tbuckley/cabot-search huggingface dataset:
Tumor Necrosis factor- and Expression of the Multidrug Resistance-Associated Genes LRP and MRP
Authors: U. Stein, W. Walther, C. M. Laurencot, R. H. Shoemaker, G. L. Scheffer, R. J. Scheper
Journal: JNCI Journal of the National Cancer Institute (1997)

Background and Purpose: Cancer cells that express P-glycoprotein, multidrug resistance-associated protein (MRP), or lung resistance protein (LRP) have demonstrated resistance to a wide variety of chemotherapeutic drugs. Recently, we reported that human colon carcinoma cells that express all three proteins exhibit reduced P-glycoprotein gene expression and a loss of multidrug resistance after exposure to tumor necrosis factor-α, a hormone-like protein produced by cells of the immune system. In this study, we examined the effects of tumor necrosis factor- a on MRP and LRP gene expression in the same colon carcinoma cells. Methods: HCT15 and HCT116 colon carcinoma cells were incubated with tumor necrosis factor-α at 100 U/mL for 2, 12, 24, 48, or 72 hours; alternatively, cells transfected with an expression vector containing a human tumor necrosis factor-α complementary DNA were studied. The effects of tumor necrosis factor-α on MRP and LRP messenger RNA expression were evaluated by means of reverse transcription and the polymerase chain reaction; effects on MRP and LRP protein expression were examined by use of specific monoclonal antibodies and flow cytometry. The flow cytometry data were analyzed by use of the twosided, nonparametric Mann-Whitney rank sum test. Results: Treatment with exogenous tumor necrosis factor-α reduced the level of LRP messenger RNA in both cell types in an apparently timedependent fashion; in HCT15 cells, almost no LRP messenger RNA was detected after 48 hours of treatment. In contrast, the level of MRP messenger RNA was increased in HCT116 cells by such treatment, but the level in HCT15 cells was unchanged. Treatment with exogenous tumor necrosis factor-α induced changes in LRP and MRP protein expression in the two cell types that paralleled the changes found for messenger RNA. In transfected cells, the endogenous production of tumor necrosis factor-α reduced LRP gene expression (both messenger RNA and protein) and increased MRP gene expression (both messenger RNA and protein), regardless of cell type. Conclusion: In human colon carcinoma cells, tumor necrosis factor-α influences MRP and LRP gene expression in opposite ways. The findings for LRP gene expression parallel our earlier findings for P-glycoprotein expression in these cells. Implication: In developing strategies for overcoming multidrug resistance in tumor cells, the possibility that an agent can suppress one or more mechanisms of drug resistance and enhance others should be considered.
Mechanotransduction of Rat Aortic Vascular Smooth Muscle Cells Requires RhoA and Intact Actin Filaments
Authors: Kotaro Numaguchi, Satoru Eguchi, Tadashi Yamakawa, Evangeline D. Motley, Tadashi Inagami
Journal: Circulation Research (1999)

Abstract —The growth-promoting effect of mechanical stress on vascular smooth muscle cells (VSMCs) has been implicated in the progress of vascular disease in hypertension. Extracellular signal–regulated kinases (ERKs) have been implicated in cellular responses, such as vascular remodeling, induced by mechanical stretch. However, it remains to be determined how mechanical stretch activates ERKs. The cytoskeleton seems the most likely candidate for force transmission into the interior of the cell. Therefore, we examined (1) whether the cytoskeleton involves mechanical stretch–induced signaling, (2) whether Rho is activated by stretch, and (3) whether Rho mediates the stretch-induced signaling in rat cultured VSMCs. Mechanical stretch activated ERKs, with a peak response observed at 20 minutes, followed by a significant increase in DNA synthesis. Treatment with the ERK kinase-1 inhibitor, PD98059, inhibited the stretch-induced increase in DNA synthesis. Cytochalasin D, which selectively disrupts the network of actin filaments, markedly inhibited stretch-induced ERK activation. In the control state, RhoA was observed predominantly in the cytosolic fraction, but it was translocated in part to the particulate fraction in response to mechanical stretch. Botulinum C3 exoenzyme, which inactivates Rho p21 (known to participate in the reorganization of the actin cytoskeleton), attenuated stretch-induced ERK activation. Inhibition of Rho kinase (p160ROCK) also suppressed stretch-induced ERK activation dose dependently. Our results suggest that mechanotransduction in VSMCs is dependent on intact actin filaments, that Rho is activated by stretch, and that Rho/p160ROCK mediates stretch-induced ERK activation and vascular hyperplasia.
Effects of Dipyridamole on the Dog Heart-Lung Preparation
Authors: J. Simaan, G. Fawaz
Journal: Cardiovascular Research (1968)

