tbuckley/cabot-search huggingface dataset:
Abstract IA21: Using viruses to advance T cell therapy for malignancy.
Authors: Miyuki Yanagisawa, Minhtran Ngo, Cliona M. Rooney, Ann Marie Leen, Juan Vera, Helen E. Heslop, Malcolm K. Brenner
Journal: Cancer Research (2013)

Abstract Virus-specific T cells effectively prevent and treat viral diseases after stem cell transplantation and have produced complete remissions (CRs) in patients with EBV-positive malignancy outside the transplant setting. The success of EBV-specific T cells is thought to be due to the strong viral antigens expressed by these tumors and the vaccine effect of endogenous EBV. We tested if this endogenous viral vaccine effect could be exploited for the treatment of non-viral malignancy by engrafting chimeric antigen receptors specific for the disialoganglioside,GD2 (GD2.CAR) on EBV-specific T cells and comparing their in vivo expansion with that of GD2.CAR-engrafted CD3-activated T cells (ATCs) in patients with relapsed neuroblastoma. Transgenic EBV-CTLs were detected at higher levels than GD2.CAR-ATCs and 6 of 8 patients without disease at infusion remain tumor-free, while 6 of 11 with disease had tumor responses including 3 CRs. However the expected increase in frequency of EBV-specific T cells in patient blood was not observed, perhaps because EBV was well-controlled in these patients.1,2 To improve this vaccine effect, we looked to VZV, for which a potent, but safe commercially-available vaccine exists. We identified five VZV antigens that we predicted would be presented to the immune system early after infection, generated overlapping peptide libraries (pepmixes) for each and used them to stimulate T- cells from both naturally-infected and vaccinated individuals. T cells expanded in vitro and were antigen-specific as measured on day 9 using γ-IFN ELIspot analysis. T cells specific for all five antigens increased in frequency in response to VZV vaccination. VZV-specific T cells transduced with a GD2.CAR retained their ability to respond to VZV antigens and acquired the ability to eliminate GD2+ tumor cells. Ultimately, we plan to combine GD2.CAR-engrafted, VZV-specific T cells with VZV vaccination for the treatment of patients with relapsed GD2+ tumors. References: 1 Pule et al. Nat Med. 2008 Nov;14(11):1264-70 2 Louis et al. Blood. 2011 Dec 1;118(23):6050-6 Citation Format: Miyuki Yanagisawa, Minhtran Ngo, Cliona M. Rooney, Ann Marie Leen, Juan Vera, Helen E. Heslop, Malcolm K. Brenner. Using viruses to advance T cell therapy for malignancy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA21.
Crucial Role of Stromal Cell–Derived Factor-1α in Neointima Formation After Vascular Injury in Apolipoprotein E–Deficient Mice
Authors: Andreas Schober, Sandra Knarren, Michael Lietz, Elisa A. Lin, Christian Weber
Journal: Circulation (2003)

Recent evidence indicates that stromal cell-derived factor-1alpha (SDF-1alpha) is expressed in human atherosclerotic plaques, whereas high plasma levels are clinically associated with stable coronary artery disease. Herein, we investigate the involvement of SDF-1alpha in neointimal formation after vascular injury.SDF-1alpha was detected by immunohistochemistry in carotid arteries of apolipoprotein E-deficient (apoE-/-) mice at various stages of neointima formation after wire-induced injury. Double immunofluorescence revealed that SDF-1alpha staining was mostly confined to smooth muscle cells (SMCs). Furthermore, SDF-1alpha plasma levels peaked 1 day after vascular injury. Treatment of apoE-/- mice after carotid injury with a neutralizing SDF-1alpha monoclonal antibody for 3 weeks reduced neointimal lesion area by 44% (n=5, P<0.05) compared with isotype control. In SDF-1alpha antibody-treated apoE-/- mice, neointimal SMC content was decreased (21.7+/-2% versus 39.4+/-4%, n=5, P=0.005), whereas the relative content of neointimal macrophages remained unchanged. As shown by flow cytometry, carotid injury resulted in a marked expansion of circulating Sca-1+lineage- progenitor cells (PBPCs) in the peripheral blood of apoE-/- mice after 1 day, which was mediated by SDF-1alpha. Systemic injection of isolated PBPCs after vascular injury demonstrated their recruitment to neointimal lesions, where they can adopt an SMC-like phenotype.SDF-1alpha plays an instrumental role in neointimal formation after vascular injury in apoE-/- mice by regulating neointimal SMC content. This contribution appears to be attributable to SDF-1alpha-dependent recruitment of circulating SMC progenitor cells.
NOTES ON A MODIFICATION OF THE WASSERMANN REACTION: With a Preliminary Examination of 102 Cases at the Northcote Police Hospital, Bombay
Authors: F. D. Bana
Journal: BMJ (1915)

