tbuckley/cabot-search huggingface dataset:
MGMT methylation status correlates with temozolomide-mediated radiosensitization in a panel of GBM orthotopic xenografts
Authors: J. N. Sarkaria, B. L. Carlson, P. A. Decker, M. J. Schroeder, G. J. Kitange, K. V. Ballman, C. James
Journal: Journal of Clinical Oncology (2006)

1509 Background: Lack of MGMT methylation in GBM tumors is associated with a worse outcome with combined radiation (RT) and temozolomide (TMZ) therapy, and it is unclear whether non-methylated tumors benefit from TMZ treatment. Methods: The potential benefits of concomitant or adjuvant TMZ relative to methylation status were evaluated in 10 GBM tumors established from patient samples and maintained by serial passage in mice. For each tumor line, 32 mice with established orthotopic xenografts were randomized to A) placebo, B) TMZ PO daily × 5 (120 mg/kg or 66 mg/kg, as indicated) C) RT, 2 Gy bid × 10 fx., D) combined TMZ and RT, and mice were followed until moribund. Efficacy was evaluated by regression modeling and Kaplan-Meier statistical analyses. Results: Six lines with non-methylated MGMT (GBM10, 14, 26, 28, 36, 43) and 4 with methylated MGMT (GBM8, 12, 16, 34) were evaluated, and complete results are available in 6 lines. In all tumor lines and at both dose levels, there was a significant benefit for TMZ relative to placebo (p&lt;0.003). Both methylated tumors (GBM8 and 12) and one non-methylated tumor (GBM14) were markedly sensitive to TMZ with greater than a 50 day extension in survival with monotherapy. Individually and in a pooled analysis, there was no evidence for a synergistic interaction between TMZ and RT in the non-methylated tumors (p=0.91 for pooled analysis). In contrast, there was a striking degree of synergy in GBM12 (p&lt;0.001) and at least additive effects of combined treatment in GBM8 (5 of 8 mice still surviving in the RT/TMZ arm). In a pooled analysis of these 2 MGMT methylated tumors, there was a trend towards synergy (p=0.11). Conclusions: TMZ treatment did not sensitize MGMT non-methylated tumors to radiation, and with one exception, these non-methylated tumors were only modestly sensitive to TMZ alone. In contrast, treatment with TMZ appears to sensitize MGMT-methylated tumors to radiation and monotherapy is associated with marked and significant benefit. [Table: see text] No significant financial relationships to disclose.
Relationship of plasma levels of chlordiazepoxide and metabolites to clinical response
Authors: K M Lin, R O Friedel
Journal: American Journal of Psychiatry (1979)

The authors report on the relationship between the antianxiety effects of chronically administered chlordiazepoxide (CDX) and plasma levels of CDX and two of its metabolites, desmethylchlordiazepoxide (DMCDX) and demoxepam (DMX). Fifteen subjects with moderate to severe anxiety were studied in a double-blind, placebo-controlled, crossover design. Significant correlations were found between anxiety reduction and DMCDX and DMX plasma levels. No such correlation was observed between anxiety reduction and CDX levels. These data suggest that in chronically treated subjects, DMCDX and DMX have significant antianxiety properties which surpass those of CDX itself.
Case 28-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Richard L. Kradin, Eugene J. Mark
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 65-year-old man was admitted to the hospital because of a chronic cough, dyspnea, and an infiltrate in the right lower lobe.He was well until nine months earlier, when he was seen at another hospital because of a cough. X-ray films of the chest (Fig. 1) showed low lung volumes; peripheral rounded opacities were evident in both lower lobes and ranged from 3 to 10 cm in diameter; both costophrenic angles were blunted; no lymphadenopathy was detected; the heart and bony thorax appeared normal. Review of another x-ray film of the chest, obtained eight months previously, . . .
A balancing act in cardiac hypertrophy
Authors: Scot J. Matkovich
Journal: Cardiovascular Research (2016)

This editorial refers to ‘The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy’ by L. Liu et al. , pp. 56–65. 

