tbuckley/cabot-search huggingface dataset:
Reversal of Tumor Immune Inhibition Using a Chimeric Cytokine Receptor
Authors: Ann M Leen, Sujita Sukumaran, Norihiro Watanabe, Somala Mohammed, Jacqueline Keirnan, Ryu Yanagisawa, Usanarat Anurathapan, David Rendon, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, Juan F Vera
Journal: Molecular Therapy (2014)

The success of adoptively transferred tumor-directed T cells requires them to survive and expand in vivo. Most tumors, however, employ immune evasion mechanisms, including the production of inhibitory cytokines that limit in vivo T-cell persistence and effector function. To protect tumor-directed T cells from such negative influences, we generated a chimeric cytokine receptor in which the interleukin (IL) 4 receptor exodomain was fused to the IL7 receptor endodomain. We thereby inverted the effects of tumor-derived IL4 so that the proliferation and activation of tumor directed cytotoxic T cells was enhanced rather than inhibited in the tumor microenvironment, resulting in superior antitumor activity. These transgenic T cells were only activated in the tumor environment since triggering required exposure to both tumor antigen (signal 1) and tumor-derived IL4 (signal 2). This selectivity supports future clinical adaptation. The success of adoptively transferred tumor-directed T cells requires them to survive and expand in vivo. Most tumors, however, employ immune evasion mechanisms, including the production of inhibitory cytokines that limit in vivo T-cell persistence and effector function. To protect tumor-directed T cells from such negative influences, we generated a chimeric cytokine receptor in which the interleukin (IL) 4 receptor exodomain was fused to the IL7 receptor endodomain. We thereby inverted the effects of tumor-derived IL4 so that the proliferation and activation of tumor directed cytotoxic T cells was enhanced rather than inhibited in the tumor microenvironment, resulting in superior antitumor activity. These transgenic T cells were only activated in the tumor environment since triggering required exposure to both tumor antigen (signal 1) and tumor-derived IL4 (signal 2). This selectivity supports future clinical adaptation.
The Democratization of the Oncogene
Authors: Anh T. Le, Robert C. Doebele
Journal: Cancer Discovery (2014)

The identification of novel, oncogenic gene rearrangements in inflammatory myofibroblastic tumor demonstrates the potential of next-generation sequencing (NGS) platforms for the detection of therapeutically relevant oncogenes across multiple tumor types, but raises significant questions relating to the investigation of targeted therapies in this new era of widespread NGS testing.
TCT-732 Paraoxonase 1 Gene Polymorphism Does Not Affect Clopidogrel Response Variability But Is Associated with Clinical Outcome After Percutaneous Coronary Intervention
Authors: Jin Joo Park, Kyung Woo Park, Jeehoon Kang, Ki-Hyun Jeon, Si-Hyuck Kang, Jung-Kyu Han, Sang Eun Lee, Han-Mo Yang, Hae-Young Lee, Hyun-Jae Kang, Bon-Kwon Koo, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2012)
Sleep Apnea Is Associated with Subclinical Myocardial Injury in the Community. The ARIC-SHHS Study
Authors: Gabriela Querejeta Roca, Susan Redline, Naresh Punjabi, Brian Claggett, Christie M. Ballantyne, Scott D. Solomon, Amil M. Shah
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality, although the underlying mechanisms are not well understood.Objectives: We aimed to determine whether more severe OSA, measured by the Respiratory Disturbance Index (RDI), is associated with subclinical myocardial injury and increased myocardial wall stress.Methods: A total of 1,645 participants (62.5 ± 5.5 yr and 54% women) free of coronary heart disease and heart failure and participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies underwent overnight polysomnography and measurement of high-sensitivity troponin T (hs-TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP).Measurements and Main Results: OSA severity was defined using conventional clinical categories: none (RDI ≤ 5), mild (RDI 5–15), moderate (RDI 15–30), and severe (RDI > 30). Hs-TnT, but not NT-proBNP, was associated with OSA after adjusting for 17 potential confounders (P = 0.02). Over a median of 12.4 (interquartile range, 11.6–13.1) years follow-up, hs-TnT was related to risk of death or incident heart failure in all OSA categories (P ≤ 0.05 in each category).Conclusions: In middle-aged to older individuals, OSA severity is independently associated with higher levels of hs-TnT, suggesting that subclinical myocardial injury may play a role in the association between OSA and risk of heart failure. OSA was not associated with NT-proBNP levels after adjusting for multiple possible confounders.
Weir's Guide to Medical Museums in Britain
Authors: A. Paton
Journal: BMJ (1994)

Sue Weir Royal Society of Medicine, pounds sterling 10, pp 239 ISBN 1-85315-206-4

