tbuckley/cabot-search huggingface dataset:
Promoting Behavioral Science Research in Diabetes
Authors: David G. Marrero, Mark Peyrot, Sanford Garfield
Journal: Diabetes Care (2001)

Diabetes is unique among chronic illnesses in the degree that patient behavior influences both the application and outcomes of therapy. Indeed, there is emerging evidence suggesting that in order to effectively implement intensive regimens designed to achieve optimal glycemic control, it is necessary to address a variety of behavioral issues among diabetic patients. Despite this observation, federal agencies have historically funded a disproportionately small amount of behavioral science research in diabetes. On 18 and 19 November 1999, the National Institutes of Health addressed this issue by hosting an invitational conference focusing specifically on behavioral science research in diabetes. The goals of the conference were 1 ) to illuminate the integral role that behavioral science has played in the success of research designed to reduce the considerable personal, social, and fiscal burden associated with diabetes (notably, this includes large clinical trials such as the Diabetes Control and Complications Trial, the U.K. Prospective Diabetes Study, and the Diabetes Prevention Program); 2 ) to demonstrate …
False- positive and false-negative rate after positron emission tomography/computer tomography scan for mediastinal staging in non-small-cell lung cancer
Authors: Kalliopi Athanassiadi, Athanasia Makrygianni, Evangelos Balis, Nektarios Alevizopoulos, Michael Vaslamatzis, Christina Vourlakou
Journal: European Respiratory Journal (2014)

OBJECTIVE: To assess positron emission tomography (PET)-chest computed tomography (CT) scan in non-small-cell lung cancer (NSCLC) for mediastinal staging.  MATERIAL and METHOD: Fifty patients with NSCLC were assessed by thoracic CT scan and 18-fluoro-2-deoxy-d-glucose PET-CT for mediastinal staging and were prospectively included in the study. All operable stages were included along with Stage IIIa and IIIb after downstaging with chemotherapy. CT scan was considered negative if lymph nodes were  RESULTS: There were 3 of 35 (8.6%) false-negatives (FNs) in Group A and none in Group B. Multilevel pN2 was detected in one case, while in 2 cases there was only subcarinal involvement. One FP was detected in Group A (station 5) and 6 FPs in Group B (multilevel pN2). PET-CT for mediastinal staging showed 8.6% of FNs in Group A, representing the incidence of pN2 in thoracotomy, while 40% of FPs in Group B, representing the percentage of downstaged patients who normally would have been denied surgery.  CONCLUSION: A PET-CT should be considered a tool that is carefully evaluated by the multidisciplinary team of thoracic surgeons, pulmonologists and oncologists in order to individualize every patient and offer him the best treatment, especially in cases after induction chemotherapy.
EPITHELIOMATA AFTER RADIOTHERAPY OF THE SPINE
Authors: R. H. MEARA
Journal: British Journal of Dermatology (1968)

British Journal of DermatologyVolume 80, Issue 9 p. 620-620 EPITHELIOMATA AFTER RADIOTHERAPY OF THE SPINE R. H. MEARA, R. H. MEARA 132 Harley Street, W.1.Search for more papers by this author R. H. MEARA, R. H. MEARA 132 Harley Street, W.1.Search for more papers by this author First published: September 1968 https://doi.org/10.1111/j.1365-2133.1968.tb12364.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume80, Issue9September 1968Pages 620-620 RelatedInformation
Keeping up: learning in the workplace
Authors: Jeremy C Wyatt, Frank Sullivan
Journal: BMJ (2005)

The amount of biomedical knowledge doubles every 20 years, and new classes of drug (such as phosphodiesterase 4 inhibitors) become available when lectures at medical school are over.Therefore, a practice risks fossilising after doctors finish professional training.Many continuing medical education or continuing professional development activities help doctors carry on learning and improving their skills.These activities include courses, conferences, mailed educational materials, weekly grand rounds, journal clubs, and using internet sites.In many countries, evidence of this process is needed for doctors to continue to practice.Although these activities may increase knowledge, their impact on clinical practice is variableThe aim of traditional medical education is to commit knowledge to memory and then use this knowledge in the workplace.The way knowledge is learnt influences its recall and application to work.One tactic to improve the process is to ensure that learning happens in the clinical workplace.Lessons are learnt faster and recalled more reliably when they originate in everyday experience.Learning in the workplace means spending a minute here or three minutes there to find answers prompted by the clinical questions and learning opportunities that come up in every working day, rather than doing continuing medical education for an intensive two hours a week, or a few days a year.Workplace learning is hard to achieve.It emphasises problem solving and learning skills-such as how to find relevant answers fast-not learning facts.
ALF—A Simulation Framework for Genome Evolution
Authors: Daniel A. Dalquen, Maria Anisimova, Gaston H. Gonnet, Christophe Dessimoz
Journal: Molecular Biology and Evolution (2011)

