tbuckley/cabot-search huggingface dataset:
Therapy of chronic myelogenous leukemia with allogeneic bone marrow transplantation.
Authors: P McGlave, D Arthur, R Haake, D Hurd, W Miller, G Vercellotti, D Weisdorf, T Kim, N Ramsay, J Kersey
Journal: Journal of Clinical Oncology (1987)

From December 1982 to January 1986, 57 patients received allogeneic bone marrow transplantation as therapy for Philadelphia chromosome (Ph') positive chronic myelogenous leukemia (CML). All patients were prepared for transplantation with cyclophosphamide 60 mg/kg (day -6, -5) and fractionated total body irradiation, 165 cGy twice daily (day -4, -3, -2, -1) and received major histocompatibility (MHC) matched donor marrow (day 0). All patients received graft-v-host disease (GVHD) prophylaxis with methotrexate, prednisone, and either antithymocyte globulin (ATG) (55 patients) or OKT3 infusion (two patients). The projected survival of 29 chronic phase patients is 64% (95% confidence interval [Cl] 42% to 86%); and of 28 accelerated phase patients, 30% (95% Cl, 12% to 48%) at 30 months (P = .005). Multivariate regression analysis of pretransplant patient characteristics demonstrated that the presence of chronic phase and age less than 30 years were the only prognostic features studied that independently predicted survival. No evidence of persistent or recurrent disease has occurred in chronic phase patients; however, reappearance of the Ph' was observed in seven accelerated-phase patients, and hematologic relapse occurred in three of these seven patients. The incidence of grade II to IV acute GVHD is 63% (95% Cl, 50% to 76%) at 100 days, and that of extensive chronic GVHD is 53% (95% Cl, 33% to 74%) at 30 months. The median Karnofsky activity assessment of survivors is 100% (range, 60% to 100%), and all activity assessments less than 100% can be attributed to complications of GVHD. Bone marrow transplantation therapy for CML after preparation with cyclophosphamide and fractionated total body irradiation results in a high proportion of disease-free survival in chronic-phase patients. Survival in accelerated phase is significantly worse and is associated with relapse. GVHD has emerged as a significant cause of morbidity and mortality in this study.
Antidote reverses anticoagulant effects of factor Xa inhibitors in minutes, studies show
Authors: S. Mayor
Journal: BMJ (2015)

Bleeding is a potential complication with factor Xa inhibitors, but two studies reported in the New England Journal of Medicine have shown that the anticoagulant activity of apixaban and rivaroxaban was reversed within minutes by andexanet, an agent designed to block the anticoagulant effects of these inhibitors.1

The direct factor Xa inhibitors apixaban, rivaroxaban, and edoxaban are indicated for prevention of stroke in patients with non-valvar atrial fibrillation, secondary prevention and treatment of deep vein thrombosis and pulmonary embolism, and prevention of vein thrombosis after orthopaedic surgery.

The lack of a specific antidote to reverse the anticoagulant effects of these agents has been considered …
Identification and Effects of Neural Transmitters in Invertebrates
Authors: J Kehoe, E Marder
Journal: The Annual Review of Pharmacology and Toxicology (1976)

This review treats almost exclusively of investigations that have been published over the last three years (for work prior to that period see I). Preference is given to data obtained from identified neurons, in particular, from neurons for which the trans­ mitter has been evaluated biochemically as well as electrophysiologically and phar­ macologically. Finally, only those synaptic studies that deal directly with the problems of transmitter pharmacology have been considered. The first half of this review deals with recent advances in single-cell neurochemis­ try. Biochemical and histochemical work concerned with the identification of trans­ mitters in identified neurons is summarized in Table 1, and is followed by a brief consideration of some issues raised by the table and by other recent work in this field. The second half of this review covers electro physiological and pharmacological studies that clarify the role of transmitters or putative transmitters at some identified junctions, giving preferential treatment to experimental preparations and problems that have received rather extensive attention.
Bioethics Authorship in Context: How Trends in Biomedicine Challenge Bioethics
Authors: Rachel A. Ankeny, Sabina Leonelli
Journal: The American Journal of Bioethics (2011)

