tbuckley/cabot-search huggingface dataset:
Abstract 1689: The cytoprotective role of the UPR during c-Myc dependent transformation and tumor progression.
Authors: Feven Tameire, Lori S. Hart, Bo Qiu, Constantinos Koumenis
Journal: Cancer Research (2013)

Abstract The Unfolded Protein Response (UPR) is a conserved cellular adaptation program that is elicited due to the accumulation of unfolded proteins in the endoplasmic reticulum (ER). The PERK-pEIF2A-ATF4 arm of UPR is triggered by ER stress and primarily serves in the global attenuation of protein translation, and promotes cell survival via selective upregulation of stress induced genes. We recently showed that oncogenic Myc activation initiates UPR due to the accumulation of unfolded proteins in the ER. Using multiple genetic models, we demonstrated that ablation of UPR signaling leads to decreased cell survival in vitro and reduced tumor growth in vivo. The proto-oncogene c-Myc has been shown to activate both pro-tumorigenic and anti-tumorigenic pathways. In c-Myc driven cancers, the pro-apoptotic state is bypassed via a yet undefined pro-survival mechanism. We are interested in elucidating the role of UPR in promoting activation of pro-survival pathways during c-Myc induced tumorigenesis. We previously demonstrated that autophagy, one such pro-survival pathway, is induced and sustained during c-Myc activation in a PERK dependent manner. Moreover, genetic and pharmacological inhibition of autophagy in c-Myc induced cells decreases cell survival. Using a Qiagen Autophagy PCR Array system we screened for autophagy genes that were differentially expressed in a c-Myc dependent manner. Preliminary results indicate that several genes that regulate different steps of autophagy such as ATG9b, ATG5 and ATG16L1 are upregulated upon c-Myc induction, which was validated by qPCR. In PERK-/- MEFs, ATG5 and ATG16L1 were not upregulated and LC3B processing, a marker of autophagy induction, was significantly attenuated upon c-Myc activation. This indicates that PERK is required for the induction of autophagy genes upon c-Myc activation. To further investigate the role of the PERK-pEIF2A-ATF4 arm of UPR in cell survival during c-Myc induction, we looked at the transcription factor ATF4 which is a major downstream mediator of PERK. Using ATF4-/- MEFs, we observed significant cell death and decreased clonogenic survival upon c-Myc activation compared to ATF4+/+ MEFs. We are currently investigating how ATF4 is mediating cell survival during c-Myc induction. Our findings establish that UPR plays as an activator of pro-survival pathways such as autophagy and therefore UPR can be targeted as a therapy modality in c-Myc driven cancers. This research is supported by NIH grant 5R01CA139362-04 Citation Format: Feven Tameire, Lori S. Hart, Bo Qiu, Constantinos Koumenis. The cytoprotective role of the UPR during c-Myc dependent transformation and tumor progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1689. doi:10.1158/1538-7445.AM2013-1689
Effect of long term treatment with oxitropium bromide on airway secretion in chronic bronchitis and diffuse panbronchiolitis.
Authors: J Tamaoki, A Chiyotani, E Tagaya, N Sakai, K Konno
Journal: Thorax (1994)

