tbuckley/cabot-search huggingface dataset:
HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity
Authors: Monica Fedele, Rosa Visone, Ivana De Martino, Giancarlo Troncone, Dario Palmieri, Sabrina Battista, Andrea Ciarmiello, Pierlorenzo Pallante, Claudio Arra, Rosa Marina Melillo, Kristian Helin, Carlo Maria Croce, Alfredo Fusco
Journal: Cancer Cell (2006)
Proteolytic activity in the human stomach during digestion and its correlation with the augmented histamine test.
Authors: S J Rune
Journal: Gut (1966)

EDITORIAL SYNOPSIS A highly significant correlation has been found between proteolytic activity in the stomach during digestion of food and the level of gastric secretion during histamine stimu- lation.It is concluded that the augmented histamine test gives an acceptable impression of the secretory activity of the stomach during normal digestion.This is not true for basal secretion.
Protein degradation systems in viral myocarditis leading to dilated cardiomyopathy
Authors: H. Luo, J. Wong, B. Wong
Journal: Cardiovascular Research (2009)

The primary intracellular protein degradation systems, including the ubiquitin-proteasome and the lysosome pathways, have been emerging as central regulators of viral infectivity, inflammation, and viral pathogenicity. Viral myocarditis is an inflammatory disease of the myocardium caused by virus infection in the heart. The disease progression of viral myocarditis occurs in three distinct stages: acute viral infection, immune cell infiltration, and cardiac remodelling. Growing evidence suggests a crucial role for host proteolytic machineries in the regulation of the pathogenesis and progression of viral myocarditis in all three stages. Cardiotropic viruses evolve different strategies to subvert host protein degradation systems to achieve successful viral replication. In addition, these proteolytic systems play important roles in the activation of innate and adaptive immune responses during viral infection. Recent evidence also suggests a key role for the ubiquitin-proteasome and lysosome systems as the primary effectors of protein quality control in the regulation of cardiac remodelling. This review summarizes the recent advances in understanding the direct interaction between cardiotropic viruses and host proteolytic systems, with an emphasis on coxsackievirus B3, one of the primary aetiological agents causing viral myocarditis, and highlights possible roles of the host degradation systems in the pathogenesis of viral myocarditis and its progression to dilated cardiomyopathy.
Long-Term Coronary Vascular Response to <sup>32</sup> P β-Particle–Emitting Stents in a Canine Model
Authors: Allen J. Taylor, Patrick D. Gorman, Andrew Farb, Timothy G. Hoopes, Renu Virmani
Journal: Circulation (1999)

Background —The arterial placement of 32 P β-particle–emitting stents in various experimental animal models results in discordant effects on neointimal formation. We studied the vascular effects of β-particle–emitting stents in normal canine coronary arteries because compared with pigs and rabbits, the canine model may more closely mimic the vascular response of humans. Methods and Results —Thirty stents (control nonradioactive, n=10; low-activity 32 P, 3.5 to 6.0 μCi, n=11; high-activity 32 P, 6.5 to 14.4 μCi, n=8) were implanted in normal canine coronary arteries through the use of a single balloon inflation at nominal pressure. Histological analysis after 15 weeks included the measurement of neointimal and adventitial area and thickness. Neointimal fibrin area was measured with the use of computer-assisted color segmentation on Movat pentachrome sections. Luminal stenosis was significantly increased in 32 P stents compared with control stents (44.6±16.8% versus 32.7±10.8%; P =0.05) and was highest in the high-activity group (45.5±24.3%). No evidence of an “edge effect” was seen in adjacent, nonstented coronary segments. All 32 P stents showed incomplete vascular healing as indicated by a dose-dependent increase in fibrin area with increasing stent activity. Arterial radiation resulted in a decrease in adventitial size, which was maximal for high-activity 32 P stents, indicating an inhibitory effect on the adventitial response to injury. Conclusions — 32 P β-particle–emitting stents have adverse vascular effects at 15 weeks in the canine normal coronary artery model. Vascular brachytherapy with this device causes increased neointimal formation and prominent, dose-dependent lack of healing.
Long-Term Results of Laparoscopic Gastrectomy for Gastric Cancer: A Large-Scale Case-Control and Case-Matched Korean Multicenter Study
Authors: Hyung-Ho Kim, Sang-Uk Han, Min-Chan Kim, Woo Jin Hyung, Wook Kim, Hyuk-Joon Lee, Seung Wan Ryu, Gyu Seok Cho, Kyo Young Song, Seong Yeob Ryu
Journal: Journal of Clinical Oncology (2014)

