tbuckley/cabot-search huggingface dataset:
Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen
Authors: M. Martín, A. Lluch, M.A. Seguí, A. Ruiz, M. Ramos, E. Adrover, Á. Rodríguez-Lescure, R. Grosse, L. Calvo, C. Fernandez-Chacón, M. Roset, A. Antón, D. Isla, P. Martínez del Prado, L. Iglesias, J. Zaluski, A. Arcusa, J.M. López-Vega, M. Muñoz, J.R. Mel
Journal: Annals of Oncology (2006)
Thrombelastography‐guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial
Authors: Lesley De Pietri, Marcello Bianchini, Roberto Montalti, Nicola De Maria, Tommaso Di Maira, Bruno Begliomini, Giorgio Enrico Gerunda, Fabrizio di Benedetto, Guadalupe Garcia‐Tsao, Erica Villa
Journal: Hepatology (2015)

Bleeding is a feared complication of invasive procedures in patients with cirrhosis and significant coagulopathy (as defined by routine coagulation tests) and is used to justify preprocedure use of fresh frozen plasma (FFP) and/or platelets (PLT). Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (international normalized ratio [INR] and platelet count), and its use may avoid unnecessary blood product transfusion in patients with cirrhosis and significant coagulopathy (defined in this study as INR >1.8 and/or platelet count <50 × 10(9) /L) who will be undergoing an invasive procedure. Sixty patients were randomly allocated to TEG-guided transfusion strategy or standard of care (SOC; 1:1 TEG:SOC). The TEG group would receive FFP if the reaction time (r) was >40 min and/or PLT if maximum amplitude (MA) was <30 mm. All SOC patients received FFP and/or PLT per hospital guidelines. Endpoints were blood product use and bleeding complications. Baseline characteristics of the two groups were similar. Per protocol, all subjects in the SOC group received blood product transfusions versus 5 in the TEG group (100% vs. 16.7%; P < 0.0001). Sixteen SOC (53.3%) received FFP, 10 (33.3%) PLT, and 4 (13.3%) both FFP and PLT. In the TEG group, none received FFP alone (P < 0.0001 vs. SOC), 2 received PLT (6.7%; P = 0.009 vs. SOC), and 3 both FFP and PLT (not significant). Postprocedure bleeding occurred in only 1 patient (SOC group) after large-volume paracentesis.In patients with cirrhosis and significant coagulopathy before invasive procedures, TEG-guided transfusion strategy leads to a significantly lower use of blood products compared to SOC (transfusion guided by INR and platelet count), without an increase in bleeding complications. Remarkably, even in patients with significant coagulopathy, postprocedure bleeding was rare, indicating that TEG thresholds should be reevaluated.
Diagnostic Markers for Early Detection of Ovarian Cancer
Authors: Irene Visintin, Ziding Feng, Gary Longton, David C. Ward, Ayesha B. Alvero, Yinglei Lai, Jeannette Tenthorey, Aliza Leiser, Ruben Flores-Saaib, Herbert Yu, Masoud Azori, Thomas Rutherford, Peter E. Schwartz, Gil Mor
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Early detection would significantly decrease the mortality rate of ovarian cancer. In this study, we characterize and validate the combination of six serum biomarkers that discriminate between disease-free and ovarian cancer patients with high efficiency. Experimental Design: We analyzed 362 healthy controls and 156 newly diagnosed ovarian cancer patients. Concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA-125 were determined using a multiplex, bead-based, immunoassay system. All six markers were evaluated in a training set (181 samples from the control group and 113 samples from OC patients) and a test set (181 sample control group and 43 ovarian cancer). Results: Multiplex and ELISA exhibited the same pattern of expression for all the biomarkers. None of the biomarkers by themselves were good enough to differentiate healthy versus cancer cells. However, the combination of the six markers provided a better differentiation than CA-125. Four models with &amp;lt;2% classification error in training sets all had significant improvement (sensitivity 84%-98% at specificity 95%) over CA-125 (sensitivity 72% at specificity 95%) in the test set. The chosen model correctly classified 221 out of 224 specimens in the test set, with a classification accuracy of 98.7%. Conclusions: We describe the first blood biomarker test with a sensitivity of 95.3% and a specificity of 99.4% for the detection of ovarian cancer. Six markers provided a significant improvement over CA-125 alone for ovarian cancer detection. Validation was performed with a blinded cohort. This novel multiplex platform has the potential for efficient screening in patients who are at high risk for ovarian cancer.
Acute Subarachnoid Hemorrhage
Authors: K. York Chynn
Journal: JAMA (1975)