BACKGROUND--Anticholinergic bronchodilator drugs improve lung function in chronic bronchitis but less is known of their effects on the volume and physical properties of sputum in conditions associated with excessive airway secretions. This study examines the effects of the regular use of oxitropium bromide in such patients. METHODS--The study was conducted in a parallel, double blind, placebo controlled fashion. Patients were divided into two groups: the first group (n = 17) received oxitropium bromide from a metered dose inhaler (two puffs three times daily; 100 micrograms/puff) for eight weeks, and the second group (n = 16) received placebo. Lung function was measured as forced expiratory volume in one second (FEV1) and vital capacity. In evaluating airway secretion, daily amount of expectorated sputum, percentage solid composition, viscoelastic properties including elastic modulus and dynamic viscosity, and sputum microbiology were determined. RESULTS--Oxitropium bromide increased FEV1 and decreased the mean (SE) sputum production from 61(4) to 42(3) g/day after treatment, whereas placebo had no effect. Bacterial density and sputum flora were unchanged, but solid composition and elastic modulus increased from 2.52(0.43)% to 3.12(0.34)%, and 68(12) dyne/cm2, respectively, in the group taking oxitropium bromide. CONCLUSIONS--Regular treatment with oxitropium bromide not only improves airflow limitation but also reduces sputum production, probably through the inhibition of both mucus secretion and water transport, the latter component being predominant.
Curzio's Case of Scleroderma
Authors: I. CAPUSAN
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 January 1972Curzio's Case of SclerodermaI. CAPUSAN, M.D.I. CAPUSAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-1-146_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Drs. Rodnan and Benedek, in their article, published in 1962 (1), consider, together with others, that the first convincing description of scleroderma is found in the monograph written in Italian by Dr. Carlo Curzio and printed in Naples in 1753.In my recently published review (2) of the problem of the authenticity of this case, I have concluded that it was not a case of progressive (systemic) sclerosis, but a case of Buschke's scleredema. The arguments for this opinion are:1. The disease developed at first at the level of the neck, extending to the face, arms,...References1. RODNAN G and BENEDEK T: An historical account of the study of progressive systemic sclerosis (diffuse scleroderma). Ann Intern Med 57:305-319, 1962 LinkGoogle Scholar2. CAPUSAN I: Sclérodermie ou scléroedème? Commentaires à propos du cas publié en 1753 par le Dr. C. Curzio de Naples. Minerva Derm 46:43-47, 1971 Google Scholar3. BUSCHKE A: Über das Sklerödem und seine Beziehung zur Sklerodermie. Derm Wschr 70:17, 1920 Google Scholar4. WOLTERS M: Beitrag zur Kenntnis der Sklerodermie. Arch Derm Syph (Berlin) 24:692, 1892 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: I. CAPUSAN, M.D.Affiliations: Clinic of Dermatology Cluj Romania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFibrotic diseasesThe development of systemic sclerosis classification criteriaScleroderma and scleroderma-like disordersSclerodermaBIBLIOGRAPHY OF SECONDARY SOURCES ON THE HISTORY OF DERMATOLOGY.Scleroderma in the childSignorina Galieri's Scleroderma or ScleredemaGERALD P. RODNAN, M.D. 1 January 1972Volume 76, Issue 1 Page: 146-146 Keywords Scleroderma ePublished: 1 December 2008 Issue Published: 1 January 1972 PDF downloadLoading ...
The 1170 A–P single-nucleotide polymorphism (SNP) in the Her-2/neu protein (HER2) as a minor histocompatibility antigen (mHag)
Authors: L Wenandy, T Kollgaard, A Letsch, R S Andersen, D Stather, T Seremet, I M Svane, L Vindeløv, M H Andersen, P thor Straten
Journal: Leukemia (2009)
Formyl peptide-induced chemotaxis of human polymorphonuclear leukocytes does not require either marked changes in cytosolic calcium or specific granule discharge. Role of formyl peptide receptor reexpression (or recycling).
Authors: H D Perez, F Elfman, S Marder, E Lobo, H E Ives
Journal: Journal of Clinical Investigation (1989)

We examined the role of intracellular and extracellular calcium on the ability of human polymorphonuclear leukocytes to migrate chemotactically and reexpress (or recycle) formyl peptide receptors when challenged with the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). Extracellular calcium was not required for either optimal chemotactic responses or receptor reexpression. Depletion and chelation of intracellular calcium resulted in significant diminution in the ability of polymorphonuclear leukocytes to release the specific granule constituents lactoferrin and vitamin B12-binding protein during the process of chemotaxis, but had no effect on the capability of these cells to respond chemotactically. Similarly, chelation of intracellular calcium did not affect the ability of these cells to reexpress a population of formyl peptide receptors. Inhibition of receptor reexpression, by a nonagglutinating derivative of wheat-germ agglutinin, was associated with inhibition of chemotactic responses to FMLP. Thus, it appears that large changes in cytosolic free calcium are not necessary for formyl peptide-induced polymorphonuclear leukocyte chemotaxis. In contrast, continuous reexpression (or recycling) of formyl peptide receptors is required for polymorphonuclear leukocyte chemotactic responses to FMLP, a process that appears to be independent from specific granule fusion with plasma membrane.
Tumour necrosis factor-related apoptosis-inducing ligand is a novel therapeutic target in pulmonary arterial hypertension
Authors: Abdul G Hameed, Nadine D Arnold, Janet Chamberlain, Josephine A Pickworth, Claudia Paiva, Sarah Dawson, Simon Cross, Lu Long, Lan Zhao, Nicholas W Morrell, David C Crossman, Christopher MH Newman, David G Kiely, Sheila E Francis, Allan Lawrie
Journal: The Lancet (2013)
England's NHS faces a funding crisis, report says
Authors: N. Hawkes
Journal: BMJ (2014)