The oncologic outcomes of laparoscopy-assisted gastrectomy for the treatment of gastric cancer have not been evaluated. The aim of this study is to validate the efficacy and safety of laparoscopic gastrectomy for gastric cancer in terms of long-term survival, morbidity, and mortality retrospectively.The study group comprised 2,976 patients who were treated with curative intent either by laparoscopic gastrectomy (1,477 patients) or open gastrectomy (1,499 patients) between April 1998 and December 2005. The long-term 5-year actual survival analysis in case-control and case-matched population was conducted using the Kaplan-Meier method. The morbidity and mortality and learning curves were evaluated.In the case-control study, the overall survival, disease-specific survival, and recurrence-free survival (median follow-up period, 70.8 months) were not statistically different at each cancer stage with the exception of an increased overall survival rate for patients with stage IA cancer treated via laparoscopy (laparoscopic group; 95.3%, open group: 90.3%; P < .001). After matching using a propensity scoring system, the overall survival, disease-specific survival, and recurrence-free survival rates were not statistically different at each stage. The morbidity of the case-matched group was 15.1% in the open group and 12.5% in the laparoscopic group, which also had no statistical significance (P = .184). The mortality rate was also not statistically significant (0.3% in the open group and 0.5% in the laparoscopic group; P = 1.000). The mean learning curve was 42.The long-term oncologic outcomes of laparoscopic gastrectomy for patients with gastric cancer were comparable to those of open gastrectomy in a large-scale, multicenter, retrospective clinical study.
National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications
Authors: Hannah Blencowe, Simon Cousens, Mikkel Z Oestergaard, Doris Chou, Ann-Beth Moller, Rajesh Narwal, Alma Adler, Claudia Vera Garcia, Sarah Rohde, Lale Say, Joy E Lawn
Journal: The Lancet (2012)
Collecting Duct Sodium Reabsorption in Deoxycorticosterone-Treated Rats
Authors: John A. Haas, Theresa J. Berndt, Stephen P. Youngberg, Franklyn G. Knox
Journal: Journal of Clinical Investigation (1979)

In vitro studies of isolated, perfused, cortical collecting tubules have demonstrated that prior chronic deoxycorticosterone acetate (DOCA) treatment increases sodium reabsorption in this nephron segment, yet sodium balance in vivo is maintained. To evaluate the effect of chronic DOCA treatment on collecting duct sodium reabsorption in vivo, we compared fractional sodium delivery (FD(Na)%) out of the superficial late distal tubule with the fraction of sodium remaining at the base and the tip of the papillary collecting duct during extracellular fluid volume expansion in untreated, salt-treated, and DOCA-salt-treated rats. In untreated rats, FD(Na)% to the distal tubule was 6.5+/-1.0%, and to the base was 8.7+/-1.6% (Delta2.2+/-0.9%, P < 0.05). FD(Na)% to the tip was 4.9+/-1.1%, significantly less than FD(Na)% to the base (Delta3.7+/-1.1%, P < 0.01). In salt-treated rats, FD(Na)% to the distal tubule was 8.3+/-0.8%, and to the base was 10.4+/-1.1%. FD(Na)% to the tip was 5.9+/-0.6%, significantly less than FD(Na)% to the base (Delta 4.6+/-1.0%, P < 0.005). In DOCA-salt-treated rats, FD(Na)% to the distal tubule was 16.1+/-2.6% and to the base was 9.5+/-1.9% (Delta 6.6+/-1.7%, P < 0.005). FD(Na)% to the tip was 5.9+/-1.2%, also significantly less than FD(Na)% to the base (Delta 3.6+/-1.1%, P < 0.01). We conclude that (a) in DOCA-salt-treated rats, sodium delivery to the end of the superficial distal tubule is greater than in untreated or salt-treated rats; (b) in DOCA-salt-treated rats, sodium delivery to the end of the superficial distal tubule is greater than to the base of the papillary collecting duct, suggesting stimulation of sodium reabsorption in the cortical and(or) outer medullary collecting duct; and (c) sodium reabsorption by the papillary collecting duct is unaffected by chronic DOCA-salt treatment in the volume-expanded rat.
Immature thymocytes become sensitive to calcium-mediated apoptosis with the onset of CD8, CD4, and the T cell receptor expression: a role for bcl-2?
Authors: S Andjelić, N Jain, J Nikolić-Zugić
Journal: The Journal of Experimental Medicine (1993)