AFTER a preliminary accouint of the early experim-lents on immuliitlnity, including the biological test for lhunman blood worklied out by Tristclhowitclh, Nuttall, and otlers,
ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome
Authors: S Schnittger, C Eder, S Jeromin, T Alpermann, A Fasan, V Grossmann, A Kohlmann, T Illig, N Klopp, H-E Wichmann, K-A Kreuzer, C Schmid, P Staib, R Peceny, N Schmitz, W Kern, C Haferlach, T Haferlach
Journal: Leukemia (2012)
Compliance in screening programmes
Authors: D Torgerson, C Donaldson
Journal: BMJ (1994)

able extent of the lesions; the fact that "double covered" skin of the buttock was affected; the lack of lesions on habitually exposed sites; the association with profound tanning and lentiginosis in the same distribution; and the spontaneous resolution of some lesions when the patient stopped using the sunbed.Recent reports of sunbed-induced poro- keratosis34 (a histologically identifiable disorder of keratinisation, which is occasionally associated with squamous cell carcinoma) support the argu- ment that ultraviolet A sunbeds can cause discrete keratinising skin lesions.The current concerns in this patient are itch and cosmetic, but the small risk of malignant change in actinic keratoses may be important in relatively young patients with hundreds of lesions.Interestingly, appreciable itch is a feature of the hyperkeratosis that precedes the development of tumours in mice exposed to ultraviolet A.'
Recognition and Treatment of Anthrax—Reply
Authors: Thomas V. Inglesby, Donald A. Henderson
Journal: JAMA (1999)

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
Gene expression profiling in MDS and AML: potential and future avenues
Authors: K Theilgaard-Mönch, J Boultwood, S Ferrari, K Giannopoulos, J M Hernandez-Rivas, A Kohlmann, M Morgan, B Porse, E Tagliafico, C M Zwaan, J Wainscoat, M M Van den Heuvel-Eibrink, K Mills, L Bullinger
Journal: Leukemia (2011)
The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells
Authors: Jenny Zhang, Dereje Jima, Andrea B. Moffitt, Qingquan Liu, Magdalena Czader, Eric D. Hsi, Yuri Fedoriw, Cherie H. Dunphy, Kristy L. Richards, Javed I. Gill, Zhen Sun, Cassandra Love, Paula Scotland, Eric Lock, Shawn Levy, David S. Hsu, David Dunson, Sandeep S. Dave
Journal: Blood (2014)
Lack of Protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis
Authors: Tal Burstyn-Cohen, Mary Jo Heeb, Greg Lemke
Journal: Journal of Clinical Investigation (2009)

Protein S (ProS) is a blood anticoagulant encoded by the Pros1 gene, and ProS deficiencies are associated with venous thrombosis, stroke, and autoimmunity. These associations notwithstanding, the relative risk that reduced ProS expression confers in different disease settings has been difficult to assess without an animal model. We have now described a mouse model of ProS deficiency and shown that all Pros1-/- mice die in utero,from a fulminant coagulopathy and associated hemorrhages. Although ProS is known to act as a cofactor for activated Protein C (aPC), plasma from Pros1+/- heterozygous mice exhibited accelerated thrombin generation independent of aPC, and Pros1 mutants displayed defects in vessel development and function not seen in mice lacking protein C. Similar vascular defects appeared in mice in which Pros1 was conditionally deleted in vascular smooth muscle cells. Mutants in which Pros1 was deleted specifically in hepatocytes, which are thought to be the major source of ProS in the blood, were viable as adults and displayed less-severe coagulopathy without vascular dysgenesis. Finally, analysis of mutants in which Pros1 was deleted in endothelial cells indicated that these cells make a substantial contribution to circulating ProS. These results demonstrate that ProS is a pleiotropic anticoagulant with aPC-independent activities and highlight new roles for ProS in vascular development and homeostasis.
The Spectrum of Drug-Induced Pulmonary Disease
Authors: E. C. ROSENOW
Journal: Annals of Internal Medicine (1972)

