tbuckley/cabot-search huggingface dataset:
A Comparative Genomic Approach for Identifying Synthetic Lethal Interactions in Human Cancer
Authors: Raamesh Deshpande, Michael K. Asiedu, Mitchell Klebig, Shari Sutor, Elena Kuzmin, Justin Nelson, Jeff Piotrowski, Seung Ho Shin, Minoru Yoshida, Michael Costanzo, Charles Boone, Dennis A. Wigle, Chad L. Myers
Journal: Cancer Research (2013)

Synthetic lethal interactions enable a novel approach for discovering specific genetic vulnerabilities in cancer cells that can be exploited for the development of therapeutics. Despite successes in model organisms such as yeast, discovering synthetic lethal interactions on a large scale in human cells remains a significant challenge. We describe a comparative genomic strategy for identifying cancer-relevant synthetic lethal interactions whereby candidate interactions are prioritized on the basis of genetic interaction data available in yeast, followed by targeted testing of candidate interactions in human cell lines. As a proof of principle, we describe two novel synthetic lethal interactions in human cells discovered by this approach, one between the tumor suppressor gene SMARCB1 and PSMA4, and another between alveolar soft-part sarcoma-associated ASPSCR1 and PSMC2. These results suggest therapeutic targets for cancers harboring mutations in SMARCB1 or ASPSCR1 and highlight the potential of a targeted, cross-species strategy for identifying synthetic lethal interactions relevant to human cancer.
Variants in the VEGFA Gene and Treatment Outcome after Anti-VEGF Treatment for Neovascular Age-related Macular Degeneration
Authors: Farshad Abedi, Sanjeewa Wickremasinghe, Andrea J. Richardson, Enes Makalic, Daniel F. Schmidt, Sukhpal S. Sandhu, Paul N. Baird, Robyn H. Guymer
Journal: Ophthalmology (2012)
Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma
Authors: D ROBINSON, S YING, A BENTLEY, Q MENG, J NORTH, S DURHAM, A KAY, Q HAMID
Journal: Journal of Allergy and Clinical Immunology (1993)
Heparanase Is Involved in the Pathogenesis of Proteinuria as a Result of Glomerulonephritis
Authors: Vicki Levidiotis, Craig Freeman, Chris Tikellis, Mark E. Cooper, David A. Power
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The β-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by selectively degrading the negatively charged side chains of heparan sulfate proteoglycans within the glomerular basement membrane. A loss of negatively charged heparan sulfate proteoglycans may result in alteration of the permselective properties of the glomerular basement membrane, loss of glomerular epithelial and endothelial cell anchor points, and liberation of growth factors. In this study, therefore, the role of heparanase in passive Heymann nephritis (PHN) was examined. Normal glomeruli showed low-level heparanase expression as determined by immunohistochemistry and Western blot analysis. Days 5, 14, and 28 of PHN were associated with an increase in endothelial and glomerular epithelial cell heparanase. Reverse transcription–PCR confirmed a significant increase in mRNA at day 21 of disease (<i>P</i> &lt; 0.0004). Furthermore, urinary and glomerular heparanase activities were significantly increased at days 5 and 21 of disease, respectively. Western blot analysis of isolated glomeruli separated into membrane- and cytosol-enriched protein fractions showed that the active 58-kD heparanase species was increased but restricted to the cytosol of diseased glomeruli at day 21. The inactive 65-kD precursor, however, was found in membrane and cytosol-diseased fractions, suggesting cell membrane processing. Complement depletion prevented glomerular heparanase expression; in addition, administration of a polyclonal anti-heparanase antibody significantly reduced urinary protein excretion at day 5 of disease to 62 ± 11 mg/d compared with 203 ± 43 and 159 ± 18 mg/d in the normal rabbit serum– and normal saline-treated experimental groups, respectively (<i>P</i> &lt; 0.002). Proteinuria was reduced in the absence of any altered glomerular C5b-9 activity, sheep IgG deposition, or rat anti-sheep antibody titers. These data suggest that heparanase contributes to the pathogenesis of proteinuria in PHN. E-mail: Vicki.Levidiotis@austin.org.au
Physician-assisted suicide
Authors: J. J. van Delden
Journal: BMJ (1998)

Ed Robert F Weir Indiana University Press, £24.95, pp 266 ISBN 0 253 33282 6

During the first Dutch study into euthanasia and other end-of-life decisions (for the Remmelink committee in 1991), we asked doctors involved in euthanasia cases why they chose euthanasia instead of assisted suicide and vice versa.