During intrathymic negative selection by clonal deletion, crosslinking of the T cell receptor (TCR) induces cell death by delivering an apoptotic signal(s) to the nucleus along a calcium-dependent pathway. We investigated the reactivity of early precursor-containing thymocytes to Ca(2+)-induced signals, and discovered a breakpoint in their sensitivity to calcium-mediated cell death (CMCD). CD25+CD8-4- TCR- (triple negative [TN]) thymocytes stimulated with a calcium ionophore maintain their viability and precursor activity. By contrast, their immediate progeny, CD25-CD8lo4loTCR alpha beta lo (triple low [TL]) cells react to calcium elevation by abrogation of precursor activity and apoptotic cell death. This developmental difference is specific for CMCD, since both CD25+TN and CD25-TL cells are susceptible to steroid-induced apoptosis. The presence of bcl-2 mRNA correlates directly to the resistance to CMCD-CD25+ TN cells express it and CD25-TL cells do not. These experiments show that thymocytes become sensitive to Ca(2+)-induced apoptosis as soon as they begin to express molecules that mediate thymic selection, and suggest that a concomitant downregulation of bcl-2 may mediate this phenomenon.
C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response
Authors: Debra Gershov, SunJung Kim, Nathan Brot, Keith B. Elkon
Journal: The Journal of Experimental Medicine (2000)

