tbuckley/cabot-search huggingface dataset:
Abstract LB-141: Multiple protein secretion profiling analysis of cancer cells at single cell and small cell colony level with integrated barcode chip
Authors: Young Shik Shin, Kiwook Hwang, Rong Fan, James R. Heath
Journal: Cancer Research (2010)

Abstract Pathophysiology of a complex disease such as cancer requires capability to analyze highly heterogeneous cellular events at single cell level, which can measure large numbers of molecular events from individual cells to be analyzed in statistically meaningful manner. Here we report on an approach that integrates microfluidic cell handling and in situ protein secretion profiling to assess the functional heterogeneity of single cells, with extensions to small cell colonies. We measured a dozen proteins secreted from cells for the most aggressive type of primary brain tumor, glioblastoma multiforme (GBM). We observed functional phenotypes in terms of secreted proteins with profound cellular heterogeneity but still in a statistically meaningful manner. The unique features that we confirmed from single cell analysis can present additional useful information to the conventional bulk analysis. Combining physical status of the system such as cell-cell distance and the protein secretion profiles enables to study tumor microenvironment. We further demonstrate the potential application of this platform to the clinic by analyzing solid tumor cells derived from a GBM patient. This platform is inexpensive, requires minute amounts of cells and yields large volume of molecular information, showing great potential for clinical assessment of cellular characteristics in human disease lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-141.
Multiple Factors in the Prediction of Risk of Proliferative Diabetic Retinopathy
Authors: Lawrence I. Rand, Andrzej S. Krolewski, Lloyd M. Aiello, James H. Warram, Richard S. Baker, Takashi Maki
Journal: New England Journal of Medicine (1985)

To identify risk factors for the development of proliferative diabetic retinopathy, we compared 111 patients with long-standing insulin-dependent diabetes who had proliferative retinopathy (cases) with 81 patients with diabetes of similar duration (an average of 26 years) who did not have proliferative diabetic retinopathy (controls). The cases had diabetes that was more difficult to manage, as evidenced by their more frequent blood sugar levels above 200 mg per deciliter (11 mmol per liter) on routine clinic visits (odds ratio, 1.6 for each increment of 10 per cent in the relative frequency), and they expended less effort in managing their diabetes, as indicated by their less frequent testing of urine for sugar (odds ratio, 0.3). Among those who did not have myopia, the cases also had an excess of the HLA-DR phenotypes 4/0, 3/0, or X/X (odds ratio, 10.0). Among those with myopia, these phenotypes did not carry an increased risk of proliferative retinopathy. These results support a multifactorial model for the development of proliferative diabetic retinopathy; however, the mechanisms of action of the identified factors remain unknown. (N Engl J Med 1985; 313: 1433–8.)
Multiple GPCR conformations and signalling pathways: implications for antagonist affinity estimates
Authors: Jillian G. Baker, Stephen J. Hill
Journal: Trends in Pharmacological Sciences (2007)

Antagonist affinity measurements have traditionally been considered important in characterizing the cell-surface receptors present in a particular cell or tissue. A central assumption has been that antagonist affinity is constant for a given receptor-antagonist interaction, regardless of the agonist used to stimulate that receptor or the downstream response that is measured. As a consequence, changes in antagonist affinity values have been taken as initial evidence for the presence of novel receptor subtypes. Emerging evidence suggests, however, that receptors can possess multiple binding sites and the same receptor can show different antagonist affinity measurements under distinct experimental conditions. Here, we discuss several mechanisms by which antagonists have different affinities for the same receptor as a consequence of allosterism, coupling to different G proteins, multiple (but non-interacting) receptor sites, and signal-pathway-dependent pharmacology (where the pharmacology observed varies depending on the signalling pathway measured).
Update in Occupational and Environmental Respiratory Disease 2007
Authors: Tim S. Nawrot, Ernesto Alfaro-Moreno, Benoit Nemery
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Several original epidemiologic studies showing associations between specific environmental or occupational exposures and adverse respiratory effects were published in 2007. Such studies in large populations often rely, by necessity, on crude endpoints, such as mortality, respiratory symptoms obtained by questionnaires, or simple pulmonary function measurements. Although such observational studies may point to causal links between (presumed) exposure and disease, they must be completed by further epidemiologic studies that use more refined endpoints and/or more sophisticated designs, and by experimental studies that are needed to provide plausibility as well as mechanistic explanations for the observed findings. Thus, in an editorial, Kaufman (1) pointed to the importance to integrate epidemiologic and toxicology approaches to elucidate the mechanism of the effects of air pollution on health.
Manual of Pediatric Hematology and Oncology
Authors: Ruth Andrea Seeler
Journal: JAMA (1990)

