tbuckley/cabot-search huggingface dataset:
Abstract 2888: Dendritic cell-targeted lentiviral vector vaccines overcome tolerance to generate a protective T-cell immune response to breast cancer antigens ERBB2 and α-lactalbumin
Authors: Paul D. Bryson, Xiaolu Han, Norman Truong, Pin Wang
Journal: Cancer Research (2014)

Abstract Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. In contrast, active immunotherapy through therapeutic vaccination has yet to be proven clinically effective for breast cancer. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To achieve this in vivo, we have pseudotyped lentiviral vector vaccines with a modified Sindbis Virus glycoprotein that targets the C-type lectin DC-SIGN, which is expressed on DCs. We hypothesized that utilizing these DC-targeting lentiviral vectors as a breast cancer vaccine could lead to an improved immune response against self antigens found in breast cancer tumors. Such an improved immune response may help to prevent or slow tumor growth in breast cancer models. To test these hypotheses, we have constructed lentiviral vectors encoding each of the breast cancer antigens, human Her2 (ERBB2) and mouse alpha-lactalbumin (Lalba). Single injections were able to amplify antigen-specific CD8 T cells to 1.6% of total CD8 T cells in BALB/cJ mice and 0.7% in transgenic ERBB2 mice. This compares favorably with recently published vector vaccines, which have elicited 0.9% and &amp;lt;0.1% antigen-specific CD8 T cells under similar conditions. In addition, DC-targeted immunization of these mice completely inhibited tumor growth in a foreign antigen environment (ERBB2 + wt BALB/cJ), while it significantly reduced the rate of tumor growth in a self-antigen environment (Lalba + BALB/cJ or ERBB2 + FVB/Tg.MMTV.f.huHER2 #5). Our data show that these vectors alone can provide an effective therapy. Future studies may be able to improve these responses by combining DC-targeted immunization with established methods of reducing cancer immunosuppression. Thus, lentivector vaccines may be an excellent component to future clinical vaccine trials, either by themselves or in combination with other chemo- and immunotherapies. Citation Format: Paul D. Bryson, Xiaolu Han, Norman Truong, Pin Wang. Dendritic cell-targeted lentiviral vector vaccines overcome tolerance to generate a protective T-cell immune response to breast cancer antigens ERBB2 and α-lactalbumin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2888. doi:10.1158/1538-7445.AM2014-2888
The Differential Diagnosis of Gall Bladder Disease
Authors: Martin E. Rehfuss
Journal: Annals of Internal Medicine (1927)

Article1 August 1927The Differential Diagnosis of Gall Bladder DiseaseMARTIN E. REHFUSS, M.D.MARTIN E. REHFUSS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-1-2-80 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe gall bladder must be considered as an integral part of the hepatoenteric system. We must think of the liver as one unit and the intestinal tract as the other unit, the two associated by connecting links which the French call the hepatoenteric circulation. This conception is vitally important, as it emphasizes the complete dependence of one link of the chain on the other portion, the afferent chain connecting the digestive tract to the liver and the biliary tract, the great efferent chain. The liver, like the kidneys, is to a large degree the excretory organ. The biliary tract is... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pa.*Presented at the Cleveland Clinical Week of the American College of Physicians, February 23, 1927. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1927Volume 1, Issue 2Page: 80-91KeywordsBiliary systemBladderGastrointestinal tractKidneysLiver ePublished: 1 December 2008 Issue Published: 1 August 1927 PDF downloadLoading ...
Heterogeneity of human Platelets
Authors: Simon Karpatkin, Arthur Charmatz
Journal: Journal of Clinical Investigation (1969)