Cardiac hypertrophy is the process of cardiac myocyte enlargement, typically in response to the need to generate greater levels of contractile force. One of the best examples of adaptive, non-pathological hypertrophy is the expansion of cardiac myocyte volume and sarcomere content that occurs during postnatal development. Initially, compensatory hypertrophy that occurs as a result of persistent hypertension or aortic stenosis can become maladaptive in the longer term, leading to alterations in myocyte electrical stability, sarcolemmal integrity, and potential myocyte loss. The molecular basis of hypertrophy initiation and progression has been well studied, with a host of genetic manipulations in model animal hearts used to define key chromatin remodelling events, alterations in transcription of coding and noncoding mRNA, and post-translational protein modifications required for execution of the hypertrophic programme. However, endogenous pathways that serve to limit the extent of hypertrophy have typically received less attention (Figure 1). 



Figure 1 
Upper panel: summary of the previous literature demonstrating that H19 balances transcription of Igf2; less H19 leads to greater Igf2 levels. Lower panel: findings from Liu et al. (this issue) that in the mouse heart, H19 (acting primarily through generation of miR-675) serves to limit growth responses. Higher H19 and miR-675 levels decrease hypertrophy induction.



In this issue of Cardiovascular Research , Liu …
Abstract P5-08-16: Local immunologic environment related with tumor infiltrating lymphocytes (TIL) and PD-1/PD-L1 expression in early stage breast cancer
Authors: M Okabe, U Toh, N Iwakuma, M Mishima, A Kawahara, M Kage, K Itoh, Y Akagi
Journal: Cancer Research (2016)

Abstract Purpose: Recent studies have shown that local immune environment revealed with programmed death 1(PD-1)/programmed death ligand 1(PD-L1) and tumor infiltrating lymphocytes(TIL) affects the tumor-growth and prognosis. In this study, we evaluated the tumor local immune environments using immunohistological staining for analysis of PD-1/PD-L1 expression and TIL of tumor local in operable early-stage breast cancer. Method: A total of 100 surgical specimens of stageI-III invasive breast carcinoma paraffinembedded between 1995 and 2005 were analyzed. Immunohistological staining for PD-1, PD-L1, PTEN, CD3, CD8, and CD163 were performed by the conventional PAP method. In addition, intratumoral and intrastromal TILs and macrophages were simultaneously stained by anti-CD3, CD8, CD163 antibodies and measured by 'Win ROOF' computer software (version 5.7, Mitani Corporation, Japan). Results: Intratumoral PD-1 expressed significantly higher in triple negative breast cancer (TNBC) compared to other subtype BC (p=0.0094), intratumoral and intrastromal CD3+ lymphocytes and CD163+ macrophages were also significantly higher in TNBC, respectively (CD3: p=0.0002; 0.0139 and CD163: p=0.0043; 0.0270). PTEN loss was also more frequently observed in TNBC (p=0.0475). In addition, after a median 5-year follow-up, patients of luminal A subtype with lower PD-L1 and PTEN expression showed better disease free survival (DFS) with a significant difference (p=0.0148, p=0.0475). Conclusion: Local expression of PD-1/PD-L1 antigens on tumor cells, CD3+ lymphocytes, CD163+ macrophages infiltration singnificantly increased in early-stage TNBC. PTEN expression on tumor local might be associated with DFS in patients with early-stage BC. Citation Format: Okabe M, Toh U, Iwakuma N, Mishima M, Kawahara A, Kage M, Itoh K, Akagi Y. Local immunologic environment related with tumor infiltrating lymphocytes (TIL) and PD-1/PD-L1 expression in early stage breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-16.
Abstract 18396: In-vivo Assessment of Wall Stiffness and Wall Shear Stress in Human Coronary Arteries using Computed Tomography Angiography
Authors: Sotirios Katranas, Anastasios Kelekis, Teodoros Theodoridis, Alexandros Tzanis, Yiannis Chatzizisis, George Giannoglou
Journal: Circulation (2010)

