tbuckley/cabot-search huggingface dataset:
Congress Saved Peer Review
Authors: Alan G. Williams
Journal: JAMA Surgery (2014)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
Abstract 968: Invadopodia formation and microparticle release are required for cancer cell extravasation in vivo
Authors: Hon S. Leong, Amy E. Robertson, Amber A. Ablack, Eva A. Turley, Ann F. Chambers, John D. Lewis
Journal: Cancer Research (2011)

Abstract During the metastatic process, cancer cells must undergo trans-endothelial migration from the vessel lumen into underlying tissue in a process known as extravasation. Little is known about the dynamic mechanical aspects of this process. To address this, we performed real-time, sub-cellular resolution intravital imaging of human cancer cells during arrest, intravascular migration and extravasation using a shell-less avian embryo xenograft model. We find that extravasation occurs at endothelial junctions and that the majority of extravasation events occurred during the 12 hours subsequent to the intravenous injection of cancer cells. In the majority of extravasation events, long cytoplasmic extensions identified as invadopodia were observed prior to extravasation which breached underlying endothelium. We observed the release of microparticles during these invadopodial extension events prior to extravasation, and this resulted in a ∼40% reduction in cell volume post-extravasation. Based on this, we hypothesized that invadopodia are required for extravasation, and that cancer cell extravasation could be abrogated by inhibiting factors required for invadopodia function. We found that treatment with Src kinase inhibitors significantly reduced invadopodia formation in vivo and resulted in a ∼60% decrease in extravasation events when compared to vehicle treated controls. Furthermore, a higher proportion of cells in the Src kinase inhibitor-treated animals remained intravascular compared to vehicle control. In conclusion, we determined that 1) extravasation occurs at junctions between adjacent endothelial cells, 2) cancer cells form invadopodia that breach the endothelial layer prior to successful extravasation and 3) cancer cells undergoing extravasation release cancer microparticles into both the vessel lumen and tissue interstitium with a corresponding decrease in cell volume. Pharmacological inhibition of invadopodia by Src kinase inhibitors (Bosutinib, Dasatinib) reduces cancer cell extravasation, revealing a novel and potentially important mechanism of action against metastatic cancers. 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 968. doi:10.1158/1538-7445.AM2011-968
Significance of block distal to the His bundle induced by atrial pacing in patients with chronic bifascicular block.
Authors: R C Dhingra, C Wyndham, R Bauernfeind, S Swiryn, P C Deedwania, T Smith, P Denes, K M Rosen
Journal: Circulation (1979)

Twenty-one of 496 (4%) patients with chronic bifascicular block, studied and followed prospectively, had block distal to the His bundle (BDH) induced by atrial pacing during initial electrophysiologic studies. In six, BDH was noted during pacing-induced atrioventricular (AV) nodal Wenckebach periods (at paced rates of 150--190 beats/min), with BDH in the short HH cycles after the AV nodal blocked P (lond cycle). The AH interval was normal in all six patients and HV was normal in four. None of the six patients has developed AV block during a mean follow-up of 5.33 +/- 0.48 years. In 15 patients, pacing-induced BDH was noted during intact AV nodal conduction (paced rate of 80--200 beats/min). The AH interval was prolonged in one, and HV was prolonged in 10 of the 15 patients. During a mean follow-up of 3.4 +/- 0.59 years, seven of these patients developed AV block, one had treadmill-provoked AV block, and two died suddenly (major morbid event in 10 of 15 patients). In conclusion, BDH induced by atrial pacing is an infrequent finding in patients with bifascicular block, and can be a functional as well as a pathologic response. The latter is associated with a high risk of major morbid events (AV block and sudden death).
Highly heterogeneous Phl p 5-specific T cells from patients with allergic rhinitis differentially recognize recombinant Phl p 5 isoallergens☆☆☆
Authors: Peter A. Würtzen, Margit Wissenbach, Henrik Ipsen, Albrecht Bufe, John Arnved, R.J.Joost van Neerven
Journal: Journal of Allergy and Clinical Immunology (1999)
Functional Imaging Studies: Linking Mind and Basic Neuroscience
Authors: Robert G. Shulman
Journal: American Journal of Psychiatry (2001)