This is an Author's Original Manuscript of an article whose final and definitive form, the Version of Record, has been published in The American Journal of Bioethics 2011. Available online at: http://www.tandfonline.com/ or DOI: 10.1080/15265161.2011.603808
Deficiency of the Fas Apoptosis Pathway Without Fas Gene Mutations in Pediatric Patients With Autoimmunity/Lymphoproliferation
Authors: Umberto Dianzani, Manuela Bragardo, Daniela DiFranco, Carla Alliaudi, Paola Scagni, Donatella Buonfiglio, Valter Redoglia, Sara Bonissoni, Antonio Correra, Irma Dianzani, Ugo Ramenghi
Journal: Blood (1997)
More sinning than sinned against
Authors: Fiona Godlee
Journal: BMJ (2015)

Among the statistical sins of England’s health secretary, Jeremy Hunt, summarised and rebutted this week by David Craven (doi:10.1136/bmj.h6358), we might soon have to include an assertion by Hunt that patients will die if junior doctors strike. But an Analysis article this week indicates otherwise. David Metcalfe and colleagues have taken a systematic look at studies reporting mortality data from doctors strikes’ around the world (doi:10.1136/bmj.h6231). Of the six studies from developed countries, none showed an increase in mortality. Indeed, in two cases mortality fell during strikes. The authors conclude that, given this evidence, and provided …
The CD40 Antigen and its Ligand
Authors: J Banchereau, F Bazan, D Blanchard, F Brière, J P Galizzi, C van Kooten, Y J Liu, F Rousset, S Saeland
Journal: Annual Review of Immunology (1994)

CD40 is an integral membrane protein found on the surface of B lymphocytes, dendritic cells, follicular dendritic cells, hematopoietic progenitor cells, epithelial cells, and carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which is a member of the tumor necrosis factor receptor superfamily. The CD40 gene maps to human chromosome 20q11-2-q13-2. CD40 binds to a ligand (CD40-L) which is an approximately 35 kDa glycoprotein of 261 aa, a member of the tumor necrosis factor superfamily. The CD40-L gene maps to human chromosome Xq24. This CD40-L is expressed on activated T cells, mostly CD4+ but also some CD8+ as well as basophils/mast cells. The CD40-L is defective in the X-linked hyper-IgM syndrome. Cross-linking of CD40 with immobilized anti-CD40 or cells expressing CD40-L induces B cells to proliferate strongly, and addition of IL-4 or IL-13 allows the generation of factor-dependent long-term normal human B cell lines and the secretion of IgE following isotype switching. Addition of IL-10 results in very high immunoglobulin production with limited cell proliferation. IL-10 induces naive B cells to produce IgG3, IgG1, and IgA1, and further addition of TGF beta permits the secretion of IgA2. Several evidences suggest that CD40-dependent activation of B cells is important for the generation of memory B cells within the germinal centers: (i) CD40 activated germinal center B cells cultured in the presence of IL-4 acquire a memory B cell phenotype, (ii) CD40 activated B cells can undergo isotype switching, (iii) the deficit of CD40-L results in the hyper-IgM syndrome characterized by lack of germinal centers in secondary lymphoid organ follicles and lack of IgG, IgA, and IgE, and (iv) CD40-L positive T cells are present in secondary follicles. Thymic epithelial cells, activated monocytes, and dendritic cells express CD40 antigen which may be involved in an enhanced cytokine production by these cells, allowing an amplification of T cell proliferation. Finally, as other members of the tumor necrosis factor receptor family have been shown to bind several ligands, it is possible that CD40 may bind other ligands that may trigger CD40 on different cell types such as hematopoietic cells or epithelial cells.
The Inescapable Influence of Noncoding RNAs in Cancer
Authors: Brian D. Adams, Eleni Anastasiadou, Manel Esteller, Lin He, Frank J. Slack
Journal: Cancer Research (2015)

