tbuckley/cabot-search huggingface dataset:
Ets-1 is a critical regulator of Ang II-mediated vascular inflammation and remodeling
Authors: Y. Zhan
Journal: Journal of Clinical Investigation (2005)

Ang II is a central mediator of vascular inflammation and remodeling. The transcription factor Ets-1 is rapidly induced in vascular smooth muscle and endothelial cells of the mouse thoracic aorta in response to systemic Ang II infusion. Arterial wall thickening, perivascular fibrosis, and cardiac hypertrophy are significantly diminished in Ets1–/– mice compared with control mice in response to Ang II. The induction of 2 known targets of Ets-1, cyclin-dependent kinase inhibitor p21CIP and plasminogen activator inhibitor–1 (PAI-1), by Ang II is markedly blunted in the aorta of Ets1–/– mice compared with wild-type controls. Expression of p21CIP in VSMCs leads to cellular hypertrophy, whereas expression of p21CIP in endothelial cells is associated with cell cycle arrest, apoptosis, and endothelial dysfunction. PAI-1 promotes the development of perivascular fibrosis. We have identified monocyte chemoattractant protein–1 (MCP-1) as a novel target for Ets-1. Expression of MCP-1 is similarly reduced in Ets1–/– mice compared with control mice in response to Ang II, which results in significantly diminished recruitment of T cells and macrophages to the vessel wall. In summary, our results support a critical role for Ets-1 as a transcriptional mediator of vascular inflammation and remodeling in response to Ang II.
S-1 Plus Cisplatin with Concurrent Radiotherapy for Locally Advanced Non-small Cell Lung Cancer: A Multi-Institutional Phase II Trial (West Japan Thoracic Oncology Group 3706)
Authors: Yukito Ichinose, Takashi Seto, Tomonari Sasaki, Takeharu Yamanaka, Isamu Okamoto, Koji Takeda, Masahiro Tanaka, Nobuyuki Katakami, Toshiyuki Sawa, Shinzoh Kudoh, Hideo Saka, Yasumasa Nishimura, Kazuhiko Nakagawa, Masahiro Fukuoka
Journal: Journal of Thoracic Oncology (2011)
Abstract ES2-2: Triple Negative Breast Cancer: Subtypes, Molecular Targets, and Therapeutic Approaches
Authors: JA Pietenpol
Journal: Cancer Research (2012)

Abstract The term “triple negative breast cancer” (TNBC) is used to classify 10%–20% of all breast cancers that lack estrogen receptor (ER) and progesterone receptor expression as well as amplification of the human epidermal growth factor receptor 2 (HER2)1. Disease heterogeneity and the absence of well-defined molecular targets have made treatment of TNBC challenging. To make significant clinical advances for TNBC patients, integrative and comprehensive genomic and molecular analyses of TNBC are required to understand the complexity of the disease as well as to allow identification of homogeneous subsets and ‘driver pathways’ that can then be therapeutically targeted. In response to this need, we compiled an extensive number of TNBC gene expression (GE) profiles and initiated molecular subtyping of the disease2. We identified two basal-like TNBC subtypes with cell cycle and DDR GE signatures (BL1 and BL2); two mesenchymal subtypes with high expression of genes involved in differentiation and growth factor pathways (M and MSL); an immunomodulatory (IM) type; and a luminal subtype driven by androgen signaling (LAR). Differential GE was used to designate 25 TNBC cell line models representative of these subtypes. Predicted ‘driver’ signaling pathways were pharmacologically targeted in these preclinical models as proof of concept that analysis of distinct GE signatures can inform therapy selection. Representative BL1 and BL2 subtype cell lines preferentially respond to cisplatin. Mesenchymal, basal, and luminal subtype lines with aberrations in PI3K signaling have the greatest sensitivity, in general, to phosphatidylinositol 3-kinase (PI3K) inhibitors. The LAR subtype cell lines express AR and are uniquely sensitive to bicalutamide (AR antagonist). We have also developed “TNBCtype,” a web-based subtyping tool for candidate TNBC tumor samples using our GE metadata and classification methods3. The approaches used and data generated have value for biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies. 1. Dent, R., Trudeau, M., Pritchard, K.I., Hanna, W.M., Kahn, H.K., Sawka, C.A., Lickley, L.A., Rawlinson, E., Sun, P., and Narod, S.A. (2007). Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13, 4429–4434. 2. Lehmann, B.D., Bauer, J.A., Chen, X., Sanders, M.E., Chakravarthy, A.B., Shyr, Y., and Pietenpol, J.A. (2011). Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121: 2750–67. 3. Chen, X., Li, J., Gray, W.H., Lehmann, B.D., Bauer, J.A., Shyr, Y., and Pietenpol, J.A. (2012). TNBCtype: A Subtyping Tool for Triple-Negative Breast Cancer. Cancer informatics 11, 147–156. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES2-2.
565. Acceleration of Fracture Healing with Adenovirally Transduced Human BMP-2 and -6 Genes in Horse Metatarsal Osteotomy and Ostectomy Models
Authors: Akikazu Ishihara, Alicia L. Bertone, Alan L. Litsky, John S. Mattoon, Stephen E. Weisbrode
Journal: Molecular Therapy (2006)