The imaging of brain activity with positron emission tomography (PET) and functional magnetic resonance imaging has assumed a central position in psychiatry. Functional imaging signals arise from changes in the neurophysiological parameters of glucose and oxygen consumption mediated by blood flow.Recent in vivo (13)C nuclear magnetic resonance (NMR) neurochemical studies have established a quantitative coupling between the rates of glucose oxidation and glutamate neurotransmitter flux in rats and humans, thereby linking measured neurophysiological parameters to brain function.These results show that in the awake, resting, and unstimulated states, 70%-80% of brain energy consumption is devoted to the same glutamate/glutamine neurotransmitter signaling as are the small percentages stimulated by tasks. Furthermore, in anesthetized animals, in which unstimulated activity is reduced, the total signal rather than a particular increment is required for a response.On this basis, the total signal, as well as the difference in the signal, measures cortical neurotransmitter flux. The total signal in a region therefore contains valuable information about required brain activity. Although signal change is often more easily measured, certain PET and (13)C NMR methods can quantify total regional signal activity and thereby provide another measure of neurotransmitter activity.
MyD88 Signaling in B Cells Regulates the Production of Th1-dependent Antibodies to AAV
Authors: Muriel Sudres, Séverine Ciré, Virginie Vasseur, Léa Brault, Sylvie Da Rocha, Florence Boisgérault, Christine Le Bec, David Alexandre Gross, Véronique Blouin, Bernard Ryffel, Anne Galy
Journal: Molecular Therapy (2012)

The administration of recombinant adeno-associated viral vectors (rAAV) for gene transfer induces strong humoral responses through mechanisms that remain incompletely characterized. To investigate the links between innate and adaptive immune responses to the vector, rAAVs were injected intravenously into mice deficient in cell-intrinsic components of innate responses (Toll-like receptors (TLRs), type-1 interferon (IFN) or inflammasome signaling molecules) and AAV-specific antibodies were measured. Of all molecules tested, only MyD88 was critically needed to mount immunoglobulin G (IgG) responses since MyD88−/− mice failed to develop high levels of AAV-specific IgG2 and IgG3, regardless of capsid serotype injected. None of the TLRs tested was essential here, but TLR9 ensured a Th1-biased antibody responses. Indeed, capsid-specific Th1 cells were induced upon injection of rAAV1, as directly confirmed with an epitope-tagged capsid, and the priming and development of these Th1 cells required T cell-extrinsic MyD88. Cell transfer experiments showed that autonomous MyD88 signaling in B cells, but not T cells, was sufficient to produce Th1-dependent IgGs. Therefore, rAAV triggers innate responses, at least via B cells, controlling the development of capsid-specific Th1-driven antibodies. MyD88 emerges as a critical and pivotal regulator of both T- and B-cell adaptive immunity against AAV. The administration of recombinant adeno-associated viral vectors (rAAV) for gene transfer induces strong humoral responses through mechanisms that remain incompletely characterized. To investigate the links between innate and adaptive immune responses to the vector, rAAVs were injected intravenously into mice deficient in cell-intrinsic components of innate responses (Toll-like receptors (TLRs), type-1 interferon (IFN) or inflammasome signaling molecules) and AAV-specific antibodies were measured. Of all molecules tested, only MyD88 was critically needed to mount immunoglobulin G (IgG) responses since MyD88−/− mice failed to develop high levels of AAV-specific IgG2 and IgG3, regardless of capsid serotype injected. None of the TLRs tested was essential here, but TLR9 ensured a Th1-biased antibody responses. Indeed, capsid-specific Th1 cells were induced upon injection of rAAV1, as directly confirmed with an epitope-tagged capsid, and the priming and development of these Th1 cells required T cell-extrinsic MyD88. Cell transfer experiments showed that autonomous MyD88 signaling in B cells, but not T cells, was sufficient to produce Th1-dependent IgGs. Therefore, rAAV triggers innate responses, at least via B cells, controlling the development of capsid-specific Th1-driven antibodies. MyD88 emerges as a critical and pivotal regulator of both T- and B-cell adaptive immunity against AAV.
FEDERAL TRADE COMMISSION REQUESTS USE OF OFFICIAL NAMES
Authors: L. L. Bracken
Journal: JAMA (1918)