Most respondents had strong opinions about how they complied (if at all) with patients' requests to end their life. Doctors who performed euthanasia regarded asking patients to take the deadly drugs themselves, as in assisted suicide, as abandoning them at the “moment supreme.” On the other hand, doctors who …
The Enriched Sequencing Method for Detection of K-Ras Mutations Enhances the Identification of Primary Resistant Colorectal Cancers to Panitumumab
Authors: Luciano Stumbo, Mario Rosario D'Andrea, Giampietro Gasparini, L Felicioni, Salvatore Tumolo, Ida Pavese, Roberto Bordonaro, Roberto Labianca, Domenico Bilancia, Gianni Sanna, Mario Airoldi, Angela Buonadonna, Vita Leonardi, Stefano Jacobelli, Antonio Marchetti
Journal: Annals of Oncology (2013)
Is Eosinophil Dependence of Pulmonary Allergic Inflammation in Mice Really Strain Specific?
Authors: S.I. Ochkur, E.A. Jacobsen, C. Protheroe, R.S. Pero, K.R. O'Neill, A.G. Taranova, D.C. Colbert, A. Doyle, C.G. Irvin, N.A. Lee, J.J. Lee
Journal: Journal of Allergy and Clinical Immunology (2008)
Viral infection induces dependence of neuronal M2 muscarinic receptors on cyclooxygenase in guinea pig lung.
Authors: R M Kahn, O A Okanlami, D B Jacoby, A D Fryer
Journal: Journal of Clinical Investigation (1996)

Inhibitory M2 muscarinic receptors on parasympathetic nerve endings in the lungs decrease release of acetylcholine, inhibiting vagally induced bronchoconstriction. Neuronal M2 receptor function can be studied using selective agonists and antagonists such as pilocarpine and gallamine. In pathogen-free guinea pigs indomethacin (1 mg/kg) did not alter the effect of either gallamine or pilocarpine, thus in pathogen free animals neuronal M2 muscarinic receptors function independently of cyclooxygenase products. However, in guinea pigs infected with virus, (which causes temporary loss of M2 receptor function), and then allowed to recover for 8 wk (to allow recovery of M2 receptors), indomethacin prevented both gallamine's potentiation and pilocarpine's inhibition of vagally induced bronchoconstriction. This new effect of indomethacin was not blocked by the addition of a 5-lipoxygenase inhibitor, AA861. However, the selective COX II inhibitor, L-745,337, had the same effect as indomethacin. Since exposure to ozone also caused neuronal M2 receptors to become dependent upon cyclooxygenase the effects of viral infection are likely to be due to inflammation. Thus, despite apparent recovery of normal M2 receptor function after viral infection or ozone, linkage of these receptors is chronically altered such that they become largely dependent on the activity of COX II.
Lymphangioleiomyomatosis--presence of receptor tyrosine kinases and the angiogenesis factor VEGF-A as potential therapeutic targets
Authors: H. Watz, K. Engels, S. Loeschke, M. Amthor, D. Kirsten, H. Magnussen
Journal: Thorax (2007)

Lymphangioleiomyomatosis (LAM) is a rare systemic disorder in women occurring either sporadically (sporadic LAM) or in association with tuberous sclerosis (TS-LAM). It is caused by proliferating smooth muscle-like LAM cells, which lead to a progressive cystic destruction of the lungs and abdominal tumours (renal angiomyolipomas and/or axial lymph node lesions). LAM cells express receptors for oestrogen and progesterone and stain positive for HMB-45, an antibody against the melanoma-related antigen.1 LAM fulfils the criteria of a neoplastic disease with enhanced proliferation,2 metastasising processes,3 increased migratory activity and invasiveness of LAM cells.4 Currently, an effective treatment interfering with these processes does not exist. Growth factors such as platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) have been identified to enhance LAM and renal angiomyolipoma cell proliferation in vitro.2,5 …
Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?
Authors: R. Leonard, J. O'Shaughnessy, S. Vukelja, V. Gorbounova, C.A. Chan-Navarro, D. Maraninchi, N. Barak-Wigler, J.J. McKendrick, W.G. Harker, A.S. Bexon, C. Twelves
Journal: Annals of Oncology (2006)
Deposition of C3, C9 neoantigen and vitronectin (S-protein of complement) in lichen planus pemphigoides
Authors: H. HINTNER, N. SEPP, K. DAHLBACK, B. DAHLBAK, P. FRITSCH, S.M. BREATHNACH
Journal: British Journal of Dermatology (1990)