Introduction; Treatment of delayed or nonunion fractures can be challenging. Bone morphogenetic protein-2 (BMP-2) is one of the most studied growth factors associated with bone healing, and successful induction of bone formation by BMP-2 has been demonstrated both in vitro and in vivo. The less investigated member of BMP family, BMP-6, currently received attention because it may contribute bone formation by an alternative mechanism compared to other BMPs. This study was to compare the efficacy of BMP-2 and -6 genes transduced by adenoviral vector (Ad) in an acceleration of bone healing using two different sizes of unstable fracture models using horses.
Abstract 5: Synthesis and biological evaluation of 5, 5’ substituted apogossypol and apogossypolone derivatives as pan-active inhibitors of anti-apoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins
Authors: Jun Wei, William J. Placzek, John L. Stebbins, John C. Reed, Maurizio Pellecchia, Paul B. Fisher, Rupesh Dash, Catriona Jamieson, Shinichi Kitada
Journal: Cancer Research (2011)

Abstract Overexpression of anti-apoptotic Bcl-2 family proteins is commonly related with tumor maintenance, progression, and chemoresistance. Inhibition of these anti-apoptotic proteins is an attractive approach for cancer therapy. Guided by nuclear magnetic resonance (NMR) binding assays and computational docking studies, a series of 5, 5’ substituted Apogossypol and Apogossypolone derivatives was synthesized and identified pan-active antagonists of anti-apoptotic Bcl-2 family proteins, with binding potency in the low micromolar to nanomolar range. Apogossypol derivative BI97C1 inhibits the binding of BH3 peptides to Bcl-XL, Bcl-2 and Mcl-1 with IC50 values of 0.31, 0.32 and 0.20 µM, respectively. In a cellular assay, BI97C1 potently inhibits cell growth in the H460 human lung cancer and PC-3 human prostate cancer cell lines with EC50 values of 0.40 and 0.13 µM, respectively, and effectively induces apoptosis of the BP3 human lymphoma cell line (EC50 = 0.049 µM) in a dose-dependent manner. Apogossypolone derivative BI97D1 also potently inhibit cell growth in many cancer cell lines. BI97C1 and BI97D1 further display in vivo efficacy in transgenic mice in which Bcl-2 is overexpressed in splenic B-cells and also demonstrated superior single-agent antitumor efficacy in mouse xenograft model and represent promising drug leads for the development of novel apoptosis-based therapies for cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5. doi:10.1158/1538-7445.AM2011-5
Fetal and Maternal
Authors: Mary F. Block
Journal: JAMA (1981)

<i>Fetal and Maternal Medicine</i>makes a much needed transition between pertinent basic science areas and clinical practice. Other books in this field have emphasized either management techniques or basic research contributions, but the efforts of the authors in this case have resulted in an integrated combination of both, which is most welcome. The stated purpose of the book is to bring into focus the field of perinatal medicine, where recent advances from several related fields have combined to benefit both mother and fetus. The basic science portion of the book is generally lucid and readable, particularly the complex areas of fetal and maternal endocrinology and pathophysiology. The unique aspect of the organization of this book, however, is the joint handling by obstetrician and pediatrician of several subject areas. This approach is a particularly effective method of discussing the clinical problems of Rh isoimmunization and erythroblastosis, management of maternal diabetes and
Afghan health workers should be allowed home to treat people
Authors: R. Dobson
Journal: BMJ (2002)

Afghan health professionals who fled abroad should be allowed to return home to help rebuild their country, without jeopardising their refugee status, says the BMA.