Hurrah, hurrah, hurrah! An affordable, readable, portable book for pediatricians, family practitioners, and house officers or students taking electives in pediatric hematology/oncology. Dr Lanzkowsky has combined the best of his two previous volumes into an updated manual. Dr Lanzkowsky's extensive clinical experience provides a cohesiveness to the presentation of the clinical problems. Greater space and detail are allotted to the common disorders and their uncommon presentations, while the rarer diagnoses are there, but considerably abridged. The reader will need to pursue zebras elsewhere. Each chapter includes the little "how to's" so necessary to a prompt diagnosis. Of necessity the manual is chock-full of tables and graphs to guide the reader to the correct diagnosis. After arriving at a diagnosis, however, the physician will need other sources for the latest molecular biological information, ie, this is not the text that explains on which band of what autosome a dominant hereditary trait
Pustulosis palmoplantaris associated with chronic recurrent multifocal osteomyelitis of the mandible
Authors: C.U. Brand, N. Yawalkar, B. Ballmer-Weber, L.R. Braathen
Journal: British Journal of Dermatology (1996)

Journal Article Pustulosis palmoplantaris associated with chronic recurrent multifocal osteomyelitis of the mandible Get access C.U. Brand, C.U. Brand Department of Dermatology University of Berne Inselspital 3010 Berne Switzerland Search for other works by this author on: Oxford Academic Google Scholar N. Yawalkar, N. Yawalkar Department of Dermatology University of Berne Inselspital 3010 Berne Switzerland Search for other works by this author on: Oxford Academic Google Scholar B. Ballmer‐Weber, B. Ballmer‐Weber Department of Dermatology University of Berne Inselspital 3010 Berne Switzerland Search for other works by this author on: Oxford Academic Google Scholar L.R. Braathen L.R. Braathen Department of Dermatology University of Berne Inselspital 3010 Berne Switzerland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 5, 1 May 1996, Pages 977–979, https://doi.org/10.1111/j.1365-2133.1996.tb06342.x Published: 01 May 1996
Whatalotwegot--the messages in drug advertisements
Authors: R E Ferner, D K Scott
Journal: BMJ (1994)

Advertisers are increasingly using symbols to circumvent logical argument when trying to persuade people (the "targets" of the advertisement) to make choices that are not strictly rational. Symbols can convey covert meanings and awaken or exploit subconscious feelings, such as a desire for power or a fear of doing harm. Some of the ways in which pharmaceutical advertisements use these techniques are examined: advertising by contagion; adding to our worries; polarity of choices; teasers; idealisation. Rational prescribing should be based on logic, but advertisements do not depend on logical arguments for their most powerful effects: the advertisers may subvert us by appealing to our unconscious desires.
Knock your SOCS off!
Authors: Derek LeRoith, Peter Nissley
Journal: Journal of Clinical Investigation (2005)

The growth hormone/IGF-1-signaling (GH/IGF-1-signaling) system is involved in numerous physiological processes during normal growth and development and also in the aging process. Understanding the regulation of this system is therefore of importance to the biologist. Studies conducted over the past decade have shown that the JAK/STAT pathways are involved in GH signaling to the nucleus. More recently, evidence has been presented that a member of the SOCS family, SOCS2, is a negative regulator of GH signaling. This story began several years ago with the dramatic demonstration of gigantism in the SOCS2-knockout mouse. A more specific definition of the role of SOCS2 in GH signaling is provided in this issue of the JCI by the demonstration that the overgrowth phenotype of the SOCS2-/- mouse is dependent upon the presence of endogenous GH and that administration of GH to mice lacking both endogenous GH and SOCS2 produced excessive growth.
Spectrum of Liver Disease in Type 2 Diabetes and Management of Patients With Diabetes and Liver Disease
Authors: Keith G. Tolman, Vivian Fonseca, Anthony Dalpiaz, Meng H. Tan
Journal: Diabetes Care (2007)

It is estimated that 20.8 million people, i.e., 7.0% of the U.S. population, have diabetes (1). Type 2 diabetes, with its core defects of insulin resistance and relative insulin deficiency, accounts for 90–95% of those with the disease. Another 5.2 million people are estimated to have undiagnosed type 2 diabetes. It is the sixth leading cause of death (1) in the U.S. and accounts for 17.2% of all deaths for those aged >25 years (2).