Introduction: Wall stiffness has been an important factor in the pathophysiology of coronary artery disease. The in-vivo non-invasive assessment of the role of wall stiffness in atherosclerosis has not been studied. Hypothesis: Atherosclerotic regions as well as their adjacent areas are characterized by decreased wall stiffness and lower wall shear stress (WSS) compared to non-atherosclerotic regions. Methods: Using 128-computed tomography angiography 10 coronary arteries (6 left anterior descending arteries and 4 right coronary arteries) were 3D-reconstructed. Thirty eight atherosclerotic regions of interest were identified, and the non-atherosclerotic regions served as controls. A computational grid was created in the reconstructed arteries in diastole and the WSS was calculated in each region of interest using computational fluid dynamics. In each region of interest plaque morphology measurements were performed in both cardiac phases and the wall stiffness was measured with the formula ΔP x V/ΔV, where...
Ward 55
Authors: J J Frey
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract B40: A two-microRNA signature in urinary exosomes for diagnosis of prostate cancer
Authors: Peter Mouritzen, Jacob Christian Fredsøe, Thorarinn Blondal, Anne Karin Rasmussen, Michael Borre, Christa Haldrup, Ditte Andreasen, Niels Tolstrup, Torben Falck Ørntoft, Karina Dalsgaard Sørensen
Journal: Cancer Research (2016)

Abstract Antibody based detection of circulating prostate specific antigen (PSA) remains an important test in the diagnosis of prostate cancer. Unfortunately the test identifies a high number of false positives which require further testing to confirm the presence of cancer including several biopsies taken from the prostate itself. Whereas the performance of biopsies on individuals is associated with discomfort and risk of serious side effects, the invasive test also represents an expense to health care systems. Given the high number of false positives, the PSA test is therefore the direct cause of unnecessary suffering of healthy individuals and costs to health systems. To investigate the possibilities for developing a non-invasive and more specific test, we have developed different technologies enabling the detection of prostate cancer microRNA biomarkers in exosomes derived from urine from non-prostate massaged men. The first of these technologies is a highly sensitive LNA™-based qPCR platform for microRNA detection, which enables profiling in biofluids where microRNA levels are extremely low. At this point we have already applied this platform on thousands of biofluid samples including serum/plasma and urine to establish normal reference ranges for circulating microRNAs as well as to identify biomarkers of disease. The second technology is a simple exosome precipitation system which only requires low speed centrifugation to harvest urine exosomes. We have combined our developed technologies and applied this on cell-free urine from two different cohorts of approximately 220 patients each, to identify a number of differentially regulated microRNAs in urine from prostate cancer bearing individuals. Prostate cancer specific signatures have been obtained by different combinations of these differentially regulated microRNAs. The smallest signature is composed of two microRNAs which allows constructing receiver operating characteristic curves with areas under the curve well above 0.8. Citation Format: Peter Mouritzen, Jacob Christian Fredsøe, Thorarinn Blondal, Anne Karin Rasmussen, Michael Borre, Christa Haldrup, Ditte Andreasen, Niels Tolstrup, Torben Falck Ørntoft, Karina Dalsgaard Sørensen. A two-microRNA signature in urinary exosomes for diagnosis of prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B40.
Nationwide outbreak of Salmonella enterica serotype 4,[5],12:i:- infection associated with consumption of dried pork sausage, France, November to December 2011
Authors: C M Gossner, D van Cauteren, S Le Hello, F  X Weill, E Terrien, S Tessier, C Janin, A Brisabois, V Dusch, V Vaillant, N Jourdan-da Silva
Journal: Eurosurveillance (2012)