A resolution from the BMA to the annual general assembly of the World Medical Association (WMA) in Washington, DC, next week will also urge national governments and international agencies to commit funds to rebuilding the …
Fats and atheroma: an inquest.
Authors: J McMichael
Journal: BMJ (1979)

All well-controlled trials of cholesterol-reducing diets and drugs have failed to reduce coronary (CHD) mortality and morbidity. Nevertheless, commercial, professional, and even government-sponsored propaganda continues. Experimentally some vegetable oils and hardened fats can be more damaging to arteries than butter. There are other hazards to heart muscle from vegetable oils. Israelis consume a high polyunsaturated fat diet equal to that recommended for prevention of CHD in USA but their CHD incidence is very high. Urban Bedouins are also affected. The primary clofibrate prevention trial underlines unacceptable risks which could apply also to diets. Official medical endorsement of these cholesterol reducing measures should be withdrawn.
Secretion of plasminogen activator by human polymorphonuclear leukocytes. Modulation by glucocorticoids and other effectors.
Authors: A Granelli-Piperno, J D Vassalli, E Reich
Journal: The Journal of Experimental Medicine (1977)

Purified human PMNs secrete plasminogen activator. This secretion is stimulated by Con A and low concentrations of PMA, and is inhibited by low concentrations of glucocorticoids, and by cAMP, actinomycin D, and cycloheximide. In contrast, the release of granule-bound enzymes, such as elastase, is achieved only at higher concentrations of PMA, and is not affected by any of the inhibitors that block plasminogen activator production. These results show that the production of plasminogen activatory by PMNs is controlled by agents that affect inflammations, and that this control is not shared by other lytic enzymes known to be associated with these cells. This suggests a particular role for plasminogen activator in the response pattern of PMNs and also supports the concept, previously developed for macrophages, that the secretion of this enzyme is correlated with cell migration in vivo.
Glucocorticoids and cultured human skin cells: specific intracellular binding and structure-activity relationships
Authors: M. PONEC
Journal: British Journal of Dermatology (1982)

Cytosol fractions of both cultured human skin fibroblasts and epidermal keratinocytes contain macromolecules that bind glucocorticoids with high affinity. Using the cytosol of cultured keratinocytes good correlation has been found between the displacement of radiolabelled glucocorticoids (3H‐hydrocortisone, 3H‐dexamethasone and 3H‐triamcinolone acetonide) by a variety of glucocorticoids and the clinical efficacy. The structure‐binding relationship studies revealed the relative contribution of various substituents on the steroid molecule for the binding affinity of the steroids. The introduction of a double bond at C1–C2, the presence of 9α:‐fluoro atom or 1β‐hydroxy group and tlie esterification of the 17α‐hydroxy group caused an increase, whereas esterification of the hydroxy group on C21 leads to marked decrease of the affinity of the steroid.
Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells
Authors: Paul Kievit, Jane K. Howard, Michael K. Badman, Nina Balthasar, Roberto Coppari, Hiroyuki Mori, Charlotte E. Lee, Joel K. Elmquist, Akihiko Yoshimura, Jeffrey S. Flier
Journal: Cell Metabolism (2006)
COMPARATIVE EFFECTIVENESS OF U.S. POPULATION SCREENING STRATEGIES FOR CORONARY HEART DISEASE (CHD): EVALUATION OF FRAMINGHAM RISK SCORE (FRS), SOCIETY FOR HEART ATTACK PREVENTION AND EDUCATION (SHAPE), TEXAS HEART ATTACK PREVENTION BILL, JUPITER, AND TREAT-ALL APPROACHES
Authors: Benjamin Z. Galper, Y. Claire Wang, Andrew J. Einstein
Journal: Journal of the American College of Cardiology (2012)
Abstract 4210: Oxidative stress, DNA damage, and apoptosis mediated by arsenic trioxide in lung carcinoma cells
Authors: Alice M. Walker, Jacqueline J. Stevens, Paul B. Tchounwou
Journal: Cancer Research (2011)