Liver disease is an important cause of death in type 2 diabetes. In the population-based Verona Diabetes Study (3), cirrhosis was the fourth leading cause of death and accounted for 4.4% of diabetes-related deaths. The standardized mortality ratio (SMR), i.e., the relative rate of an event compared with the background rate, for cirrhosis was 2.52 compared with 1.34 for cardiovascular disease (CVD). In another prospective cohort study (4), cirrhosis accounted for 12.5% of deaths in patients with diabetes.

Diabetes, by most estimates, is now the most common cause of liver disease in the U.S. Cryptogenic cirrhosis, of which diabetes is, by far, the most common cause, has become the third leading indication for liver transplantation in the U.S. (5,6). Virtually the entire spectrum of liver disease is seen in patients with type 2 diabetes. This includes abnormal liver enzymes, nonalcoholic fatty liver disease (NAFLD), cirrhosis, hepatocellular carcinoma, and acute liver failure. In addition, there is an unexplained association of diabetes with hepatitis C. Finally, the prevalence of diabetes in cirrhosis is 12.3–57% (7). Thus, patients with diabetes have a high prevalence of liver disease and patients with liver disease have a high prevalence of diabetes.

The management of diabetes in patients with liver disease is theoretically complicated by liver-related alterations in drug metabolism, potential interactions between the drugs, and a low, albeit …
Prognostic Significance of Left Ventricular Dyssynchrony by Phase Analysis of Gated SPECT in Medically Treated Patients With Dilated Cardiomyopathy
Authors: Li Wang, Min-Fu Yang, Min Cai, Shi-Hua Zhao, Zuo-Xiang He, Yue-Tao Wang
Journal: Clinical Nuclear Medicine (2013)

The study aimed to investigate the value of clinical variables and rest gated single-photon emission computed tomography (SPECT) in predicting cardiac deaths in medically treated dilated cardiomyopathy (DCM) patients.This is a retrospective study. Fifty-six consecutive hospitalized DCM patients who underwent rest gated SPECT myocardial perfusion imaging were initially recruited. Patients were further excluded for receiving heart transplantation, cardiac resynchronization treatment, and noncardiac death during follow-up. The remaining 48 medically treated DCM patients were selected into the final analysis. Phase analysis of gated SPECT was conducted to identify left ventricular (LV) dyssynchrony. Cardiac death during follow-up was considered as the only endpoint. Univariate and multivariate Cox proportional hazards regression analysis were performed to identify the independent predictors of cardiac death. Kaplan-Meier cumulative survival analysis with stratification was performed, and survival curves were compared by log-rank test.The mean age was 47.5 ± 15.8 years (range, 15-76 yrs) and 85.4% were men. The mean LV ejection fraction was 22.2 ± 7.7%. During the follow-up period (22.7 ± 5.1 mos), 12 (25.0%) cardiac deaths occurred. Compared to survivors, patients with cardiac death had lower body mass index (BMI, P = 0.010), higher percent of prolonged QRS duration (QRSD, P = 0.043), and severe LV dyssynchrony (P = 0.002). Multivariate Cox analysis demonstrated that severe LV dyssynchrony [hazard ratio = 9.607, 95% confidential interval (95% CI) 2.064-44.713, P = 0.004] and BMI (hazard ratio = 0.851, 95% CI 0.732-0.989, P = 0.036) were predictive of cardiac death.Left ventricular dyssynchrony assessed by phase analysis of gated SPECT and BMI are predictive of cardiac death in medically treated DCM patients.
Tetrachloroethylene-contaminated drinking water and the risk of breast cancer.
Authors: A Aschengrau, C Paulu, D Ozonoff
Journal: Environmental Health Perspectives (1998)