AMPHETAMINE abuse and poisoning may lead to acute subarachnoid hemorrhage, clinically indistinguishable from ruptured berry aneurysm or arteriovenous malformation. The purposes of this communication are to call attention to such rare but serious complications of amphetamine abuse and to report an interesting angiographic feature of vasculitis demonstrable only on early angiography. <h3>Report of a Case</h3> A 19-year-old girl was brought to St. Luke's Hospital Center emergency room because she was stuporous and had paralysis of the right side since early that morning. She had enjoyed good health until the day before admission when she smoked marihuana, took amphetamine and cocaine orally, and began to complain of severe generalized headache and nausea and became drowsy. On physical examination she was a stuporous young girl rolling about in bed. She was responsive to noxious stimuli and moved her left arm and leg spontaneously. There was paralysis of her right upper and lower
A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis
Authors: Seo-Hyun Choi, Zhen-Yu Hong, Jae-Kyung Nam, Hae-June Lee, Junho Jang, Ran Ji Yoo, Yong Jin Lee, Chang Young Lee, Kyung Hwan Kim, Seungwoo Park, Young Hoon Ji, Yun-Sil Lee, Jaeho Cho, Yoon-Jin Lee
Journal: Clinical Cancer Research (2015)

Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF.Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became evident throughout the irradiated tissues. Accompanied by the collagen deposition, vascular EndMT (endothelial-to-mesenchymal transition) began to develop in the early phase of RIPF, before the appearance of EMT (epithelial-to-mesenchymal transition) of alveolar epithelial (AE) II cells in the substantive fibrotic phase. Concomitant with the EndMT, we detected vascular endothelial cell (EC)-specific hypoxic damage in the irradiated lung tissues. In human pulmonary artery endothelial cells (HPAEC), the radiation-induced EndMT via activation of TGFβ-R1/Smad signaling was dependent on HIF1α expression. A novel HIF1α inhibitor, 2-methoxyestradiol (2-ME), inhibited the irradiation-induced EndMT via downregulation of HIF1α-dependent Smad signaling. In vivo, 2-ME inhibited the vascular EndMT, and decreased the collagen deposition associated with RIPF. Furthermore, HIF1α-related EndMT was observed also in human RIPF tissues.We provide the first evidence that an EndMT occurs in RIPF development and that the EndMT may be effectively inhibited by modulating vascular EC-specific hypoxic damage.
Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study
Authors: Kirk R. Schultz, W. Paul Bowman, Alexander Aledo, William B. Slayton, Harland Sather, Meenakshi Devidas, Chenguang Wang, Stella M. Davies, Paul S. Gaynon, Michael Trigg, Robert Rutledge, Laura Burden, Dean Jorstad, Andrew Carroll, Nyla A. Heerema, Naomi Winick, Michael J. Borowitz, Stephen P. Hunger, William L. Carroll, Bruce Camitta
Journal: Journal of Clinical Oncology (2009)

Purpose Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods We evaluated whether imatinib (340 mg/m 2 /d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph− ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) –identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P &lt; .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.
Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium
Authors: M Gawaz
Journal: Cardiovascular Research (2004)

Platelet-dependent thrombus formation is a key event in the pathogenesis of acute myocardial infarction (AMI). Platelets mediate both thrombotic occlusion of the entire epicardial coronary artery and also accumulate in the microcirculation resulting in impairment of microcirculation and provoking myocardial ischemia during reperfusion. In the past, our understanding of platelet function in myocardial infarction (MI) and reperfusion has extended substantially resulting in development of novel and clinically effective treatment strategies. This review summarizes the mechanisms of coronary thrombosis and consequences of platelet accumulation in reperfused myocardium. Basic pathophysiological mechanisms of platelet adhesion and secretion are reviewed first, followed by the description of the molecular steps involved in platelet-mediated thrombus formation around an atherosclerotic plaque. Next, the role of platelets in inflammation is summarized with the focus on platelet-endothelium and platelet-leukocyte interactions.
Bioengineering Models of Cell Signaling
Authors: Anand R. Asthagiri, Douglas A. Lauffenburger
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract Strategies for rationally manipulating cell behavior in cell-based technologies and molecular therapeutics and understanding effects of environmental agents on physiological systems may be derived from a mechanistic understanding of underlying signaling mechanisms that regulate cell functions. Three crucial attributes of signal transduction necessitate modeling approaches for analyzing these systems: an ever-expanding plethora of signaling molecules and interactions, a highly interconnected biochemical scheme, and concurrent biophysical regulation. Because signal flow is tightly regulated with positive and negative feedbacks and is bidirectional with commands traveling both from outside-in and inside-out, dynamic models that couple biophysical and biochemical elements are required to consider information processing both during transient and steady-state conditions. Unique mathematical frameworks will be needed to obtain an integrated perspective on these complex systems, which operate over wide length and time scales. These may involve a two-level hierarchical approach wherein the overall signaling network is modeled in terms of effective "circuit" or "algorithm" modules, and then each module is correspondingly modeled with more detailed incorporation of its actual underlying biochemical/biophysical molecular interactions.
Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population.
Authors: D J Hart, T D Spector, P Brown, P Wilson, D V Doyle, A J Silman
Journal: Annals of the Rheumatic Diseases (1991)