In computational evolutionary biology, verification and benchmarking is a challenging task because the evolutionary history of studied biological entities is usually not known.Computer programs for simulating sequence evolution in silico have shown to be viable test beds for the verification of newly developed methods and to compare different algorithms.However, current simulation packages tend to focus either on gene-level aspects of genome evolution such as character substitutions and insertions and deletions (indels) or on genome-level aspects such as genome rearrangement and speciation events.Here, we introduce Artificial Life Framework (ALF), which aims at simulating the entire range of evolutionary forces that act on genomes: nucleotide, codon, or amino acid substitution (under simple or mixture models), indels, GC-content amelioration, gene duplication, gene loss, gene fusion, gene fission, genome rearrangement, lateral gene transfer (LGT), or speciation.The other distinctive feature of ALF is its user-friendly yet powerful web interface.We illustrate the utility of ALF with two possible applications: 1) we reanalyze data from a study of selection after globin gene duplication and test the statistical significance of the original conclusions and 2) we demonstrate that LGT can dramatically decrease the accuracy of two well-established orthology inference methods.ALF is available as a stand-alone application or via a web interface at http://www.cbrg.ethz.ch/alf.
Tamoxifen and the isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients.
Authors: C K Osborne, V J Wiebe, W L McGuire, D R Ciocca, M W DeGregorio
Journal: Journal of Clinical Oncology (1992)

PURPOSE The antiestrogen tamoxifen is effective in therapy for breast cancer. However, its use is limited by the eventual development of acquired tamoxifen resistance in many patients. The mechanisms responsible for tamoxifen resistance remain unknown; loss of estrogen receptor (ER), selection of hormone-independent breast cancer clones, or alterations in serum tamoxifen levels after long-term use do not explain acquired resistance in most patients. Using an experimental model in which human breast cancer cells develop resistance in athymic mice treated with tamoxifen, we have recently shown that acquired resistance is associated with markedly reduced cellular concentrations of tamoxifen and by isomerization of the trans-4-hydroxy metabolite to the less potent cis isomer. MATERIALS AND METHODS Using a sensitive high-performance liquid chromatography (HPLC) assay, we have now measured levels of tamoxifen and its major metabolites in a series of 14 tumors from patients treated with tamoxifen. The duration of therapy ranged from 1 month to 6 years. RESULTS Tumor tamoxifen levels varied over a wide range. Low concentrations were observed in tumors from eight patients, all demonstrating progressive disease at the time of biopsy after a minimum duration of treatment of 6 months. Six tumors had moderate to high tamoxifen levels, two from patients responding to tamoxifen, one from a patient with stable disease, and three from patients with disease progression. Both the cis and trans isomers of the potent antiestrogenic metabolite 4-hydroxy-tamoxifen were detected in 11 tumors. Six tumors had high ratios of the cis to trans isomer (1.10:2.06), all from patients not responding to tamoxifen. The five tumors with low cis:trans ratios included the two tumors from responding patients and three from patients with progression. All but one of the 11 nonresponding patients had either a low tumor tamoxifen level, a high cis:trans ratio, or both. CONCLUSION This study clearly demonstrates a wide range of tumor tamoxifen levels and accumulation of the less antiestrogenic cis isomer of 4-hydroxytamoxifen in some patients on tamoxifen therapy. Additional study is necessary to determine if these metabolic profiles are related to the development of tamoxifen resistance.
Myocardial Structure, Function, and Scar in Patients With Type 1 Diabetes Mellitus
Authors: Evrim B. Turkbey, Jye-Yu C. Backlund, Saul Genuth, Aditya Jain, Cuilian Miao, Patricia A. Cleary, John M. Lachin, David M. Nathan, Rob J. van der Geest, Elsayed Z. Soliman, Chia-Ying Liu, João A.C. Lima, David A. Bluemke
Journal: Circulation (2011)

