tbuckley/cabot-search huggingface dataset:
Abstract 12424: Antibodies to Malondialdehyde Oxidized LDL Predict Cardiovascular Events During Log-Term Follow-Up In High Risk Coronary Artery Disease Patients
Authors: Giuseppe Maiolino, Maurizio Cesari, Luigi Pedon, Marlena Barisa, Giacomo Rossitto, Teresa Maria Seccia, Leopoldo Pagliani, Renzo De Toni, Mario Zanchetta, Achille Cesare Pessina, Gian Paolo Rossi
Journal: Circulation (2011)

Background. Low-density lipoproteins (LDLs) accumulate in the sub-endothelial extracellular space where they are transformed by macrophages to oxidized LDL (oxLDL). OxLDL are held to play a key rol...
Early Induction of Apoptosis in Hematopoietic Cell Lines After Exposure to Flavopiridol
Authors: Bernard W. Parker, Gurmeet Kaur, Wilberto Nieves-Neira, Mohammed Taimi, Glenda Kohlhagen, Tsunehiro Shimizu, Michael D. Losiewicz, Yves Pommier, Edward A. Sausville, Adrian M. Senderowicz
Journal: Blood (1998)
Chemical peeling in ethnic skin: an update
Authors: A. Salam, O.E. Dadzie, H. Galadari
Journal: British Journal of Dermatology (2013)

Journal Article Chemical peeling in ethnic skin: an update Get access A. Salam, A. Salam Charing Cross Hospital Imperial College Healthcare NHS Trust London U.K Search for other works by this author on: Oxford Academic Google Scholar O.E. Dadzie, O.E. Dadzie Department of Dermatology and Histopathology The North West London Hospitals NHS Trust Northwick Park Hospital Watford Road Harrow HA1 3UJ, UK Search for other works by this author on: Oxford Academic Google Scholar H. Galadari H. Galadari College of Medicine and Health Sciences United Arab Emirates University Al Ain United Arab Emirates Correspondence Hassan Galadari. E‐mail: hgaladari@uaeu.ac.ae Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 169, Issue s3, 1 October 2013, Pages 82–90, https://doi.org/10.1111/bjd.12535 Published: 01 October 2013
Abstract 18132: A Phase 1 Study of Ranolazine in Pulmonary Arterial Hypertension
Authors: Mardi Gomberg-Maitland, Robert Schilz, Anuj Mediratta, Karima Addetia, Sandra Coslet, Hunter Gilles, Ron Oudiz
Journal: Circulation (2014)

Introduction: Pulmonary arterial hypertension (PAH) causes right ventricular (RV) ischemia and failure. Agents that treat left ventricular ischemia may share elements of pathophysiology making cross development of anti-anginal agents an important opportunity for improving PAH care. Adapting new drugs across these disease populations warrants a structured approach. Hypothesis: Ranolazine improves RV ischemia, acutely improving pulmonary vascular resistance, and with daily dosing, improves RV function. Methods: A single center randomized placebo-controlled trial to assess the acute vasoreactivity (up to 360 minutes) and safety of ranolazine in PAH. This was followed by a 12-week phase Ib. Patients underwent monthly clinical evaluations and 12-week study of objective clinical assessments. Results: 12 PAH patients enrolled: 5 idiopathic, 1 hereditary, 1 anorexigen, 2 connective tissue disease and 1 congenital heart disease. Patients were on monotherapy with oral or continuous infusion, or on a combination of ...
899. Stable Gene Expression under the Control of the β-Globin LCR in Hematopoietic Cells after Transduction with Integrating Helper-Dependent Adeno-AAV Vectors
Authors: Hongjie Wang, Dmitry Shayakhmetov, Qiliang Li, Thalia Papayannopoulou, George Stamatoyannopolous, André Lieber
Journal: Molecular Therapy (2004)