Human platelets have been separated into two extreme density populations by centrifugation in specific density media. A large-heavy platelet population with specific gravity > 1.055 and a light-small population with specific gravity < 1.046 were obtained, each representing approximately 15-20% of the total population volume. The average volume per platelet of the separated large-heavy and light-small platelet populations was 12 and 5 mu(3) respectively. When data are expressed per milliliter platelets or per gram wet weight, the large-heavy platelet population had a 2-fold greater glycogen content, 1.3-fold greater orthophosphate content, 1.3-fold greater total adenine nucleotide content, 4.2-fold greater rate of glycogenolysis, 2.6-fold greater rate of glycolysis, 2.9-fold greater rate of protein synthesis, and 5.7-fold greater rate of glycogen synthesis. Significant differences were not obtained with respect to total lipid content or total lipid synthesis. The large-heavy platelet had a 2.5-fold greater resistance to osmotic shock as measured by adenosine triphosphate (ATP) or adenosine diphosphate (ADP) release. These data, as well as diisopropyl fluorophosphate (DFP(32)) survival curves in rabbits, indicate that large-heavy platelets have a greater metabolic potential and suggest that they may be the young platelets which progress with age to light-small platelets with a diminished metabolic potential.
The relationship between socioeconomic status, quality of life and healthcare access in COPD: A systematic review
Authors: Sofia Georgopoulou, Alison J. Wright, John Weinman, Helen Booth, Hannah Thornton, Patrick White
Journal: European Respiratory Journal (2011)

Introduction:  Socioeconomic deprivation is a significant health determinant in COPD. To examine the relationship between socio-economic status (SES), Quality of Life (QoL) and healthcare access in COPD, we conducted a systematic review.   Methods:  Medline,Embase,WebofScience,PsychInfo,IBSS,IngentaConnect and CINAHL were searched for quantitative studies published in English (1947-2011). Articles reporting association between SES and any aspect of QoL and healthcare access were included.   Results:  After screening 6889 papers and assessment of 1088 abstracts 76 studies were reviewed. Studies were categorised depending on outcome measures into either quality of life (n=45) or healthcare access (n=31). Quality of life included: disease severity, exacerbations, psychological status, physical functioning/activity, pulmonary function/respiratory symptoms and mobility. 66.7% (n=30) of the studies yielded a negative effect of low SES on QoL, 28.9% (n=13) showed no effect and 4.4% (n=2) found a positive influence. Healthcare access involved: hospitalisation rates, prescription patterns, medication adherence/use and diagnostic procedures. 61.3% (n=19) provided data for the negative influence of socioeconomic deprivation on healthcare access, 29% (n=9) showed no effect while 9.7% (n=3) found a favourable influence.   Conclusion:  A consistent association between low SES and unfavourable outcomes in various domains of both QoL and healthcare access was found. Findings suggest a need to investigate the reasons for this negative association between SES and outcome in COPD. The possible explanatory role of factors such as patients beliefs and behaviour are being explored in an ongoing cohort study.
Abstract 14810: Sam68 Promotes Nf-kb Signaling and Inflammation and Impedes the Recovery of Arterial Injury
Authors: Shuling Han, Junlan Zhou, Gangjian Qin
Journal: Circulation (2014)

Background: The role of Src-associated in mitosis 68 kDa (Sam68) protein in cardiovascular biology has not been studied. A recent report suggests that Sam68 suppresses TNF-α-mediated NF-kB activation. Since NF-kB plays a critical role in vascular inflammation and injury via generation of inflammatory cytokines and recruitment of inflammatory cells, we sought to dissect the molecular mechanism by which Sam68 regulates NF-kB signaling and its functional significance during vascular injury. Methods &amp; Results: The endothelial denudation injury was induced in the carotid arteries of Sam68-null (Sam68 -/- ) and WT mice. Sam68 -/- mice displayed an accelerated re-endothelialization ( P &lt;0.05 at day 5 post-injury) and attenuated neointima formation (by 2.2 folds, P &lt;0.05, at day 14), which was associated with a reduced number of macrophages and lowered expression of pro-inflammatory cytokines (i.e., TNF-alpha, MCP-1 and IL-6) in the injured vessels. In cultured Raw264.7 macrophages, knockdown of Sam68 resulted in a significant reduction in the TNF-α-induced expression of TNF-α, MCP-1, and IL-6 and in the level of nuclear phospho-p65, which indicates attenuated NF-kB activation. These results were confirmed in peritoneal macrophages and macrophages differentiated from bone-marrow mononuclear cells of Sam68 -/- and WT mice. To identify molecular mechanisms, Raw264.7 cells were treated with TNF-α and Vehicle, followed by Sam68 co-immunoprecipitation and mass-spectrometric identification of the Sam68-interacting proteins. We found that TNF-α treatment results in altered interactions of Sam68 with 22 cytosolic, cytoskeletal, and nuclear proteins. Further experiments are under way to validate their involvement in the NF-kB signaling. Conclusions: Our results for the first time suggest that Sam68 promotes pro-inflammatory response in injured arteries and impedes recovery, and this effect may be partially attributable to the exaggerated NF-kB activity.
WHO holds hearings on tobacco control treaty
Authors: Tudor Toma
Journal: BMJ (2000)