Asked to recommend places of medical interest open to the public, most doctors would be hard put to name more than a handful: the Chelsea Physic Garden, the old operating theatre near Guy's, the former naval hospital at Netley on the Solent perhaps. They will be astonished to learn that Sue Weir--nurse; qualified London tourist guide; and wife of an ear, nose, and throat …
Hemoglobin O Arab in Four Negro Families and Its Interaction with Hemoglobin S and Hemoglobin C
Authors: Paul F. Milner, Colin Miller, Robert Grey, Michael Seakins, Wilfried W. DeJong, L. N. Went
Journal: New England Journal of Medicine (1970)

Abstract Hemoglobin O Arab (α2β2 121 Glu → Lys) was found in 25 members of four apparently unrelated Negro families in the West Indian island of Jamaica. In each family the propositus had Hb SO disease. Two cases had been mistakenly diagnosed as Hb SC disease. Two persons heterozygous for both Hb C and Hb O Arab were found in these families, and Hb O Arab β thalassemia in one other relative. The clinical course and symptomatology of Hb SO disease is comparable to that in Hb SD (α2β2 121 Glu → GluNH2) disease and more severe than Hb SC disease. In vitro mixtures of Hb O Arab and Hb S change from a liquid to a gel phase at total hemoglobin concentrations weaker than those required to gel pure Hb S, whereas mixtures of Hb S with Hb A or Hb C require a stronger total hemoglobin concentration before gelling will occur. Oxygen dissociation studies on red cells containing Hb SO show a lowered oxygen affinity comparable to that found in homozygous sickle-cell anemia and outside the range for subjects with sickle-...
Alternate-Day Steroid Therapy in Lupus Nephritis
Authors: GEORGE L. ACKERMAN
Journal: Annals of Internal Medicine (1970)

Six patients with lupus nephritis were treated with a program of alternate-day steroid therapy using doses of 100 or 120 mg of prednisone every other day. Five of the patients had lupus glomerulonephritis; one had lupus glomerulitis. After 6 to 8 months of treatment there was histologic evidence of improvement of the renal lesion in all of the patients. During this time renal function improved in five patients. In one patient with severe lupus glomerulonephritis, creatinine clearance decreased by 30% early in treatment and then become stable. Improvement and stabilization of renal function were maintained after the steroid dosage was subsequently reduced. Beta1C globulin levels were normal after treatment in all of the patients. High-dose steroid therapy given in this way was tolerated very well. The patients remained free of Cushingoid changes and displayed a striking appearance of good health and well-being.
PNEUMONIA MIGRANS INVOLVING THE WHOLE OF BOTH LUNGS, FOLLOWED BY EMPYEMA: RECOVERY
Authors: J. Bannerman
Journal: BMJ (1909)

NITROUS OXIDE. [ TIM BRTIS 201 as to formulate this into a so-called "law," "a positive reaction denotes active syphilis."As a general statement, however, this cannot be correct.Tabes and general paralysis can scarcely be described as active syphilis, yet, as we have seen, the serum in these diseases gives a positive reaction in 70 to 90 per cent. of cases.In the spinal fluid it may be held even to be injurious rather than beneficial, since it has a definite affinity for so important a constituent of normal nervous tissue as lecithin.Further, its occurrence in the serum and spinal fluid of general paralysis and tabes, while it adds another argument to the clinical evidence connecting these diseases with syphilis, in no sense proves that connexion incontestablv.We have pleasure in thanking Dr. Mott for the interest he has taken in our work, and the assistance he has ren- dered us throughout.We also acknowledge with pleasure
1.58 rheumatoid factor binding is influenced by the N-Glycans of their IGG targets
Authors: I Magorivska, I Jeremic, S Herman, L E Munoz, R Bilyy, M Herrmann
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> In autoimmune conditions, like rheumatoid arthritis (RA), the own immune system attacks the body and causes inflammation. One of the consequences of inflammation during autoimmune diseases is a changed glycosylation profile of IgG antibodies. RA is not only characterised by an altered N-glycan structure bound to the Fc portion of IgG molecules but also by circulating rheumatoid factors (RF) that recognizes the Fc portion of IgG as antigen. The aim of our work was to investigate the glycosylation of immune complexes circulating in the blood of patients with seropositive and seronegative RA. <h3>Material and Methods</h3> Sera from 70 patients with RA (RF positive n = 43 and RF negative n = 27) and 8 healthy donors (control) have been used in the analysis. (I) Random serum IgG-complexes were captured with F(ab')<sub>2</sub> fragments of anti-human-IgG and analysed by ELISA for their interaction with anti-human-IgG, anti-human-IgM, AAL lectin (fucose-specific) and LCA lectin (manose-specific). (II) The IgG complexes eluted from the ELISA-plates were analysed by Western Blots for the presence of IgG, IgM and AAL as well as LCA binding. (III) IgG affinity purified with AAL-, SNA- and jacalin-agarose columns was tested by ELISA as target for IgM rheumatoid factor. <h3>Results</h3> (I) The accessibility of fucose residues for the AAL lectin of circulating IgG complexes was much higher in patients with RA when compared to healthy donors. This reactivity was independent of the presence of IgM-RF. The accessibility of mannose residues for the LCA lectin of circulating IgG complexes was much higher in patients with RA when compared to healthy donors. This reactivity was only to be observed in the presence of IgM-RF. (II) Western Blot confirmed an increased presence of IgM in IgG complexes from seropositive patients with RA. The fucosylation of IgG did not differ much between all groups. (III) No difference was detected in IgM-RF affinity towards positive and negative fractions of AAL- and SNA-reactive IgG. However, IgM-RF displayed a reduced binding to the minor IgG fraction isolated with jacalin-affinity chromatography. <h3>Conclusion</h3> In not-denatured IgG circulating in patients with RA the glycan shows a lower accessibility for the fucose-specific AAL lectin, independent of the presence of IgM-RF. In contrast, the increased binding of the LCA lectin is due to the presence of IgM complexed to IgG. IgM-RF did not discriminate between IgG reactive with AAL and SNA lectin. AAL – Aleuria aurantia <i><b>lectin</b></i> (α-1,6 core fucose) LCA – Lens culimaris agglutinin (α-mannose) SNA - Sambucus nigra agglutinin (α-2,6-sialic acid)
TB in Migrant Farmworkers-Reply
Authors: Stephen Ciesielski
Journal: JAMA (1994)