C-reactive protein (CRP) is a serum protein that is massively induced as part of the innate immune response to infection and tissue injury. As CRP has been detected in damaged tissues and is known to activate complement, we assessed whether apoptotic lymphocytes bound CRP and determined the effect of binding on innate immunity. CRP bound to apoptotic cells in a Ca2+-dependent manner and augmented the classical pathway of complement activation but protected the cells from assembly of the terminal complement components. Furthermore, CRP enhanced opsonization and phagocytosis of apoptotic cells by macrophages associated with the expression of the antiinflammatory cytokine transforming growth factor β. The antiinflammatory effects of CRP required C1q and factor H and were not effective once cells had become necrotic. These observations demonstrate that CRP and the classical complement components act in concert to promote noninflammatory clearance of apoptotic cells and may help to explain how deficiencies of the classical pathway and certain pentraxins lead to impaired handling of apoptotic cells and increased necrosis with the likelihood of immune response to self.
Transforming Growth Factor β Receptor I Kinase Inhibitor Down-Regulates Cytokine Secretion and Multiple Myeloma Cell Growth in the Bone Marrow Microenvironment
Authors: Toshiaki Hayashi, Teru Hideshima, Aaron N. Nguyen, Olivier Munoz, Klaus Podar, Makoto Hamasaki, Kenji Ishitsuka, Hiroshi Yasui, Paul Richardson, Sarvajit Chakravarty, Alison Murphy, Dharminder Chauhan, Linda S. Higgins, Kenneth C. Anderson
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Transforming growth factors (TGFs) have pleiotropic biological effects on tumor cells and their environment. In multiple myeloma (MM), we have reported that bone marrow stromal cells (BMSCs) from MM patients produce more TGF-β1 than BMSCs from healthy donors, which in turn induces interleukin (IL)-6 secretion. We show here that the TGF-β receptor I kinase inhibitor SD-208 significantly decreases secretion of both IL-6 and vascular endothelial growth factor (VEGF) from BMSCs, as well as tumor cell growth triggered by MM cell adhesion to BMSCs. Experimental Design: Cytokine production and MM cell proliferation triggered by TGF-β1 or adhesion to BMSCs were examined in the presence or absence of SD-208. Effects of SD-208 on TGF-β1–induced signaling pathways triggering IL-6 and VEGF transcription in BMSCs were also delineated. Results: SD-208 significantly inhibits not only transcription but also secretion of both IL-6 and VEGF from BMSCs triggered by either TGF-β1 or adhesion of MM cells to BMSCs. Moreover, SD-208 decreased tumor cell growth triggered by MM cell adhesion to BMSCs. SD-208 works, at least in part, by blocking TGF-β1–triggered nuclear accumulation of Smad2/3 and hypoxia-inducible factor 1α, as well as related production of IL-6 and VEGF, respectively. Conclusions: These studies indicate that SD-208 inhibits production of cytokines mediating MM cell growth, survival, drug resistance, and migration in the BM milieu, thereby providing the preclinical rationale for clinical evaluation of SD-208 to improve patient outcome in MM.
Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis
Authors: M. Chadeau-Hyam, R.C.H. Vermeulen, D.G.A.J. Hebels, R. Castagné, G. Campanella, L. Portengen, R.S. Kelly, I.A. Bergdahl, B. Melin, G. Hallmans, D. Palli, V. Krogh, R. Tumino, C. Sacerdote, S. Panico, T.M.C.M. de Kok, M.T. Smith, J.C.S. Kleinjans, P. Vineis, S.A. Kyrtopoulos, P. Georgiadis, M. Botsivali, C. Papadopoulou, A. Chatziioannou, I. Valavanis, R. Gottschalk, D. van Leeuwen, L. Timmermans, H.C. Keun, T.J. Athersuch, P. Lenner, B. Bendinelli, E.G. Stephanou, A. Myridakis, M. Kogevinas, F. Saberi-Hosnijeh, L. Fazzo, M. de Santis, P. Comba, H. Kiviranta, P. Rantakokko, R. Airaksinen, P. Ruokojarvi, M.S. Gilthorpe, S. Fleming, T. Fleming, Y.-K. Tu, B. Jonsson, T. Lundh, K.-L. Chien, W.J. Chen, W.-C. Lee, C.K. Hsiao, P.-H. Kuo, H. Hung, S.-F. Liao
Journal: Annals of Oncology (2014)
Addition of Histamine to Interleukin 2 Treatment Augments Type 1 T-Cell Responses in Patients with Melanoma <i>In vivo</i>: Immunologic Results from a Randomized Clinical Trial of Interleukin 2 with or without Histamine (MP 104)
Authors: Anne Marie Asemissen, Carmen Scheibenbogen, Anne Letsch, Kristoffer Hellstrand, Fredrik Thorén, Kurt Gehlsen, Alexander Schmittel, Eckhard Thiel, Ulrich Keilholz
Journal: Clinical Cancer Research (2005)

