tbuckley/cabot-search huggingface dataset:
Abstract 2799: Adoptive immunotherapy for pediatric solid tumors with CAR-T cells (chimeric antigen receptor bearing T cells) targeting ALK (anaplastic lymphoma kinase, CD246)
Authors: Alec Walker, Paola Lopomo, William Babbitt, Marc Vigny, Crystal L. Mackall, Rimas J. Orentas
Journal: Cancer Research (2014)

Abstract Neuroblastoma is the most common non-CNS tumor in children. High-risk disease has a dire prognosis and new treatment strategies are need. The identification of unique cell-surface proteins expressed on tumor cells, yet not expressed on normal tissues, has been challenging for pediatric malignancies. However, identification of such antigens allows for the development of new immune-based therapies featuring Ig-like binding motifs. The cell surface tyrosine kinase ALK (CD246, anaplastic lymphoma kinase) is a promising target for neuroblastoma in that it is expressed in either native, mutated, or over-expressed forms on the plasma membrane surface of the tumor cell and may contribute to disease progression or severity. We identified antibodies that bind to extracellular domains of ALK, sequenced their variable regions, and used this sequence information to construct chimeric antigen receptors (CARs). Primary human T lymphocytes were then transduced with retroviral gene vectors expressing a series of ALK-specific CAR. We tested CARs that incorporated both different structural and signaling motifs. Transduced T cells demonstrated ALK-specific cytolytic activity against ALK-expressing tumors and produced Th1 cytokines upon culture in the presence of tumor. In exploring different iterations of CAR domain structure we found that the scFv domains created from the heavy and light variable domains of ALK-specific immunoglobulin could be interchanged with respect to their orientation in the context of CAR tertiary protein structure. Moreover, ALK-specific scFv functioned whether expressed in a short format, that is as a single domain proximal to the T cell membrane, or in a long format, that is extended away from the plasma membrane using an IgG1-derived spacer domain composed of CH2 and CH3. Using a xenogeneic NSG mouse model for neuroblastoma, human ALK-specific CAR-expressing T cells were found to eradicate ALK-positive tumor, when IL-7 was included to support T cell persistence. These data argue for the continued evaluation of ALK-specific CARs in pre-clinical studies. Citation Format: Alec Walker, Paola Lopomo, William Babbitt, Marc Vigny, Crystal L. Mackall, Rimas J. Orentas. Adoptive immunotherapy for pediatric solid tumors with CAR-T cells (chimeric antigen receptor bearing T cells) targeting ALK (anaplastic lymphoma kinase, CD246). [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 2799. doi:10.1158/1538-7445.AM2014-2799
Abstract 2191: Chronic Partial Unloading Improves {beta}-adrenergic Response and Normalizes Gene Expression in Failing Rat Hearts
Authors: Jian Wang, Masaki Tsukashita, Takeshi Nishina, Akira Marui, Eiji Yoshikawa, Hiroyuki Muranaka, Tadashi Ikeda, Masashi Komeda
Journal: Circulation (2007)
Measured and perceived bronchodilation: results of a placebo-controlled cross-over trial comparing formoterol and salmeterol in asthma patients
Authors: T.R.J. Schermer, W.J. Hoff, A.P.M. Greefhorst, J.P.H.M. Creemers, A.P. Sips
Journal: American Journal of Respiratory and Critical Care Medicine (1999)
A salutary experience: On the receiving end
Authors: R. Kendell
Journal: BMJ (2000)

the condition, which often obscures the causative link.For those patients with the disease, further potentially harmful interventions should be avoided.As exemplified in case 1, however, cholesterol embolism may occur without instrumentation, and the diagnosis should not be dismissed in such cases.Contributors: PJD, LL, EJC, GG, CDP, TC, and ANW were involved in the clinical care of the patients.PJD and ANW conceived, researched, and wrote the paper, and reviewed and revised the final manuscript.TC reported on the biopsy specimens, provided the histopathology photomicrographs, and reviewed the final manuscript.GG was involved in the initial
Association of an Endovascular-First Protocol for Ruptured Abdominal Aortic Aneurysms With Survival and Discharge Disposition
Authors: Brant W. Ullery, Kenneth Tran, Venita Chandra, Matthew W. Mell, Edmund J. Harris, Ronald L. Dalman, Jason T. Lee
Journal: JAMA Surgery (2015)