Gene therapy of sickle cell disease requires stable, relatively high level, regulated, lineage-specific expression of the γ-globin gene. In the absence of the globin locus control region (LCR), the globin genes are subjected to strong position effects when they are transferred into cultured CD34+ cells or erythroleukemic cell lines. It has been shown that the globin LCR can fully overcome position effects and silencing of linked genes. Integrating viral vectors are still the tool of choice to ensure stable gene delivery to cells that undergo extensive clonal expansion such as HSCs. Our goal was to construct new integrating Adenovirus-AAV hybrid vectors that achieve stable high-level, regulated, erythroid-specific globin gene expression without position effects or silencing. The project is based on two findings: i) adenovirus (Ad) vectors containing the Ad35 fiber (Ad5/35) efficiently transduce human CD34+ cells, particularly subsets with stem cell capacity; and ii) incorporation of AAV ITRs into Ad vectors devoid of all viral genes (Ad.AAV) with an insert capacity of 30kb mediates efficient random vector integration and allows for stable gene transfer into human hematopoietic stem cells. We have produced helper-dependent (HD) Ad5/35.AAV vectors that contain the 22kb β-globin LCR(5′HS-5 to 5′HS-1) and the 3kb 3′HS-1 controlling the expression of GFP, γ-globin, or β-globin (Ad.AAV-LCR-GFP, Ad.AAV-LCR-γ, or Ad.AAV-LCR-β, respectively). Vector titers were > 5× 1012 genomes per ml with   40,000 genomes per cell.
Bush urged to lift cash ban to groups offering abortion
Authors: Sara Pennington
Journal: BMJ (2001)

Family planning organisations are calling on the US president, George Bush, to lift his “global gag rule” restricting reproductive health services in developing countries; this call comes after a study found that women run a 1 in 65 risk of dying in pregnancy and childbirth.

The report, released on International Women's Day, shows that women in developing countries are 33 times more likely to die of reproductive, health related causes than women in industrialised nations.

The study's findings fuelled protests last week by agencies threatened with cutbacks to their activities after President Bush reinstated a rule prohibiting the use of US …
Wrong-Site Surgery, Retained Surgical Items, and Surgical Fires
Authors: Susanne Hempel, Melinda Maggard-Gibbons, David K. Nguyen, Aaron J. Dawes, Isomi Miake-Lye, Jessica M. Beroes, Marika J. Booth, Jeremy N. V. Miles, Roberta Shanman, Paul G. Shekelle
Journal: JAMA Surgery (2015)

Serious, preventable surgical events, termed never events, continue to occur despite considerable patient safety efforts.To examine the incidence and root causes of and interventions to prevent wrong-site surgery, retained surgical items, and surgical fires in the era after the implementation of the Universal Protocol in 2004.We searched 9 electronic databases for entries from 2004 through June 30, 2014, screened references, and consulted experts.Two independent reviewers identified relevant publications in June 2014.One reviewer used a standardized form to extract data and a second reviewer checked the data. Strength of evidence was established by the review team. Data extraction was completed in January 2015.Incidence of wrong-site surgery, retained surgical items, and surgical fires.We found 138 empirical studies that met our inclusion criteria. Incidence estimates for wrong-site surgery in US settings varied by data source and procedure (median estimate, 0.09 events per 10,000 surgical procedures). The median estimate for retained surgical items was 1.32 events per 10,000 procedures, but estimates varied by item and procedure. The per-procedure surgical fire incidence is unknown. A frequently reported root cause was inadequate communication. Methodologic challenges associated with investigating changes in rare events limit the conclusions of 78 intervention evaluations. Limited evidence supported the Universal Protocol (5 studies), education (4 studies), and team training (4 studies) interventions to prevent wrong-site surgery. Limited evidence exists to prevent retained surgical items by using data-matrix-coded sponge-counting systems (5 pertinent studies). Evidence for preventing surgical fires was insufficient, and intervention effects were not estimable.Current estimates for wrong-site surgery and retained surgical items are 1 event per 100,000 and 1 event per 10,000 procedures, respectively, but the precision is uncertain, and the per-procedure prevalence of surgical fires is not known. Root-cause analyses suggest the need for improved communication. Despite promising approaches and global Universal Protocol evaluations, empirical evidence for interventions is limited.
A Computer Simulation Approach to Assessing Therapeutic Intervention Points for the Prevention of Cytokine‐Induced Cartilage Breakdown
Authors: C. J. Proctor, C. Macdonald, J. M. Milner, A. D. Rowan, T. E. Cawston
Journal: Arthritis & Rheumatology (2013)