The World Health Organization (WHO) last week conducted two days of public hearings on the proposed global tobacco treaty known as the Framework Convention on Tobacco Control.

Several tobacco companies told the hearings that they planned to reduce, in the long term, the harm caused by their products.

Representatives of 160 organisations—including a diverse range of public health agencies, community organisations, academic institutions and all major tobacco multinationals and state companies—gave verbal evidence.

All groups involved in public health …
New Rh Antibody
Authors: A. S. Wiener
Journal: BMJ (1953)

MMICALJOURLa bed-pan, but did not complain of any dizziness or other symptoms.About ten minutes after the completion of the injec- tion he began to regain his colour and by this time his bleeding had stopped.When the patient was last seen about nine weeks after the injection of pituitrin, he had had no further haemoptysis nor even any staining of his sputum.It is, of course, possible that this control was purely coincidental, but when the suddenness of the arrest of the haemorrhage is considered, together with the case reports of Rist and Trimble and Wood, it appears that this therapeutic measure is the only effective method available in the control of haemoptysis without resorting to ligature of the vessels, and even that is practicable only if the side from which the bleeding takes ']ace is known.-Iam, etc.,
Direct medical costs of lung cancer in Oran hospital
Authors: Abdelmajid Snouber, Malika Metahri, Abdellatif Bennani, Souad Kebbati, Saada Chougrani, Malika Guermaz
Journal: European Respiratory Journal (2012)

Objective: To analyse epidemiological profile of lung cancer and to evaluate expenses inherent in its diagnostic and therapeutic management.  Methods: Retrospective study of all cases of lung cancer notified during the period 2004-2008 in our chest clinic.Data concerning epidemiological characters and expenses which take into account,hospitalisation,diagnostic tests and treatment,were kept in an Epi-Info software package(Epi-info,version 6.0).  Results: Among 130 cases,127 were studied.The mean age of our population was 66 years,age more than 50 years represented 80% of cases,66,7% were male and 33,3% were female.Tobacco smoking concerned 91% of our patients.Thoracic pain respresented 20,6% of cases and cough 13% of cases.Frequent localisation of lung cancer was right upper lobar 68% and tumoral extension represented 80% of cases.Histological predominant lung cancer was epidermoide carcinoma with 35% of case followed by adenocarcinoma with 15% of cases.Global cost of hospitalisation was of 157086,86£ with a mean cost per patient of 1208,36£.Global cost of diagnostic tests was of 13350,71£ with a mean cost per patient of 102,69£ and global cost of of treatment was of 88395,17£ with a mean cost per patient of 679,95£.  Conclusion: Lung cancer management in hospital level remain problematic taken into account tobacco smoking threat and the higher expenses inherent in hospitalisation, diagnosis and treatment of the disease.The interest of a national plan against lung cancer is necessary to improve its management and to rationalize expenses.
Optimal Control of Glycemia Among Critically Ill Patients
Authors: Greet Van den Berghe, Roger Bouillon
Journal: JAMA (2004)

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
Trisomy 7-harbouring non-random duplication of the mutant MET allele in hereditary papillary renal carcinomas
Authors: Zhengping Zhuang, Won-Sang Park, Svetlana Pack, Laura Schmidt, Alexander O. Vortmeyer, Evgenia Pak, Thu Pham, Robert J. Weil, Sonja Candidus, Irina A. Lubensky, W. Marston Linehan, Berton Zbar, Gregor Weirich
Journal: Nature Genetics (1998)
Granulocyte colony-stimulating factor in toxic epidermal necrolysis (TEN) and Chelsea &amp; Westminster TEN protocol
Authors: A. De Sica-Chapman, G. Williams, N. Soni, C.B. Bunker
Journal: British Journal of Dermatology (2009)

