 10 maximum voluntary cough manoeuvres. Coughs were performed at functional residual capacity. Inspiratory volume (IV) preceding cough efforts was calculated by integration of flow. Expiratory muscle strength was assessed by measuring twitch gastric pressure (TwPga) in response to magnetic stimulation. EMGabd data was normalised to EMGabd twitch compound muscle action potential and PCFR data normalised to predicted peak flow rate (PEFRp). The analysis of data was restricted to gender and expressed per unit IV. <h3>Results</h3> Subjects were matched for age, gender, BMI and had normal lung function. All measures of cough intensity were significantly higher in chronic cough compared to healthy controls, irrespective of gender (Table 1). However, this was not due to increased activation of the abdominal muscles since there were no significant differences in EMG (p&gt;0.2) or due to increased expiratory muscle strength (p&gt;0.36). There was no significant difference in Poes/IV and Pga/IV between male and female patients or controls (p&gt;0.28), but female cough subjects produced significantly higher PCFR/IV compared to males (p&lt;0.01). <h3>Conclusions</h3> Cough intensity is increased in patients with chronic cough, during MVC. This raises the possibility that cough intensity in these patients may contribute to cough severity and health status. The mechanism is unclear and deserves further investigation in studies of VC and spontaneous cough.
Screening for CAD in asymptomatic patients with type 2 diabetes did not reduce risk for cardiac events
Authors: Michael E. Farkouh
Journal: Annals of Internal Medicine (2009)

Source Citation Young LH, Wackers FJ, Chyun DA, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301:1547-55. 19366774
Low Oesophageal Perforation at Gastroscopy
Authors: C. F. J. Cropper, P. Houghton, P. Kidd
Journal: BMJ (1950)

COMMENTCase 1 is of interest in that it demonstrates the wellknown radio-sensitivity of dysgerminomata.In spite of metastases when the patient was first seen, the disease was under control two-and-a-half years later.Case 2 occurred in a patient comparatively young for this disease, though there have been several cases recorded in younger children.Russell (1938) reported a case in a child of 4 and McNally (1945) one in a child of 5. Novak's (1946) youngest patient was 6.A few other extra-ovarian dysgerminomata have been reported, and, while the occurrence of the growth in such sites may be due to nests of embryonic tissue remaining behind during the course of development, it could also be explained by metastatic spread from a minute primary tumour.In Case 2 there did not seem to be any primary ovarian tumour.The accepted treatment for localized dysgerminomata is excision of the affected tube and ovary, as recurrence in the other ovary is rare.Most authorities advise irradiation afterwards only if recurrence occurs, since it is obviously undesirable completely to destroy the patient's ovarian function, as the disease occurs in the young and the growth is usually of moderate malignancy only.The history of Case 2, however, suggests that this may not always be the wisest course.For those of adult age with hypoplasia genitalis there is obviously no objection to giving x-ray treatment post-operatively as a routine, nor is there when bilateral growths have been removed.Where metastases are present x-ray therapy gives comparatively good results, especially when one considers the poor prognosis of malignant disease arising in the young.These cases were admitted under the care of Mr. Victor Riddell (who performed the operation on the first case) and Mr. M. F. Nicholls, and my thanks are due to them and to Mr. J.
Localized linear IgA disease and platelet abnormalities
Authors: C. Condon, P. Cotter, J.F. Lyons
Journal: British Journal of Dermatology (1994)

Journal Article Localized linear IgA disease and platelet abnormalities Get access C. Condon, C. Condon Department of Dermatology, South Infirmary Hospital Search for other works by this author on: Oxford Academic Google Scholar P. Cotter, P. Cotter Department of Haematology, Cork Regional Hospital, Cork, Ireland Search for other works by this author on: Oxford Academic Google Scholar J.F. Lyons J.F. Lyons Department of Dermatology, South Infirmary Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 1, 1 July 1994, Pages 139–141, https://doi.org/10.1111/j.1365-2133.1994.tb08476.x Published: 01 July 1994
Age of menarche in Indian female basketball and volleyball players at different competitive levels.
Authors: R Mokha, L S Sidhu
Journal: British Journal of Sports Medicine (1989)

Data for the age of menarche have been collected on 98 female volleyball players and 75 basketball players. The players belonged to four different levels of competition: international, national, intervarsity and district. Menarche is significantly delayed in players as compared with the controls. There is a continuous trend of increase in the age of menarche with the increasing levels of competition; menarche is more delayed in players playing at a higher level than those at the lower levels of competition.
Benevolent 'world war' declared humanity's longtime disease foes
Authors: Charles Marwick
Journal: JAMA (1984)