In Reply.  —Dr Richard's work in Ohio is a valuable contribution to the surveillance of TB among migrant farmworkers. The 11% prevalence of purified protein derivative positivity he reports is surprisingly low. Other studies and surveys have reported positivity rates three to five times higher. 1,2 It would have been interesting to know the demographic profile of those tested. In the only population-based study 3 using a random sample of migrant farmworkers, among African Americans, we found a purified protein derivative positivity rate of more than 50% and a prevalence of active disease more than 300 times the national average.  I agree completely with Dr Richard's conclusion that a national computerized database for migrant farmworkers is needed. The National Migrant Resource Project in Austin, Tex, had been developing plans for such a system, but there has been no funding available for this purpose. I suggest that the Centers for Disease
Visit to Havenwyck Hospital
Authors: William Palmer
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Handbook of Operative Urological Surgery
Authors: Duncan E. Govan
Journal: JAMA (1964)

The authors present a short, concise summation of the operative techniques of genitourinary surgery, together with brief accounts of the theory of the operations and their practical management. In the preface to the edition, the authors have stated their object in presenting a short book which may well be of value to senior students and those taking higher examinations in surgery, as well as surgeons without special urological training. There is no question that this text fits that purpose admirably, as it deals with almost all aspects of urological surgery in a concise, clear manner. Quite obviously, the very nature of the book has precluded much theory; rather, the volume has dealt almost entirely with the practical aspects of operative surgery, presenting a sufficient amount of didactic theory to aid the uninitiated in a proper appreciation of the problems. The drawings and photographs are quite superb. This fact, coupled with
Foreign Programs of Medical Care and Their Lessons
Authors: Franz Goldmann
Journal: New England Journal of Medicine (1946)

IT IS a simple matter to state that complete medical care of the finest type is wanted for the greatest possible number of people at the least possible expense, but it is a Herculean task to translate such a need into a practical and workable plan. In the course of some sixty years, various types of medical-care programs have been tried out in a score of foreign countries. There is a wealth of experience regarding the relative merits of the basic methods of organizing and administering programs for the care of the sick. Some of the fundamental principles introduced late . . .
Abstract 2638: Association between Adriamycin-induced autophagy and senescence in breast cancer cells
Authors: Xu Di, Molly L. Bristol, Kristoffer Valerie, Amy J. Hawkins, David A. Gewirtz
Journal: Cancer Research (2011)