The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease.
Mutant Cohesin in Premature Ovarian Failure
Authors: Sandrine Caburet, Valerie A. Arboleda, Elena Llano, Paul A. Overbeek, Jose Luis Barbero, Kazuhiro Oka, Wilbur Harrison, Daniel Vaiman, Ziva Ben-Neriah, Ignacio García-Tuñón, Marc Fellous, Alberto M. Pendás, Reiner A. Veitia, Eric Vilain
Journal: New England Journal of Medicine (2014)

Premature ovarian failure is a major cause of female infertility. The genetic causes of this disorder remain unknown in most patients. Using whole-exome sequence analysis of a large consanguineous family with inherited premature ovarian failure, we identified a homozygous 1-bp deletion inducing a frameshift mutation in STAG3 on chromosome 7. STAG3 encodes a meiosis-specific subunit of the cohesin ring, which ensures correct sister chromatid cohesion. Female mice devoid of Stag3 are sterile, and their fetal oocytes are arrested at early prophase I, leading to oocyte depletion at 1 week of age.
Role of the 5-Lipoxygenase–activating Protein (FLAP) in Murine Acute Inflammatory Responses
Authors: Robert S. Byrum, Jennifer L. Goulet, Richard J. Griffiths, Beverly H. Koller
Journal: The Journal of Experimental Medicine (1997)

Leukotrienes are potent inflammatory mediators synthesized from arachidonic acid (AA) predominately by cells of myeloid origin. The synthesis of these lipids is believed to be dependent not only on the expression of the enzyme 5-lipoxygenase (5-LO), which catalyzes the first steps in the synthesis of leukotrienes, but also on expression of a nuclear membrane protein termed the 5-LO–activating protein (FLAP). To study the relationship of these two proteins in mediating the production of leukotrienes in vivo and to determine whether the membrane protein FLAP has additional functions in various inflammatory processes, we have generated a mouse line deficient in this protein. FLAP-deficient mice develop normally and are healthy. However, an array of assays comparing inflammatory reactions in FLAP-deficient mice and in normal controls revealed that FLAP plays a role in a subset of these reactions. Although examination of DTH and IgE-mediated passive anaphylaxis showed no difference between wild-type and FLAP-deficient animals, mice without FLAP possessed a blunted inflammatory response to topical AA and had increased resistance to platelet-activating factor–induced shock compared to controls. Also, edema associated with Zymosan A–induced peritonitis was markedly reduced in animals lacking FLAP. To determine whether these differences relate solely to a deficit in leukotriene production, or whether they reflect an additional role for FLAP in inflammation, we compared the FLAP-deficient mice to 5-LO–deficient animals. Evaluation of mice lacking FLAP and 5-LO indicated that production of leukotrienes during inflammatory responses is dependent upon the availability of FLAP and did not support additional functions for FLAP beyond its role in leukotriene production.
Neural Stem Cell–Mediated Enzyme/Prodrug Therapy for Glioma: Preclinical Studies
Authors: Karen S. Aboody, Joseph Najbauer, Marianne Z. Metz, Massimo D’Apuzzo, Margarita Gutova, Alexander J. Annala, Timothy W. Synold, Larry A. Couture, Suzette Blanchard, Rex A. Moats, Elizabeth Garcia, Soraya Aramburo, Valerie V. Valenzuela, Richard T. Frank, Michael E. Barish, Christine E. Brown, Seung U. Kim, Behnam Badie, Jana Portnow
Journal: Science Translational Medicine (2013)