We conducted a population-based case-control study to evaluate the relationship between cases of breast cancer and exposure to tetrachloroethylene (PCE) from public drinking water ( n = 258 cases and 686 controls). Women were exposed to PCE when it leached from the vinyl lining of water distribution pipes. The relative delivered dose was estimated using an algorithm that accounted for residential history, water flow, and pipe characteristics. Only small increases in breast cancer risk were seen among ever-exposed women either when latency was ignored or when 5 to 15 years of latency was considered. No or small increases were seen among highly exposed women either when latency was ignored or when 5 years of latency was considered. However, the adjusted odds ratios (ORs) were more increased for highly exposed women when 7 and 9 years of latency, respectively, were considered (OR 1.5 95% CI 0.5-4.7 and OR 2.3, 95% CI 0.6-8.8 for the 75th percentile, and OR 2.7, 95% CI 0.4-15.8 and OR 7.6, 95% CI 0.9-161.3 for the 90th percentile). The number of highly exposed women was too small for meaningful analysis when more years of latency were considered. Because firm conclusions from these data are limited, we recently undertook a new study with a large number of more recently diagnosed cases.
KIT with D816 mutations cooperates with CBFB-MYH11 for leukemogenesis in mice
Authors: Ling Zhao, Jan J. Melenhorst, Lemlem Alemu, Martha Kirby, Stacie Anderson, Maggie Kench, Shelley Hoogstraten-Miller, Lauren Brinster, Yasuhiko Kamikubo, D. Gary Gilliland, P. Paul Liu
Journal: Blood (2011)
<i>In vivo</i> Evaluation of Ixabepilone (BMS247550), A Novel Epothilone B Derivative, against Pediatric Cancer Models
Authors: Jennifer K. Peterson, Chandra Tucker, Edward Favours, Pamela J. Cheshire, Jeremy Creech, Catherine A. Billups, Richard Smykla, Francis Y.F. Lee, Peter J. Houghton
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Vinca alkaloids, agents that cause depolymerization of microtubules, are highly active in treatment of many pediatric cancers. In contrast, taxanes, agents that stabilize microtubules, are far less effective against the same cancer types. The purpose of the current study was to evaluate the antitumor activity of ixabepilone, an epothilone B derivative representing a new class of microtubule-stabilizing antimitotic agent in a wide variety of pediatric solid tumor models. Experimental Design: Ixabepilone was administered i.v. every 4 days for three doses to scid mice bearing s.c. human rhabdomyosarcoma (three lines), neuroblastoma (four), Wilms' tumors (six), osteosarcoma (four), or brain tumors (seven). Tumor diameters were measured weekly, and tumor growth or regressions were determined. Pharmacokinetic studies were done following a single administration of drug at the maximum tolerated dose (MTD) level (10 mg/kg). Results: At the MTD (10 mg/kg), ixabepilone induced objective responses (all tumors in a group achieved ≥50% volume regression) in three of three rhabdomyosarcoma lines, three of five neuroblastomas, six of seven Wilms' tumor models, two of six osteosarcoma, and four of eight brain tumor models. However, the dose-response curve was steep with only 2 of 19 tumors models regressing (≥50%) at 4.4 mg/kg. In comparison, paclitaxel administered at the MTD on the same schedule failed to induce objective regressions of three tumor lines that were highly sensitive to treatment with ixabepilone. Pharmacokinetics following single i.v. administration of ixabepilone at its MTD (10 mg/kg) were biexponential with Cmax of 12.5 μmol/L, elimination half-life of 19.2 hours, and total area under the curve of 5.8 μmol/L-h. The achieved drug exposure of ixabepilone at this efficacious MTD dose level in mice is similar to those achieved in patients given the recommended phase II dose of 40 mg/m2 by either 1- or 3-hour infusion every 3 weeks, a regimen that has shown significant anticancer activity in phase II clinical trials in adult patients. Conclusions: Administered at doses ranging from 66% to 100% of its MTD in mice, the epothilone B derivative ixabepilone shows broad spectrum activity against a panel of pediatric tumor xenograft models. Pharmacokinetic analysis indicates that the systemic ixabepilone exposure achieved in mice at its MTD is similar to that achieved in patients at the recommended phase II dose of 40 mg/m2 administered every 3 weeks. Importantly, the present results showed a clear distinction in sensitivity of pediatric solid tumors to this epothilone derivative compared with paclitaxel.
Reporting of sample size calculation in randomised controlled trials: review
Authors: P. Charles, B. Giraudeau, A. Dechartres, G. Baron, P. Ravaud
Journal: BMJ (2009)