The techniques of modern molecular biology are opening promising avenues for the World Health Organization's long-sought goal for the ultimate control of six major tropical diseases—malaria, filariasis, trypanosomiasis, leprosy, schistosomiasis, and leishmaniasis. Among the recent advances in some of these diseases: A candidate vaccine against leprosy is currently undergoing clinical trials; A vaccine against malaria is in sight, and improved drugs, including a new agent from the People's Republic of China, are under active investigation; A new drug for the management and perhaps even prevention of onchocerciasis, or river blindness, is undergoing an extended field trial; Finally, a well-studied and highly promising candidate vaccine against the rotavirus responsible for diarrheal diseases of infants and children is at hand and may be ready for use in a year or two. In addition, novel strategies are being instituted for the better control of many of the
Abstract 2912: Development of potent SHP2 inhibitors for <i>in vivo</i> studies
Authors: Yiyu Ge, Harshani R. Lawrence, Liwei Chen, Latanya M. Scott, Said M. Sebti, Nicholas J. Lawrence, Jie Wu
Journal: Cancer Research (2012)

Abstract The Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) is a positive transducer of growth factor, cytokine, integrin, and hormone signaling pathways which regulates processes such as cell proliferation, differentiation, adhesion, migration, and apoptosis and plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with various kinds of leukemia, and solid tumors. This makes SHP2 an attractive target for anticancer therapy. We are developing SHP2 inhibitors as novel anticancer drugs. Previously, we have reported on SPI-112 and its methyl ester prodrug SPI-112Me. However, the poor solubility of SPI-112Me has become an obstacle for in vivo studies. In ongoing study, we generate SPI-112 analogs to further improve physicochemical properties of these SHP2 inhibitors, such as solubility and cell permeability. To this aim, we synthesized SPI-112 derivatives containing various phosphotyrosine mimics and their prodrugs. SPI-112 derivatives of SHP2 inhibitors having improved properties have been obtained in this effort. 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 2912. doi:1538-7445.AM2012-2912
Liposomal modular complexes for simultaneous targeted delivery of bioactive gases and therapeutics
Authors: Melvin E. Klegerman, Michael Wassler, Shao-Ling Huang, Yuejiao Zou, Hyunggun Kim, Harnath S. Shelat, Christy K. Holland, Yong-Jian Geng, David D. McPherson
Journal: Journal of Controlled Release (2009)
Angiotensin-(1-7) Formation in the Intact Human Heart
Authors: Lawrence S. Zisman, Glenn E. Meixell, Michael R. Bristow, Charles C. Canver
Journal: Circulation (2003)

Several enzymes that hydrolyze angiotensin I (Ang I) and Ang II to Ang-(1-7) have been identified, but their relative importance in the intact human heart is not known.Intracoronary (IC) 123I-Ang I was administered to 4 heart transplantation recipients. Arterial and coronary sinus (CS) samples were taken before and after coadministration of IC enalaprilat. 123I-Ang metabolites were separated by high-pressure liquid chromatography, and 123I-Ang-(1-7) and 123I-Ang II were quantified across the myocardial circulation. 123I-Ang II formation (as measured by fractional conversion) at steady state was 0.43+/-0.05 and was reduced to 0.042+/-0.02 after IC enalaprilat (P<0.01). The fractional conversion of 123I-Ang-(1-7) was 0.198+/-0.032 but was reduced to 0.06+/-0.01 during IC enalaprilat (P<0.01). Net Ang II production at steady state was 2720+/-704 pg/min. Ang-(1-7) production was 3489+/-768 pg/min. After IC enalaprilat, Ang II production fell to 436+/-66.8 pg/min (P<0.05 versus Ang II production). After suppression of Ang II production with enalaprilat, there was net uptake of Ang-(1-7): -289+/-144 pg/min (P<0.05).Ang-(1-7) was formed in the intact human myocardial circulation and was decreased when Ang II formation was suppressed. These data indicate that the major pathway for Ang-(1-7) generation in the intact human heart was dependent on substrate availability of Ang II. Ang-(1-7)-forming enzymes that demonstrate substrate preference for Ang II are likely to play an important role in the regulation of Ang-(1-7) formation in the intact human heart.
Functional Impairment and Internet Use Among Older Adults
Authors: S. Ryan Greysen, Carie Chin Garcia, Rebecca L. Sudore, Irena Stijacic Cenzer, Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2014)

Discussion | In a decade with increasing emphasis and accountability for glycemic control and cardiovascular risk management among patients with diabetes, we found that patients with diabetes have experienced a disproportionate reduction in in-hospital mortality over time and a complete reversal in risk of mortality relative to patients without diabetes.This interesting trend warrants additional study to elucidate its origins.Potential explanations include coincident improvements in inpatient glycemic control, improvements in outpatient glycemic control, improved nonglycemic cardiovascular risk management among patients with diabetes, and/or advances in therapies for diseases that disproportionately affect patients with diabetes.