Journal Article Deposition of C3, C9 neoantigen and vitronectin (S‐protein of complement) in lichen planus pemphigoides Get access H. HINTNER, H. HINTNER Department of Dermatology, University of Innsbruck, Innsbruck, Austria Dr H. Hintner, Department of Dermatology, University of Innsbruck, Anichstrasse 35, A‐6020 Innsbruck, Austria. Search for other works by this author on: Oxford Academic Google Scholar N. SEPP, N. SEPP Department of Dermatology, University of Innsbruck, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar K. DAHLBÄCK, K. DAHLBÄCK Department of Dermatology, University of Lund, Lund, Sweden Search for other works by this author on: Oxford Academic Google Scholar B. DAHLBÂK, B. DAHLBÂK Department of Clinical Chemistry, Malmö General Hospital, MalmoU, Sweden Search for other works by this author on: Oxford Academic Google Scholar P. FRITSCH, P. FRITSCH Department of Dermatology, University of Innsbruck, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar S.M. BREATHNACH S.M. BREATHNACH Department of Medicine (Dermatology), Charing Cross and Westminster Medical School, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 1, 1 July 1990, Pages 39–47, https://doi.org/10.1111/j.1365-2133.1990.tb01822.x Published: 01 July 1990
Dual Functions of the Homeoprotein DLX4 in Modulating Responsiveness of Tumor Cells to Topoisomerase II-Targeting Drugs
Authors: Bon Q. Trinh, Song Yi Ko, Nicolas Barengo, Shiaw-Yih Lin, Honami Naora
Journal: Cancer Research (2012)

Topoisomerase II (TOP2)-targeting poisons such as anthracyclines and etoposide are commonly used for cancer chemotherapy and kill tumor cells by causing accumulation of DNA double-strand breaks (DSB). Several lines of evidence indicate that overexpression of TOP2A, the gene encoding topoisomerase IIα, increases sensitivity of tumor cells to TOP2 poisons, but it is not clear why some TOP2A-overexpressing (TOP2A-High) tumors respond poorly to these drugs. In this study, we identified that TOP2A expression is induced by DLX4, a homeoprotein that is overexpressed in breast and ovarian cancers. Analysis of breast cancer datasets revealed that TOP2A-high cases that also highly expressed DLX4 responded more poorly to anthracycline-based chemotherapy than TOP2A-high cases that expressed DLX4 at low levels. Overexpression of TOP2A alone in tumor cells increased the level of DSBs induced by TOP2 poisons. In contrast, DLX4 reduced the level of TOP2 poison-induced DSBs irrespective of its induction of TOP2A. DLX4 did not stimulate homologous recombination-mediated repair of DSBs. However, DLX4 interacted with Ku proteins, stimulated DNA-dependent protein kinase activity, and increased erroneous end-joining repair of DSBs. Whereas DLX4 did not reduce levels of TOP2 poison-induced DSBs in Ku-deficient cells, DLX4 stimulated DSB repair and reduced the level of TOP2 poison-induced DSBs when Ku was reconstituted in these cells. Our findings indicate that DLX4 induces TOP2A expression but reduces sensitivity of tumor cells to TOP2 poisons by stimulating Ku-dependent repair of DSBs. These opposing activities of DLX4 could explain why some TOP2A-overexpressing tumors are not highly sensitive to TOP2 poisons.
Improvement of interinstitutional agreement on interpretation of stress echocardiograms by standardization of image display and reading criteria
Authors: H. Lethen, R. Hoffmann, T. Marwick, M. Arnese, P. Fioretti, A. Pingitore, E. Picano, T. Buck, R. Erbel, F.A. Flachskampf, P. Hanrath
Journal: Journal of the American College of Cardiology (1998)
What Happened in Laramie
Authors: Daniel S. Klein
Journal: Annals of Internal Medicine (1999)