<b>Objectives</b> To assess quality of reporting of sample size calculation, ascertain accuracy of calculations, and determine the relevance of assumptions made when calculating sample size in randomised controlled trials. <b>Design</b> Review. <b>Data sources</b> We searched MEDLINE for all primary reports of two arm parallel group randomised controlled trials of superiority with a single primary outcome published in six high impact factor general medical journals between 1 January 2005 and 31 December 2006. All extra material related to design of trials (other articles, online material, online trial registration) was systematically assessed. Data extracted by use of a standardised form included parameters required for sample size calculation and corresponding data reported in results sections of articles. We checked completeness of reporting of the sample size calculation, systematically replicated the sample size calculation to assess its accuracy, then quantified discrepancies between a priori hypothesised parameters necessary for calculation and a posteriori estimates. <b>Results</b> Of the 215 selected articles, 10 (5%) did not report any sample size calculation and 92 (43%) did not report all the required parameters. The difference between the sample size reported in the article and the replicated sample size calculation was greater than 10% in 47 (30%) of the 157 reports that gave enough data to recalculate the sample size. The difference between the assumptions for the control group and the observed data was greater than 30% in 31% (n=45) of articles and greater than 50% in 17% (n=24). Only 73 trials (34%) reported all data required to calculate the sample size, had an accurate calculation, and used accurate assumptions for the control group. <b>Conclusions</b> Sample size calculation is still inadequately reported, often erroneous, and based on assumptions that are frequently inaccurate. Such a situation raises questions about how sample size is calculated in randomised controlled trials.
Newspaper Reporting of Screening Mammography
Authors: Michael Rosen
Journal: Annals of Internal Medicine (2002)

Letters3 September 2002Newspaper Reporting of Screening MammographyMichael Rosen, MDMichael Rosen, MDHuntington, NY 11743Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-5_Part_1-200209030-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The paper by Wells and colleagues on newspaper reporting of screening mammography (1) was clearly biased and thus bad science. The authors criticize the sources the newspapers used, but are we to assume that the National Cancer Institute, the American Cancer Society, radiologists, the National Institutes of Health, and data presented at medical conferences are all unreliable and biased? Are they duping the U.S. public into performing mammography on women 40 to 49 years of age for some purpose other than to protect their welfare? If that were the case, would these people and institutions perhaps not ...References1. Wells J, Marshall P, Crawley B, Dickersin K. Newspaper reporting of screening mammography. Ann Intern Med. 2001;135:1029-37. [PMID: 11747381] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Huntington, NY 11743 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoNewspaper Reporting of Screening Mammography Jane Wells , Phillip Marshall , Barbara Crawley , and Kay Dickersin Newspaper Reporting of Screening Mammography Joel G. Ray Newspaper Reporting of Screening Mammography Joel G. Ray Metrics 3 September 2002Volume 137, Issue 5_Part_1Page: 373-374KeywordsInformation storage and retrievalMammographyProspective studiesPublic policyRadiologists ePublished: 3 September 2002 Issue Published: 3 September 2002 CopyrightCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Malaria in Drug Addicts
Authors: Rodger L. Bick
Journal: JAMA (1971)

<h3>To the Editor.—</h3> We have recently observed eight cases of malaria due to the use of needles in common by heroin addicts. All eight were cases of<i>Plasmodium vivax</i>infection. Three of these were related as man, wife, and sister; the other five have not admitted to a common pathway, but have acknowledged the use of heroin intravenously during a six-week period. All eight of these individuals gave a history of longterm heroin use, and all have complained of chills and fever of approximately four weeks' duration. Two of these patients were admitted as cases of fever of unknown orign (FUO), one to a psychiatric ward for observation, one as a patient with hepatitis, and four as known contacts. The patient with hepatitis and one of the patients with FUO demonstrated a positive Australia antigen by latex particle fixation. The other patients were negative for Australia antigen. Present studies are