Preclinical investigations suggest that histamine dihydrochloride (HDC) protects T cells and natural killer cells from inhibition by monocyte-derived reactive oxygen metabolites and synergizes with interleukin (IL) 2 in inducing T-cell activation. Here, we investigate whether this mechanism is operational in patients with melanoma treated with HDC as an adjunct to IL-2.Melanoma patients having liver metastases were treated with IL-2 with or without HDC within a randomized, multicenter, phase III trial. The effect of HDC on type 1 and type 2 T-cell cytokine production was investigated in peripheral blood samples from 19 patients with the use of intracellular cytokine flow cytometry. Melanoma-specific T-cell responses were analyzed in eight HLA-A2-positive patients.Frequencies of CD3+ T cells producing IFN-gamma (type 1 T cells) in response to phorbol myristate acetate/ionomycin increased (median, 1.8-fold) in patients receiving IL-2 plus HDC but not in those receiving IL-2 alone (P < 0.01 for comparison between arms). In contrast, the number of IL-13-producing type 2 T cells that increased in patients after treatment with IL-2 was not modulated by HDC. Melanoma- and tyrosinase-specific IFN-gamma and IL-13-producing T cells were detected in two of four HLA-A2-positive patients with melanoma following treatment with HDC + IL-2.Treatment of patients with stage IV melanoma with HDC in combination with IL-2 increases type 1 T-cell responses and may promote induction of melanoma-specific T cells. These effects are of relevance for tumor immunotherapy and provide a potential mechanism for the clinical efficacy of HDC added to IL-2.
Repeated exposure to organic material alters inflammatory and physiological airway responses
Authors: B-M. Sundblad, I. von Scheele, L. Palmberg, M. Olsson, K. Larsson
Journal: European Respiratory Journal (2009)

Farmers and smokers are repeatedly exposed to airborne organic material. We hypothesised that farmers and smokers show altered airway responses to inhaled organic, pro-inflammatory agents. A total of 11 farmers, 12 smokers and 12 controls underwent lipopolysaccharide (LPS) bronchial challenge and spent 3 h in a pig barn. Lung function, exhaled nitric oxide and bronchial responsiveness were assessed and nasal lavage fluid and induced sputum were also collected. Symptoms and body temperature were recorded before and after exposures. Following exposure to the pig barn, bronchial responsiveness, exhaled nitric oxide, sputum interleukin (IL)-6, nasal lavage cell count and IL-8 were increased to a greater extent in controls compared to farmers. The sputum IL-6 response was also attenuated in farmers after LPS challenge. The response shown by smokers following exposure to the pig barn was similar to that of controls regarding measurements of exhaled nitric oxide, IL-8 in nasal lavage and IL-6 in sputum, but more similar to farmers concerning bronchial responsiveness and the cell numbers present in nasal lavage. Sputum IL-8 showed a greater increase in smokers than in the other groups following LPS challenge. We conclude that individuals who are repeatedly exposed to organic material develop an adaptation to the effects of acute exposure to inhaled organic material.
Protection Against Oxidized Low-Density Lipoprotein–Induced Vascular Endothelial Cell Death by Integrin-Linked Kinase
Authors: Xiuwu Zhang, Kang Hu, Chuan-Yuan Li
Journal: Circulation (2001)

Background Integrin-linked kinase (ILK) is a protein that plays important roles in extracellular matrix-mediated signaling. It has been shown that ILK is expressed preferentially in cardiac and skeletal muscles. Evidence points to its role as an upstream regulator of protein kinase B, a critical player in apoptosis. Because oxidized LDL (oxLDL) is thought to promote atherogenesis by causing the apoptosis of endothelial cells, we investigated the potential roles that ILK may play in oxLDL-induced apoptosis in vascular endothelial cells. Methods and Results Transcriptional and translational levels of ILK were investigated with reverse-transcriptase polymerase chain reaction and Western analysis. oxLDL treatment induced both the transcription and the translation of the ILK gene in endothelial cells. A recombinant adenovirus vector encoding the ILK gene was constructed to investigate its potential role in oxLDL-induced apoptosis in human umbilical vein endothelial cells and mouse lymphoid vein endothelial cells transformed by simian virus 40. In both types of cells, overexpression of the ILK gene significantly prevented oxLDL-induced apoptosis or cell death, as evaluated by 2 independent assay methods. Furthermore, we showed that ILK could inhibit oxLDL-induced upregulation of the kinase activity of p38 mitogen-activated protein kinase, which is often associated with stress-induced pro-apoptotic signal transduction. Finally, examination of other factors, such as bcl-2, bcl-xl, caspase 3, and caspase 9, demonstrated significant changes that were correlated with oxLDL treatment and ILK overexpression. Conclusion ILK may be an important factor involved in the regulation of oxLDL-induced apoptosis in vascular endothelial cells. Modifying its activity may be a useful approach for prevention of endothelial cell injury in oxLDL-induced atherosclerosis.
Expression and function of a nonglycosylated major histocompatibility class I antigen.
Authors: J Miyazaki, E Appella, H Zhao, J Forman, K Ozato
Journal: The Journal of Experimental Medicine (1986)