Journal Article Effects of Dipyridamole on the Dog Heart-Lung Preparation Get access Joseph Simaan, Joseph Simaan From the Department of Pharmacology, School of Medicine, American University of Beirut, Beirut, Lebanon Search for other works by this author on: Oxford Academic PubMed Google Scholar George Fawaz George Fawaz From the Department of Pharmacology, School of Medicine, American University of Beirut, Beirut, Lebanon Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 2, Issue 1, January 1968, Pages 68–72, https://doi.org/10.1093/cvr/2.1.68 Published: 01 January 1968 Article history Received: 15 August 1966 Published: 01 January 1968
Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality
Authors: Kiichiro Yano, Patricia C. Liaw, Janet M. Mullington, Shu-Ching Shih, Hitomi Okada, Natalya Bodyak, Peter M. Kang, Lisa Toltl, Bryan Belikoff, Jon Buras, Benjamin T. Simms, Joseph P. Mizgerd, Peter Carmeliet, S. Ananth Karumanchi, William C. Aird
Journal: The Journal of Experimental Medicine (2006)

Sepsis, the systemic inflammatory response to infection, is a leading cause of morbidity and mortality. The mechanisms of sepsis pathophysiology remain obscure but are likely to involve a complex interplay between mediators of the inflammatory and coagulation pathways. An improved understanding of these mechanisms should provide an important foundation for developing novel therapies. In this study, we show that sepsis is associated with a time-dependent increase in circulating levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in animal and human models of sepsis. Adenovirus-mediated overexpression of soluble Flt-1 (sFlt-1) in a mouse model of endotoxemia attenuated the rise in VEGF and PlGF levels and blocked the effect of endotoxemia on cardiac function, vascular permeability, and mortality. Similarly, in a cecal ligation puncture (CLP) model, adenovirus–sFlt-1 protected against cardiac dysfunction and mortality. When administered in a therapeutic regimen beginning 1 h after the onset of endotoxemia or CLP, sFlt peptide resulted in marked improvement in cardiac physiology and survival. Systemic administration of antibodies against the transmembrane receptor Flk-1 but not Flt-1 protected against sepsis mortality. Adenovirus-mediated overexpression of VEGF but not PlGF exacerbated the lipopolysaccharide-mediated toxic effects. Together, these data support a pathophysiological role for VEGF in mediating the sepsis phenotype.
Growth of the Literature on the Topic of Personality Disorders
Authors: Roger K. Blashfield, Vincent Intoccia
Journal: American Journal of Psychiatry (2000)

The authors assessed the growth of the literature on the topic of personality disorders before and after publication of DSM-III.A MEDLINE search was conducted for journal articles concerning the personality disorders that were published from 1966 to 1995.Contrary to the authors' prediction, the growth of this literature was slower after the publication of DSM-III in 1980 than it was before that date. Other areas of psychopathology, such as Alzheimer's disease and posttraumatic stress disorder, have literatures whose growth rates since 1980 have exceeded their growth rates before publication of DSM-III.Over one-half of the individual personality disorders (e.g., histrionic and passive-aggressive) have either very small literatures or literatures with negative growth rates. Only three personality disorders (i.e., antisocial, borderline, and schizotypal) have modestly growing literatures.
Smoking Cessation after Acute Myocardial Infarction: Effects of a Nurse-Managed Intervention
Authors: C. Barr Taylor
Journal: Annals of Internal Medicine (1990)