Abstract This report summarizes information presented at the 2015 Keystone Symposium on “MicroRNAs and Noncoding RNAs in Cancer.” Nearly two decades after the discovery of the first miRNA, the role of noncoding RNAs in developmental processes and the mechanisms behind their dysregulation in cancer has been steadily elucidated. Excitingly, miRNAs have begun making their way into the clinic to combat diseases such as hepatitis C and various forms of cancer. Therefore, at this Keystone meeting, novel findings were presented that enhance our view on how small and long noncoding RNAs control developmental timing and oncogenic processes. Recurring themes included (i) how miRNAs can be differentially processed, degraded, and regulated by ribonucleoprotein complexes, (ii) how particular miRNA genetic networks that control developmental process, when disrupted, can result in cancer disease, (iii) the technologies available to therapeutically deliver RNA to combat diseases such as cancer, and (iv) the elucidation of the mechanism of actions for long noncoding RNAs, currently a poorly understood class of noncoding RNA. During the meeting, there was an emphasis on presenting unpublished findings, and the breadth of topics covered reflected how inescapable the influence of noncoding RNAs is in development and cancer. Cancer Res; 75(24); 5206–10. ©2015 AACR.
Diversity and Selectivity of Receptor-G Protein Interaction
Authors: T Gudermann, F Kalkbrenner, G Schultz
Journal: The Annual Review of Pharmacology and Toxicology (1996)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Targeting lysosomal Ca<sup>2+</sup>to reduce reperfusion injury
Authors: Osamu Tsukamoto, Hiroshi Asanuma, Masafumi Kitakaze
Journal: Cardiovascular Research (2015)

This editorial refers to 'Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore' by S.M. Davidson et
Diagnosis and Treatment of Fat Embolism
Authors: J A Moylan, M A Evenson
Journal: Annual Review of Medicine (1977)

Fat emboli syndrome is one of the major causes of early posttraumatic respiratory distress. Careful attention to the multiple factors associated with the early resuscitative period can minimize this lethal complication of multisystem injury. The use of high-dose steroids and appropriate ventilatory support will decrease the high mortality rate associated with this disease syndrome once it has developed.
P-096 Gastric Carcinoma and curative surgery predictive factors: Retrospective analysis of 60 Tunisian cases
Authors: N. Chraiet, Y. Ben Romdhane, M. Serghini, H. Raies, M. Ayadi, K. Meddeb, A. Mokrani, Y. Yahyaoui, A. Filali, A. Mezlini
Journal: Annals of Oncology (2015)
Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia.
Authors: P Anderlini, R S Benjamin, F C Wong, H M Kantarjian, M Andreeff, S M Kornblau, S O'Brien, B Mackay, M S Ewer, S A Pierce
Journal: Journal of Clinical Oncology (1995)

PURPOSE To estimate the incidence of idarubicin (IDA)-related cardiomyopathy in acute myeloid leukemia (AML) and myelodysplasia (MDS). PATIENTS AND METHODS We analyzed a group of 127 AML/MDS patients who received IDA-based induction and postremission or salvage therapy and achieved a complete remission (CR) that lasted &gt; or = 12 weeks for the development of IDA-related congestive heart failure (CHF). CHF was defined as definite if a resting left ventricular ejection fraction (LVEF) of &lt; or = 45% measured by radionuclide ventriculogram (RV) accompanied the clinical diagnosis of CHF, which had to be made during or within 6 months of receiving IDA and for which no other cause was apparent; without RV confirmation, the diagnosis was considered probable. Patients who had RVs performed were evaluated for decreasing LVEF. Older age (&gt; or = 70 years), prior/sequential anthracycline/mitoxantrone (anthraquinone) therapy, and cardiac disease/hypertension were evaluated as risk factors for the development of CHF. RESULTS One hundred fifteen patients were assessable (median age, 40 years; median dose, 96 mg/m2). Sixty-five had RVs performed during therapy; 43 had risk factors. The probability of IDA-related cardiomyopathy was 5% at a cumulative IDA dose of 150 to 290 mg/m2, with 18 patients receiving doses greater than 150 mg/m2. At a cumulative IDA dose of 150 mg/m2, the probability of a mild or greater asymptomatic decrease probability of a mild or greater asymptomatic decrease in LVEF (&gt; or = 10% to a level &lt; or = 50%) was 18%, whereas the probability of a moderate or greater asymptomatic decrease in LVEF (&gt; or = 15% to a level &lt; or = 45%) was 7%. No patient with asymptomatic LVEF decreases developed CHF. CHF was more frequent in patients with prior/sequential exposure to anthracyclines/mitoxantrone (P = .01). CONCLUSION In this patient group, IDA-related cardiomyopathy was uncommon with cumulative IDA doses of up to 290 mg/m2. Asymptomatic LVEF decreases were more frequent, but their predictive value for the development of CHF is unclear.
Identification of the (Pro)renin Receptor as a Novel Regulator of Low-Density Lipoprotein Metabolism
Authors: Xifeng Lu, Marcel E. Meima, Jessica K. Nelson, Vincenzo Sorrentino, Anke Loregger, Saskia Scheij, Dick H.W. Dekkers, Monique T. Mulder, Jeroen A.A. Demmers, Geesje M-Dallinga-Thie, Noam Zelcer, A.H. Jan Danser
Journal: Circulation Research (2015)