<h3>To the Editor:</h3> —Nothing is further from the intention of this commission than to attempt to influence the editorial or advertising policy of any publication, but it is believed that an effort should be made to secure the general use of the new official names in connection with the drugs, licenses to manufacture which have been granted by this commission. To this end we suggest thatThe Journal of the American Medical Association(if such course meets its approval) use the official names "Arsphenamine," "Procaine," "Barbital," etc., in connection with all advertisements of the products and all articles in which they are referred to.
Homograft aortic valve replacement: seven years' experience with antibiotic-treated valves.
Authors: S K Khanna, J K Ross, J L Monro
Journal: Thorax (1981)

One hundred and sixty-five patients had their aortic valve replaced with antibiotic-sterilised homograft. In all cases, a two-layered freehand technique of valve implantation was used. Tailoring (narrowing) of the annulus was required in 29 cases, and an aortic root gusset was used to enlarge the non-coronary sinus in 68 cases. There was an early mortality of 1.8% and late mortality of 2.4%. The actuarial survival rate was 95% at a maximum follow-up of seven years. The incidence of valvar regurgitation (early diastolic murmur) was 11.5% up to six months after operation and an additional 7.2% subsequent to this. Overall, it was trivial in 10.3%, mild in 7.8%, and moderate in 0.6%. Most valve regurgitation was non-progressive and actuarial analysis showed 74% regurgitation-free valves at the end of seven years. The age of the donor and the valve storage time showed some relationship to valve deterioration. Special attention has been paid to the control of hypertension to prevent accelerated graft degeneration. The results suggest that this has been successful. Anticoagulant therapy was not used and thromboembolism has not been seen in patients undergoing isolated aortic valve replacement. There was one case of miliary tuberculosis after homograft valve replacement but no pyogenic or fungal endocarditis occurred. No haemolysis, calcification, or valvar stenosis were observed. This series, followed for a maximum of seven years, shows excellent sustained valve performance and a very low incidence of important postoperative regurgitation, with 91.8% of the survivors symptom-free.
Cholera Toxin Disrupts Barrier Function by Inhibiting Exocyst-Mediated Trafficking of Host Proteins to Intestinal Cell Junctions
Authors: Annabel Guichard, Beatriz Cruz-Moreno, Berenice Aguilar, Nina M. van Sorge, Jennifer Kuang, Adrianne A. Kurkciyan, Zhipeng Wang, Saiyu Hang, Guillaume P. Pineton de Chambrun, Declan F. McCole, Paula Watnick, Victor Nizet, Ethan Bier
Journal: Cell Host & Microbe (2013)

Cholera toxin (CT), a virulence factor elaborated by Vibrio cholerae, is sufficient to induce the severe diarrhea characteristic of cholera. The enzymatic moiety of CT (CtxA) increases cAMP synthesis in intestinal epithelial cells, leading to chloride ion (Cl−) efflux through the CFTR Cl− channel. To preserve electroneutrality and osmotic balance, sodium ions and water also flow into the intestinal lumen via a paracellular route. We find that CtxA-driven cAMP increase also inhibits Rab11/exocyst-mediated trafficking of host proteins including E-cadherin and Notch signaling components to cell-cell junctions in Drosophila, human intestinal epithelial cells, and ligated mouse ileal loops, thereby disrupting barrier function. Additionally, CtxA induces junctional damage, weight loss, and dye leakage in the Drosophila gut, contributing to lethality from live V. cholerae infection, all of which can be rescued by Rab11 overexpression. These barrier-disrupting effects of CtxA may act in parallel with Cl− secretion to drive the pathophysiology of cholera.
Disulfiram doesn't always prevent drinking
Authors: Elizabeth Rasche González
Journal: JAMA (1981)