Study Objective: To determine the effect of a nurse-managed intervention for smoking cessation in patients who have had a myocardial infarction. Design: Randomized, with a 6-month treatment period and a 6-month follow-up. Setting: Kaiser Foundation hospitals in Redwood City, Santa Clara, Hayward, and San Jose, California. Patients: Sequential sample of 173 patients, 70 years of age or younger, who were smoking before hospitalization for acute myocardial infarction. Eighty-six patients were randomly assigned to the intervention and 87 to usual care; 130 patients (75%) completed the study and were available for follow-up. Intervention: Nurse-managed and focused on preventing relapse to smoking, the intervention was initiated in the hospital and maintained thereafter primarily through telephone contact. Patients were given an 18-page manual that emphasized how to identify and cope with high-risk situations for smoking relapse. Measurements and Main Results: One year after myocardial infarction, the smoking cessation rate, verified biochemically, was 71% in the intervention group compared with 45% in the usual care group, a 26% difference (95% CI, 9.5% to 42.6%). Assuming that all surviving patients lost to follow-up were smoking, the 12-month smoking cessation rate was 61% in the intervention group compared with 32% in the usual care group, a 29% difference (95% CI, 14.5% to 43.5%). Patients who either resumed smoking within 3 weeks after infarction or expressed little intention of stopping in the hospital were unlikely to have stopped by 12 months. Conclusions: A nurse-managed smoking cessation intervention largely conducted by telephone, initiated in the hospital, and focused on relapse prevention can significantly reduce smoking rates at 12 months in patients who have had a myocardial infarction.
Targeting Tumor Hypoxia: Suppression of Breast Tumor Growth and Metastasis by Novel Carbonic Anhydrase IX Inhibitors
Authors: Yuanmei Lou, Paul C. McDonald, Arusha Oloumi, Stephen Chia, Christina Ostlund, Ardalan Ahmadi, Alastair Kyle, Ulrich auf dem Keller, Samuel Leung, David Huntsman, Blaise Clarke, Brent W. Sutherland, Dawn Waterhouse, Marcel Bally, Calvin Roskelley, Christopher M. Overall, Andrew Minchinton, Fabio Pacchiano, Fabrizio Carta, Andrea Scozzafava, Nadia Touisni, Jean-Yves Winum, Claudiu T. Supuran, Shoukat Dedhar
Journal: Cancer Research (2011)

Abstract Carbonic anhydrase IX (CAIX) is a hypoxia and HIF-1–inducible protein that regulates intra- and extracellular pH under hypoxic conditions and promotes tumor cell survival and invasion in hypoxic microenvironments. Interrogation of 3,630 human breast cancers provided definitive evidence of CAIX as an independent poor prognostic biomarker for distant metastases and survival. shRNA-mediated depletion of CAIX expression in 4T1 mouse metastatic breast cancer cells capable of inducing CAIX in hypoxia resulted in regression of orthotopic mammary tumors and inhibition of spontaneous lung metastasis formation. Stable depletion of CAIX in MDA-MB-231 human breast cancer xenografts also resulted in attenuation of primary tumor growth. CAIX depletion in the 4T1 cells led to caspase-independent cell death and reversal of extracellular acidosis under hypoxic conditions in vitro. Treatment of mice harboring CAIX-positive 4T1 mammary tumors with novel CAIX-specific small molecule inhibitors that mimicked the effects of CAIX depletion in vitro resulted in significant inhibition of tumor growth and metastasis formation in both spontaneous and experimental models of metastasis, without inhibitory effects on CAIX-negative tumors. Similar inhibitory effects on primary tumor growth were observed in mice harboring orthotopic tumors comprised of lung metatstatic MDA-MB-231 LM2-4Luc+ cells. Our findings show that CAIX is vital for growth and metastasis of hypoxic breast tumors and is a specific, targetable biomarker for breast cancer metastasis. Cancer Res; 71(9); 3364–76. ©2011 AACR.
Successful treatment of primary cutaneous follicle centre lymphoma with topical 5% imiquimod
Authors: A. Stavrakoglou, V.L. Brown, I. Coutts
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Imiquimod, a topical immune response modifier, has potent antitumour activity through local augmentation of innate and cell‐mediated immunity.1 It is increasingly being used to treat a wide variety of cutaneous tumours, including cutaneous T‐cell lymphomas.2, 3 It has not previously been shown to be fully efficacious for the treatment of cutaneous B‐cell lymphoma. We report a 59‐year‐old man with primary cutaneous follicle centre lymphoma successfully treated with topical 5% imiquimod. Our patient presented with a 5‐year history of multiple asymptomatic lesions grouped over the lateral surface of his upper right arm. Individual lesions had gradually appeared and enlarged over this time. Examination revealed smooth‐surfaced soft dermal papules and nodules (Fig. 1a). There was no associated palpable lymphadenopathy, nor organomegaly. Skin biopsy showed a lymphoid lesion involving superficial and deep dermis. The epidermis was intact and a Grenz zone was present (Fig. 2). On higher magnification, the infiltrate was noted to be polymorphic and composed of intermixed small and large lymphoid cells, with sparse germinal centres.
Spatial Vectorcardiograms in Normal Dogs
Authors: LEO HORAN, G. E. BURCH, J. A. CRONVICH
Journal: Circulation Research (1957)