<h3>Importance</h3> Mortality after an open surgical repair of a ruptured abdominal aortic aneurysm (rAAA) remains high. The role and clinical benefit of ruptured endovascular aneurysm repair (rEVAR) have yet to be fully elucidated. <h3>Objective</h3> To evaluate the effect of an endovascular-first protocol for patients with an rAAA on perioperative mortality and associated early clinical outcomes. <h3>Design, Setting, and Participants</h3> Retrospective review of a consecutive series of patients presenting with an rAAA before (1997-2006) and after (2007-2014) implementation of an endovascular-first treatment strategy (ie, protocol) at an academic medical center. <h3>Main Outcomes and Measures</h3> Early mortality, perioperative morbidity, discharge disposition, and overall survival. <h3>Results</h3> A total of 88 patients with an rAAA were included in the analysis, including 46 patients in the preprotocol group (87.0% underwent an open repair and 13.0% underwent an rEVAR) and 42 patients in the intention-to-treat postprotocol group (33.3% underwent an open repair and 66.7% underwent an rEVAR;<i>P</i> = .001). Baseline demographics were similar between groups. Postprotocol patients died significantly less often at 30 days (14.3% vs 32.6%;<i>P</i> = .03), had a decreased incidence of major complications (45.0% vs 71.8%;<i>P</i> = .02), and had a greater likelihood of discharge to home (69.2% vs 42.1%;<i>P</i> = .04) after rAAA repair compared with preprotocol patients. Kaplan-Meier analysis demonstrated significantly greater long-term survival in the postprotocol period (log-rank<i>P</i> = .002). One-, 3-, and 5-year survival rates were 50.0%, 45.7%, and 39.1% for open repair, respectively, and 61.9%, 42.9%, and 23.8% for rEVAR, respectively. <h3>Conclusions and Relevance</h3> Implementation of a contemporary endovascular-first protocol for the treatment of an rAAA is associated with decreased perioperative morbidity and mortality, a higher likelihood of discharge to home, and improved long-term survival. Patients with an rAAA and appropriate anatomy should be offered endovascular repair as first-line treatment at experienced vascular centers.
1006. Preliminary Results of a Phase I Trial Using Retroviral Gene Transfer of G156A MGMT To Protect Hematopoiesis during BG and BCNU Therapy of Advanced Malignancies
Authors: Jane Reese, Karen Lingas, Pamela Ksenich, Colin Sweeney, Omer Koc, Stanton Gerson
Journal: Molecular Therapy (2004)

