tbuckley/cabot-search huggingface dataset:
Human pulmonary macrophage-derived mucus secretagogue.
Authors: Z Marom, J H Shelhamer, M Kaliner
Journal: The Journal of Experimental Medicine (1984)

Human pulmonary macrophages (PM) obtained from surgically removed human lung tissue released a factor after exposure to activated zymosan that caused cultured human airways to release increased amounts of radiolabeled mucous glycoproteins. The factor was released maximally after 4-8 h of zymosan exposure and caused a dose-related increase in glycoprotein release; it was termed macrophage-derived mucus secretagogue (MMS). MMS release was produced in a dose-dependent fashion by activated but not by nonactivated zymosan. The activation of zymosan was C3 dependent, and C3b-coated Sepharose was also an effective stimulant. The data suggested that cell surface activation of the PM was a sufficient stimulus to cause MMS release and that both C3-dependent activation as well as Fc receptor activation were effective. The synthesis of MMS was sensitive to cycloheximide, and no active MMS was detectable intracellularly. To determine if MMS might be one of the oxidative derivatives of arachidonic acid, PM were incubated with cyclooxygenase and lipoxygenase inhibitors before activation. These maneuvers did not influence MMS generation. MMS-rich supernatants were then extracted into organic solvents or exposed to lipophilic resin; in both cases, MMS remained in the aqueous phase. Thus, MMS is not a derivative of arachidonic acid. Sequential fractionation of MMS on ultramembrane and gel filtration followed by isoelectric focusing and gel filtration indicated that MMS is a small (approximately 2000 daltons), acidic (pI, 5.15) molecule. Therefore, surface activation of human PM results in the synthesis and release of a small acidic molecule that causes airway mucous glands to secrete increased quantities of mucous glycoproteins.
Human Prostaglandin Transporter Gene ( <i>hPGT</i> ) is Regulated by Fluid Mechanical Stimuli in Cultured Endothelial Cells and Expressed in Vascular Endothelium in Vivo
Authors: James N. Topper, Jiexing Cai, George Stavrakis, Keith R. Anderson, Elizabeth A. Woolf, Barbara A. Sampson, Frederick J. Schoen, Dean Falb, Michael A. Gimbrone
Journal: Circulation (1998)

Background —biomechanical forces generated by blood flow within the cardiovascular system have been proposed as important modulators of regional endothelial phenotype and function. This process is thought to involve the regulation of vascular gene expression by physiological fluid mechanical stimuli such as fluid shear stresses. Methods and Results —We demonstrate sustained upregulation of a recently identified gene encoding a human prostaglandin transporter ( hPGT ) in cultured human vascular endothelium exposed to a physiological fluid mechanical stimulus in vitro. This biomechanical induction is selective in that steady laminar shear stress is sufficient to upregulate the hPGT gene at the level of transcriptional activation, whereas a comparable level of turbulent shear stress (a nonphysiological stimulus) is not. Various biochemical stimuli, such as bacterial endotoxin and the inflammatory cytokines recombinant human interleukin 1β cytokines (rhIL-1β) and tumor necrosis factor-α (TNF-α), did not significantly induce hPGT . Using a specific antiserum to hPGT, we demonstrate endothelial expression within the arterial vasculature and the microcirculation of highly vascularized tissues such as the heart. Conclusions —Our results identify hPGT as an inducible gene in vascular endothelium and suggest that biomechanical stimuli generated by blood flow in vivo may be important determinants of hPGT expression. Furthermore, this demonstration of regulated endothelial expression of hPGT implicates this molecule in the regional metabolism of prostanoids within the cardiovascular system.
Molecular Fingerprinting and Autocrine Growth Regulation of Endothelial Cells in a Murine Model of Hepatocellular Carcinoma
Authors: Eduard Ryschich, Paulius Lizdenis, Carina Ittrich, Axel Benner, Simone Stahl, Alf Hamann, Jan Schmidt, Percy Knolle, Bernd Arnold, Günter J. Hämmerling, Ruth Ganss
Journal: Cancer Research (2006)

