tbuckley/cabot-search huggingface dataset:
Efforts Underway To Curb Drug Shortages
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (2011)

Anationwide shortage of many cancer drugs shows signs of easing, at least temporarily, according to officials at the U.S. Food and Drug Administration. But sudden shifts in drug availability remain a concern, placing cancer patients at continuing risk for harm, doctors say. “Obviously, it’s a worrisome situation because the system is so fragile,” said Peter Adamson, M.D ., chief of the division of clinical pharmacology and therapeutics at the Children’s Hospital of Philadelphia and chair of the Children’s Oncology Group. “There’s no advance warning of an impending problem and the FDA gets engaged only when a shortage begins.” In recent weeks, shortages in cytarabine injections raised the specter not just of disruptions in cancer
A profibrotic role for thymic stromal lymphopoietin in systemic sclerosis
Authors: Alicia Usategui, Gabriel Criado, Elena Izquierdo, Manuel J Del Rey, Patricia E Carreira, Pablo Ortiz, Warren J Leonard, José L Pablos
Journal: Annals of the Rheumatic Diseases (2013)

[corrected] Systemic sclerosis (SSc) is an autoimmune disease characterised by progressive fibrosis. Although SSc shares pathogenetic features with other autoimmune diseases, the participation of profibrotic Th2 cytokines is unique to SSc, but the mechanisms of Th2 skewing are unknown. We have analysed the expression and function of thymic stromal lymphopoietin (TSLP), a central regulator of Th2-mediated allergic inflammation, in human SSc, primary lung fibrosis and in a mouse model of scleroderma.TSLP expression was analysed by immunohistochemistry in human SSc skin, primary lung fibrosis and mouse bleomycin-induced skin fibrosis, and by quantitative RT-PCR in mouse skin and cultured fibroblasts. The regulation of TSLP expression by specific toll-like receptors (TLR)-2, -3 and -4 agonists was analysed in human dermal fibroblast cultures. The role of TSLP in skin fibrosis and local cytokine expression was analysed in TSLP receptor (TSLPR)-deficient mice.TSLP was overexpressed by epithelial cells, mast cells and fibroblasts in human SSc skin and lung fibrosis, and in the bleomycin model of scleroderma. In cultured human and mouse skin fibroblasts, TSLP expression was inducible by activation of TLR, particularly TLR3. In TSLPR-deficient mice, bleomycin-induced fibrosis was significantly reduced in parallel with significantly reduced local expression of IL-13.These data provide the first evidence of TSLP overexpression in SSc and other non-allergic fibrotic conditions, and demonstrate a profibrotic role that is potentially meditated by specific changes in the local cytokine milieu. Thus, modulating TSLP may have antifibrotic therapeutic implications.
Copper Binding by Tetrathiomolybdate Attenuates Angiogenesis and Tumor Cell Proliferation through the Inhibition of Superoxide Dismutase 1
Authors: Jose C. Juarez, Oscar Betancourt, Steven R. Pirie-Shepherd, Xiaojun Guan, Melissa L. Price, David E. Shaw, Andrew P. Mazar, Fernando Doñate
Journal: Clinical Cancer Research (2006)

Abstract Purpose: A second-generation tetrathiomolybdate analogue (ATN-224; choline tetrathiomolybdate), which selectively binds copper with high affinity, is currently completing two phase I clinical trials in patients with advanced solid and advanced hematologic malignancies. However, there is very little information about the mechanism of action of ATN-224 at the molecular level. Experimental Design: The effects of ATN-224 on endothelial and tumor cell growth were evaluated in cell culture experiments in vitro. The antiangiogenic activity of ATN-224 was investigated using the Matrigel plug model of angiogenesis. Results: ATN-224 inhibits superoxide dismutase 1 (SOD1) in tumor and endothelial cells. The inhibition of SOD1 leads to inhibition of endothelial cell proliferation in vitro and attenuation of angiogenesis in vivo. The inhibition of SOD1 activity in endothelial cells is dose and time dependent and leads to an increase in the steady-state levels of superoxide anions, resulting in the inhibition of extracellular signal-regulated kinase phosphorylation without apparent induction of apoptosis. In contrast, the inhibition of SOD1 in tumor cells leads to the induction of apoptosis. The effects of ATN-224 on endothelial and tumor cells could be substantially reversed using Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, a catalytic small-molecule SOD mimetic. Conclusions: These data provide a distinct molecular target for the activity of ATN-224 and provide validation for SOD1 as a target for the inhibition of angiogenesis and tumor growth.
Epidemic reactive arthritis.
Authors: C J Eastmond
Journal: Annals of the Rheumatic Diseases (1990)