An outbreak of the monophasic variant of Salmonella enterica serotype 4,[5],12:i:- occurred in November and December 2011 in France. Epidemiological investigation and food investigation with the help of supermarket loyalty cards suggested dried pork sausage from one producer as the most likely source of the outbreak. Despite the absence of positive food samples, control measures including withdrawal and recall were implemented.
Estimating the Risk of Chronic Pain: Development and Validation of a Prognostic Model (PICKUP) for Patients with Acute Low Back Pain
Authors: Adrian C. Traeger, Nicholas Henschke, Markus Hübscher, Christopher M. Williams, Steven J. Kamper, Christopher G. Maher, G. Lorimer Moseley, James H. McAuley
Journal: PLoS Medicine (2016)

Background Low back pain (LBP) is a major health problem. Globally it is responsible for the most years lived with disability. The most problematic type of LBP is chronic LBP (pain lasting longer than 3 mo); it has a poor prognosis and is costly, and interventions are only moderately effective. Targeting interventions according to risk profile is a promising approach to prevent the onset of chronic LBP. Developing accurate prognostic models is the first step. No validated prognostic models are available to accurately predict the onset of chronic LBP. The primary aim of this study was to develop and validate a prognostic model to estimate the risk of chronic LBP. Methods and Findings We used the PROGRESS framework to specify a priori methods, which we published in a study protocol. Data from 2,758 patients with acute LBP attending primary care in Australia between 5 November 2003 and 15 July 2005 (development sample, n = 1,230) and between 10 November 2009 and 5 February 2013 (external validation sample, n = 1,528) were used to develop and externally validate the model. The primary outcome was chronic LBP (ongoing pain at 3 mo). In all, 30% of the development sample and 19% of the external validation sample developed chronic LBP. In the external validation sample, the primary model (PICKUP) discriminated between those who did and did not develop chronic LBP with acceptable performance (area under the receiver operating characteristic curve 0.66 [95% CI 0.63 to 0.69]). Although model calibration was also acceptable in the external validation sample (intercept = −0.55, slope = 0.89), some miscalibration was observed for high-risk groups. The decision curve analysis estimated that, if decisions to recommend further intervention were based on risk scores, screening could lead to a net reduction of 40 unnecessary interventions for every 100 patients presenting to primary care compared to a "treat all" approach. Limitations of the method include the model being restricted to using prognostic factors measured in existing studies and using stepwise methods to specify the model. Limitations of the model include modest discrimination performance. The model also requires recalibration for local settings. Conclusions Based on its performance in these cohorts, this five-item prognostic model for patients with acute LBP may be a useful tool for estimating risk of chronic LBP. Further validation is required to determine whether screening with this model leads to a net reduction in unnecessary interventions provided to low-risk patients.
Brief Communication: Agglutination of 2,4-Dinitrophenyl-Tagged Normal Human Leukocytes by Concanavalin A: Possible Relationship to Their Ability To Evoke Production of Leukemia-Associated Antibodies23
Authors: Rolf F. Barth, K. R. Madyastha, P. R. Madyastha
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Brief Communication: Agglutination of 2,4-Dinitrophenyl-Tagged Normal Human Leukocytes by Concanavalin A: Possible Relationship to Their Ability To Evoke Production of Leukemia-Associated Antibodies Get access Rolf F. Barth, Rolf F. Barth Search for other works by this author on: Oxford Academic PubMed Google Scholar K. R. Madyastha, K. R. Madyastha Search for other works by this author on: Oxford Academic PubMed Google Scholar P. R. Madyastha P. R. Madyastha Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 1, January 1975, Pages 73–76, https://doi.org/10.1093/jnci/54.1.73 Published: 01 January 1975 Article history Received: 26 August 1974 Accepted: 29 October 1974 Published: 01 January 1975
The future educational needs of psychiatrists
Authors: R R Grinker
Journal: American Journal of Psychiatry (1975)

The author states the psychiatry must work at defining its boundaries as a discipline before the question of how to educate future practitioners can be answered. The medical student is presented with a bewildering array of approaches to psychiatric treatment and is pressured to choose quickly. The author calls for collaboration among the various parts of psychiatry--social psychiatry, community psychiatry, research, biochemistry, etc.--with other university faculties such as the humanities and basic sciences. The goal of this collaboration would be to produce a mature professional capable of dealing with the whole person. He also calls for a greater emphasis on research to equip psychiatry with the necessary knowledge to establish its role in our ever-changing contemporary society.
Broad-Spectrum Antifungal Prophylaxis in Patients With Cancer at High Risk for Invasive Mold Infections: Counterpoint
Authors: Johan Maertens, Kristel Buvé, Elias Anaissie
Journal: Journal of the National Comprehensive Cancer Network (2008)