To use a novel computational approach to examine the molecular pathways involved in cartilage breakdown and to use computer simulation to test possible interventions for reducing collagen release.We constructed a computational model of the relevant molecular pathways using the Systems Biology Markup Language, a computer-readable format of a biochemical network. The model was constructed using our experimental data showing that interleukin-1 (IL-1) and oncostatin M (OSM) act synergistically to up-regulate collagenase protein levels and activity and initiate cartilage collagen breakdown. Simulations were performed using the COPASI software package.The model predicted that simulated inhibition of JNK or p38 MAPK, and overexpression of tissue inhibitor of metalloproteinases 3 (TIMP-3) led to a reduction in collagen release. Overexpression of TIMP-1 was much less effective than that of TIMP-3 and led to a delay, rather than a reduction, in collagen release. Simulated interventions of receptor antagonists and inhibition of JAK-1, the first kinase in the OSM pathway, were ineffective. So, importantly, the model predicts that it is more effective to intervene at targets that are downstream, such as the JNK pathway, rather than those that are close to the cytokine signal. In vitro experiments confirmed the effectiveness of JNK inhibition.Our study shows the value of computer modeling as a tool for examining possible interventions by which to reduce cartilage collagen breakdown. The model predicts that interventions that either prevent transcription or inhibit the activity of collagenases are promising strategies and should be investigated further in an experimental setting.
Abstract 2043: Even Minimal Interruptions in Chest Compression for Ventilation Significantly Decreases Coronary Perfusion Pressure
Authors: Tao Yu, Giuseppe Ritagno, Jun H Cho, Shijie Sun, Max H Weil, Wanchun Tang
Journal: Circulation (2008)

We have previously reported, on the basis of experimental studies, that interruptions of CPR as little as 10 seconds adversely affect the outcomes of CPR. We therefore investigated interruptions of only 5 seconds for delivering ventilation, which corresponds to the current AHA algorithm in which of 30 compressions followed by 2 ventilations are mandated. We hypothesized that even 5 seconds interruption significantly reduces CPP and with significant delay prior to restoring pre-interruption levels. Ventricular fibrillation (VF) was induced and untreated for 15 minutes in 33 male domestic pigs weighting 40±3 Kg. Chest compressions delivered with the aid of mechanical compressor (Thumper, 1000, MI Instruments) with a rate of 100/min. Ventilations were administrated with a compression / ventilation ratio of 30:2 such that 2 ventilations were delivered over a 5 seconds interval. CPP was continuously measured as the difference between comparison diastolic and simultaneous left atrial pressure. CPP significantly decreased during interruptions for ventilation from 20.5±12.8 mmHg to 9.8±6.7 mmHg( P &lt;0.001). After chest compressions were restarted, the CPP increased to 12.5±7.6 mmHg after first compression( P &lt;0.001). A total of 12±7 compressions over a mean interval of 7.2±4.3 seconds was required prior to restoration of CPP to levels corresponding to those that preceded the interruption. As little as the five seconds of interruption in chest compression currently mandated for 30 to 2 ventilations during CPR significantly reduced CPP and delayed restoration of CPP to its pre-interruption level.
Inhibition of angiogenesis and MMP-9 expression by PCK3145 is mediated through targeting of the Akt signaling pathway
Authors: Nicholas Shukeir, Seema Garde, Ani Arakelian, Gaoping Chen, Borhane Annabi, Richard Beliveau, Jinzi J. Wu, Chandra Panchal, Shafaat A. Rabbani
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Adenocarcinoma of the prostate gland is among the leading malignancies in men with high morbidity and mortality rates due to the development of skeletal metastases. PSP-94, one of the three predominant proteins produced by normal prostate gland, is absent in late stage prostate cancer which supports its potential tumor suppressor role. Previous studies carried out in our laboratory have shown the ability of PSP-94 and PCK3145 (amino acids 31–45 of PSP-94) to suppress prostate cancer growth and development of skeletal metastases. Recently, a phase IIa clinical trial carried out in patients with hormone refractory prostate cancer and treated with PCK3145 resulted in disease stabilization. Furthermore, treatment with PCK3145 caused either a stabilization or reduction of MMP-9 levels in these patients. In the current study we evaluated the possible mechanism(s) of action of PCK3145. For these studies, rat prostate cancer MatLyLu cells were treated with different concentrations of PCK3145. Total cellular RNA and conditioned media were collected. PCK3145 treatment resulted in a significant dose dependent reduction in MMP-9 mRNA and protein levels as analyzed by real time RT-PCR, Western blot analysis and zymography. No significant effect on MMP-2 production was seen. Furthermore, treatment of MatLyLu cells with different doses of PCK3145 resulted in a dose dependent reduction in the levels of p-Erk and p-Akt. For in vivo studies, male Copenhagen rats were inoculated either subcutaneously or via intracardiac injections with MatLyLu cells to develop primary tumor growth or experimental skeletal metastases, respectively. Animals were treated with different doses of PCK3145 (1.0–100.0μg/kg) and at the end of the study their tumors were excised and analyzed. PCK3145 caused a dose dependent reduction in tumor volume and a significant decrease in MMP-9 production and neovascularization as assessed by immunohistochemical analysis of primary tumors. These effects were due to the ability of PCK3145 to inhibit p-Erk and p-Akt production by primary tumors. Similarly PCK3145 treatment caused a significant reduction in skeletal tumor burden, delay in hind limb paralysis and inhibition of MMP-9 expression. Collectively, the results obtained from these studies show that the ability of PCK3145 to reduce tumor growth and delay the development of skeletal metastases is in part due to its ability to reduce the levels of MMP-9 and tumor angiogenesis, effects which are mediated through the reduction of active Akt kinase previously reported to modulate the expression of several genes including MMP-9. The results obtained from these studies provide evidence for the mechanism of action of PCK3145 which can be selectively targeted alone or in combination with other therapeutic agents for prostate cancer patients.
CERTAIN BASES OF PHYSICAL THERAPY
Authors: Thomas P. Sprunt
Journal: Annals of Internal Medicine (1934)