Background— We report relationships between cardiovascular disease risk factors and myocardial structure, function, and scar in patients with type 1 diabetes mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Methods and Results— Cardiac magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus. Gadolinium cardiac magnetic resonance was also obtained in 741 patients. The mean age was 49±7 years; 52% were men; and mean duration of diabetes mellitus was 28±5 years. Associations of cardiovascular disease risk factors with cardiac magnetic resonance parameters were examined with linear and logistic regression models. History of macroalbuminuria was positively associated with left ventricular mass (by 14.8 g), leading to a significantly higher ratio of left ventricular mass to end-diastolic volume (by 8%). Mean hemoglobin A 1c levels over the preceding 22 years were inversely associated with end-diastolic volume (−3.0 mL per unit mean hemoglobin A 1c percent) and stroke volume (−2.3 mL per unit mean hemoglobin A 1c percent) and positively related to the ratio of elevated left ventricular mass to end-diastolic volume (0.02 g/mL per unit). The overall prevalence of myocardial scar was 4.3% by cardiac magnetic resonance and 1.4% by clinical adjudication of myocardial infarction. Both mean hemoglobin A 1c (odds ratio, 1.5 [95% confidence interval, 1.0–2.2] per unit) and macroalbuminuria (odds ratio, 3.5 [95% confidence interval, 1.2–9.9]) were significantly associated with myocardial scar and traditional cardiovascular disease risk factors. Conclusions— In addition to traditional cardiovascular disease risk factors, elevated mean hemoglobin A 1c and macroalbuminuria were significantly associated with alterations in left ventricular structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT00360893 and NCT00360815.
Night-Shift Work and Risk of Colorectal Cancer in the Nurses' Health Study
Authors: E. S. Schernhammer, F. Laden, F. E. Speizer, W. C. Willett, D. J. Hunter, I. Kawachi, C. S. Fuchs, G. A. Colditz
Journal: JNCI Journal of the National Cancer Institute (2003)

Exposure to light at night suppresses the physiologic production of melatonin, a hormone that has antiproliferative effects on intestinal cancers. Although observational studies have associated night-shift work with an increased risk of breast cancer, the effect of night-shift work on the risk of other cancers is not known. We prospectively examined the relationship between working rotating night shifts and the risk of colorectal cancers among female participants in the Nurses' Health Study. We documented 602 incident cases of colorectal cancer among 78 586 women who were followed up from 1988 through 1998. Compared with women who never worked rotating night shifts, women who worked 1–14 years or 15 years or more on rotating night shifts had multivariate relative risks of colorectal cancer of 1.00 (95% confidence interval [CI] = 0.84 to 1.19) and 1.35 (95% CI = 1.03 to 1.77), respectively (Ptrend = .04). These data suggest that working a rotating night shift at least three nights per month for 15 or more years may increase the risk of colorectal cancer in women.
Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer
Authors: Diana L. Moughon, Huanhuan He, Shiruyeh Schokrpur, Ziyue Karen Jiang, Madeeha Yaqoob, John David, Crystal Lin, M. Luisa Iruela-Arispe, Oliver Dorigo, Lily Wu
Journal: Cancer Research (2015)

Abstract Malignant ascites is a common complication in the late stages of epithelial ovarian cancer (EOC) that greatly diminishes the quality of life of patients. Malignant ascites is a known consequence of vascular dysfunction, but current approved treatments are not effective in preventing fluid accumulation. In this study, we investigated an alternative strategy of targeting macrophage functions to reverse the vascular pathology of malignant ascites using fluid from human patients and an immunocompetent murine model (ID8) of EOC that mirrors human disease by developing progressive vascular disorganization and leakiness culminating in massive ascites. We demonstrate that the macrophage content in ascites fluid from human patients and the ID8 model directly correlates with vascular permeability. To further substantiate macrophages' role in the pathogenesis of malignant ascites, we blocked macrophage function in ID8 mice using a colony-stimulating factor 1 receptor kinase inhibitor (GW2580). Administration of GW2580 in the late stages of disease resulted in reduced infiltration of protumorigenic (M2) macrophages and dramatically decreased ascites volume. Moreover, the disorganized peritoneal vasculature became normalized and sera from GW2580-treated ascites protected against endothelial permeability. Therefore, our findings suggest that macrophage-targeted treatment may be a promising strategy toward a safe and effective means to control malignant ascites of EOC. Cancer Res; 75(22); 4742–52. ©2015 AACR.
New target for T regs
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