Abstract Lung cancer is one of the most lethal and common of cancers in the world, causing up to 3 million deaths annually. Arsenic trioxide (ATO) has been used in the treatment of relapsed/refractory acute promyelocytic leukemias. However, its effects on lung cancer are not known. We hypothesize that ATO may also have a bioactivity against lung cancer, and its mechanisms of action may involve apoptosis, DNA damage and changes in stress-related proteins in lung cancer cells. Using lung cancer (A549) cells as test model, mthe effects of ATO were examined by 6-diamidine-2 phenylindole (DAPI) nuclear staining for apoptosis, commet assay for genotoxicity ane western blotanalysis for stress protein (Hsp 70 and cfos) expression. Morphological changes of apoptosis (condensed chromatin and apoptotic bodies) were observed with DAPI and cell shrinkage and membrane blebbing without DAPI at 4 and 6µg/ml of ATO. The comet assay data revealed that DNA damage was significant as indicated by increased of the precent of DNA damage, tailmoment and tail length. There was significant increase in Hsp70 expression and significant decrease in cfos in ATO-treated cells compared to controls. ATO is cytotoxic to lung cancer cells and its toxicity is mediated via oxidative stress and DNA damage leading to apoptosis. However, further studies are warranted to understand its specific molecular mechanisms of toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4210. doi:10.1158/1538-7445.AM2011-4210
Teaching students in the community
Authors: M Seabrook, T Evans, P Booton
Journal: BMJ (1994)

EDITOR, - Diane Plampling and Angela Towle are right to highlight the potential for teaching in community health service trusts.1 The potential for community based teaching is wider then they suggest. We have just completed a research project on this, during which we interviewed a broad range of stakeholders.2 We found great enthusiasm for teaching medical students among primary health care practitioners, including health visitors, district …
Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay.
Authors: A P Hollander, T F Heathfield, C Webber, Y Iwata, R Bourne, C Rorabeck, A R Poole
Journal: Journal of Clinical Investigation (1994)

A new immunoassay was developed to detect denaturation of type II collagen in osteoarthritis (OA). A peptide, alpha 1 (II)-CB11B, located in the CB11 peptide of type II collagen, was synthesized and used to produce a monoclonal antibody (COL2-3/4m) of the IgG1 (kappa) isotype. This reacts with a defined epitope in denatured but not native type II collagen and the alpha 3 chain of type XI collagen. The latter is present in very small amounts (about 1% wt/wt) in cartilage relative to the alpha 1 (II) chain. By using an enzyme-linked immunosorbent assay, type II collagen denaturation and total type II collagen content were determined. The epitope recognized by the antibody was resistant to cleavage by alpha-chymotrypsin and proteinase K which were used to extract alpha 1 (II)-CB11B from the denatured (alpha-chymotrypsin soluble) and residual native (proteinase K soluble) collagen alpha-chains, respectively, present in human femoral articular cartilage. Type II collagen content was significantly reduced from a mean (range) of 14% (9.2-20.8%) of wet weight in 8 normal cartilages to 10.3% (7.4-15.0%) in 16 OA cartilages. This decrease, which may result in part from an increased hydration, was accompanied by an increase in the percent denaturation of type II collagen in OA to 6.0% of total type II collagen compared with 1.1% in normal tissue. The percent denaturation was ordinarily greater in the more superficial zone than in the deep zone of OA cartilage.
Primary Medical Care for Families — Organization and Evaluation
Authors: Kerr L. White
Journal: New England Journal of Medicine (1967)

THE recent spate of reports on family medicine and family physicians documents the extent of public and professional concern with the problem of providing primary medical care for communities.1 2 3 4 5 6 7 8 9 Most of these reports discuss the work of family physicians and the form and content of education and training for family medicine.1 2 3 4 5 6 Only 2 provide much in the way of quantitative data7 , 8; 3 deal with the organizational problems,6 , 7 , 9 and none with evaluation of the care provided.Much of the current debate about the distribution of medical care has consisted largely of repetitious recitals of alleged inadequacies in contemporary medical education . . .
Affluent Drowning Victims; Manacled Minds-Reply
Authors: James P. Orlowski
Journal: JAMA (1988)

<h3>In Reply.—</h3> My statement that drowning has become an accident of affluence was not intended to imply that drowning is "limited to wealthy whites," as Baca et al assert. The statement was to be understood in a global context. Swimming pools must be considered a luxury item and are a major source of drowning and near-drowning accidents only in wealthy countries. In third world countries, natural bodies of water and natural disasters are responsible for the vast majority of drowning accidents.<sup>1,2</sup>Baca et al support this assertion of an association with national affluence with their own statements that 63% of drownings with minority victims occur in swimming pools and that swimming pools exist in even the poorest neighborhoods in their community. In 1977, there were an estimated 4 million home swimming pools in the United States,<sup>3</sup>and that number exceeds 5 million now (personal communication, National Pool and
Primary Ventricular Fibrillation
Authors: Jeremy N. Ruskin
Journal: New England Journal of Medicine (1987)