Abstract In a mouse model of hepatocellular carcinogenesis, highly vascularized tumors develop through two distinct morphologic phases of neovascularization. We show that increased vascular caliber occurs first, followed by extensive vessel sprouting in late-stage carcinomas. To define molecular pathways in tumor neovascularization, endothelial cells were directly purified from normal liver and advanced tumors. Gene expression profiling experiments were then designed to identify genes enriched in the vascular compartment. We report that Cathepsin S is the major protease specifically overexpressed during vessel sprouting. We also show that the CC chemokines CCL2 and CCL3 are secreted by neovessels and stimulate proliferation through their cognate receptors in an autocrine fashion. This suggests that chemokine signaling represents the most prominent signaling pathway in tumor-associated endothelial cells and directly regulates vessel remodeling. Furthermore, high angiogenic activity is associated with attenuated lymphocyte extravasation and correlates with expression of the immunomodulatory cytokine interleukin 10. This is the first comprehensive study addressing liver-specific vascular changes in a murine autochthonous tumor model. These novel insights into liver angiogenesis infer an environmental control of neovascularization and have important implications for the design of antiangiogenic therapies. (Cancer Res 2006; 66(1): 198-211)
COPD exacerbations {middle dot} 2: Aetiology
Authors: E Sapey
Journal: Thorax (2006)

Exacerbations of COPD are thought to be caused by complex interactions between the host, bacteria, viruses, and environmental pollution. These factors increase the inflammatory burden in the lower airways, overwhelming the protective anti-inflammatory defences leading to tissue damage. Frequent exacerbations are associated with increased morbidity and mortality, a faster decline in lung function, and poorer health status, so prevention or optimal treatment of exacerbations is a global priority. In order to evolve new treatment strategies there has been great interest in the aetiology and pathophysiology of exacerbations, but progress has been hindered by the heterogeneous nature of these episodes, vague definitions of an exacerbation, and poor stratification of known confounding factors when interpreting results. We review how an exacerbation should be defined, its inflammatory basis, and the importance of exacerbations on disease progression. Important aetiologies, with their potential underlying mechanisms, are discussed and the significance of each aetiology is considered.
EFFECT OF THE SUN'S LIGHT ON A SYPHILITIC ERUPTION
Authors: C. RASCH
Journal: British Journal of Dermatology (1921)

Journal Article EFFECT OF THE SUN'S LIGHT ON A SYPHILITIC ERUPTION Get access C. RASCH C. RASCH Director of the University Dermatological Clinic at the Rigshospital Copenhagen Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 33, Issue 2, 1 February 1921, Pages 56–58, https://doi.org/10.1111/j.1365-2133.1921.tb09020.x Published: 01 February 1921
Calcified and non-calcified plaques in patients with acute coronary syndromes and non-obstructive angiographic disease
Authors: A. Schmermund, D. Baumgart, M. Adamzik, J. Ge, D. Grönemeyer, R. Selbel, C. Sehnert, G. Gorge, M. Haude, R. Erbel
Journal: Journal of the American College of Cardiology (1998)
Gender Differences in Treatment Response to Sertraline Versus Imipramine in Chronic Depression
Authors: Susan G. Kornstein, Alan F. Schatzberg, Michael E. Thase, Kimberly A. Yonkers, James P. McCullough, Gabor I. Keitner, Alan J. Gelenberg, Sonia M. Davis, Wilma M. Harrison, Martin B. Keller
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors examined gender differences in treatment response to sertraline, a selective serotonin reuptake inhibitor (SSRI), and to imipramine, a tricyclic antidepressant, in chronic depression. METHOD: A total of 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were randomly assigned to 12 weeks of double-blind treatment with sertraline or with imipramine after placebo washout. RESULTS: Women were significantly more likely to show a favorable response to sertraline than to imipramine, and men were significantly more likely to show a favorable response to imipramine than to sertraline. Gender and type of medication were also significantly related to dropout rates; women who were taking imipramine and men who were taking sertraline were more likely to withdraw from the study. Gender differences in time to response were seen with imipramine, with women responding significantly more slowly than men. Comparison of treatment response rates by menopausal status showed that premenopausal women responded significantly better to sertraline than to imipramine and that postmenopausal women had similar rates of response to the two medications. CONCLUSIONS: Men and women with chronic depression show differential responsivity to and tolerability of SSRIs and tricyclic antidepressants. The differing response rates between the drug classes in women was observed primarily in premenopausal women. Thus, female sex hormones may enhance response to SSRIs or inhibit response to tricyclics. Both gender and menopausal status should be considered when choosing an appropriate antidepressant for a depressed patient.
ACUPUNCTURE RELIEF OF CHRONIC PAIN SYNDROME CORRELATES WITH INCREASED PLASMA MET-ENKEPHALIN CONCENTRATIONS
Authors: R.Sanford Kiser, RobertJ. Gatchel, Krishin Bhatia, Manoochehr Khatami, Xing-Ya Huang, KennethZ. Altshuler
Journal: The Lancet (1983)
Biomarkers of Response to Epidermal Growth Factor Receptor Inhibitors in Non–Small-Cell Lung Cancer Working Group: Standardization for Use in the Clinical Trial Setting
Authors: David A. Eberhard, Giuseppe Giaccone, Bruce E. Johnson
Journal: Journal of Clinical Oncology (2008)