The natural killer (NK) cell is a new target for regulatory T (T reg) cell tyranny, according to a study on [page 1075][1]. Ghiringhelli and colleagues show that the antitumor activity of NK cells is snuffed out by T reg cells, allowing tumors to grow unchecked.

NK cells are innate immune cells
Mechanism of rejection of virus persistently infected tumor cells by athymic nude mice.
Authors: N Minato, B R Bloom, C Jones, J Holland, L M Reid
Journal: The Journal of Experimental Medicine (1979)

Cell lines known to be tumorigenic in the nude mouse were modified by rendering them persistently infected (P.I.) with a variety of RNA viruses, including measles, mumps, vesicular stomatitis virus, and influenza. Although as few as 100 HeLa or BHK cells produced tumors in 100% of nude mice, as many as 2 x 10(7) of the same cells P.I. with viruses failed to produce tumors. An active host response responsible for restricting the growth of the P.I. cells was suggested by the findings of marked mononuclear cell infiltrates at the inoculation sites and the inability of irradiated nude mice to reject them. An analysis of the in vitro cytotoxic activity of spleen cells from normal nude mice indicated that: (a) P.I. cell lines, but not uninfected cell lines, were susceptible to spontaneous cytotoxicity; (b) in vivo inoculation of P.I. lines induced an enhanced cytotoxic activity for P.I. targets in vitro, and this induction was not specific either for inducing virus or cell line; and (c) the effector cell had the characteristics for natural killer (NK) cells. Although the specificity of recognition of the various P.I. cell lines remains unclear, cold competition experiments indicated that blocking the killing of one P.I. cell line, e.g. HeLa-measles, could be achieved only by unlabeled homologous cells, i.e. HeLa-measles, and not by uninfected cells or other P.I. lines. A variant subline of BHK cells P.I. with VSV was selected for its ability to withstand the rejection process in nude mice. These cells formed metastatic and invasive tumors in nude mice. Although they were the most potent inducers in vivo of NK cell activity against various P.I. targets, they were the most resistant of the P.I. lines to NK cell cytotoxicity in vitro. In this system there was a good correlation between tumor rejection in vivo and susceptibility to NK cells in vitro. The present results suggest that NK cells may play a significant role in both rejection of tumor cells, and in resistance to viruses, particularly persistent infections.
TGF-β/SMAD/GLI2 Signaling Axis in Cancer Progression and Metastasis
Authors: Delphine Javelaud, Vasileia I. Alexaki, Sylviane Dennler, Khalid S. Mohammad, Theresa A. Guise, Alain Mauviel
Journal: Cancer Research (2011)

The Hedgehog (HH) and TGF-β signaling pathways represent essential regulators of cell proliferation and differentiation during embryogenesis. Pathway deregulation is a characteristic of various cancers. Recently, evidence for a convergence of these pathways at the level of the GLI2 transcription factor in the context of tumor initiation and progression to metastasis has emerged. This short review summarizes recent knowledge about GLI2 function and mechanisms of action downstream of TGF-β in cancer.
The protein product of the c-cbl protooncogene is phosphorylated after B cell receptor stimulation and binds the SH3 domain of Bruton's tyrosine kinase.
Authors: G O Cory, R C Lovering, S Hinshelwood, L MacCarthy-Morrogh, R J Levinsky, C Kinnon
Journal: The Journal of Experimental Medicine (1995)