We have extensively studied the G156A MGMT mutation which confers O6alkylguanine DNA alkyltransferase (AGT) that is resistant to O6benzylguanine (BG). In a Phase I clinical trial at our institution, BG was shown to inhibit tumor AGT at 120mg/m2 and the maximum tolerated dose of BCNU was 40 mg/m2. In the laboratory, we have shown that the retrovirus MFG-G156A-MGMT confers BG and BCNU resistance ex vivo into human CD34+ cells. We have also reported that G156A-MGMT transduced murine hematopoietic progenitors repopulate the bone marrow and can be enriched up to 1000-fold after 2 cycles of BG and BCNU. These studies demonstrate the strong capacity of this model to confer BG and BCNU resistance and a selection advantage in vivo. Based on these data, we initiated a clinical trial using gene transfer into autologous CD34+ cells in patients with advanced malignancies. Patients undergo CD34+ mobilization with G-CSF and GM-CSF. CD34+ enriched cells (CliniMACS, Miltenyi) are transduced with MFG-G156A MGMT (produced in PG13 cells by the NGVL, K. Cornetta, Director) in the presence of the fibronectin fragment CH-296 (provided by Takara Bio Inc) and the cytokine combination SCF, Tpo, and Flt-3 ligand for 86 hours. The cell culture is harvested on day 4 and the entire culture is re-infused into the patient who received BG and BCNU 48 hours prior. Patients receive subsequent cycles of BG and BCNU every 6 weeks with analysis of marrow and blood cells for evidence of gene transfer prior to each cycle. In the first three patients, the frequency of gene transfer measured by proviral containing CFU in the post transduction culture was 20 ± 7% and 6.3 ± 3 % of the cells expressed G156A-AGT by flow cytometry. An average of 4.4 ± 2 x 107viable mononuclear cells with a CD34 purity of 93 ± 5% were infused. In one patient, 10% of bone marrow CFU showed presence of the provirus 5 weeks after infusion but prior to the second cycle of BG and BCNU. In this same patient, insertion site analysis by LAM-PCR showed a similar banding pattern in both the lymphocyte-monocyte and granulocyte fractions, indicating multilineage reconsitituion by a single transduced stem cell. Our preliminary results demonstrate efficient gene transfer into cytokine stimulated CD34+ cells using the MFG-G156A-MGMT vector and these cells can be infused without toxicity. Given the strong degree of selection observed in pre-clinical models, we anticipate enrichment for transduced cells following each cycle of chemotherapy.
Statistics Notes: Presentation of numerical data
Authors: D. G Altman, J M. Bland
Journal: BMJ (1996)

The purpose of a scientific paper is to communicate, and within the paper this applies especially to the presentation of data.

Continuous data, such as serum cholesterol concentration or triceps skinfold thickness, can be summarised numerically either in the text or in tables or plotted in a graph. When numbers are given there is the problem of how precisely to specify them. As far as possible the numerical precision used should be consistent throughout a paper and especially within a table. In general, summary statistics such as means should not be given to more than one extra decimal place over the raw data. The same usually applies to measures of variability or uncertainty such as the standard deviation or standard error, though greater precision may be warranted for these quantities as they are …
Ongoing HIV dissemination during HAART
Authors: Zvi Grossman, Michael Polis, Mark B. Feinberg, Zehava Grossman, Itschak Levi, Shirley Jankelevich, Robert Yarchoan, Jacob Boon, Frank de Wolf, Joep M.A. Lange, Jaap Goudsmit, Dimiter S. Dimitrov, William E. Paul
Journal: Nature Medicine (1999)
A Decision Support Tool to Reduce Overtesting for Ceruloplasmin and Improve Adherence With Clinical Guidelines
Authors: Elliot B. Tapper, Neil Sengupta, Michelle Lai, Gary Horowitz
Journal: JAMA Internal Medicine (2015)

This before-and-after comparison study reports that physician ordering patterns of ceruloplasmin tests decreased after a decision pop-up tool was added to the electronic medical record system at Beth Israel Deaconess Medical Center.
Abstract 13052: Stability of Hospital Rankings for Acute Myocardial Infarction
Authors: Saket Girotra, Gary Rosenthal, Xin Lu, Mary Vaughan-Sarrazin, Peter Cram
Journal: Circulation (2014)