Abstract Previous studies from this laboratory demonstrated that the topoisomerase II poison, Doxorubicin, at a clinically relevant concentration of 1µM, induced a pronounced senescence response in breast cancer cells. Doxorubicin was also observed to generate a time-dependent increase of autophagy within 72 hrs by multiple approaches, including acridine orange staining (AOS), downregulation of p62 (indicative of autophagic flux), LC3 puncta formation and electron microscopy. The current studies were designed to investigate the potential relationship between senescence and autophagy in response to Doxorubicin in breast cancer cells. Silencing of ATM by the pharmacological inhibitors, caffeine or KU55933, or by small interfering RNA abrogated doxorubicin-induced senescence, as demonstrated by decreased β -galactosidase staining as well as down-regulation of p21 expression. At the same time, silencing/attenuation of ATM suppressed autophagy, based on decreased conversion of LC3-I to LC3-II by Western blotting, and reduced acridine orange staining. Free radicals are well-established to induce senescence, and Doxorubicin-induced senescence has been shown to be associated with free radical generation. We demonstrate that the antioxidants, glutathione (GSH) or N-acetyl cysteine (NAC), were able to collaterally suppress Doxorubicin-induced senescence and autophagy, based on reduced β-Gal staining, LC3-I to II conversion and activation of ATG5, respectively. Similarly, both senescence and autophagy induced by the topoisomerase I inhibitor, camptothecin, were suppressed by GSH or NAC. Silencing of p53 or p21 expression inhibited both Doxorubicin-induced senescence and autophagy in both breast and colon cancer cells. In contrast, a blockade of autophagy either by the pharmacological inhibitors, 3-methyl adenine or chloroquine, or genetic silencing of ATG5 or ATG7 expression, only served to delay the onset of Doxorubicin-induced senescence. Similarly, a delayed senescence response was observed when autophagy induced by camptothecin or H2O2 was blocked by chloroquine or bafilomycin in MCF-7 cells. Our studies suggest that: 1. Free radicals, ATM, p53 and p21 are involved in the signaling pathways that promote the autophagic and senescence responses to chemotherapeutic agents; 2. autophagy acts to accelerate senescence; and 3) while chemotherapy induced autophagy and senescence are closely associated, senescence can likely occur in the absence of autophagy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2638. doi:10.1158/1538-7445.AM2011-2638
Doctors call for new inquest into death of UN weapons inspector David Kelly
Authors: C. Dyer
Journal: BMJ (2011)

Doctors who question how the UK government scientist and United Nations weapons inspector David Kelly met his death have filed papers at the High Court in London seeking a judicial review of the decision by the attorney general for England and Wales, Dominic Grieve, not to allow a new inquest.

Dr Kelly, who was a weapons inspector in Iraq, was …
A Paper on FOOD AND GOITRE
Authors: R. Mccarrison
Journal: BMJ (1933)

A Paper of fats and sugars.As is well known, a meat diet is A P a p e r , .harmful in Graves's disease -and other sta-tes of -hyper- ON thyroidism, but the casein of milk is definitely beneficial. FOOD AND GOITRE*Rats fed on a milk diet are resistant to hyperthyroidization: excessive increase in metabolism and the nervous symptoms, occasioned by thyroid administration to these SIR ROBERT McCARRISON, C.I.E., M.D., D.Sc., animals, are marlkedly lessened (Abelin).
Pediatric Sedation Outside of the Operating Room: A Multispecialty International Collaboration
Authors: Joseph R. Tobin
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Reconstructive Coronary Artery Surgery
Authors: William C. Sheldon
Journal: JAMA (1970)

From May 1967 through May 1969, a total of 303 patients underwent venous autograft reconstructions for occlusive coronary artery disease, with an overall mortality of 5.6%. With subsequent experience the hospital mortality has been reduced to less than 5%. The first 100 patients have been followed-up for more than one year. Eighty-six percent of the survivors have had postoperative angiographic study, and in 86% of these the graft was demonstrated to be patent. Eighty percent had no significant residual obstruction in the artery operated upon and there was good correlation between the angiographic result and symptomatic improvement. The venous autograft technique offers immediate restoration of more effective myocardial perfusion, with attendant protection against myocardial infarction and improvement in symptoms of myocardial ischemia.
Generation of oxygen radicals and mechanisms of injury prevention.
Authors: V Castranova
Journal: Environmental Health Perspectives (1994)

Exposure to crystalline silica can result in damage to the lung parenchyma and scarring that can lead to fibrosis. Pulmonary damage may be the direct consequence of toxic interaction between quartz particles and cell membranes, or it may be due to silica-induced production of oxidant species by pulmonary phagocytes, that in turn overwhelms pulmonary antioxidant systems and causes lung injury. Data indicate that grinding or fracturing quartz particles breaks Si-O bonds and generates .Si and Si-O. radicals on the surface of the cleavage planes. Upon contact with water, these silica-based radicals can generate hydroxyl radicals (.OH). These surface radicals decay as fractured silica dust is aged. Freshly fractured quartz is significantly more potent than aged silica in directly causing lipid peroxidation, membrane damage, and cell death. Furthermore, freshly ground silica is a more potent stimulant of alveolar macrophages than aged silica. This silica-induced activation results in the production of superoxide (O2-), hydrogen peroxide (H2O2), nitric oxide (NO.), and other oxidant species that can damage lung cells. Tetrandrine, an herbal medicine that exhibits antifibrotic activity in rat models of silicosis, effectively blocks the ability of quartz to stimulate oxidant release from pulmonary phagocytes.