Epidemic reactive arthritisReactive arthritis holds a special fascination for rheuma- tologists in view of the clear role of infection in causing an aseptic synovitis.Recent years have seen not only interest but considerable advances in knowledge of the pathogenesis of this disease.Many questions remain unanswered, however, and although most patients ultimately recover some do develop more chronic problems and we remain virtually unable to influence the sequence of events.Sporadic cases constitute the most common experience of this disease and remain a fertile ground for further investigation.The recent report of Inman et al' serves to remind us, however, that epidemics of causative infection still occasionally occur.These epidemics provide a unique opportunity to observe and study the whole spectrum of reactive arthritis and its relation with a single micro- organism.We are reminded of the overlap between reactive arthritis and Reiter's syndrome and that extra-articular features, including urethritis, may occur from gastro- intestinal infection, as occurred in Reiter's original case.2This raises the question as to whether we should continue to use the term 'Reiter's syndrome' or consider the use of reactive arthritis as an all encompassing term, qualifying it as necessary with statements as to the underlying cause,3
Paying attention to carpal tunnel contents lesions: ultrasound for evaluation of carpal tunnel syndrome
Authors: Jiaan zhu, Fang Liu
Journal: Annals of the Rheumatic Diseases (2013)

We read with great interest the report by Dejaco et al 1 related to diagnosis of carpal tunnel syndrome (CTS) by ultrasound. Dejaco et al compared ultrasound measurement of median nerve cross-sectional area (CSA) at different anatomical landmarks in great detail and evaluated the value of intranerval power Doppler signals for CTS diagnosis. It provided a good data support for the ultrasonic evaluation of CTS. However, this study prompts questions on the three following points: 

1.  CSA as an important indicator for CTS diagnosis also has limitations. We do agree that CSA is the most commonly used for evaluation of nerve swelling. …
The “spaghetti technique”: An alternative to Mohs surgery or staged surgery for problematic lentiginous melanoma (lentigo maligna and acral lentiginous melanoma)
Authors: Caroline Gaudy-Marqueste, Anne-Sophie Perchenet, Anne-Marie Taséi, Nika Madjlessi, Guy Magalon, Marie-Aleth Richard, Jean-Jacques Grob
Journal: Journal of the American Academy of Dermatology (2010)
AN EXAMINATION OF THE CYTOTOXIC EFFECTS OF SILICA ON MACROPHAGES
Authors: A. C. Allison, J. S. Harington, M. Birbeck
Journal: The Journal of Experimental Medicine (1966)