The body of literature on the correlations between molecular assessments and patient outcomes after treatment with epidermal growth factor receptor (EGFR) inhibitors continues to grow. It will be important in the future to determine how to most effectively integrate molecular assays that assess the likelihood of therapeutic benefit into clinical practice. Although EGFR-targeted therapies such as erlotinib have been approved for use without molecular testing, immunohistochemistry, fluorescence in situ hybridization, and mutational analyses of the EGFR gene have all been proposed as candidates to help predict response or survival benefit from EGFR-targeted therapy in patients with non–small-cell lung cancer (NSCLC). Further prospective validation from ongoing randomized studies will be needed to fully determine which assays are best to help predict patient outcome. In addition, it will be critical for these assays to undergo standardization before widespread clinical use. The Molecular Assays in NSCLC Working Group, under the sponsorship of Genentech Inc, Roche Pharmaceuticals, and OSI Pharmaceuticals, Inc, was convened to evaluate the available molecular assays for use in the clinical trial setting and provide recommendations for application and interpretation of these tests for future clinical trials. Recommendations of the Molecular Assays in NSCLC Working Group for the use of EGFR molecular assays are presented and include guidelines for tissue storage, handling, and processing. Recommendations for the standardization of molecular assays are also discussed.
The involucrin genes of the mouse and the rat: study of their shared repeats.
Authors: P Djian, M Phillips, K Easley, E Huang, M Simon, R H Rice, H Green
Journal: Molecular Biology and Evolution (1993)

The involucrin genes of the mouse (Mus musculus) and the rat (Rattus norvegicus) have been cloned and sequenced. The coding region of each gene contains, at site P, a segment of repeats homologous to that of other nonanthropoid mammals. In contrast to the repeats of species belonging to different mammalian orders, many individual repeats of the mouse and the rat can be matched. Both before and after the divergence of the two species, these repeats have been the site of systematic alterations in nucleotide sequence. One of the alterations is the correction of nucleotides of one repeat by those of another. Corrected nucleotides may be closely linked to flanking nucleotides that are uncorrected; the systematic correction process therefore appears to be due to gene conversion. There is a stretch of 18 reiterated CAGs in the segment of repeats of the Mus gene; most of these reiterations were introduced recently, supporting the idea that the gene was generated originally from poly CAG. An antiserum to a synthetic peptide encoded by the segment of repeats of the Mus gene reveals differentiation-specific expression of the gene in the epidermis.
Host Factors and Cancer Progression: Biobehavioral Signaling Pathways and Interventions
Authors: Susan K. Lutgendorf, Anil K. Sood, Michael H. Antoni
Journal: Journal of Clinical Oncology (2010)

Whereas evidence for the role of psychosocial factors in cancer initiation has been equivocal, support continues to grow for links between psychological factors such as stress, depression, and social isolation and progression of cancer. In vitro, in vivo, and clinical studies show that stress- related processes can impact pathways implicated in cancer progression, including immuno-regulation, angiogenesis, and invasion. Contributions of systemic factors, such as stress hormones to the crosstalk between tumor and stromal cells, appear to be critical in modulating downstream signaling pathways with important implications for disease progression. Inflammatory pathways may also be implicated in fatigue and other factors related to quality of life. Although substantial evidence supports a positive effect of psychosocial interventions on quality of life in cancer, the clinical evidence for efficacy of stress-modulating psychosocial interventions in slowing cancer progression remains inconclusive, and the biobehavioral mechanisms that might explain such effects are still being established. This article reviews research findings to date and outlines future avenues of research in this area.
Two-Dose Intrapartum/Newborn Nevirapine and Standard Antiretroviral Therapy to Reduce Perinatal HIV Transmission&lt;SUBTITLE&gt;A Randomized Trial&lt;/SUBTITLE&gt;
Authors: Alejandro Dorenbaum
Journal: JAMA (2002)