On Being a Doctor2 February 1999What Happened in LaramieDaniel S. Klein, MDDaniel S. Klein, MDLaramie, WY 82070Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-3-199902020-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Matthew Shepard was found tied to a fence on the prairie east of Laramie, Wyoming, unconscious after a brutal beating. He died several days later without having regained consciousness.It was strange and disorienting for those of us in Laramie to be the focus of intense national publicity. For a while, we eclipsed the president and Kosovo as the top news story. News trucks were rolling down the streets, looking for people to interview. A friend from New York called to say that my wife was on national television; a crew had recorded the church service where she had sung. ... Author, Article, and Disclosure InformationAuthors: Daniel S. Klein, MDAffiliations: Laramie, WY 82070Corresponding Author: Daniel S. Klein, MD, 3116 Willet Drive, Laramie, WY 82070. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTransmission of Attitudes Toward Abortion and Gay Rights: Effects of Genes, Social Learning and Mate Selection 2 February 1999Volume 130, Issue 3Page: 235-236KeywordsCrimeEmergency departmentHomicideHuman sexual behaviorInfectious diseasesPerceptionPrevention, policy, and public healthSexual identityUndergraduatesUrban areas ePublished: 15 August 2000 Issue Published: 2 February 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Buthionine Sulfoximine Enhancement of Arsenic Trioxide-Induced Apoptosis in Leukemia and Lymphoma Cells Is Mediated via Activation of c-Jun NH2-Terminal Kinase and Up-regulation of Death Receptors
Authors: Duo Chen, Rosemarie Chan, Samuel Waxman, Yongkui Jing
Journal: Cancer Research (2006)

Abstract The mechanism of apoptosis induced by treatment with As2O3 alone or in combination with buthionine sulfoximine (BSO) was studied in NB4, U937, Namalwa, and Jurkat cells. As2O3 at concentrations &amp;lt;2 μmol/L induced apoptosis in NB4 cells and Namalwa cells but not in U937 and Jurkat cells. As2O3-induced apoptosis in NB4 cells and Namalwa cells correlated with increase of H2O2 and caspase activation without activation of c-Jun NH2-terminal kinase (JNK). BSO (10 μmol/L) depleted the reduced form of intracellular glutathione without inducing apoptosis but synergized with 1 μmol/L As2O3 to induce apoptosis in all four cell lines. This synergy correlated with JNK activation. Treatment with As2O3 plus BSO, but not with As2O3 alone, increased the levels of death receptor (DR) 5 protein and caspase-8 cleavage. The JNK inhibitor SP600125 inhibited the increase in DR5 protein and attenuated apoptosis induced by treatment with As2O3 plus BSO. These observations suggest that a DR-mediated pathway activated by JNK is involved in apoptosis induced by treatment with As2O3 plus BSO. (Cancer Res 2006; 66(23): 11416-22)
Ehlers Danlos syndrome and osteoporosis.
Authors: A A Deodhar, A D Woolf
Journal: Annals of the Rheumatic Diseases (1994)

Whereas IL-Ira can completely prevent the latter process,' blocking activation of the mature osteoclast requires simultaneous inhibition of TNF and IL-1.' It would therefore be logical to contemplate clinical trials in RA, inhibiting both of these cytokines and observing the effect on RA related osteoporosis as an end point.
Estrogenic or antiestrogenic therapies for multiple myeloma?
Authors: Brigitte Sola, Jack-Michel Renoir
Journal: Molecular Cancer (2007)