The relationship between the use of various drugs and pulmonary disease is being recognized with greater frequency. The means whereby drugs can cause pulmonary disease vary widely and are not well understood. Drugs such as nitrofurantoin, busulfan, methysergide, the ganglionic blockers, pituitary snuff, and sulfonamides and drugs producing the systemic lupus erythematosus syndrome probably incite a hypersensitivity pulmonary reaction. Corticosteroids are most commonly associated with the proliferation of opportunistic organisms and with mediastinal lipomatosis. Aerosolized drugs, such as cromoglycate disodium, isoproterenol, and orally ingested aspirin and propranolol, can cause bronchospasm in some persons. Pleural effusion can be caused by nitrofurantoin, methysergide, and drugs inducing systemic lupus erythematosus. Respiratory muscle paralysis has been associated with the use of neomycin, gentamicin, and other antibiotics. Many drugs can produce pulmonary disease directly or indirectly, and it is extremely important to recognize this and take a careful drug history.
Sorafenib inhibits signal transducer and activator of transcription-3 signaling in cholangiocarcinoma cells by activating the phosphatase shatterproof 2
Authors: Boris R. A. Blechacz, Rory L. Smoot, Steven F. Bronk, Nathan W. Werneburg, Alphonse E. Sirica, Gregory J. Gores
Journal: Hepatology (2009)

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is one of the key signaling cascades in cholangiocarcinoma (CCA) cells, mediating their resistance to apoptosis. Our aim was to ascertain if sorafenib, a multikinase inhibitor, may also inhibit JAK/STAT signaling and, therefore, be efficacious for CCA. Sorafenib treatment of three human CCA cell lines resulted in Tyr705 phospho-STAT3 dephosphorylation. Similar results were obtained with the Raf-kinase inhibitor ZM336372, suggesting sorafenib promotes Tyr705 phospho-STAT3 dephosphorylation by inhibiting Raf-kinase activity. Sorafenib treatment enhanced an activating phosphorylation of the phosphatase SHP2. Consistent with this observation, small interfering RNA–mediated knockdown of phosphatase shatterproof 2 (SHP2) inhibited sorafenib-induced Tyr705 phospho-STAT3 dephosphorylation. Sorafenib treatment also decreased the expression of Mcl-1 messenger RNA and protein, a STAT3 transcriptional target, as well as sensitizing CCA cells to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. In an orthotopic, syngeneic CCA model in rats, sorafenib displayed significant tumor suppression resulting in a survival benefit for treated animals. In this in vivo model, sorafenib also decreased tumor Tyr705 STAT3 phosphorylation and increased tumor cell apoptosis. Conclusion: Sorafenib accelerates STAT3 dephosphorylation by stimulating phosphatase SHP2 activity, sensitizes CCA cells to TRAIL-mediated apoptosis, and is therapeutic in a syngeneic rat, orthotopic CCA model that mimics human disease. (HEPATOLOGY 2009.)
IMMUNOLOGICAL TOLERANCE IN VITRO: KINETIC STUDIES AT THE CELLULAR LEVEL
Authors: E. Diener, W. D. Armstrong
Journal: The Journal of Experimental Medicine (1969)