The spatial vectoreardiogram was recorded on 34 normal mongrel dogs employing the equilateral tetrahedral reference system. The QRS sÊ-loop was long, narrow, and elliptical, and oriented slightly to the left, ventrad and caudad, the majority of the maximal vectors lying in the fifth sextant of the triaxial reference system in both the anterior and left sagittal plane projections. The trace was inscribed in a counterclockwise direction in the frontal and left sagittal plane projections for most of the dogs. The P and T sÊ-loops were essentially of the same configuration and had the same spatial orientation as the QRS sÊ-loops, except that T sÊ-loops were often oriented in the second sextant of the triaxial reference system in both the frontal and left sagittal plane projections.
New Insights and Observations in Three-Dimensional Echocardiographic Visualization of Ventricular Septal Defects
Authors: Richard E. Kardon, Qi Ling Cao, Navroz Masani, Lissa Sugeng, Stacey Supran, Kenneth G. Warner, Natesa G. Pandian, Gerald R. Marx
Journal: Circulation (1998)

Background —The positions, sizes, and shapes of ventricular septal defects (VSDs) can be difficult to assess by 2-dimensional echocardiography (2DE). Volume-rendered 3-dimensional echocardiography (3DE) can provide unique views of VSDs from the left ventricular (LV) side, allowing complete assessment of their circumference and spatial orientations to other anatomic structures. Methods and Results —Seventeen experimentally created defects of various locations, sizes, and shapes were imaged and reconstructed in 9 explanted porcine hearts. From an en face projection, major and minor axis diameters of the defects were measured, and these data were compared with direct anatomic measurements. Optimal reconstructions of the VSDs were obtained in all heart specimens, accurately depicting their positions and shapes. The correlations between 3DE and anatomy for the VSD major and minor axis diameters were y =1.0 x +0.3 ( r =0.88, P &lt;0.001) and y =1.0 x −1.4 ( r =0.89, P &lt;0.001), respectively. Good agreement between the 2 methods was demonstrated for all measurements. Our experience from the in vitro model was then applied to patient studies. Optimal LV en face reconstructions were obtained in 45 of 51 patients, permitting detailed assessment of the positions, sizes, and shapes of the VSDs. In the 25 patients with comparative surgical measurements, the correlations between 3DE and surgery for the VSD major and minor axis diameters were y =0.81 x +2.1 ( r =0.92, P &lt;0.001) and y =0.73 x +2.0 ( r =0.91, P &lt;0.001), respectively. Good agreement was demonstrated between measurements made by 3DE and those obtained at surgery. Conclusions —3DE provides excellent visualization of various types of VSDs. From an LV en face projection, the positions, sizes, and shapes of VSDs can be accurately determined. Such precise imaging will be beneficial for surgical and catheter-based closure of difficult perimembranous and singular or multiple muscular VSDs.
What the pulmonary specialist should know about the new inhalation therapies
Authors: B.L. Laube, H.M. Janssens, F.H.C. de Jongh, S.G. Devadason, R. Dhand, P. Diot, M.L. Everard, I. Horvath, P. Navalesi, T. Voshaar, H. Chrystyn
Journal: European Respiratory Journal (2011)