ContextA 2-dose intrapartum/newborn nevirapine regimen reduced perinatal human immunodeficiency virus (HIV) transmission in Ugandan women not receiving antenatal antiretroviral therapy (ART). However, it is unknown whether the addition of the 2-dose nevirapine regimen to standard ART would further reduce perinatal HIV transmission.ObjectiveTo determine whether a 2-dose nevirapine regimen can decrease perinatal transmission of HIV in nonbreastfeeding women receiving standard ART.Design and SettingInternational, blinded, placebo-controlled, phase 3 trial enrolling women between May 1997 and June 2000 at clinical sites providing care for HIV infection throughout the United States, Europe, Brazil, and the Bahamas.ParticipantsA total of 1270 women received nevirapine (n = 642) or placebo (n = 628). Infants were followed up for 6 months to determine HIV-infection status, which was available for 1248 deliveries.InterventionA 200-mg dose of oral nevirapine to women after onset of labor and a 2-mg/kg dose of oral nevirapine to newborns between 48 and 72 hours after birth.Main Outcome MeasuresDetection of HIV infection in infants and grade 3 and 4 toxic effects in women and newborns.ResultsAfter review by the data and safety monitoring board, the trial was stopped early because the overall transmission rates were significantly lower than assumed for the study design. Antenatal ART included zidovudine alone in 23%; combinations without protease inhibitors in 36%; and combinations with protease inhibitors in 41%. Thirty-four percent of women had elective cesarean delivery. No significant safety concerns were identified for women or infants. Detection of HIV infection occurred in 9 (1.4%; 95% confidence interval [CI], 0.6%-2.7%) of 631 nevirapine group deliveries and 10 (1.6%; 95% CI, 0.8%-2.9%) of 617 placebo group deliveries. The 95% CI for the difference in transmission rate (−0.2) between the 2 study arms ranged from −1.5% in favor of nevirapine to 1.2% in favor of placebo (P = .82, Fisher exact test). The transmission rate was higher in women with lower baseline CD4 cell counts and higher delivery HIV RNA levels, but there was no significant difference between treatment arms in any subgroup.ConclusionRisk of perinatal HIV transmission was low and no benefit from additional intrapartum/newborn nevirapine was demonstrated when women received prenatal care and antenatal ART, and elective cesarean section was made available.
Norepinephrine-induced acute heart failure in transgenic mice overexpressing erythropoietin
Authors: A Deten
Journal: Cardiovascular Research (2003)

Journal Article Norepinephrine-induced acute heart failure in transgenic mice overexpressing erythropoietin Get access Alexander Deten, Alexander Deten * aCarl-Ludwig-Institute of Physiology, Leipzig University, Liebigstraße 27, D-04103 Leipzig, Germany *Corresponding author. Tel.: +49-341-971-5500; fax: +49-341-971-5509. [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Junpei Shibata, Junpei Shibata bDepartment of Anesthesiology, Lübeck University, Ratzeburger Allee 160, D-23538 Lübeck, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Dimitri Scholz, Dimitri Scholz cDepartment of Experimental Cardiology, Max-Planck-Institute, Benekestraße 2, D-61231 Bad Nauheim, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilfried Briest, Wilfried Briest aCarl-Ludwig-Institute of Physiology, Leipzig University, Liebigstraße 27, D-04103 Leipzig, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Klaus F Wagner, Klaus F Wagner bDepartment of Anesthesiology, Lübeck University, Ratzeburger Allee 160, D-23538 Lübeck, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Roland H Wenger, Roland H Wenger aCarl-Ludwig-Institute of Physiology, Leipzig University, Liebigstraße 27, D-04103 Leipzig, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Heinz-Gerd Zimmer Heinz-Gerd Zimmer aCarl-Ludwig-Institute of Physiology, Leipzig University, Liebigstraße 27, D-04103 Leipzig, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 61, Issue 1, January 2004, Pages 105–114, https://doi.org/10.1016/j.cardiores.2003.10.026 Published: 01 January 2004 Article history Received: 02 May 2003 Revision received: 03 October 2003 Accepted: 27 October 2003 Published: 01 January 2004
Humoral Transmission of Cardiorespiratory Changes in Experimental Lung Embolism
Authors: DENIS F. J. Halmagyi, BOLESLAV STARZECKI, GEORGE J. HORNER
Journal: Circulation Research (1964)