The major histocompatibility class I antigens, expressed in most somatic cells, have carbohydrate moieties. We constructed mutant mouse MHC class I genes in which codons for the N-linked glycosylation sites were replaced by those of other amino acids. L cell transformants expressing the nonglycosylated class I antigens allowed us to investigate biological roles of carbohydrates with the highest specificity possible. The nonglycosylated antigen was unchanged in its overall serological specificities, and was recognized by alloreactive cytotoxic T cells. Further, the antigen was capable of mediating cytotoxic activity of vesicular stomatitis virus-specific T cells. These studies indicate that carbohydrates are not essential for immunological function of the MHC class I antigens. Cell surface expression of the nonglycosylated antigen was markedly reduced as compared with the native antigen, which was not attributable to accelerated degradation or rapid shedding. We conclude that the primary role of carbohydrates of the class I antigens is to facilitate the intracellular transport of the nascent proteins to the plasma membrane. The possible involvement of carbohydrate-receptor interactions in this process is discussed.
Reevaluation of Amiodarone
Authors: Zia Ahmed
Journal: Annals of Internal Medicine (1995)

Letters15 November 1995Reevaluation of AmiodaroneZia Ahmed, MD and Joel M. Goldman, MDZia Ahmed, MDBrookdale Hospital Medical Center; Brooklyn, NY 11212Search for more papers by this author and Joel M. Goldman, MDBrookdale Hospital Medical Center; Brooklyn, NY 11212Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-10-199511150-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In his comprehensive review of amiodarone, Dr. Podrid [1] discusses minor thyroid abnormalities, particularly the elevation of thyroid-stimulating hormone (TSH) levels. He does not mention the more common and more problematic elevation in thyroxine levels. Elevation of TSH levels is only transient, and levels gradually return to pretreatment values [2, 3]. In contrast, thyroxine and free thyroxine levels remain elevated [2, 3]. This condition can be confused with hyperthyroidism, which also occurs in a few patients receiving amiodarone. It can be difficult to distinguish between a euthyroid patient receiving amiodarone and an amiodarone-treated patient who has become ...References1. Podrid PJ. Amiodarone: reevaluation of an old drug. Ann Intern Med. 1995; 122:689-700. Google Scholar2. Nademanee K, Piwonka RW, Singh BN, Hershman JM. Amiodarone and thyroid function. Prog Cardiovasc Dis. 1989; 31:427-37. Google Scholar3. Wiersinga WM, Trip MD. Amiodarone and thyroid hormone metabolism. Postgrad Med J. 1986; 62:909-14. Google Scholar4. Lombardi A, Martino E, Braverman LE. Amiodarone and the thyroid. Thyroid Today. 1990; 13:1-7. Google Scholar Author, Article, and Disclosure InformationAffiliations: Brookdale Hospital Medical Center; Brooklyn, NY 11212 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 1995Volume 123, Issue 10Page: 809KeywordsHyperthyroidismThyroidThyroid-stimulating hormoneThyroxineTriiodothyronine Issue Published: 15 November 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...