Alcoholic patients sometimes contend that they can continue to drink while taking disulfiram (Antabuse). It may be true. Evidence of the claim's veracity comes from a study presented at the recent New Orleans meeting of the American Society for Clinical Pharmacology and Therapeutics and subsequently published by J. E. Peachey, MD, head, behavioral pharmacotherapy clinic, clinical institute, Addiction Research Foundation, Toronto (<i>Lancet</i>1981;1:943-944). Peachey and co-workers reported that nonalcoholic paid volunteers who were given disulfiram, then small alcoholic drinks, were able to imbibe additional ethanol without untoward effects. In the double-blind study, 18 volunteers were randomly assigned to receive either disulfiram, 3.5 mg each evening, calcium carbimide (Temposil), 0.7 mg twice a day, or placebo over a 48-hour period. Calcium carbimide is a "sensitizing drug" that is similar to disulfiram but not available in the United States. Twelve hours after the last dose of drug or placebo, the volunteers were
Percutaneous Drainage Compared with Surgery for Hepatic Hydatid Cysts
Authors: Mohammad Sultan Khuroo, Nazir A. Wani, Gul Javid, Bashir A. Khan, Ghulam N. Yattoo, Altaf H. Shah, Samoon G. Jeelani
Journal: New England Journal of Medicine (1997)

In recent years percutaneous drainage has been used successfully to treat the hepatic hydatid cysts of echinococcal disease. We performed a controlled trial to compare the safety and efficacy of percutaneous drainage with those of surgical cystectomy, the traditional treatment.
Post-Operative 5FU-Docetaxel after High-Dose of Pre-Operative Epirubicin-Cyclophosphamide for Treatment of Inflammatory Breast Cancer: Results of the FNCLCC-Pegase 07 Trial.
Authors: P. Viens, T. Palangié, J. Ferrero, P. Chollet, T. Bachelot, R. Delva, M. Fabbro, M. Janvier, J. Lotz, C. Linassier, N. Dohollou, J. Eymard, B. Leduc, J. Genève, A. Martin, J. Boher, H. Roché
Journal: Cancer Research (2009)

Abstract Purpose: to evaluate the benefit of a post-operative Fluorouracil-Docetaxel (D-5FU) regimen after pre-operative Epirubicin-Cyclophosphamide (EC) and loco-regional treatment for women with inflammatory breast cancer (IBC).Patients and Methods: Women with non-metastatic IBC, age &amp;lt;60 years, life expetancy &amp;gt;3 months, and normal hematological, hepatic and cardiac function were randomized to receive either 4 cycles of EC (epirubicin 150 mg/m² and cyclophosphamide 4000 mg/m² every 3 weeks) then mastectomy with axillary lymph node dissection and radiotherapy (ArmA) or the same treatment followed by 4 cycles of DCT-5FU (docetaxel 75 mg/m², day 1 and 5FU 2500 mg/m²/day continuous infusion, days 1-5 every 3 weeks) (ArmB). Patients (pts) with hormone receptor positive (HR+) tumors received hormonotherapy. Pts were to be followed for five years, disease-free survival (DFS) being the primary study endpoint.Results: From January 2001 to May 2005, 174 pts (87 in each arm) were enrolled. All pts received at least one cycle of intensive chemotherapy and 160 pts (92%) completed the whole intensive regimen. Pts characteristics were well balanced. Main Grade 3-4 toxicities during EC regimen were neutropenia (98%), and trombopenia (94%). Other Grade 3-4 toxicities were vomiting (53%), infection (13%), fever (9.2%) and nausea (8.6%). One patient progressed before surgery (Arm B). Among 71 pts treated with D-5FU, Gr 3-4 neutropenia occurred in 61%.As of April 2009, the median follow-up was 59.8 months. Overall 78 pts experienced at least one event: 12 (6.9%) loco-regional relapses, 58 (33.3%) metastasis, 5 (2.9%) contra-lateral breast cancers and 3 (2.9%) deaths. The estimated 3-year and 5-year disease-free survival (DFS) rates were similar in both arms, 63.0% (95%CI: 51.9-72.2) and 55.5% (95%CI: 44.3-65.3) in arm B compared to 59.8% (95%CI: 48.7-69.2) and 55.0% (95%CI: 43.9-64.7) in arm A. Despite a trend to non proportional hazards between arms (p=0.07), no significant differences were observed on 3-year (p=0.55) and 5-year DFS (p=0.81). No differences were observed on survival rates (p=0.94) with a total of 27 pts (both arms) who died during their follow up period and an estimated 5-year survival rate equal to 70% (95%CI: 59-79) in both arms.In a preliminary multivariate analysis, only HR+ and pathologic complete response in breast and nodes were predictive for 5-year DFS (p&amp;lt;0.0001 and p&amp;lt;0.01) and 5-year OS (p&amp;lt;0.001 and p&amp;lt;0.05).Conclusion: 4 cycles of post-operative D-5FU did not improve DFS or OS of IBC after pre-operative high dose EC and standard therapy. However, at 70% the 5-year survival for the whole population is of great interest. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2081.
CANCER OF THE SIGMOID FLEXURE OF THE COLON AND FIRST PART OF THE RECTUM: DEATH FROM PERFORATION
Authors: C. E. Reeves
Journal: BMJ (1853)