A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.
Blockade of Interferon Beta, but Not Interferon Alpha, Signaling Controls Persistent Viral Infection
Authors: Cherie T. Ng, Brian M. Sullivan, John R. Teijaro, Andrew M. Lee, Megan Welch, Stephanie Rice, Kathleen C.F. Sheehan, Robert D. Schreiber, Michael B.A. Oldstone
Journal: Cell Host & Microbe (2015)
Who's zooming who?
Authors: Nigel W. Bond
Journal: Behavioral and Brain Sciences (2005)

Men and women report having significantly different numbers of sexual partners, which is impossible in a large sample. Schmitt's target article is no exception. This focuses discussion on the nature of the samples, their heterogeneity, and the locale they are drawn from. Further, we query how humans determine, for example, sex ratio, in the context of large numbers.
Interleukin 1 or tumor necrosis factor can promote Coxsackie B3-induced myocarditis in resistant B10.A mice.
Authors: J R Lane, D A Neumann, A Lafond-Walker, A Herskowitz, N R Rose
Journal: The Journal of Experimental Medicine (1992)

We have previously demonstrated that bacterial lipopolysaccharide (LPS) is capable of promoting Coxsackie B3 (CB3)-induced myocarditis in genetically resistant B10.A mice. Because LPS is known to increase production of various cytokines, we tested CB3-infected, LPS-treated mice for the presence of interleukin 1 (IL-1) and tumor necrosis factor (TNF). We found significantly increased amounts of both cytokines in the sera of CB3/LPS-treated mice compared with animals treated only with LPS. We also found immunohistochemical evidence for local production of these cytokines in the cardiac tissue of CB3/LPS-treated mice. Treatment with IL-1 or TNF alone promoted CB3-induced autoimmune myocarditis in resistant B10.A mice. Myocarditis was also observed when uninfected mice were immunized with syngeneic heart extract in the presence of IL-1 or TNF.
Pharmacologic Modulation of Erythropoietin Production
Authors: J W Fisher
Journal: The Annual Review of Pharmacology and Toxicology (1988)

A model for the regulation of erythropoietin production has been presented. This model proposes that a primary O2-sensing reaction in the kidney is initiated by a decrease in ambient PO2, a rapid decrease in gas exchange in the lung, a diminished oxygen-carrying capacity of hemoglobin, a molecular deprivation of oxygen, or a decrease in renal blood flow. It is proposed that the primary oxygen-sensing reaction may trigger the release of several mediators that stimulate adenylate cyclase through a receptor-activated stimulation of a G protein in the renal cell membrane. Some of the agents that are thought to be released during hypoxia, which may trigger this cascade, are adenosine (A2 activation), eicosanoids (PGE2, PGI2, and 6-keto PGE1), oxygen-free radicals (superoxide and H2O2), and catecholamines with beta-2 adrenergic receptor agonist properties. The activation of adenylate cyclase generates cyclic AMP, which activates protein kinase A, leading to the production of a phosphoprotein that, in turn, activates a nuclear protein involved in transcription and/or translation for erythropoietin biosynthesis and/or secretion. A second part of this model concerns the effect of hypoxia on a renal cell membrane phosphodiesterase and the generation of inositol triphosphate and diacylglycerol. Diacylglycerol may interact with diacylglycerol lipase to generate arachidonic acid, which, together with arachidonic acid generated by the interaction of phospholipase A2 on membrane phospholipids, produces eicosanoids. Eicosanoids may play a secondary role in Ep production/secretion. The model further proposes that calcium levels in both renal and liver cells may be important in regulating erythropoietin biosynthesis and/or secretion. It is proposed that an increase in intracellular calcium leads to the inhibition of erythropoietin biosynthesis and/or secretion and a decrease in intracellular calcium increases erythropoietin production. The specific mechanism by which calcium regulates erythropoietin biosynthesis and secretion is not well understood. However, a good correlation is seen with several agents that decrease intracellular calcium and increase erythropoietin production as well as with other agents that increase intracellular calcium and decrease erythropoietin production. When inositol triphosphate levels are increased, an increase in the mobilization of intracellular calcium from the endoplasmic reticulum or another intracellular pool occurs. This increased intracellular calcium probably activates a calcium calmodulin kinase and produces a phosphoprotein that inhibits erythropoietin production/secretion.(ABSTRACT TRUNCATED AT 400 WORDS)