Background: Although hospital mortality for acute myocardial infarction (AMI) varies widely, little is known regarding the trajectory of mortality over time at hospitals with high and low mortality at baseline. Methods: We studied 623,488 Medicare AMI patients at 1923 hospitals during 2007-2010. We used 30-day risk-standardized mortality rates (RSMR) to stratify hospitals as bottom 25% and top 25% in 2007 (baseline) and compared their performance on AMI mortality during next 3 years. We also ranked top 25% and bottom 25% hospitals into quartiles of RSMR, each year during 2008-2010 (0 = worst mortality quartile, to 3 = lowest mortality quartile), and summed quartile ranks for each year to yield a composite score (CS: range = 0 to 9). We examined which bottom 25% and top 25% hospitals achieved low ( &lt; 1) and high CS (≤ 8). Results: Average RSMR in 2007 was 15.5% (range: 11.2%-21.6%). During 2008-2010, there was considerable overlap in AMI mortality at 481 hospitals that were top 25% (blue bars) and bottom 25% (red bars), respectively (Figure). Of bottom 25% hospitals, only 107 (22%) had persistently high mortality over next 3 years (CS &lt; 1) where as 37 (8%) hospitals had marked improvement in AMI mortality (CS ≤ 8). Similarly, only 127 (26%) of top 25% hospitals had persistently low mortality over next 3 years (CS ≤ 8) and 37 (8%) had marked worsening in AMI mortality (CS &lt; 1). Average RSMR at hospitals with persistently high mortality was 18.5% vs. 13.7% at hospitals with persistently low mortality, which led to an additional 834 Medicare deaths at high mortality hospitals. Patient and hospital characteristics were limited in differentiating hospitals with persistently high and persistently low mortality. Conclusions: Among hospitals with high and low mortality at baseline, performance on AMI mortality does not persist during subsequent years. Concentrating quality improvement efforts at a few hospitals with persistently high mortality could avoid a substantial number of AMI deaths.
Intraendothelial tubular aggregates in experimental wounds
Authors: R.A.J. EADY, G.F. ODLAND
Journal: British Journal of Dermatology (2006)

Intraendothelial tubular aggregates were found in small dermal blood vessels in three healing superficial wounds in patients receiving systemic corticosteroids. Similar inclusions were also demonstrated in two wounds in healthy subjects, but were not found in normal (unwounded) skin of either healthy subjects or steroid-treated patients. Tubular aggregates of similar structure have previously been described as occurring in ‘connective tissue’ or ‘auto-immune’ diseases, including lupus erythematosus and dermatomyositis, both in the skin and in internal organs. Although it has been suggested that such aggregates are of viral origin, their morphogenesis and significance remain undetermined. Our findings do not support a viral cause, but suggest that these structures are probably a product of regenerating endothelium.
Observations on the Influence of Force Breeding in Mice With and Without the Mammary-Tumor Agent&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: John J. Bittner
Journal: JNCI Journal of the National Cancer Institute (1961)

Females of cancerous strains Z (C3H) and D2 (DBA/2), and agent-free Zb and reciprocal (Ax × Zb)F1 females were subjected to force breeding and compared with normal breeding females allowed to nurse their young. There was no significant increase in incidence and no correlation between the time of development of mammary cancer and the number of litters in the force breeders, as compared with normal breeders. In this respect, females of subline Z (C3H) differed from animals of either sublines C3H/An or C3H/He, which confirmed the observations made previously by many workers that animals of one line should never serve as controls for experimental data obtained for mice of another subline of the same inbred strain. Comparable experimental observations have been secured by the subjection of mice of the same subline to the functional breeding test and excessive hormonal stimulation. These data would not support the theory suggested by Bagg in 1939 that prevention of nursing produced stagnation of the mammary ducts and became a major factor in the development and/or acceleration of mammary cancer in mice. Earlier it was shown that there was little milk production in the mammary glands of females that had not nursed their young and consequently little milk stagnation. A general review of the subject is included.
ATROPHY AND NECROSIS OF THE LIVER WITHOUT JAUNDICE
Authors: James F. Weir
Journal: Annals of Internal Medicine (1939)