The NHS in England faces a funding crisis this year or the next, as it runs out of easy ways to save money and service transformation remains a distant prospect, the think tank the Nuffield Trust has concluded in a new report.1

Charged with making efficiency savings of 4% a year to balance the books, commissioners and NHS trusts are missing the target by a growing margin, making smaller and smaller savings each year. In 2013-14 clinical commissioning groups made savings of less than 2% of their total spending, while NHS foundation trusts achieved 3%. Although numbers of permanent staff have been cut, spending on agency staff to fill the gaps has risen swiftly enough to swallow any savings. In 2013-14 foundation trusts’ spending on agency staff rose 27%, …
The Shaping of a Polyvalent and Highly Individual T-Cell Repertoire in the Bone Marrow of Breast Cancer Patients
Authors: Nora Sommerfeldt, Florian Schütz, Christoph Sohn, Joanna Förster, Volker Schirrmacher, Philipp Beckhove
Journal: Cancer Research (2006)

Abstract We analyzed the T-cell repertoires from the bone marrow of 39 primary operated breast cancer patients and 11 healthy female donors for the presence and frequencies of spontaneously induced effector/memory T lymphocytes with peptide-HLA-A2-restricted reactivity against 10 breast tumor-associated antigens (TAA) and 3 normal breast tissue–associated antigens by short-term IFN-γ enzyme-linked immunospot (ELISpot) analysis. Sixty-seven percent of the patients recognized TAAs with a mean frequency of 144 TAA reactive cells per 106 T cells. These patients recognized simultaneously an average of 47% of the tested TAAs. The T-cell repertoire was highly polyvalent and exhibited pronounced interindividual differences in the pattern of TAAs recognized by each patient. Strong differences of reactivity were noticed between TAAs, ranging from 100% recognition of prostate-specific antigenp141-149 to only 25% recognition of MUC1p12-20 or Her-2/neup369-377. In comparison with TAAs, reactivity to normal breast tissue–associated antigens was lower with respect to the proportions of responding patients (30%) and recognized antigens (27%), with a mean frequency of only 85/106 T cells. Healthy individuals also contained TAA-reactive T cells but this repertoire was more restricted and the frequencies were in the same range as T cells reacting to normal breast tissue–associated antigens. Our data show a highly individual T-cell repertoire for recognition of TAAs in breast cancer patients. This has potential relevance for T-cell immune diagnostics, for tumor vaccine design, and for predicting immune responsiveness. (Cancer Res 2006; 66(16): 8258-65)
856. Transduction Patterns, Enzyme Distribution, and Vector and Enzyme Transport Resulting from Unilateral Injections of AAV 7, 8, 9, or Rh10 Expressing β-Glucuronidase into Select Brain Regions of the C3H Mouse
Authors: Cassia N. Cearley, John H. Wolfe.
Journal: Molecular Therapy (2005)