Despite years of observation in coronary care units, there is still considerable uncertainty about the short-term and long-term prognostic implications of ventricular fibrillation in patients with acute myocardial infarction. Primary ventricular fibrillation, defined as fibrillation that occurs suddenly and in the absence of cardiogenic shock or advanced congestive heart failure, is thought to represent an isolated electrical event resulting from acute ischemic injury. Once reversed, it is believed to be associated with an excellent prognosis. By contrast, secondary ventricular fibrillation is characterized as a terminal or preterminal arrhythmia in patients with severe pump dysfunction and circulatory failure, in whom recovery . . .
The Systolic Murmur — Innocent or Guilty?
Authors: Herrman L. Blumgart
Journal: New England Journal of Medicine (1968)

The interpretation of the systolic murmur continues to be one of the most perplexing problems in the diagnosis of the presence or absence of heart disease. Occurring in both healthy and diseased hearts, it has a diagnostic meaning that is frequently judged on the basis of the company it keeps with more definite abnormalities.The systolic murmur occurs in everyone, well or sick, at one time or another. The long-distance track athlete or the thyrotoxic, feverish, pregnant or anemic patient may exhibit systolic murmurs over the apex or base of the heart because of increased velocity of blood flow over . . .
Three Cases Resembling Polyarteritis Nodosa Arising During Treatment with Guanethidine
Authors: H. A. Dewar, M. J. T. Peaston
Journal: BMJ (1964)

Widespread inflammation of the walls of small arteries, either in the form of classical polyarteritis nodosa or as a generalized arteritis, has been described as a result of sen- sitization of the human body to a variety of antigens.Many of these have not been of a protein nature, and then it is assumed that the incriminated substance has acquired its antigenic properties by becoming linked to a protein in the plasma.Drugs suspected of being incriminated in this way have included antibiotics such as chloramphenicol (Rose and
Understanding cell migration guidance: lessons from sex myoblast migration in C. elegans
Authors: Estella B Chen, Michael J Stern
Journal: Trends in Genetics (1998)

Studies of sex myoblast (SM) migration in the nematode Caenorhabditis elegans have shown that multiple guidance mechanisms cooperate to ensure the accurate and reproducible targeting of the SMs. Many issues arise in the analysis of SM migration, including the action of multiple guidance mechanisms, redundant sources of guidance information, the multiple uses of molecular components, and whether factors affect cell fate determination events or the guidance mechanisms themselves. These issues are common to many cell migration events and make the analysis of SM migration instructive to our general understanding of how cell migrations are controlled.
Analysis of the structural heterogeneity and polymorphism of human Ia antigens. Four distinct subsets of molecules are coexpressed in the Ia pool of both DR1,1 homozygous and DR3,W6 heterozygous B cell lines.
Authors: R S Accolla
Journal: The Journal of Experimental Medicine (1984)

Four monoclonal antibodies reacting with distinct human Ia antigenic determinants have been used to demonstrate the coexpression of four distinct subsets, NG1, NG2, H40+-3/4+, and DC1 H40--3/4+, in the Ia pool of DR heterozygous or homozygous B cell lines. By two-dimensional peptide mapping the four subsets within the same Ia pool displayed structurally different beta as well as alpha subunits. The beta chain of the NG1 subset was shown to display considerable structural polymorphism when analyzed in two cell lines with distinct DR but similar DC phenotype, LG2 (DR1,1-DC1) and Raji (DR3, W6-DC1). In contrast, the beta chains of NG2, DC1 H40+-3/4+, and DC1 H40--3/4+ subsets of LG2 cells were shown to be very similar to their homologous Raji cell counterparts, thus indicating a relatively low structural polymorphism. Furthermore, the alpha chains of either one of the four subsets expressed in LG2 cells displayed very high structural similarities to the homologous counterparts in the Raji Ia pool, thus suggesting a relatively low polymorphism for the large Ia subunits described in this study. A striking feature deduced from this study was the selective subunit association of the distinct alpha-beta heterodimers.