Article1 August 1934CERTAIN BASES OF PHYSICAL THERAPYTHOMAS P. SPRUNT, M.D., F.A.C.P.THOMAS P. SPRUNT, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-8-2-192 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDuring the past year it has fallen to my lot to become particularly interested in physical therapy. What I shall have to say is addressed not to expert physical therapists but to practicing physicians who, like myself, have had heretofore but a desultory interest in the subject and while not decrying the value of empiricism in therapeutic methods, would still wish to know something of the underlying physiological factors that may have been determined.Although physical therapy may have been over-exploited here and there during the past several years, one gets the impression that it is much more widely neglected...References BARBOUR HG: Heat-regulating mechanism of body, Physiol. Rev., 1921, i, 295. CrossrefGoogle Scholar BAZETT HC: Physiological responses to heat, Physiol. Rev., 1927, vii, 531-599. CrossrefGoogle Scholar Handbook of physical therapy, Am. Med. Assoc. Google Scholar KAHN RL: Tissue reactions in immunity; specific reacting capacities of different tissues of immunized animal, Science, 1934, lxxix, 172-175. CrossrefGoogle Scholar KOVACS J: Surface temperature and the minute blood vessels of the skin in arthritis, Jr. Am. Med. Assoc., 1933, c, 1018-1021. CrossrefGoogle Scholar LAURENS H: Physiological effects of radiation, Physiol. Rev., 1928, viii, 1-91. CrossrefGoogle Scholar LEWIS T: The blood vessels of the human skin and their responses, 1927, Shaw and Sons, Ltd., London. Google Scholar MOCKPEMBERTONCOULTER HERJS (Editors): Principles and practice of physical therapy, 1933, W. F. Prior Co., Inc. Google Scholar SEVRINGHAUS EL: A constant temperature foot cradle, Am. Jr. Med. Sci., 1934, clxxxvii, 509-511. CrossrefGoogle Scholar STARR I: On the use of heat, desiccation and oxygen in the local treatment of advanced peripheral vascular disease, Am. Jr. Med. Sci., 1934, clxxxvii, 498-509. CrossrefGoogle Scholar WHITNEY WR: Research and industry, Scientific Monthly, 1932, xxxv, 34. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Baltimore, Maryland*Read at the Chicago meeting of the American College of Physicians, April 18, 1934. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1934Volume 8, Issue 2Page: 192-197 ePublished: 1 December 2008 Issue Published: 1 August 1934 PDF downloadLoading ...
32. Efficacy and Safety of Mouse Coagulation Factor VIIa Gene Transfer in Hemophilia B Mice
Authors: Majed N. Aljamali, Paris Margaritis, Valder R. Arruda, Alexander Schlachterman, Rodney M. Camire, Katherine A. High
Journal: Molecular Therapy (2004)