AAV type 2 vector genome can be cross-packaged into multiple AAV serotypes. Our lab and others have shown that this can take advantage of the tissue tropisms of the different capsid proteins used. AAV serotypes 7, 8, 9, and Rh 10 are recently discovered serotypes from the rhesus monkey. We injected AAV vectors expressing the lysosomal enzyme |[beta]|-glucuronidase and containing capsid proteins from each of these serotypes into the brains of normal C3H mice. When injected into the brain, each serotype showed remarkably different transduction patterns and resulting enzyme spread at 2 months post-injection. AAV 9, when injected unilaterally into the hippocampus, showed vector transport to the hippocampus on the opposite side. Rh 10 showed the greatest amount of enzyme transport throughout the brain, and when injected into the thalamus, showed vector transport to other thalamic nuclei, not seen with other AAV serotypes. Injections of AAV 8 led to much less vector and enzyme transport than seen with other serotypes, suggesting that this serotype is not as specific for receptors found within the brain. The brains will be evaluated for vector and enzyme spread to specific cell types such as neurons and astrocytes using NSE and GFAP respectively. Mutant MPS VII mice will also be injected to determine if the widespread enzymatic correction results in widespread lysosomal storage correction. This information on the different AAV serotypes can be used for targeted transduction and for widespread correction in a variety of mouse lysosomal storage disease models with a neurological component.
FRI0319 Levels of IL-1β and MMP-3 are increased in the synovial fluid from knee osteoarthritis (OA) in patients with concomitant erosive hand OA
Authors: R. Ramonda, F. Oliviero, A. Scanu, C. Campana, M. Lorenzin, V. Modesti, P. Frallonardo, L. Punzi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Erosive osteoarthritis of the hand (EHOA) is believed to be a subset of HOA targeting interphalangeal (IP) joints and characterised by an abrupt onset, marked pain and functional impairment, inflammatory symptoms and signs, and a worse outcome than non-erosive HOA. Despite these characteristic features, it is still unclear if erosions are found only in predisposed patients or are a consequence of an inflammatory phase occurring in any patient with HOA. Some studies suggest that patients with EHOA share HLA or non-HLA genetic predisposition, in particular associated with a genomic region containing the interleukin (IL)-1β 5810 single nucleotide polymorphism. This would support the hypothesis the IL-1 has a role in the pathogenesis of this severe phenotype of HOA. <h3>Objectives</h3> This study was designed to assess the hypothesis that patients with EHOA share a different phenotype from those with non-EHOA. Thus, we investigated if synovial fluid (SF) levels of proinflammatory interleukin (IL)s and metalloproteinase (MMP)-3 from patients with knee OA presenting a concomitant EHOA were different from those with non-EHOA. <h3>Methods</h3> In consecutive patients with knee effusions due to OA (ACR criteria), SF was aspirated and subsequently analysed for the presence of crystals and leukocyte (WBC) counts; the remaining SF was stored at -80°C. Patients with crystals of any type and with other concomitant known arthropathies were excluded from the study. Thus, a total of 100 patients were enrolled and underwent hand X-rays which were subsequently examined for the presence of subchondral erosions in the interphalangeal joints. In all SF from patients with erosions of the hand and in 20 consecutive patients without erosions, levels of IL-1β, IL-6, IL-8 and MMP-3 were determined. Statistical analysis was performed with the Mann- Whitney nonparametric test and the Spearman test for correlations. <h3>Results</h3> Sixteen out of 100 patients (16%, 11 females, mean age 61.69±7.14), with knee OA had at least one erosion according to X-rays. Serum MMP- 3 levels were higher in EHOA patients with respect to non-EHOA (15.63±3.46 ng/ml vs 10.81±1.71 ng/ml) and the MMP-3 levels were correlated with disease duration (p&lt;0.05; r=0.38) only in the EHOA patients. Significant correlation was found in cytokine levels, particularly in IL-1β (p&lt;0.0001; r=0.91), IL-6 (p&lt;0.05; r=0.53), MMP-3 (p=0.0006; r=0.76) in EHOA patients <h3>Conclusions</h3> High levels of cytokines, only in Knee OA patients with EHOA, could suggest that this particular form of OA have a genetic predisposition for the disease and these patients may present a more severe form of general OA <h3>Disclosure of Interest</h3> None Declared
Evolution of Glomerular Filtration Rate in Proteinuric NIDDM Patients
Authors: Rogério Friedman, Jorge .L Gross
Journal: Diabetes Care (1991)

Objective To evaluate, by means of a precise method, the rate of decline of glomerular filtration rate in proteinuric non-insulin-dependent diabetic (NIDDM) patients. Research Degisn and Methods The study was comprised of seven NIDDM patients who visited an outpatient clinic and had a 24-h urinary protein excretion rate ≥500 mg in the absence of heart failure, urinary tract infection, or other nephropathies. Results Glomerular filtration rate (51Cr-labeled EDTA, single-injection protocol) and 24-h proteinuria (turbidimetric method) were assessed at periodic intervals (2–6 mo). Correlation of the measurements with time (Pearson's r, with Student's t test used to assess the significance, α = 0.05) was used to evaluate the trend of evolution of glomerular filtration rate. Renal biopsies were performed in four patients. In three of four patients, renal histopathology was consistent with the diagnosis of diabetic nephropathy (in the 4th patient measurements were not satisfactory). Neither glomerular filtration rate nor proteinuria correlated significantly with time, except in one patient who had multiple myeloma. Conclusions The decline of glomerular filtration rate in proteinuric NIDDM patients is different from that observed in insulin-dependent diabetic patients, which is probably much slower.
Zimran A, Brill-Almon E, Chertkoff R, et al. Pivotal trial with plant cell–expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood. 2011;118(22):5767–5773.
Authors: Ari Zimran, Einat Brill-Almon, Raul Chertkoff, Milan Petakov, Francisco Blanco-Favela, Eduardo Terreros Muñoz, Sergio E. Solorio-Meza, Dominick Amato, Gloria Duran, Fiorina Giona, Rene Heitner, Hanna Rosenbaum, Pilar Giraldo, Atul Mehta, Glen Park, Mici Phillips, Deborah Elstein, Gheona Altarescu, Mali Szleifer, Sharon Hashmueli, David Aviezer
Journal: Blood (2012)
Genetic Ablation of V2a Ipsilateral Interneurons Disrupts Left-Right Locomotor Coordination in Mammalian Spinal Cord
Authors: Steven A. Crone, Katharina A. Quinlan, Laskaro Zagoraiou, Steven Droho, Carlos Ernesto Restrepo, Line Lundfald, Toshiaki Endo, Jennifer Setlak, Thomas M. Jessell, Ole Kiehn, Kamal Sharma
Journal: Neuron (2008)
THE DEGENERATE TONSIL.
Authors: EDWIN PYNCHON
Journal: JAMA (1903)

