tbuckley/cabot-search huggingface dataset:
Interferon gamma induces prostaglandin G/H synthase-2 through an autocrine loop via the epidermal growth factor receptor in human bronchial epithelial cells.
Authors: K Asano, H Nakamura, C M Lilly, M Klagsbrun, J M Drazen
Journal: Journal of Clinical Investigation (1997)

The induction of prostaglandin G/H synthase (PGHS; prostaglandin endoperoxide synthase, cyclooxygenase) by proinflammatory cytokines accounts, at least in part, for the altered eicosanoid biosynthesis in inflammatory diseases. In secondary cultures of normal human bronchial epithelial cells (NHBECs), interferon-gamma (IFN-gamma, 10 ng/ml for 24 h) increased the amount of prostaglandin E2 (PGE2) released in response to stimulation with exogenous arachidonic acid (5 microM). The enhanced production of PGE2 reflected the upregulation of PGHS-2 as indicated by enhanced expression of PGHS-2 RNA and increased recovery of PGHS-2 protein in NHBECs. IFN-gamma did not alter the production of PGE2 in A549 cells (a human lung adenocarcinoma cell line) or 6-keto-PGF1alpha in human umbilical vein endothelial cells (HUVECs), although prostaglandin release and/or the expression of PGHS-2 RNA in these cell lines was upregulated by other proinflammatory cytokines. Induction of PGHS-2 RNA in IFN-gamma-treated NHBECs, which peaked at 24 h, suggested the presence of an intermediary substance regulating the expression of PGHS-2. When the binding between the epidermal growth factor (EGF) receptor and its ligands was disrupted by a neutralizing antibody (LA-1), IFN-gamma failed to upregulate the release of PGE2 and the expression of PGHS-2 RNA in NHBECs. Furthermore, IFN-gamma induced the expression of RNAs for a number of ligands at the EGF receptor TGF-alpha; heparin-binding EGF-like growth factor (HB-EGF); and amphiregulin in NHBECs, and when administered exogenously, these ligands increased PGE2 release from NHBECs. Heparin at the concentration that neutralized the function of amphiregulin, or antibodies against TGFalpha or HB-EGF also reduced the release of PGE2 from IFN-gamma-stimulated NHBECs. These data are consistent with the presence of an autocrine growth factor/EGF receptor loop regulating PGHS-2 expression and PGE2 synthesis in bronchial epithelial cells.
Successful Endoscopic Hemostasis of Duodenal Variceal Bleeding with Histoacryl
Authors: J. Labenz, G. Börsch
Journal: Endoscopy (1993)

See also: Sclerotherapy of a Bleeding Duodenal VarixEndoscopy 1982; 14(05): 187-189DOI: 10.1055/s-2007-1021618
Serial Plasma Carcinoembryonic Antigen Measurements in the Management of Metastatic Colorectal Carcinoma
Authors: ADI SHANI
Journal: Annals of Internal Medicine (1978)

Serial carcinoembryonic antigen (CEA) measurements were evaluated in a group of 263 patients undergoing systemic chemotherapy for metastatic colorectal carcinoma. Initial CEA levels were not found to be of value in predicting the likelihood of subsequent tumor response. Although a general relation between serial CEA measurements and clinical tumor measurements was noted, these measurements were discordant in a substantial proportion of patients. Tumor measurements as an index of response to therapy were strongly correlated with survival, whereas changes in CEA values and patient survival were not correlated at a statistically significant level. Serial CEA measurements were perhaps of some value in predicting progression of malignant disease, and were roughly comparable to serum alkaline phosphatase assay in assessing response of liver metastasis to chemotherapy. Overall, serial CEA measurements added little to the standard clinical assessment of patients with advanced colorectal carcinoma receiving chemotherapy.
Global classification and coding of hypersensitivity diseases – An EAACI – WAO survey, strategic paper and review
Authors: P. Demoly, L. K. Tanno, C. A. Akdis, S. Lau, M. A. Calderon, A. F. Santos, M. Sanchez‐Borges, L. J. Rosenwasser, R. Pawankar, N. G. Papadopoulos
Journal: Allergy (2014)