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening, allergic drug reaction. Skin blistering with epidermal and mucosal necrolysis with subsequent detachment from an inflamed underlying dermis is a hallmark of the condition. The pathogenesis of TEN is not well understood, accounting for controversies about its management and significant delay in initiating potentially beneficial therapy. There are no management protocols based on a robust evidence base. Objectives: Prompt recognition of the diagnosis and consensus on early management initiatives are necessary in order to improve outcomes and survival in TEN. To date, TEN management has been directed at arresting the allergic reaction and treating the complications. We have identified a need for specific medical interventions to accelerate wound regeneration. This approach has not previously been adopted in the management of TEN. Methods: We observed that in two cases of severe TEN, dramatic re-epithelialization and recovery coincided with the introduction of granulocyte colony-stimulating factor (G-CSF) for neutropenia. We explain how addition of the G-CSF promotes recovery from TEN by enhanced bioregeneration of the damaged tissues through accelerated re-epithelialization. Conclusion: G-CSF has been used for severe neutropenia in TEN, but we recommend and explain why, as in our Chelsea and Westminster protocol, G-CSF should be considered in treating severe TEN irrespective of the severity of neutropenia.
Abstract 11502: Molecular Magnetic Resonance Imaging Allows Detection of Reduced Ischemia-Reperfusion Injury in P2Y12 Knockout Mice
Authors: Alexander Maier, Daniel Dürschmied, Dominik von Elverfeldt, Karlheinz Peter, Christoph Bode, Constantin von zur Muhlen
Journal: Circulation (2014)

Introduction: Magnetic resonance imaging (MRI) for both inflammation and necrosis after coronary artery occlusion and recanalization is not availible by now. Non-invasive evaluation of myocardial ischemia-reperfusion (I/R) injury and therapeutic interventions would be of great clinical and prognostic interest. Therefore, we evaluated the impact of a simulated platelet inhibition on I/R injury by an innovative strategy of molecular MRI and compared these findings with established infarct size readout-methods.

Methods and Results: I/R injury was induced in C57BL/6N (WT) and P2Y12-/- mice by 50 minute temporary ligation of the ,,left anterior descending coronary artery“ (LAD). Two hours after reperfusion, MRI of mouse hearts pre and post injection of a contrast agent consisting of antibodies against ligand-induced binding sites of the activated platelet GPIIb/IIIa conjugated to microparticles of iron oxide (LIBS-MPIO), or a control antibody conjugated to MPIOs (control-MPIO) was performed. Thereafter, gadolinium (Gd) was injected.

Activated platelets were specifically detectable via a significant signal effect caused by LIBS-MPIO in the area of LAD occlusion in WT mice, whereas in P2Y12-/- mice no signal increase was found. Gd allowed in all groups the detection of myocardial necrosis. The extent of necrosis was significantly lower in P2Y12-/- mice (p<0.01) as well as in HE staining (p<0.001). Quantification of microthrombi and platelet-neutrophil-conjugates confirmed significantly less accumulation in P2Y12-/- mice (p<0.001), and the amount of bound MPIOs was significantly reduced to the level of WT-mice in P2Y12-/- mice (p<0.01). Echocardiography demonstrated a trend towards better preserved ejection fraction in P2Y12-/- mice (p<0.1). In Monolite Blue/TTC staining, infarct size of the area at risk was significantly lower in P2Y12-/- mice (p<0.05).

Conclusions: This dual approach of molecular MRI for detection of activated platelets and myocardial necrosis discloses reduced I/R injury in a simulated platelet inhibition strategy in mice, reflecting findings in histology with a high accuracy. Such a non-invasive imaging strategy is of clinical and prognostic interest, and shows the potential to monitor therapeutical interventions.
Abstract 1944: Divergent effects of BRAF activation in neural stem and progenitor-like glioblastoma cells
Authors: Robin G. Lerner, Yuichiro Ihara, Kate Lewis, Amelie Griveau, Brian Reichhold, Dian Qu, Martin McMahon, David Rowitch, Charles D. James, Claudia Petritsch
Journal: Cancer Research (2014)