Effects of silica, diamond dust, and carrageenan on mouse macrophages were studied by phase-contrast cine-micrography, electron microscopy, histochemical techniques for lysosomal enzymes and measurements of the release of lysosomal enzymes into the culture medium. All added materials were rapidly taken up into phagosomes, to which lysosomes became attached. In all cases lysosomal enzymes were discharged into the phagosomes to form secondary lysosomes. Within 24 hr most of the silica particles and enzyme had escaped from the secondary lysosomes and lysosomal enzymes were found in the culture media. Most macrophages were killed by this time. With nontoxic particles (diamond dust, aluminium-coated silica, or silica in the presence of the protective agent polyvinyl-pyridine-N-oxide, PVPNO) ingested particles and lysosomal enzymes were retained within the secondary lysosomes for a much longer time, and cytotoxic effects were considerably delayed or absent altogether. It is concluded that silica particles are toxic because they are efficiently taken up by macrophages and can then react relatively rapidly with the membranes surrounding the secondary lysosomes. The particles and lytic enzymes can then escape into the cytoplasm, producing general damage, and thence into the culture medium. It is suggested that hydrogen bonding of silicic acid with lipid and protein constituents of the membrane accounts for the induced permeability. Protective agents such as PVPNO are retamed in lysosomes and preferentially form hydrogen bonds with silicic acid. Carrageenan is demonstrable within macrophages by its metachromatic reaction. It brings about release of enzymes from secondary lysosomes, but much more slowly than does silica. Silica released from killed macrophages is as cytotoxic as the original preparation. It is suggested that repeated cycles of macrophage killing in vivo leads to the mobilization of fibroblasts and fibrogenesis characterizing the disease silicosis.
Airway Epithelial miRNA Expression Is Altered in Asthma
Authors: Owen D. Solberg, Edwin J. Ostrin, Michael I. Love, Jeffrey C. Peng, Nirav R. Bhakta, Lydia Hou, Christine Nguyen, Margaret Solon, Cindy Nguyen, Andrea J. Barczak, Lorna T. Zlock, Denitza P. Blagev, Walter E. Finkbeiner, K. Mark Ansel, Joseph R. Arron, David J. Erle, Prescott G. Woodruff
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Changes in airway epithelial cell differentiation, driven in part by IL-13, are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation in many systems and could contribute to epithelial abnormalities in asthma.Objectives: To determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13–regulated miRNAs.Methods: We used miRNA microarrays to analyze bronchial epithelial brushings from 16 steroid-naive subjects with asthma before and after inhaled corticosteroids, 19 steroid-using subjects with asthma, and 12 healthy control subjects, and the effects of IL-13 and corticosteroids on cultured bronchial epithelial cells. We used quantitative polymerase chain reaction to confirm selected microarray results.Measurements and Main Results: Most (12 of 16) steroid-naive subjects with asthma had a markedly abnormal pattern of bronchial epithelial miRNA expression by microarray analysis. Compared with control subjects, 217 miRNAs were differentially expressed in steroid-naive subjects with asthma and 200 in steroid-using subjects with asthma (false discovery rate < 0.05). Treatment with inhaled corticosteroids had modest effects on miRNA expression in steroid-naive asthma, inducing a statistically significant (false discovery rate < 0.05) change for only nine miRNAs. qPCR analysis confirmed differential expression of 22 miRNAs that were highly differentially expressed by microarrays. IL-13 stimulation recapitulated changes in many differentially expressed miRNAs, including four members of the miR-34/449 family, and these changes in miR-34/449 family members were resistant to corticosteroids.Conclusions: Dramatic alterations of airway epithelial cell miRNA levels are a common feature of asthma. These alterations are only modestly corrected by inhaled corticosteroids. IL-13 effects may account for some of these alterations, including repression of miR-34/449 family members that have established roles in airway epithelial cell differentiation.Clinical trial registered with www.clinicaltrials.gov (NCT 00595153).
Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)
Authors: D Koeberle, D C Betticher, R von Moos, D Dietrich, P Brauchli, D Baertschi, K Matter, R Winterhalder, M Borner, S Anchisi, P Moosmann, A Kollar, P Saletti, A Roth, M Frueh, M Kueng, R A Popescu, S Schacher, V Hess, R Herrmann
Journal: Annals of Oncology (2015)
Should patients with dementia who wander be electronically tagged? No
Authors: D. O'Neill
Journal: BMJ (2013)

Technology that allows real time tracking is being pushed by authorities to cut the costs of finding patients who have got lost. <b>Rupert McShane </b>(doi:10.1136/bmj.f3603) says GPS tracking reduces risk of harm for some patients who wander and that ethical risks are slight, but <b>Desmond O'Neill</b> thinks that care must be patient centred rather than looking for quick fixes to suit carers
Urinary Podocyte Loss Is a More Specific Marker of Ongoing Glomerular Damage than Proteinuria
Authors: Donghai Yu, Arndt Petermann, Uta Kunter, Song Rong, Stuart J. Shankland, Juergen Floege
Journal: Journal of the American Society of Nephrology (2005)