Hypersensitivity diseases are not adequately coded in the International Coding of Diseases (ICD)-10 resulting in misclassification, leading to low visibility of these conditions and general accuracy of official statistics. To call attention to the inadequacy of the ICD-10 in relation to allergic and hypersensitivity diseases and to contribute to improvements to be made in the forthcoming revision of ICD, a web-based global survey of healthcare professionals' attitudes toward allergic disorders classification was proposed to the members of European Academy of Allergy and Clinical Immunology (EAACI) (individuals) and World Allergy Organization (WAO) (representative responding on behalf of the national society), launched via internet and circulated for 6 week. As a result, we had 612 members of 144 countries from all six World Health Organization (WHO) global regions who answered the survey. ICD-10 is the most used classification worldwide, but it was not considered appropriate in clinical practice by the majority of participants. The majority indicated the EAACI-WAO classification as being easier and more accurate in the daily practice. They saw the need for a diagnostic system useful for nonallergists and endorsed the possibility of a global, cross-culturally applicable classification system of allergic disorders. This first and most broadly international survey ever conducted of health professionals' attitudes toward allergic disorders classification supports the need to update the current classifications of allergic diseases and can be useful to the WHO in improving the clinical utility of the classification and its global acceptability for the revised ICD-11.
Induction of programmed cell death in human hematopoietic cell lines by fibronectin via its interaction with very late antigen 5.
Authors: H Sugahara, Y Kanakura, T Furitsu, K Ishihara, K Oritani, H Ikeda, H Kitayama, J Ishikawa, K Hashimoto, Y Kanayama
Journal: The Journal of Experimental Medicine (1994)

Extracellular matrix (ECM) molecules such as fibronectin (FN), collagens, and laminin have important roles in hematopoiesis. However, little is known about the precise mechanisms by which ECM molecules regulate proliferation of human hematopoietic progenitor cells. In this study, we have investigated the effects of ECM molecules, particularly of FN, on the proliferation of a myeloid leukemia cell line, M07E, which proliferates in response to either human granulocyte/macrophage colony-stimulating factor (GM-CSF) or stem cell factor (SCF). The [3H]thymidine incorporation and cell enumeration assays showed that FN strikingly inhibited GM-CSF- or SCF-induced proliferation of M07E cells in a dose-dependent manner, whereas little or no inhibition was induced by collagen types I and IV. The growth suppression of M07E cells was not due to the inhibitory effect of FN on ligand binding or very early events in the signal transduction pathways from the GM-CSF or SCF receptors. DNA content analysis using flow cytometry after staining with propidium iodide revealed that the treatment of M07E cells with FN did not block the entry of the cells into the cell cycle after stimulation with GM-CSF or SCF, whereas the treatment resulted in the appearance of subdiploid peak. Furthermore, FN was found to induce oligonucleosomal DNA fragmentation and chromatin condensation in the cells even in the presence of GM-CSF or SCF, suggesting the involvement of programmed cell death (apoptosis) in the FN-induced growth suppression. The growth suppression or apoptosis induced by FN was rescued by the addition of either anti-FN antibody, anti-very late antigen 5 monoclonal antibody (anti-VLA5 mAb), or GRGDSP peptide, but not by that of anti-VLA4 mAb or GRGESP peptide, suggesting that the FN effects on M07E cells were mediated through VLA5. In addition, the FN-induced apoptosis was detectable in VLA5-positive human hematopoietic cell lines other than M07E cells, but not in any of the VLA5-negative cell lines. These results suggest that FN is capable of inducing apoptosis via its interaction with VLA5, and also raise the possibility that the FN-VLA5 interaction may contribute, at least in part, to negative regulation of hematopoiesis.
Cyclooxygenase-2 enhances α2β1 integrin expression and cell migration via EP1 dependent signaling pathway in human chondrosarcoma cells
Authors: Ju-Fang Liu, Yi-Chin Fong, Chih-Shiang Chang, Chun-Yin Huang, Hsien-Te Chen, Wei-Hung Yang, Chin-Jung Hsu, Long-Bin Jeng, Chih-Yi Chen, Chih-Hsin Tang
Journal: Molecular Cancer (2010)

Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. Interaction of COX-2 with its specific EP receptors on the surface of cancer cells has been reported to induce cancer invasion. However, the effects of COX-2 on migration activity in human chondrosarcoma cells are mostly unknown. In this study, we examined whether COX-2 and EP interaction are involved in metastasis of human chondrosarcoma.We found that over-expression of COX-2 or exogenous PGE2 increased the migration of human chondrosarcoma cells. We also found that human chondrosarcoma tissues and chondrosarcoma cell lines had significant expression of the COX-2 which was higher than that in normal cartilage. By using pharmacological inhibitors or activators or genetic inhibition by the EP receptors, we discovered that the EP1 receptor but not other PGE receptors is involved in PGE2-mediated cell migration and alpha2beta1 integrin expression. Furthermore, we found that human chondrosarcoma tissues expressed a higher level of EP1 receptor than normal cartilage. PGE2-mediated migration and integrin up-regulation were attenuated by phospholipase C (PLC), protein kinase C (PKC) and c-Src inhibitor. Activation of the PLCbeta, PKCalpha, c-Src and NF-kappaB signaling pathway after PGE2 treatment was demonstrated, and PGE2-induced expression of integrin and migration activity were inhibited by the specific inhibitor, siRNA and mutants of PLC, PKC, c-Src and NF-kappaB cascades.Our results indicated that PGE2 enhances the migration of chondrosarcoma cells by increasing alpha2beta1 integrin expression through the EP1/PLC/PKCalpha/c-Src/NF-kappaB signal transduction pathway.
Access to heart surgery for smokers: Trial of thrombolysis favours smokers
Authors: A Blesovsky
Journal: BMJ (1993)

He and many others might never have taken to smoking if there had not been a war.Nothing was known about a link with any disease then.Not even the medical profession knew-except the first few who suspected a link with lung cancer, and even that was not clear for a long time afterwards.All these survivors of the war are now at an age when they may need bypass surgery.They smoked through no fault of their own, and nobody had knowledge of possible consequences.They were encouraged to smoke and given easy access to cigarettes.They gave five years of their young lives to the defence of Britain.Are our surgeons, most of whom will be much younger, and who can have no personal experience of those days, now to deny these men treatment for physical conditions possibly engendered by their years of smoking?I hope not.
Diagnosis and Treatment of Thoracic Aneurysms
Authors: John E. Connolly
Journal: JAMA (1962)

Aneurysms of the thoracic aorta can be classified as congenital, acquired, or false ( pseudoaneurysms). Awareness of the entity of pseudoaneurysm will facilitate a correct diagnosis by simple radiographic interpretation. Congenital and acquired thoracic aortic aneurysms must be differentiated from pulmonary and mediastinal tumors. The exact diagnosis and nature of such lesions is best elucidated by an aortogram. Intravenous aortography is simpler and safer than direct retrograde catheter techniques, but does not provide as accurate visualization as does the latter technique. Left heart bypass has greatly facilitated the surgical repair of these lesions. Refinements in this technique such as the use of an open reservoir and maintenance of normal proximal aortic pressures will provide near normal renal and spinal cord blood flow while safely decompressing the left ventricle for periods of several hours of aortic crosselamping.
Prevalence and Causes of Fatal Outcome in Catheter Ablation of Atrial Fibrillation
Authors: Riccardo Cappato, Hugh Calkins, Shih-Ann Chen, Wyn Davies, Yoshito Iesaka, Jonathan Kalman, You-Ho Kim, George Klein, Andrea Natale, Douglas Packer, Allan Skanes
Journal: Journal of the American College of Cardiology (2009)
Abortions, sterilizations, and religion
Authors: D. H. Mills
Journal: JAMA (1974)

In January 1973 the Supreme Court made its compromise decisions.  It gave the patient and her physician the right to make the decision for abortion during the first trimester of pregnancy.  During the midtrimester neither the state nor the patient or her physician have absolute authority but regulations for the safety of pregnancy can be set and enforced.  During the last trimester the baby is considered viable and the state then has the authority to prohibit abortion except under emergency situations.  In 1973 Congress passed the Health Programs Extension Act which gave hospitals the right to refuse on religious grounds to allow either abortions or sterilizations.  It did not inhibit the right of those individuals with different beliefs to seek sterilization or abortion elsewhere.
Calsarcin-1 Protects Against Angiotensin-II–Induced Cardiac Hypertrophy
Authors: Derk Frank, Christian Kuhn, Martin van Eickels, Doris Gehring, Christiane Hanselmann, Stefanie Lippl, Rainer Will, Hugo A. Katus, Norbert Frey
Journal: Circulation (2007)