Pairs of sheep were connected via a unilateral carotid-jugular anastomosis in fourteen experiments. With the cross circulation open, pulmonary embolism induced in the donor sheep produced a rise in pulmonary arterial pressure, a fall in lung compliance, and an increase in ventilation in the recipient animal. The transmitted effects were more pronounced with barium sulfate lung embolism than with blood clot lung embolism. These observations are consistent with the assumption that in acute experimental lung embolism a humoral agent is being released causing constriction of the lung vessels and airways.
Rwanda 20 years on: investing in life
Authors: Agnes Binagwaho, Paul E Farmer, Sabin Nsanzimana, Corine Karema, Michel Gasana, Jean de Dieu Ngirabega, Fidele Ngabo, Claire M Wagner, Cameron T Nutt, Thierry Nyatanyi, Maurice Gatera, Yvonne Kayiteshonga, Cathy Mugeni, Placidie Mugwaneza, Joseph Shema, Parfait Uwaliraye, Erick Gaju, Marie Aimee Muhimpundu, Theophile Dushime, Florent Senyana, Jean Baptiste Mazarati, Celsa Muzayire Gaju, Lisine Tuyisenge, Vincent Mutabazi, Patrick Kyamanywa, Vincent Rusanganwa, Jean Pierre Nyemazi, Agathe Umutoni, Ida Kankindi, Christian Ntizimira, Hinda Ruton, Nathan Mugume, Denis Nkunda, Espérance Ndenga, Joel M Mubiligi, Jean Baptiste Kakoma, Etienne Karita, Claude Sekabaraga, Emmanuel Rusingiza, Michael L Rich, Joia S Mukherjee, Joseph Rhatigan, Corrado Cancedda, Didi Bertrand-Farmer, Gene Bukhman, Sara N Stulac, Neo M Tapela, Cassia van der Hoof Holstein, Lawrence N Shulman, Antoinette Habinshuti, Matthew H Bonds, Michael S Wilkes, Chunling Lu, Mary C Smith-Fawzi, JaBaris D Swain, Michael P Murphy, Alan Ricks, Vanessa B Kerry, Barbara P Bush, Richard W Siegler, Cori S Stern, Anne Sliney, Tej Nuthulaganti, Injonge Karangwa, Elisabetta Pegurri, Ophelia Dahl, Peter C Drobac
Journal: The Lancet (2014)
Nuclear Factor Erythroid 2-Related Factor 2 Drives Podocyte-Specific Expression of Peroxisome Proliferator-Activated Receptor γ Essential for Resistance to Crescentic GN
Authors: Carole Henique, Guillaume Bollee, Olivia Lenoir, Neeraj Dhaun, Marine Camus, Anna Chipont, Kathleen Flosseau, Chantal Mandet, Masayuki Yamamoto, Alexandre Karras, Eric Thervet, Patrick Bruneval, Dominique Nochy, Laurent Mesnard, Pierre-Louis Tharaux
Journal: Journal of the American Society of Nephrology (2015)

Necrotizing and crescentic rapidly progressive GN (RPGN) is a life-threatening syndrome characterized by a rapid loss of renal function. Evidence suggests that podocyte expression of the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) may prevent podocyte injury, but the function of glomerular PPARγ in acute, severe inflammatory GN is unknown. Here, we observed marked loss of PPARγ abundance and transcriptional activity in glomerular podocytes in experimental RPGN. Blunted expression of PPARγ in podocyte nuclei was also found in kidneys from patients diagnosed with crescentic GN. Podocyte-specific Pparγ gene targeting accentuated glomerular damage, with increased urinary loss of albumin and severe kidney failure. Furthermore, a PPARγ gain-of-function approach achieved by systemic administration of thiazolidinedione (TZD) failed to prevent severe RPGN in mice with podocyte-specific Pparγ gene deficiency. In nuclear factor erythroid 2-related factor 2 (NRF2)-deficient mice, loss of podocyte PPARγ was observed at baseline. NRF2 deficiency markedly aggravated the course of RPGN, an effect that was partially prevented by TZD administration. Furthermore, delayed administration of TZD, initiated after the onset of RPGN, still alleviated the severity of experimental RPGN. These findings establish a requirement for the NRF2-PPARγ cascade in podocytes, and we suggest that these transcription factors have a role in augmenting the tolerance of glomeruli to severe immune-complex mediated injury. The NRF2-PPARγ pathway may be a therapeutic target for RPGN.
Hemodynamic Studies in Tricuspid Stenosis of Rheumatic Origin
Authors: M. IRENÉ FERRER, RÉJANE M. HARVEY, MARVIN KUSCHNER, DICKINSON W. RICHARDS, ANDRÉ COURNAND
Journal: Circulation Research (1953)

Clinical data and hemodynamic measurements made by cardiac catheterization are presented in two patients with tricuspid stenosis of rheumatic origin. In one, pure tricuspid stenosis was proved by autopsy, and in the second the development of tricuspid stenosis and insufficiency was demonstrated by means of cardiocirculatory studies made 27 months apart. A detailed analysis of the pressure pattern characteristic of this type of valvular stenosis is given. The measurement of the stenosed tricuspid valve area by three methods is described and discussed.