Podocyte loss contributes to the development of glomerulosclerosis. Although podocyte detachment has been recognized as a new mechanism of podocyte loss in glomerular diseases, its time course and relationship to disease activity are not known. Urinary excretion of viable podocytes was quantified in two models of transient glomerular injury, i.e., rats with puromycin aminonucleoside-induced nephrosis (PAN) and mesangioproliferative nephropathy (anti-Thy 1.1 nephritis model), as well as in a model of continuous glomerular injury, i.e., hypertensive nephropathy (5/6-nephrectomy model), and in aging rats. The number of glomerular Wilm's tumor (WT)-1-positive podocytes and the glomerular expression of cell-cycle proteins in vivo were assessed. Urinary podocyte loss occurred in both primary (PAN) and secondary (anti-Thy 1.1 nephritis) in parallel to the onset of proteinuria. However, subsequently proteinuria persisted despite remission of podocyturia. In continuous glomerular injury, i.e., after 5/6-nephrectomy, podocyturia paralleled the course of proteinuria and of systemic hypertension, whereas no podocyturia became detectable during normal aging (up to 12 mo). Despite podocyte detachment of varying degrees, no decrease in glomerular podocyte counts (i.e., WT-1 positive nuclei) was noted in either disease model. Podocyturia in the PAN and anti-Thy 1.1 nephritis model was preceded by entry of glomerular podocytes into the cell cycle, i.e., cyclin D1, cdc2, and/or proliferating cell nuclear antigen (PCNA) expression. Podocyturia is a widespread phenomenon in glomerular disease and not simply a reflection of proteinuria because it is limited to phases of ongoing glomerular injury. The data suggest that podocyturia may become a more sensitive means to assess the activity of glomerular damage than proteinuria.
Definition of discontinuation of anti-tumour necrosis factor therapy in rheumatoid arthritis: a preliminary proposal
Authors: J Braun, J Sieper, D van der Heijde
Journal: Annals of the Rheumatic Diseases (2003)

Paired two tailed Student's t test used to test differences between baseline and six month follow up values for both patient groups.ESR, erythrocyte sedimentation rate (normal value 5-15 mm/1st h); CRP, C reactive protein (normal value <10 mg/l); VAS, visual analogue score; BASFI, Bath Ankylosing Spondylitis Functional Index (0-100); BASDAI, Bath Ankylosing Spondylitis Disease Activity Index (0-100).
Key findings and clinical implications from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study
Authors: Bradley E. Chipps, Robert S. Zeiger, Larry Borish, Sally E. Wenzel, Ashley Yegin, Mary Lou Hayden, Dave P. Miller, Eugene R. Bleecker, F. Estelle R. Simons, Stanley J. Szefler, Scott T. Weiss, Tmirah Haselkorn
Journal: Journal of Allergy and Clinical Immunology (2012)
A NOTE ON INJURIES TO THE FEMALE URETER
Authors: A. L. Robinson
Journal: BMJ (1921)

Gy7naecologicalCondition3.I neecl only refer again to the tllree conditions: rupture Df an ectopic gestation, actute salpinaitis, and acute septic metritis, and to say that when tlhe patient is an adult femnale one must always bear them in miind,In conclusion, geutlemen, it is a nlatter of congratula- Lion that while the cauises of an " acute abdomen " are not apparently on the wvane, tlhe gravity of the condition is becoming more and more recognized, and its early ,liagnosis, which is a matter of supreme value, arrived at in a mu.ch larger number of instances.WVe must look forward to the day wlhen all "actute abdomens" will be recognized witlhin the first few hours of their sudden onset, and surgical treatment carried out with the least possible delay.
PAX2 is activated by estradiol in breast cancer cells of the luminal subgroup selectively, to confer a low invasive phenotype
Authors: David Beauchemin, Catherine Lacombe, Céline Van Themsche
Journal: Molecular Cancer (2011)

Abstract Background Metastasis is the leading cause of death among breast cancer patients. Identifying key cellular factors controlling invasion and metastasis of breast cancer cells should pave the way to new therapeutic strategies efficiently interfering with the metastatic process. PAX2 (paired box 2) transcription factor is expressed by breast cancer cells in vivo and recently, it was shown to negatively regulate the expression of ERBB2 (erythroblastic leukemia viral oncogene homolog 2, HER-2/neu), a well-documented pro-invasive and pro-metastastic gene, in luminal/ERalpha-positive (ERα+) breast cancer cells. The objective of the present study was to investigate a putative role for PAX2 in the control of luminal breast cancer cells invasion, and to begin to characterize its regulation. Results PAX2 activity was higher in cell lines from luminal compared to non-luminal subtype, and activation of PAX2 by estradiol was selectively achieved in breast cancer cell lines of the luminal subtype. This process was blocked by ICI 182780 and could be antagonized by IGF-1. Knockdown of PAX2 in luminal MCF-7 cells completely abrogated estradiol-induced downregulation of ERBB2 and decrease of cell invasion, whereas overexpression of PAX2 in these cells enhanced estradiol effects on ERBB2 levels and cell invasion. Conclusions The study demonstrates that PAX2 activation by estradiol is selectively achieved in breast cancer cells of the luminal subtype, via ERα, and identifies IGF-1 as a negative regulator of PAX2 activity in these cells. Further, it reveals a new role for PAX2 in the maintenance of a low invasive behavior in luminal breast cancer cells upon exposure to estradiol, and shows that overexpression and activation of PAX2 in these cells is sufficient to reduce their invasive ability.
H2 receptor antagonists and prokinetics in dyspepsia: a critical review
Authors: P Bytzer
Journal: Gut (2002)