The (pro)renin receptor ([P]RR) interacts with (pro)renin at concentrations that are >1000× higher than observed under (patho)physiological conditions. Recent studies have identified renin-angiotensin system-independent functions for (P)RR related to its association with the vacuolar H(+)-ATPase.To uncover renin-angiotensin system-independent functions of the (P)RR.We used a proteomics-based approach to purify and identify (P)RR-interacting proteins. This resulted in identification of sortilin-1 (SORT1) as a high-confidence (P)RR-interacting protein, a finding which was confirmed by coimmunoprecipitation of endogenous (P)RR and SORT1. Functionally, silencing (P)RR expression in hepatocytes decreased SORT1 and low-density lipoprotein (LDL) receptor protein abundance and, as a consequence, resulted in severely attenuated cellular LDL uptake. In contrast to LDL, endocytosis of epidermal growth factor or transferrin remained unaffected by silencing of the (P)RR. Importantly, reduction of LDL receptor and SORT1 protein abundance occurred in the absence of changes in their corresponding transcript level. Consistent with a post-transcriptional event, degradation of the LDL receptor induced by (P)RR silencing could be reversed by lysosomotropic agents, such as bafilomycin A1.Our study identifies a renin-angiotensin system-independent function for the (P)RR in the regulation of LDL metabolism by controlling the levels of SORT1 and LDL receptor.
Connexins help fill the Gap: markers and therapeutic targets for chronic nonhealing wounds
Authors: P.E. Martin
Journal: British Journal of Dermatology (2015)

Journal Article Connexins help fill the Gap: markers and therapeutic targets for chronic nonhealing wounds Get access P.E. Martin P.E. Martin Department of Life Sciences School of Health and Life Sciences Glasgow Caledonian University Glasgow G4 0BA U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 5, 1 November 2015, Pages 1123–1124, https://doi.org/10.1111/bjd.14193 Published: 01 November 2015
Treatment of CNS relapse in children with acute lymphoblastic leukemia: A Pediatric Oncology Group study.
Authors: N J Winick, S D Smith, J Shuster, S Lauer, M D Wharam, V Land, G Buchanan, G Rivera
Journal: Journal of Clinical Oncology (1993)

PURPOSE To assess the efficacy and toxicity of chemotherapy and cranial radiation for the treatment of children with acute lymphoblastic leukemia (ALL) following first isolated CNS relapse. PATIENTS AND METHODS One hundred twenty children were treated on Pediatric Oncology Group (POG) protocol 8304. All children had received prophylactic CNS therapy during their initial treatment. The treatment protocol included a four-drug reinduction and six weekly doses of triple intrathecal therapy (TIT). Cranial radiation, 24 Gy, was followed by monthly TIT. Systemic consolidation and maintenance therapy included 6-week cycles of mercaptopurine/methotrexate (6MP/MTX) and vincristine/cyclophosphamide (VCR/CTX), with randomization to intervening pulses of prednisone/doxorubicin (PDN/DOX) or teniposide (VM26)/cytarabine (Ara-C) for a total of 88 weeks. RESULTS All 120 patients achieved a second complete remission. There have been 61 protocol failures. Thirty-five patients had a bone marrow relapse, four with simultaneous CNS involvement and one with concurrent testicular leukemia. Thirteen patients had a second isolated CNS relapse, 10 a testicular relapse, and two relapsed in other sites. One patient died in remission. Overall event-free survival (EFS) at 4 years was 46% +/- 7%. The toxicity associated with this protocol was minimal except for leukoencephalopathy, which occurred in 20 (17%) patients. The treatment comparison between VM26/Ara-C or PDN/DOX pulses showed a trend toward superior EFS (P = .12) in favor of VM-26/Ara-C. CONCLUSION To date, this represents the largest series of patients with ALL treated uniformly for an isolated CNS relapse. Since marrow relapse remains the primary site of failure, future protocols must intensify systemic therapy.
Surveillance and Data Capture to Assess Trauma Care Capacity in Low- and Middle-Income Countries
Authors: Grace Hsiung, Colin Gause, Fizan Abdullah
Journal: JAMA Surgery (2015)