Management of invasive mold infections in patients with prolonged neutropenia and hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) has been hampered by the difficulty in diagnosing these infections. Definite diagnosis invariably centers on histologic identification of hyphae in tissue or on culture from a sterile body site. Therefore, most practitioners have relied on prophylaxis and empiric therapy. Currently, emphasis is shifting from routine prophylaxis and empiric therapy to screening of patients with neutropenia at high risk so that clinicians can administer appropriate antifungal therapy early, when it can potentially improve patient outcome. Non–culture-based microbiologic tools are at the forefront of this paradigm shift. Commercially available methods to detect fungal antigens and sophisticated techniques to detect fungal DNA may be used as screening tools during the highest risk period. Together with assessment of clinical signs, cultures, and especially CT scanning, these methods are useful for starting antifungal therapy preemptively. While awaiting further evaluation of these tools during the postengraftment period of allogeneic HSCT, mold-active prophylaxis targeting the subgroup of patients with severe acute or chronic GVHD may be justified. However, some critical issues have not yet been adequately addressed, including the generalizability of study results, impact of mucositis and gastrointestinal GVHD on drug bioavailability, need for therapeutic drug monitoring, impact of prophylaxis on the performance of diagnostic assays, and optimal treatment of breakthrough invasive fungal infections.
Patients with secondary acute myelocytic leukemia (AML) receiving "timed" sequential chemotherapy.
Authors: Z A Arlin, S J Kempin, R Mertelsmann, T S Gee, B Clarkson
Journal: Journal of Clinical Oncology (1983)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1983.1.8.513 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 6583323 Patients with secondary acute myelocytic leukemia (AML) receiving "timed" sequential chemotherapy. Z A ArlinxZ A ArlinSearch for articles by this author , S J KempinxS J KempinSearch for articles by this author , R MertelsmannxR MertelsmannSearch for articles by this author , T S GeexT S GeeSearch for articles by this author , B ClarksonxB ClarksonSearch for articles by this author https://doi.org/10.1200/JCO.1983.1.8.513 PDF "Patients with secondary acute myelocytic leukemia (AML) receiving "timed" sequential chemotherapy.." Journal of Clinical Oncology, 1(8), p. 513© 1983 by American Society of Clinical Oncology
In Vivo Growth and Antigenic Properties of a Rat Sarcoma Induced by Moloney Sarcoma Virus2
Authors: J. M. Jones, F. Jensen, B. Veit, J. D. Feldman
Journal: JNCI Journal of the National Cancer Institute (1974)

The growth and antigenic properties of a BN Moloney sarcoma (MST) were examined in syngeneic (BN) and allogeneic (lewis) rats. In BN rats, MST doses of 5 × 106 cells and higher were invariably fatal, and tumor growth was most rapid when MST was injected intraperitoneally. lewis rats were completely resistant to MST doses up to 5×l07 cells. lewis rats produced a greater cell-mediated cytotoxicity response than did BN rats, directed chiefly to AgB antigens, and they yielded less anti-gs-1 antibody. Growth of MST in BN rats was inhibited by immune spleen cells and MP lectin, was not affected by phytohemagglutinin or concanavalin A, and was enhanced by immune serum. Lewis rats, hyperimmunized with MST, produced antibody to alloantigens and to tumorspecific and virus-related antigens. Antitumor antibody could be eluted from growing solid tumors of either host. Studies with enriched radiolabeled anti-AgB antibody showed that MST cells carried about 50% of the alloantigen content of normal BN cells, but that amount was sufficient to provoke a brisk immune response in lewis rats.