When normal mouse spleen, cells in suspension are cultured in vitro in the presence of polymer from S. adelaide flagellin, an immune response can be obtained as measured at the level of single antibody-forming cells. Cultures were stimulated with different doses of antigen, ranging from 0.2 ng to 3 microg/ml of tissue culture fluid and it was found that the peak number of approximately 500 antibody-forming cells per 10(6) harvested cells by day 4 was antigen dose dependent, 2-20 ng/ml being the optimal concentration. When more than 1 microg/ml of polymer from S. adelaide together with either 20 ng/ml of polymer from S. waycross or with 4 x 10(6) sheep erythrocytes were placed in the system, unresponsiveness to S. adelaide, but immunity to the other antigens occurred simultaneously. Cells made immunologically tolerant in vitro to S. adelaide H antigens were transferred into syngeneic lethally irradiated recipients and challenged with the same antigen. The adoptive immune capacity in these mice, as measured at the level of the immunologically competent cell was reduced by 80-90% as compared with relevant controls. Attempts to induce low zone tolerance in vitro were without success. To study the kinetics of tolerance induction in vitro, cells were cultured with tolerogenic doses of antigen for various periods of time, washed, and subsequently cultured with immunogenic doses of antigen for 4 days. It was found, that immunological tolerance may be induced to a significant degree in vitro within a period of 15 min. Similar results were obtained when spleen cells were exposed for various lengths of time to tolerogenic doses of antigen but at a temperature of 4 degrees C instead of 37 degrees C. The results are taken as suggestive evidence that the initial step in tolerance induction is related to the direct interaction between the surface of immune competent cells and antigen molecules.
Ether Vapor as a Diagnostic Agent.
Authors: Emerson M. Sutton
Journal: JAMA (1898)

Peoria, Ill., July 11, 1898. <h3>To the Editor:</h3> —About a year ago I began experimenting with ether as a means of diagnosis of intestinal perforations, and concluded that it would be much more practical and better than hydrogen gas, as advocated by Professor Senn, since it is always at hand and necessitates no special apparatus, aside from what is already found in the surgeon's possession, and further, no objections can be given to its use on account of noxious properties, unfounded as these objections may be as to the hydrogen gas. The quantity of ether being infinitesimal ([unk]j or less being sufficient to give up the necessary vapor, which is diluted many, many times by the air that carries it) absolute freedom from anesthesia is assured. The method is simple: A small quantity of ether is poured into the bottle accompanying the aspirator of so-called French pattern. A soft rubber
Management of depression in adults
Authors: Markku Timonen, Timo Liukkonen
Journal: BMJ (2008)

A study by the World Health Organization ranked depression the fourth global burden of disease and found it to be the largest non-fatal burden of disease, with nearly 12% of total years lived with disability. 1 According to the cross sectional WHO world health survey, carried out in all regions of the world (60 countries), the one year prevalence of a depressive episode (international classification of diseases, 10th revision) was 3.2% (95% confidence interval 3.0% to 3.5%).In patients with several medical conditions the prevalence of depression exceeds that of the general population, 2 with 5-10% of patients affected in primary care and 10-14% of patients under general hospital care. 3The diagnosis and treatment of depression by general practitioners is not, however, always optimal. 4 5 We review the presentation and assessment of depression and discuss the options for its effective treatment and management.
Vascular Dysfunction in Chronic Obstructive Pulmonary Disease
Authors: John D. Maclay, David A. McAllister, Nicholas L. Mills, Finny P. Paterson, Christopher A. Ludlam, Ellen M. Drost, David E. Newby, William MacNee
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), which may in part be attributable to abnormalities of systemic vascular function. It is unclear whether such associations relate to the presence of COPD or prior smoking habit.To undertake a comprehensive assessment of vascular function in patients with COPD and healthy control subjects matched for smoking history.Eighteen men with COPD were compared with 17 healthy male control subjects matched for age and lifetime cigarette smoke exposure. Participants were free from clinically evident cardiovascular disease.Pulse wave velocity and pulse wave analysis were measured via applanation tonometry at carotid, radial, and femoral arteries. Blood flow was measured in both forearms using venous occlusion plethysmography during intrabrachial infusion of endothelium-dependent vasodilators (bradykinin, 100-1,000 pmol/min; acetylcholine, 5-20 microg/min) and endothelium-independent vasodilators (sodium nitroprusside, 2-8 microg/min; verapamil, 10-100 microg/min). Tissue plasminogen activator (t-PA) was measured in venous plasma before and during bradykinin infusions. Patients with COPD have greater arterial stiffness (pulse wave velocity, 11 +/- 2 vs. 9 +/- 2 m/s; P = 0.003; augmentation index, 27 +/- 10 vs. 21 +/- 6%; P = 0.028), but there were no differences in endothelium-dependent and -independent vasomotor function or bradykinin-induced endothelial t-PA release (P > 0.05 for all).COPD is associated with increased arterial stiffness independent of cigarette smoke exposure. However, this abnormality is not explained by systemic endothelial dysfunction. Increased arterial stiffness may represent the mechanistic link between COPD and the increased risk for cardiovascular disease associated with this condition.
Purpura after Administration of Piperazine
Authors: A. Shanker, J. Gulati
Journal: BMJ (1960)