Background— We have previously shown that deficiency for the z-disc protein calsarcin-1 (CS1) sensitizes the heart to calcineurin signaling and to stimuli of pathological hypertrophy. In the present study we asked whether overexpression of CS1 might exhibit antihypertrophic effects, and therefore we tested this hypothesis both in vitro and in vivo. Methods and Results— Adenoviral gene transfer of CS1 into neonatal cardiomyocytes inhibited hypertrophy as a result of Gq-agonist stimulation, including angiotensin-II (Ang-II), endothelin-1, and phenylephrine. Consistently, Adenoviral gene transfer of CS1 also led to the reduction of increased levels of atrial natriuretic factor (mRNA) and the calcineurin-sensitive gene MCIP1.4, suggesting that CS1 inhibits calcineurin-dependent signaling. Furthermore, we generated CS1-overexpressing transgenic mice (CS1Tg). Unchallenged CS1Tg mice did not exhibit a pathological phenotype as assessed by echocardiography and analysis of cardiac gene expression. Likewise, when subjected to long-term infusion of Ang-II, both CS1Tg and wild-type mice developed a similar degree of arterial hypertension. Yet, in contrast to wild-type mice, Ang-II–treated CS1Tg animals did not display cardiac hypertrophy. Despite the absence of hypertrophy, both fractional shortening and dP/dt max were preserved in CS1Tg Ang-II–treated mice as assessed by echocardiography and cardiac catherization, respectively. Moreover, induction of the hypertrophic gene program (atrial natriuretic factor, brain natriuretic peptide) was markedly blunted, and expression of the calcineurin-dependent gene MCIP1.4 was significantly reduced in CS1Tg mice, again consistent with an inhibitory role of CS1 on calcineurin. Conclusions— The sarcomeric protein CS1 prevents Ang-II–induced cardiomyocyte hypertrophy at least in part via inhibition of calcineurin signaling. Thus, overexpression of CS1 might represent a novel approach to attenuate pathological cardiac hypertrophy.
Prevalence of pyruvate kinase deficiency among the chinese: Determination by the quantitative assay
Authors: Chi‐Shun Feng, Sophia S. Tsang, Ying‐Tat Mak
Journal: American Journal of Hematology (1993)

Abstract The prevalence of pyruvate kinase (PK) deficiency among the Chinese population has not been established. Fung et al. ( Arch Dis Child 44:373–376, 1969) and Wu et al. ( Am J Hematol 20:139–144, 1985) indicate 3.4% and 2.1% PK deficiency prevalence rates, respectively, the higher figure based on Beutler's screening test [3] without confirmatory testing. Neither figure is consistent with the occurrence of hemolytic anemia from this cause in the experiences of hematologists in Hong Kong. Using the standard quantitative assay, we measured PK activity in blood samples from 1,100 local Chinese people. The assay was automated on a centrifugal analyzer, and the results were expressed in IU per gram of hemoglobin (IU/g Hb). Blood samples from 497 healthy male adults were measured, and PK activity was found to have a range of 15.2 ± 5.2 (mean ± 2 SD). A total of 100 cord blood samples were also measured, and the reference interval for this subgroup was 17.7 ± 4.8. Additionally, samples from 503 anaemic patients were measured, and all were found to have values above the lower limit of the reference interval. The prevalence of PK deficiency among the Hong Kong Chinese population determined by this study was &lt; 0.1%.
blockers for heart failure with reduced ejection fraction
Authors: D. G. Waller, J. R. Waller
Journal: BMJ (2011)

#### Case scenario

A 74 year old man attends the surgery for review of his longstanding heart failure. He has an exercise tolerance of just a few yards, limited by breathlessness. His jugular venous pressure is not raised, he has no ankle oedema, and the lung bases are clear. There is no evidence of fluid overload. A recent echocardiogram showed an ejection fraction of less than 25%. He has a history of type 2 diabetes mellitus and stage 2 chronic obstructive pulmonary disease with limited reversibility. His current treatment is with ramipril 10 mg daily and furosemide 80 mg daily, in addition to aspirin, simvastatin, and salbutamol and ipratropium inhalers. Should he be prescribed a β blocker?