High-grade gliomas are extremely difficult to treat because they are invasive and therefore not curable by surgical resection; the toxicity of current chemo- and radiation therapies limits the doses that can be used. Neural stem cells (NSCs) have inherent tumor-tropic properties that enable their use as delivery vehicles to target enzyme/prodrug therapy selectively to tumors. We used a cytosine deaminase (CD)-expressing clonal human NSC line, HB1.F3.CD, to home to gliomas in mice and locally convert the prodrug 5-fluorocytosine to the active chemotherapeutic 5-fluorouracil. In vitro studies confirmed that the NSCs have normal karyotype, tumor tropism, and CD expression, and are genetically and functionally stable. In vivo biodistribution studies demonstrated NSC retention of tumor tropism, even in mice pretreated with radiation or dexamethasone to mimic clinically relevant adjuvant therapies. We evaluated safety and toxicity after intracerebral administration of the NSCs in non-tumor-bearing and orthotopic glioma-bearing immunocompetent and immunodeficient mice. We detected no difference in toxicity associated with conversion of 5-fluorocytosine to 5-fluorouracil, no NSCs outside the brain, and no histological evidence of pathology or tumorigenesis attributable to the NSCs. The average tumor volume in mice that received HB1.F3.CD NSCs and 5-fluorocytosine was about one-third that of the average volume in control mice. On the basis of these results, we conclude that combination therapy with HB1.F3.CD NSCs and 5-fluorocytosine is safe, nontoxic, and effective in mice. These data have led to approval of a first-in-human study of an allogeneic NSC-mediated enzyme/prodrug-targeted cancer therapy in patients with recurrent high-grade glioma.
Human Anatomy: Depicting the Body from the Renaissance to Today; Human Remains: Dissection and its Histories
Authors: Sanjay A Pai
Journal: BMJ (2006)

I t is almost easy to forget, in this age of molecular biology, the central roles that anatomy and pathologic anatomy have played in medical science for the past four and a half centuries. Most histories of medicine deal with anatomy in brief and concentrate only on Andreas Vesalius, who, in 1543 published De Humani Corporis Fabrica , in which he dealt a severe blow to Galenic theories about the structure of the human body. Two new books have human anatomy and dissection at their cores, while addressing different facets of the history of anatomy.

Art meets anatomy in Human Anatomy , while Human Remains deals with the links between anatomy and anthropology. The first sentence of Human Anatomy is “The body was never a free gift”—something that the author of Human Remains seems to question. The …
Demand Pacemaker Malfunction Due to Abnormal Sensing
Authors: MENASHE B. WAXMAN, NEIL D. BERMAN, GINES SANZ, EUGENE DOWNAR, PAUL MENDLER, KENNETH W. G. TAYLOR
Journal: Circulation (1974)

Two cases with external demand pacemakers are presented because of abnormal prolongation in the pacing interval. In both cases, pacemaker inhibition was caused by signals which were not recorded by the conventional surface electrocardiograms. In one case, inhibition was related to a partial lead fracture which generated a voltage transient in the region of the T wave. In the other case, inhibition was caused by current emitted from a faulty pacemaker unit. In both cases precise localization of the problem was possible by simple bedside recordings and measurements.
Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure
Authors: Takayoshi Tsutamoto, Atsuyuki Wada, Keiko Maeda, Naoko Mabuchi, Masaru Hayashi, Takashi Tsutsui, Masato Ohnishi, Masahide Sawaki, Masanori Fujii, Takehiro Matsumoto, Toshiki Matsui, Masahiko Kinoshita
Journal: Journal of the American College of Cardiology (2001)
The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2.
Authors: G M Bell, J Fargnoli, J B Bolen, L Kish, J B Imboden
Journal: The Journal of Experimental Medicine (1996)

CD2, a cell surface glycoprotein expressed on T cells and natural killer cells, can couple to signaling pathways that result in T cell proliferation. An Src-like protein tyrosine kinase, p56lck, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity of p56lck, suggesting that an interaction with p56lck contributes to CD2-mediated signaling. Herein, we investigate the mechanism by which CD2 associates with p56lck. We demonstrate that CD2 and p56lck associate when coexpressed in nonlymphoid cells, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p56lck mediates its interactions with CD2. Using truncation mutants of CD2, we identify two regions in the cytoplasmic domain of CD2 involved in binding p56lck. Each region contains a proline-rich sequence that, in the form of a synthetic peptide, directly binds p56lck. Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p56lck.