AUTOMATIC CLOTTING TIMER BRDIrrJOAL with this apparatus.Much time is saved wvhen large numbers of tests have to be performed, especially if Owren's methods are boing used.Just as important is the fact that much more reliab!e and reproducible results are obtained by using this automatic time-recording apparatus than with the hand-wate--bath techniqu?.The apoaratus was made for us by Evans Electroselenium Ltd., Colchester Road, Halstead, Essex.Cheap disposable glass tubes to fit the apparatus can be obtained from C. E.
Characterisation of hepatitis B virus X protein mutants in tumour and non-tumour liver cells using laser capture microdissection
Authors: Massimo Iavarone, Jean-Baptiste Trabut, Oona Delpuech, Françoise Carnot, Massimo Colombo, Dina Kremsdorf, Christian Bréchot, Valérie Thiers
Journal: Journal of Hepatology (2003)
Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension
Authors: M.J. Olsson, L. Juhlin
Journal: British Journal of Dermatology (2002)

Journal Article Long‐term follow‐up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension Get access M.J. Olsson, M.J. Olsson Department of Medical Sciences, Section of Dermatology and Venereology, University Hospital, SE‐751 85 Uppsala, Sweden Dr Mats J.Olsson. E‐mail: mats.olsson@medsci.uu.se Search for other works by this author on: Oxford Academic Google Scholar L. Juhlin L. Juhlin Department of Medical Sciences, Section of Dermatology and Venereology, University Hospital, SE‐751 85 Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 5, 1 November 2002, Pages 893–904, https://doi.org/10.1046/j.1365-2133.2002.04837.x Published: 01 November 2002 Article history Accepted: 30 January 2002 Published: 01 November 2002
Results of a Phase III, Randomized, Placebo-Controlled Study of Sorafenib in Combination With Carboplatin and Paclitaxel As Second-Line Treatment in Patients With Unresectable Stage III or Stage IV Melanoma
Authors: Axel Hauschild, Sanjiv S. Agarwala, Uwe Trefzer, David Hogg, Caroline Robert, Peter Hersey, Alexander Eggermont, Stephan Grabbe, Rene Gonzalez, Jens Gille, Christian Peschel, Dirk Schadendorf, Claus Garbe, Steven O'Day, Adil Daud, J. Michael White, Chenghua Xia, Kiran Patel, John M. Kirkwood, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2009)

This phase III, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of sorafenib with carboplatin and paclitaxel (CP) in patients with advanced melanoma who had progressed on a dacarbazine- or temozolomide-containing regimen.A total of 270 patients were randomly assigned to receive intravenous paclitaxel 225 mg/m2 plus intravenous carboplatin at area under curve 6 (AUC 6) on day 1 of a 21-day cycle followed by either placebo (n = 135) or oral sorafenib 400 mg (n = 135) twice daily on days 2 to 19. The primary efficacy end point was progression-free survival (PFS); secondary and tertiary end points included overall survival and incidence of best response, respectively.The median PFS was 17.9 weeks for the placebo plus CP arm and 17.4 weeks for the sorafenib plus CP arm (hazard ratio, 0.91; 99% CI, 0.63 to 1.31; two-sided log-rank test P = .49). Response rate was 11% with placebo versus 12% with sorafenib. Dermatologic events, grade 3 thrombocytopenia, diarrhea, and fatigue were more common in patients treated with sorafenib plus CP versus placebo plus CP.In this study, the addition of sorafenib to CP did not improve any of the end points over placebo plus CP and cannot be recommended in the second-line setting for patients with advanced melanoma. Both regimens had clinically acceptable toxicity profiles with no unexpected adverse events. A trial of similar design for the first-line treatment of patients with advanced melanoma (intergroup trial E2603) is currently ongoing.