Heart failure is characterised by neurohormonal activation, particularly of the sympathetic nervous system and the renin-angiotensin-aldosterone system.1 Reducing this activation with an angiotensin converting enzyme (ACE) inhibitor has been the mainstay of heart failure management for many years. β adrenoceptor antagonists (β blockers) used to be contraindicated in heart failure, owing to the risk of decompensation when they were given in doses licensed for treatment of angina or hypertension. However, raised concentrations of catecholamines in plasma (a marker of sympathetic nervous system activation) correlate with disease severity, disease progression, and a poorer prognosis, and may therefore contribute to deterioration of cardiac function.2 3 Re-evaluation of the potential for low dose β blockers to ameliorate these consequences showed overwhelmingly that they reduce morbidity and mortality in heart failure with reduced left ventricular ejection fraction (LVEF). These drugs are now a cornerstone of effective management of symptoms and prognosis.3

Three β blockers are licensed in the UK for treatment of heart failure: carvedilol, bisoprolol, and nebivolol. Carvedilol is a non-selective β blocker and has vasodilatory effects owing to α1 adrenoceptor blockade. The other two drugs …
Growth of preschool children at high risk for asthma 2 years after discontinuation of fluticasone
Authors: Theresa W. Guilbert, David T. Mauger, David B. Allen, Robert S. Zeiger, Robert F. Lemanske, Stanley J. Szefler, Robert C. Strunk, Leonard B. Bacharier, Ronina Covar, Christine A. Sorkness, Lynn M. Taussig, Fernando D. Martinez
Journal: Journal of Allergy and Clinical Immunology (2011)
Editor profile: Guest editor of special issue “Drug Delivery System and Pharmaceutical Technology”
Authors: Chuanbin Wu
Journal: Acta Pharmaceutica Sinica B (2014)

Prof. Chuanbin Wu currently is a Professor in Pharmaceutics, Deputy Dean in the School of Pharmaceutical Sciences at Sun Yat-sen University, and Head of Guangdong Provincial Research Center of Drug Delivery (GPRCDD). He also services as the Member of Chinese Pharmacopoeia Commission, the committee member of Pharmaceutics in China Pharmaceutical Association, and chair of the committee of pharmaceutics in Guangdong Pharmaceutical Association. Prof. Wu got his Ph.D. degree in Industrial Pharmaceutics from the University of Texas at Austin in 1999, obtained Master degree from Beijing Medical University in 1992, and received Bachelor degree from China Pharmaceutical University in 1986. He had 12 years of industrial experience in USA as servicing at Johnson & Johnson, Novartis, Actavis and Watson Nutriceuticals from Senior Scientist, Group Leader, Product Development Manager to R&D Director. He joined Sun Yat-sen University as a faculty member since the end of 2005. Prof. Wu׳s research interests focus upon novel pharmaceutical technologies, drug delivery systems and super-generic formulation development.

Prof. Wu was frequently invited to give presentations in international and national conferences. He has published over 150 peer-reviewed scientific papers and over 50 granted patents or patent applications. He also services as an Associate Editor for the journal of Pharmacy Today and the Editorial Board Member of several journals such as Drug Development and Industrial Pharmacy, Acta Pharmaceutica Sinica, Journal of International Pharmaceutical Research, Asian Journal of Pharmaceutical Sciences, Acta Pharmaceutica Sinica B, and Journal of Guangdong Pharmaceutical University. Prof. Wu was the Chair of organizing committee of the 1st and 2nd International Symposium on Industrial Pharmacy and Clinical Pharmacy.
Trial stopped early after rosuvastatin found to cut the risk of heart attack and stroke by 44% in healthy people
Authors: R. Dobson
Journal: BMJ (2008)

Statins reduce the risk of cardiovascular events by 44% in people who do not have high cholesterol but have raised high sensitivity C reactive protein, a study has shown ( New England Journal of Medicine 2008;359:195-207, doi:10.1056/NEJMoa0807646).

Results from the JUPITER trial (Justification for the Use of Statins in Primary Prevention Intervention) also show that rosuvastatin reduced heart attacks alone by 54% in the same group of people. The combined primary end point was myocardial infarction, stroke, arterial revascularisation, hospitalisation for unstable angina, or death from cardiovascular causes.

The manufacturer of rosuvastatin, AstraZeneca, described the 44% drop in cardiovascular events as the greatest relative risk reduction seen in a large placebo controlled study of statins, but there were warnings about the implications.

John Abramson, author of Overdosed America: The Broken Promise of American Medicine and a clinical …