Drug treatment of patients with functional dyspepsia is controversial but H(2) receptor antagonists have been the mainstay of treatment. For patients with symptoms suggestive of dysmotility, prokinetics such as cisapride have been used. A large number of clinical trials have been unable to produce definite answers as to whether any of these treatment modalities are truly efficacious. This is partly due to the fact that the methodology and reporting of the majority of trials evaluating the symptomatic effects of H(2) receptor antagonists and cisapride are severely flawed. Based on the current literature, H(2) receptor antagonists may possibly have a therapeutic gain of approximately 20% over placebo. Evaluating the therapeutic gain of cisapride is more difficult but meta-analyses indicate a somewhat larger effect.
Significance of interleukin-13 receptor alpha 2-targeted glioblastoma therapy
Authors: B. Thaci, C. E. Brown, E. Binello, K. Werbaneth, P. Sampath, S. Sengupta
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) remains one of the most lethal primary brain tumors despite surgical and therapeutic advancements. Targeted therapies of neoplastic diseases, including GBM, have received a great deal of interest in recent years. A highly studied target of GBM is interleukin-13 receptor α chain variant 2 (IL13Rα2). Targeted therapies against IL13Rα2 in GBM include fusion chimera proteins of IL-13 and bacterial toxins, nanoparticles, and oncolytic viruses. In addition, immunotherapies have been developed using monoclonal antibodies and cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor–modified T cells. Advanced therapeutic development has led to the completion of phase I clinical trials for chimeric antigen receptor–modified T cells and phase III clinical trials for IL-13–conjugated bacterial toxin, with promising outcomes. Selective expression of IL13Rα2 on tumor cells, while absent in the surrounding normal brain tissue, has motivated continued study of IL13Rα2 as an important candidate for targeted glioma therapy. Here, we review the preclinical and clinical studies targeting IL13Rα2 in GBM and discuss new advances and promising applications.
Effects of Dipyridamole on Anastomotic Blood Flow in Experimental Myocardial Infarction
Authors: J. R. Rees, V. J. Redding
Journal: Cardiovascular Research (1967)

Using a technique of 133Xenon clearance, the effect of intravenous dipyridamole, 0·5 mg/kg body weight, on anastomotic blood flow was determined on each of 10 days following experimental myocardial infarction in the dog. There was little effect at 2 hr, but after 24 hr there was an increase in the mean clearance rate, which was greater after 48 hr, and persisted to the tenth day.
A conversation with Rudolf Jaenisch
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2015)

Rudolf Jaenisch of the Whitehead Institute at MIT is a remarkable scientist at the center of the study of epigenetics. Jaenisch (Figure 1) created the very first transgenic mice and did the first experiment showing that therapeutic cloning could correct a genetic defect. He also conducted the first proof of principle experiments with induced pluripotent stem (iPS) cells to correct sickle cell anemia and Parkinson disease in rodents. Hear more of his stories about his first scientific experiments, how to effectively mentor trainees, and his views on the ethics of stem cell use on the JCI website at http://www.jci.org/videos/cgms
Coronary atheroma regression trials
Authors: M.F. Oliver, None MAAS Steering Committee, John Elliott, Harvey White, Paul Seed, L.E. Ramsay, W.W. Yeo, P.R. Jackson, G.F. Watts, B. Lewis, J.N.H. Brunt, A.V. Swan, Sandeep Gupta, RichardJ. Frankel, MalcolmJ. Boyd
Journal: The Lancet (1992)