Abstract Glioblastoma multiforme (GBM) are heterogeneous tumors that are refractory to radiation and traditional chemotherapeutics. Separate studies have identified populations of neural stem and progenitor -like GBM cells, however the contribution of these cells types to tumor progression and the response to targeted therapy are poorly understood. Small molecules (such as vemurafenib) targeting the most common MAPK-activating mutation, BRAFV600E, are currently entering clinical trials for treatment of high-grade glioma. Understanding the contribution of different cell types to treatment responses will be necessary for the design of effective adjuvant therapeutic strategies. We show that activating MAPK pathway gene mutations in GBM correlate with elevated expression levels of oligodendrocyte precursor (OPC) and neural stem cell (NSC)-associated genes. Cells expressing CD133 and NG2 coexist in human GBM and BRafV600E expressing mouse neurosphere cultures, and maintain some of their respective neural stem and progenitor-like properties. In isogenic mouse cells expressing BRafV600E, NG2+ cells expand rapidly and symmetrically, while rates of asymmetric division are unaffected in slow-proliferating CD133+ cells. Tracing of proliferation rate with the membrane-associated dye PKH-26 reveals heterogeneity in the proliferation rate of CD133+ cells, but not proliferative NG2+ cells. BRAF-targeted inhibition of human GBM cells with PLX4720, the tool compound of vemurafenib, reduces S-phase entry of NG2+ cells, yet CD133+ cells are less affected. Interestingly targeted inhibition of components of the asymmetric division machinery selectively disrupts G2-M progression in CD133+ cells. The functionally divergent populations of CD133-expressing NSC-like cells will likely be therapeutically problematic with mono-therapeutic approaches. These data point to a differential regulation of key cell cycle processes between CD133+ stem-like cells and NG2+ OPC-like cells, that will inform the intelligent design of compound treatment strategies. Note: This abstract was not presented at the meeting. Citation Format: Robin G. Lerner, Yuichiro Ihara, Kate Lewis, Amelie Griveau, Brian Reichhold, Dian Qu, Martin McMahon, David Rowitch, Charles D. James, Claudia Petritsch. Divergent effects of BRAF activation in neural stem and progenitor-like glioblastoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1944. doi:10.1158/1538-7445.AM2014-1944
PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models
Authors: Helen Y. Zou, Luc Friboulet, David P. Kodack, Lars D. Engstrom, Qiuhua Li, Melissa West, Ruth W. Tang, Hui Wang, Konstantinos Tsaparikos, Jinwei Wang, Sergei Timofeevski, Ryohei Katayama, Dac M. Dinh, Hieu Lam, Justine L. Lam, Shinji Yamazaki, Wenyue Hu, Bhushankumar Patel, Divya Bezwada, Rosa L. Frias, Eugene Lifshits, Sidra Mahmood, Justin F. Gainor, Timothy Affolter, Patrick B. Lappin, Hovhannes Gukasyan, Nathan Lee, Shibing Deng, Rakesh K. Jain, Ted W. Johnson, Alice T. Shaw, Valeria R. Fantin, Tod Smeal
Journal: Cancer Cell (2015)
Press: A cry of pain and anger
Authors: J. Laurance
Journal: BMJ (2000)

It was the Times that broke the story. Under the headline “Struck off doctor elected to GMC” (1 May), it carried the first account of what, by any standards, was a major electoral upset. Just as Tony Blair was about to receive a bloody nose from London voters, and William Hague from those in the Romsey byelection, Britain's doctors were making their opinion felt of efforts by their leaders to reform the General Medical Council.

At first glance, the result seemed simply perverse. In a byelection for the GMC last month 50 candidates stood for one place on the disciplinary body, whose slogan is “Protecting patients, guiding doctors.” Over 45 000 doctors voted, 23% of the total on the medical register. The result suggested that many who completed their ballot papers would prefer to see the GMC's slogan reversed to read “Protecting doctors, guiding patients.”

Two of the three doctors who topped the poll had themselves been found guilty of serious professional misconduct by the GMC in the past. Jennifer Colman, who won with 5719 votes, was struck off the medical register in 1987 for neglect of a patient and racial abuse of a colleague. She was restored to …