Ablation of hypertrophied tonsils is a procedure which has become generally indorsed by the profession of medicine, though in earlier years its advocates were less numerous and many sturdy opponents contended that the proper course to pursue was to patiently await Nature's cure by absorption or, as most often worded, until the patient would outgrow the trouble. It is not strange, when even physicians indorsed such practice, that patients easily became converted thereto, particularly as the natural tendency is toward procrastination in matters pertaining to health. Eventually some of the more pronounced evil results due to enlarged tonsils became so patent that procrastination was forced to give way to operative treatment, though many of the lesser evils due to this cause, not being thus recognized, were neglected, and the patient later became a serious sufferer thereby. Through the so-called process of absorption different results and structural formations follow in different
Infrequently Encountered Pseudomonas Species Causing Infection in Humans
Authors: GERALD L. GILARDI
Journal: Annals of Internal Medicine (1972)

Although many nonfermentative, Gram-negative bacteria of the genus Pseudomonas are saprophytes and contaminate human clinical specimens, it has become increasingly apparent that these microorganisms may also serve as pathogens under certain conditions. The clinical significance and antimicrobial susceptibilities of infrequently encountered Pseudomonas species, identified according to current schemata, are examined. Seventeen cases are cited in which strains of P. putida, P. fluorescens, P. cepacia, P. pseudoalcaligenes, P. putrefaciens, P. stutzeri, and P. maltophilia were isolated in pure culture and were judged to be responsible for the infectious process. Some of these species were highly resistant to antibiotics, and there was no single antibiotic to which all species were susceptible.
On Internal Urethrotomy
Authors: W. F. Teevan
Journal: BMJ (1878)

36Istrictures in highly irritable urethrse, which admitted the passage of a No. 4 and No. 6 catheter respectively, but resented further dilatation, which always set up constitutional disturbance.One case was admitted with complete retention; and hot bath, chloroform, opiate enemata, and the evacuation of the bladder by the aspirator, having failed to ob-
Familial aortic dissection/aneurysm associated with patent ductus arteriosus: a new entity?
Authors: Philippe Khau Van Kien, Alain Lalande, Caroline Bonnet, Arnaud Dellinger, Annie Petit, Anne Nivelon-Chevallier, François Brunotte, Xavier Jeunemaitre, Jean-Eric Wolf
Journal: Journal of the American College of Cardiology (2002)
Birth Control by The FDA
Authors: G. G. Liddle
Journal: JAMA (1970)

<h3>To the Editor.—</h3> News has just arrived that the Commissioner of the Food and Drug Administration has proposed that manufacturers of birth control pills may be forced to enclose in each package of pills a lengthy warning about the hazards of their use. There are three things wrong with his proposal: Because of news coverage of Senator Nelson's hearings on the oral contraceptives, women have already been warned of risks. As a result, thousands are said to have stopped taking the pills, and some unwanted pregnancies have been reported. Some women of lively imagination who have never had any trouble while taking the pills, when they read the proposed "What You Should Know About Birth Control Pills," are going to develop one or more of the following: mental depression, swelling, headaches, nervousness, dizziness, fatigue, backache, changes in appetite and sex drive, pain when urinating, nausea and vomiting, or