Multiple myeloma (MM) is a common hematological malignancy which remains incurable due to both intrinsic and acquired resistance to conventional or more novel drugs. Estrogenic and antiestrogenic compounds are very promising drugs for the treatment of MM. Indeed, they inhibit cell proliferation in vitro. They block cell cycle and/or induce apoptosis even in drug-resistant MM cells but not normal B cells. They interfere with survival pathways often deregulated in myelomas. They co-operate with conventional drugs to enhance apoptosis or to overcome resistance. In vivo, they act also on tumoral angiogenesis in xenograft models. As a whole, they possess all the criteria which render them attractive for a new therapeutic strategy. Importantly, they are well-tolerated at the doses tested in vitro or in vivo, encouraging the rapid onset of critical trials.
Sensitivity of Acid-Fast Staining for <i>Mycobacterium tuberculosis</i> in Formalin-fixed Tissue
Authors: Hajime Fukunaga, Tomoyuki Murakami, Toshikazu Gondo, Kazuo Sugi, Tokuhiro Ishihara
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Microscopic examination of tissue sections of mycobacterial lesions frequently results in few or no bacilli seen, even if the lesions appear active histologically. This might be due to the effects of the fixative fluid and/or organic solvent, both of which are conventionally used to make tissue sections for histopathology, on the acid-fast staining of bacteria. The present study was performed to examine how formalin and xylene lower the sensitivity of acid-fast staining for Mycobacterium tuberculosis and to clarify the meaning of the staining result in tissue sections. Microscopic observation of mycobacteria smeared on glass slides revealed that both of these agents greatly reduced the sensitivity of acid-fast staining. Moreover, the number of bacilli was calculated in 30 samples of paraffin-embedded granulomatous lesions using acid-fast microscopy and real-time polymerase chain reaction. The numbers of bacilli present that were estimated by real-time polymerase chain reaction were considerably higher than those counted with a microscope. These results suggest that the bacilli are frequently missed or underestimated with acid-fast microscopy on formalin-fixed, paraffin-embedded tissue.
The relationship between toe-out angle during gait and progression of medial tibiofemoral osteoarthritis
Authors: A. Chang, D. Hurwitz, D. Dunlop, J. Song, S. Cahue, K. Hayes, L. Sharma
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> A greater knee adduction moment increases risk of medial tibiofemoral osteoarthritis (OA) progression. Greater toe-out during gait shifts the ground reaction force vector closer to the centre of the knee, reducing the adduction moment. The present study was designed to test whether greater toe-out is associated with lower likelihood of medial OA progression. <h3>Methods:</h3> Baseline assessments included: kinematic/kinetic gait parameters using an optoelectronic camera system, force platform and inverse dynamics to calculate three-dimensional external knee moments; toe-out angle (formed by the line connecting heel strike and toe-off plantar surface centres of pressure and the forward progression line; knee pain; and full-limb alignment. Knee <i>x</i>-rays (semi-flexed) were obtained at baseline and at 18 months, with progression noted as medial joint space grade worsening. With logistic regression, odds ratios (ORs) for progression/5° toe-out were estimated. <h3>Results:</h3> In the 56 subjects (59% women, mean age 66.6 years, body mass index (BMI) 29), baseline toe-out angle was less in knees with than without progression (difference –4.4, 95% CI –8.5 to –0.3). Greater toe-out was associated with reduced likelihood of progression (OR 0.60, 95% CI 0.37 to 0.98). Adjusting for age, gender, BMI, pain severity and disease severity, the OR was 0.62, 95% CI 0.36 to 1.06. Adjusting for adduction moment (second peak), the OR was 0.72, 95% CI 0.40 to 1.28. <h3>Conclusions:</h3> Osteoarthritic knees that progressed had less toeing-out than knees without progression. Greater toe-out was associated with a lower likelihood of progression. Adjustment for covariates did not alter the OR, although the 95% CI included 1. Further adjustment for adduction moment did alter the OR, consistent with the possibility that a mechanism of the effect may be via lowering of the adduction moment.
Patient Safety in the Cardiac Operating Room: Human Factors and Teamwork
Authors: Joyce A. Wahr, Richard L. Prager, J.H. Abernathy, Elizabeth A. Martinez, Eduardo Salas, Patricia C. Seifert, Robert C. Groom, Bruce D. Spiess, Bruce E. Searles, Thoralf M. Sundt, Juan A. Sanchez, Scott A. Shappell, Michael H. Culig, Elizabeth H. Lazzara, David C. Fitzgerald, Vinod H. Thourani, Pirooz Eghtesady, John S. Ikonomidis, Michael R. England, Frank W. Sellke, Nancy A. Nussmeier
Journal: Circulation (2013)
Pierre M. Galletti: A Personal Reflection
Authors: Robert M. Nerem
Journal: Annual Review of Biomedical Engineering (2000)

[Figure: see text] ▪ Abstract Pierre Galletti, my friend and colleague, passed away on March 8, 1997, having left his mark on the emerging field of biomedical engineering. He was a pioneering researcher, making his impact in such fields as heart-lung bypass, artificial organs, and tissue engineering. He was a dedicated teacher and a mentor to many. He not only provided leadership in the establishment of the medical school at Brown University, but also helped start Morehouse School of Medicine in Atlanta. He was an entrepreneur and an individual who realized that ultimately basic science only impacts patient care when new technology is made available to the public. He served the bioengineering community in many ways, later in life becoming active in public policy, and as the second president of the American Institute for Medical and Biological Engineering, more than anyone focused this organization on its public policy role. He was the consummate biomedical engineer, a person of great vision, a man for all seasons.
A Date With Death: Management of Time-Based and Contingent Suicidal Intent
Authors: Thomas G. Gutheil, Diane Schetky
Journal: American Journal of Psychiatry (1998)

The patient who voices suicidal intent in terms of the future or in terms of certain life contingencies presents special difficulties for the therapist. The authors outline the challenges posed by this problem for assessment, clinical management, and risk management.The authors examined and analyzed case examples from both clinical and risk-management aspects.Problematic cases can be grouped into categories that offer insight as to management. The authors discuss this area and offer suggestions for appropriate clinical responses to this challenge.The authors recommend that therapists 1) treat the expressed "date with death" as a communication to be explored, 2) explore the problem of helplessness while monitoring their own countertransference responses, 3) assess the patient's competence to inform clinicians about suicidal state, and 4) readily use involuntary commitment.