Top of pageAbstract
One major complication of replacement therapy with clotting factors in patients with hemophilia A and B is the development of inhibitory antibodies that neutralize and inactivate the administered protein. Infusion of recombinant human factor VIIa (NovoSeven) into hemophilic patients bypasses the risk of antibody formation and provides a successful alternative approach to achieving normal hemostasis. We generated a recombinant adeno-associated virus (AAV) vector delivering an engineered mouse factor VII gene under the control of liver-specific promoter. The gene product is cleaved intracellularly and secreted as an activated mFVIIa. The levels of mFVII, measured by our in house ELISA, were about two to three fold of the baseline in HB mice, four and eight weeks after AAV injection into their spleen. This was accompanied by shortening of clotting times measured in the plasma of these mice (PTs and aPTTs). Additionally, in vivo tail clip assay showed a partial correction of bleeding in AAV treated HB mice compared to non-treated HB mice. Thrombin-antithrombin (TAT) levels did not change significantly in the treated HB mice up to 6 months post injection at 1.2×1012 vg/mouse dose, although an increase was seen at a higher dose. The survival rate was also similar between the treated and non-treated HB mice. In a follow-up study, we have generated transgenic mice with a range of levels of mFVIIa to analyze levels of expression that afford optimal efficacy and safety. We conclude that elevated and effective levels of activated murine factor VII can be achieved by AAV-mediated, liver-directed transgene delivery. This novel approach improves hemostasis in hemophilic mice with apparently no risk for thrombosis at this dose.
The Incorporation of 6-Mercaptopurine-S35 into the Nucleic Acids of Sensitive and Nonsensitive Transplantable Mouse Tumors
Authors: Samuel Bieber, L. S. Dietrich, Gertrude B. Elion, George H. Hitchings, Daniel S. Martin
Journal: Cancer Research (1961)

Summary  The incorporation of 6-mercaptopurine-S35 into the deoxyribonucleic acids of several mouse tumors has been studied, with the use of standard chemotherapeutic regimens. No correlation could be found between the concentration of 6-mercaptopurine incorporated and the degree of inhibition of the tumor. Furthermore, a mercaptopurine-resistant subline of Adenocarcinoma 755 incorporated more of the analog than did the sensitive line.
Low‐dose alemtuzumab in refractory/relapsed chronic lymphocytic leukemia: Genetic profile and long‐term outcome from a single center experience
Authors: Mariarita Sciumè, Daniele Vincenti, Gianluigi Reda, Nicola Orofino, Ramona Cassin, Diana Giannarelli, Gianluca Gaidano, Davide Rossi, Agostino Cortelezzi
Journal: American Journal of Hematology (2015)

Relapsed/refractory chronic lymphocytic leukemia (CLL) represents a clinical challenge, in particular when high risk gene mutations occur. In this setting, alemtuzumab was recognized to be effective. This retrospective study evaluates long-term efficacy and tolerability of low-dose alemtuzumab in relapsed/refractory CLL and correlates clinical outcome with biological feature. Sixty-two consecutive patients (median age 68 years) were evaluated; alemtuzumab was administered 30 mg weekly for up to 18 weeks. Among the patients included in the analysis, 37% were fludarabine-refractory, 33.3% carried a TP53 disruption, 14.8% a NOTCH1 mutation and 9% a SF3B1 mutation. Overall response rate (ORR) was 61.3% (complete remission 25.8%). After a median follow-up of 43 months, overall survival (OS) and progression free survival (PFS) were 43.1 and 15 months, respectively; while ORR was 77.8% for patients carrying TP53 disruptions (OS 33.8 months) and 43.5% for fludarabine-refractory patients (OS 30 months). Noteworthy, long-term survivors (OS ≥ 36 months) were 54.8%. None of the biological poor risk factors negatively impacted on ORR, PFS and OS. Grade ≥3 cytopenia occurred in 24.2% patients, 6.5% experienced a grade ≥3 non-CMV infection and no grade ≥3 CMV-event occurred. In conclusion, low dose-alemtuzumab is safe and effective in relapsed/refractory CLL, also in a long-term follow-up and high-risk genetic subgroups.