AIn sevr caes of dysmenorrhoa, the pn is not only, to be found in the lumbar, sacral, pubic, and iliac region8, but extends down the inner part of the thighs, and often in he mammm.In some cases of amenorrhnaa, a vicarious discharge has flowed from the breasts.
Percutaneous Tricuspid Valve Replacement in Congenital and Acquired Heart Disease
Authors: Philip A. Roberts, Younes Boudjemline, John P. Cheatham, Andreas Eicken, Peter Ewert, Doff B. McElhinney, Sharon L. Hill, Felix Berger, Danyal Khan, Dietmar Schranz, John Hess, Michael D. Ezekowitz, David Celermajer, Evan Zahn
Journal: Journal of the American College of Cardiology (2011)
Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment.
Authors: C L Wolfe, R E Sievers, F L Visseren, T J Donnelly
Journal: Circulation (1993)

Although previous investigators have demonstrated that myocardial preconditioning reduces infarct size, the mechanisms of cardioprotection associated with preconditioning are not completely understood.To test the hypothesis that preconditioning (four 5-minute episodes of ischemia each followed by 5 minutes of reperfusion) reduces infarct size by depleting cardiac glycogen stores and attenuating the degree of intracellular acidosis during subsequent prolonged left coronary artery occlusion, preconditioned and control rats were subjected to 45 minutes of left coronary artery occlusion and 120 minutes of reflow immediately after preconditioning (groups 1P and 1C, respectively) or after 30 minutes (groups 2P+30m and 2C), 1 hour (groups 3P+60m and 3C), or 6 hours (groups 4P+360m and 4C) of nonischemic recovery after preconditioning but before prolonged ischemia. In each group, cardiectomy was performed in selected rats immediately before prolonged ischemia for cardiac glycogen assay. In selected animals, 31P magnetic resonance spectroscopy was performed to monitor intracellular pH and measure high-energy phosphate levels during ischemia and reperfusion. Group 1P rats demonstrated marked glycogen depletion after preconditioning compared with controls (0.72 +/- 0.39 [n = 9] versus 5.67 +/- 1.73 [n = 12] mg glucose/g wet wt; p < 0.001 versus group 1C) that was associated with attenuation of intracellular acidosis during ischemia, as measured by 31P magnetic resonance spectroscopy (6.8 +/- 0.3 [n = 11] versus 6.2 +/- 0.3 [n = 9] pH units; p < 0.01), and marked infarct size reduction (0.3 +/- 0.6% [n = 7] versus 38.1 +/- 11.3% [n = 7], infarct size divided by risk area; p < 0.0001). During ischemia, there were no differences in myocardial ATP or phosphocreatine levels or in any hemodynamic determinant of myocardial oxygen demand between groups 1P and 1C. In preconditioned rats that were allowed to recover before ischemia (groups 2P+30m, 3P+60m, and 4P+360m), the time course of glycogen repletion paralleled the loss of protection from ischemic injury.Glycogen depletion and the attenuation of intracellular acidosis during ischemia appear to be important factors in delaying irreversible injury and reducing infarct size in this animal model of myocardial preconditioning.