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RORγt inhibitors suppress TH17 responses in inflammatory arthritis and inflammatory bowel disease
Authors: Jelle de Wit, M. Hussein Al-Mossawi, Michael H. Hühn, Carolina V. Arancibia-Cárcamo, Karen Doig, Benjamin Kendrick, Roger Gundle, Peter Taylor, Terri Mcclanahan, Erin Murphy, Hongjun Zhang, Ken Barr, J. Richard Miller, Xiao Hu, Thomas D. Aicher, Rodney W. Morgan, Gary D. Glick, Dennis Zaller, Craig Correll, Fiona Powrie, Paul Bowness
Journal: Journal of Allergy and Clinical Immunology (2015)
Association of impaired left ventricular twisting-untwisting with vascular dysfunction, neurohumoral activation and impaired exercise capacity in hypertensive heart disease
Authors: Ignatios Ikonomidis, Stavros Tzortzis, Helen Triantafyllidi, John Parissis, Costas Papadopoulos, Kyriaki Venetsanou, Paraskevi Trivilou, Ioannis Paraskevaidis, John Lekakis
Journal: European Journal of Heart Failure (2015)
Independent home use of Brain Painting improves quality of life of two artists in the locked-in state diagnosed with amyotrophic lateral sclerosis
Authors: Elisa Mira Holz, Loic Botrel, Andrea Kübler
Journal: Brain-Computer Interfaces (2015)

This study reports the use of Brain Painting, a BCI application for creative expression, which was implemented at the homes of two end-users in the locked-in state. Both are artists who had gradually lost the ability to paint after being diagnosed with amyotrophic lateral sclerosis. The usability of the BCI in expert-independent use was evaluated by the end-users. End-user HP painted in 152 sessions within 22 months (in total: 255 h), end-user JT in 158 sessions within 15 months (in total: 168 h). With an accuracy of 70–90%, BCI control was mostly moderate to high. Both end-users were highly satisfied with the BCI as an assistive device. Brain Painting re-enabled them to be creatively active in their home environment and thus improved their feelings of happiness, usefulness, self-esteem, well-being, and consequently quality of life, and supports social inclusion. This long-term evaluation study suggests that BCI is a valuable tool for people in the locked-in state.
Implementation Science for Global Oncology: The Imperative to Evaluate the Safety and Efficacy of Cancer Care Delivery
Authors: Neo M. Tapela, Tharcisse Mpunga, Nadine Karema, Ignace Nzayisenga, Temidayo Fadelu, Frank R. Uwizeye, Lisa R. Hirschhorn, Marie Aimee Muhimpundu, Jean Paul Balinda, Cheryl Amoroso, Claire M. Wagner, Agnes Binagwaho, Lawrence N. Shulman
Journal: Journal of Clinical Oncology (2015)

Purpose The development of cancer care treatment facilities in resource-constrained settings represents a challenge for many reasons. Implementation science—the assessment of how services are set up and delivered; contextual factors that affect delivery, treatment safety, toxicity, and efficacy; and where adaptations are needed—is essential if we are to understand the performance of a treatment program, know where the gaps in care exist, and design interventions in care delivery models to improve outcomes for patients. Methods The field of implementation science in relation to cancer care delivery is reviewed, and the experiences of the integrated implementation science program at the Butaro Cancer Center of Excellence in Rwanda are described as a practical application. Implementation science of HIV and tuberculosis care delivery in similar challenging settings offers some relevant lessons. Results Integrating effective implementation science into cancer care in resource-constrained settings presents many challenges, which are discussed. However, with carefully designed programs, it is possible to perform this type of research, on regular and ongoing bases, and to use the results to develop interventions to improve quality of care and patient outcomes and provide evidence for effective replication and scale-up. Conclusion Implementation science is both critical and feasible in evaluating, improving, and supporting effective expansion of cancer care in resource-limited settings. In ideal circumstances, it should be a prospective program, established early in the lifecycle of a new cancer treatment program and should be an integrated and continual process.