Article1 May 1939ATROPHY AND NECROSIS OF THE LIVER WITHOUT JAUNDICEJAMES F. WEIR, M.D., F.A.C.P.JAMES F. WEIR, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-12-11-1845 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptJaundice is probably the symptom which leads all others in attracting attention to hepatic disease. In its absence, the occurrence of ascites, pruritus, hematemesis, melanoderma, or enlargement of the liver or spleen may indicate the presence of hepatic disease. There are, however, many hepatic conditions not associated with these symptoms and signs and, in such cases, diagnosis must rest largely on suspicion. In the recognition of subclinical cases, a clue is frequently obtained from careful scrutiny of the history and close observation of the patient. In doubtful cases, a review of possible etiologic factors may lead to further search for...References1. BLOOMFIELD AL: The natural history of chronic hepatitis (cirrhosis of the liver), Am. Jr. Med. Sci., 1938, cxcv, 429-444. CrossrefGoogle Scholar2. JONESEATON CMFB: The prognostic significance of a spontaneous diuresis in acute or subacute disease of the liver, New England Jr. Med., 1935, ccxiii, 907-918. CrossrefGoogle Scholar3. WEIRCOMFORT JFMW: Toxic cirrhosis caused by cinchophen, Arch. Int. Med., 1933, lii, 685-724. CrossrefGoogle Scholar4. SNELLCOMFORT AMMW: Hepatic lesions presumably secondary to pancreatic lithiasis and atrophy: report of two cases, Am. Jr. Digest. Dis. and Nutr., 1937, iv, 215-218. CrossrefGoogle Scholar5. WILSONGOODPASTURE JDEW: Yellow atrophy of the liver; acute, subacute and healed, Arch. Int. Med., 1927, xl, 377-385. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota*Submitted for publication May 18, 1938. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAbstracts of Current Literature 1 May 1939Volume 12, Issue 11Page: 1845-1854KeywordsAscitesAtrophyLiverLiver diseasesNecrosisPruritusSigns and symptomsSpleen ePublished: 1 December 2008 Issue Published: 1 May 1939 PDF downloadLoading ...
A Living Substance as Such, and as Organism.
Authors: Andrews, Gwendolen (Foulke) Mrs. E. A. Andrews,
Journal: JAMA (1898)

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
What is the optimal diet for cardiovascular health
Authors: Thomas E. Kottke
Journal: BMJ (2003)

Fruits, vegetables, grains, and fish should be advised for everyone over a lifetime 

This article originally appeared in BMJ USA 

After 25 years of follow-up in the Seven Countries Study, death rates from coronary heart disease (CHD) ranged from 268 per 1000 in East Finland to 25 per 1000 in Crete, Greece.1 This difference is one order of magnitude, and more than 90% of the variance across cohorts is attributable to differences in consumption of saturated fat. A systematic review of randomized controlled trials, published in this issue of BMJ USA , contributes to the evidence that the association between a low-fat diet and low death rates from CHD is causal.2 To take the next step and apply this information to practice, we need to answer four questions:

Among the Seven Countries Study cohorts, consumption of dairy products was …
Innovative Uses and Emerging Technologies in Endoscopy
Authors: J. Van Den Bogaerde, D. Sorrentino
Journal: Endoscopy (2013)

Endoscopy is a fast moving field, and new techniques are constantly emerging. In recent decades, gastrointestinal endoscopy has evolved and branched out from a visual diagnostic modality, using fibreoptic bundles, to enhanced video and computer assisted imaging, with impressive interventional capabilities. Some new endoscopic techniques will be too complex or expensive to make the leap into general gastroenterology practice, others already show major progress in the management of digestive diseases. In this chapter we will discuss some of the emerging techniques and technologies used to increase the diagnostic yield in the colon and small intestine including third eye retroscopes, colon capsule endoscopy, bal‐ loon and spiral enteroscopy and confocal laser endomicroscopy. We will also discuss over the scope clip (OTSC) devices, a relatively simple and inexpensive tool potentially capable of closing noninvasively intestinal perforations and allowing the removal of infiltrating tu‐ mors. Experimental modalities such as natural orifice translumenal endoscopic surgery (NOTES) will also be discussed, with emphasis on their future clinical use. We will also fo‐ cus on endoscopic ultrasonography (EUS), which has moved from an experimental techni‐ que to a valuable established diagnostic modality which not only competes with modern imaging modalities such as MRI, but is also particularly useful in the interventional setting especially in pancreatic and hepatobiliary pathology. We will also discuss the importance of training endoscopists in the use of these new techniques and we will offer some speculation on which of them may become really useful in routine patient care or remain restricted to large teaching hospitals.