X-linked agammaglobulinemia, a B cell immunodeficiency, is caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The absence of a functional Btk protein leads to a failure of B cell differentiation and antibody production. B cell receptor stimulation leads to the phosphorylation of the Btk protein and it is, therefore, likely that Btk is involved in B cell receptor signaling. As a nonreceptor tyrosine kinase, Btk is likely to interact with several proteins within the context of a signal transduction pathway. To understand such interactions, we have generated glutathione S-transferase fusion proteins corresponding to different domains of the human Btk protein. We have identified a 120-kD protein present in human B cells as being bound by the SH3 domain of Btk and which, after B cell receptor stimulation, is one of the major substrates of tyrosine phosphorylation. We have shown that this 120-kD protein is the protein product of c-cbl, a protooncogene, which is known to be phosphorylated in response to T cell receptor stimulation and to interact with several other tyrosine kinases. Association of the SH3 domain of Btk with p120cbl provides evidence for an analogous role for p120cbl in B cell signaling pathways. The p120cbl protein is the first identified ligand of the Btk SH3 domain.
Evolution of Sequence Recognition by Restriction-Modification Enzymes: Selective Pressure for Specificity Decrease
Authors: Akito Chinen, Yasuhiro Naito, Naofumi Handa, Ichizo Kobayashi
Journal: Molecular Biology and Evolution (2000)

Several type II restriction-modification (RM) gene complexes kill host bacterial cells that have lost them, through attack on the chromosomal recognition sites of these cells. Two RM gene complexes recognizing the same sequence cannot simultaneously enjoy such stabilization through postsegregational host killing, because one will defend chromosomal sites from attack by the other. In the present work, we analyzed intrahost competition between two RM gene complexes when the recognition sequence of one was included in that of the other. When the EcoRII gene complex, recognizing 5'-CCWGG (W = A, T), is lost from the host, the SsoII gene complex, which recognizes 5'-CCNGG (N = A, T, G, C), will prevent host death by protecting CCWGG sites on the chromosome. However, when the SsoII (CCNGG) gene complex is lost, the EcoRII (CCWGG) gene complex will be unable to prevent host death through attack by SsoII on 5'-CCSGG (S = C, G) sites. These predictions were verified in our experiments, in which we analyzed plasmid maintenance, cell growth, cell shape, and chromosomal DNA. Our results demonstrate the presence of selective pressure for decrease in the specificity of recognition sequence of RM systems in the absence of invading DNA.
Interaction between innate immunity and Ro52-induced antibody causes Sjögren's syndrome-like disorder in mice
Authors: Barbara M Szczerba, Paulina Kaplonek, Nina Wolska, Anna Podsiadlowska, Paulina D Rybakowska, Paromita Dey, Astrid Rasmussen, Kiely Grundahl, Kimberly S Hefner, Donald U Stone, Stephen Young, David M Lewis, Lida Radfar, R Hal Scofield, Kathy L Sivils, Harini Bagavant, Umesh S Deshmukh
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Autoantibodies reactive with Ro52 are often found in sera of patients with Sjögren's syndrome (SS). This study was undertaken to investigate the role of Ro52-induced immune responses in pathogenesis of SS. Methods New Zealand Mixed (NZM) 2758 mice were immunised with Ro52 in alum adjuvant. Control mice were immunised either with maltose-binding protein or injected with alum alone. Mice were monitored for anti-Ro52 antibody, sialoadenitis and pilocarpine-induced salivation. Antibody binding to salivary gland (SG) cells was analysed in vivo and in vitro by immunofluorescence. Sera from immunised mice were passively transferred into untreated or alum injected NZM2758 mice. Results By day 30 post-immunisation, Ro52 immunised mice generated immunoprecipitating anti-Ro52 antibodies and they had the maximum drop in saliva production. Both Ro52 immunised and control mice showed evidence of mild sialoadenitis. However, only Ro52 immunised mice had antibody deposition in their SG. Passive transfer of Ro52-immune sera induced SG dysfunction in recipient mice, only if the recipients were primed with alum. In vitro, antibodies from Ro52-immune sera were internalised by a SG cell line and this uptake was inhibited by cytochalasin D treatment. Conclusions Our data show for the first time that antibodies induced by Ro52 are capable of inducing SG dysfunction, and that this phenomenon is dependent on the activation of innate immunity. The mouse model described in this study implies that autoantibody deposition in the SG might be an important step in the induction of xerostomia and pathogenesis of SS.