tbuckley/cabot-search huggingface dataset:
Increased gliadin antibodies in dermatitis herpetiformis and pemphigoid
Authors: MARIANNE KIEFFER, R.StC. BARNETSON
Journal: British Journal of Dermatology (1983)

Journal Article Increased gliadin antibodies in dermatitis herpetiformis and pemphigoid Get access MARIANNE KIEFFER, MARIANNE KIEFFER Immunology Division, Department of Pathology, Adenbrooke's Hospital, Cambridge and Department of Dermatology, Gentofte Hospital, Hellerup, Denmark Dr M. Kieffer, Department of Dermatology, Gentofte Hospital, DK‐2900 Hellerup, Denmark. Search for other works by this author on: Oxford Academic Google Scholar R.StC. BARNETSON R.StC. BARNETSON Department of Dermatology, The Royal Infirmary, Edinburgh Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 108, Issue 6, 1 June 1983, Pages 673–678, https://doi.org/10.1111/j.1365-2133.1983.tb01079.x Published: 01 June 1983 Article history Accepted: 27 October 1982 Published: 01 June 1983
The Human Multidrug Resistance Protein MRP5 Transports Folates and Can Mediate Cellular Resistance against Antifolates
Authors: Peter Wielinga, Jan Hendrik Hooijberg, Sjofn Gunnarsdottir, Ietje Kathmann, Glen Reid, Noam Zelcer, Kasper van der Born, Marcel de Haas, Ingrid van der Heijden, Gertjan Kaspers, Jan Wijnholds, Gerrit Jansen, Godefridus Peters, Piet Borst
Journal: Cancer Research (2005)

Abstract Members of the multidrug resistance protein family, notably MRP1-4/ABCC1-4, and the breast cancer resistance protein BCRP/ABCG2 have been recognized as cellular exporters for the folate antagonist methotrexate (MTX). Here we show that MRP5/ABCC5 is also an antifolate and folate exporter based on the following evidence: (a) Using membrane vesicles from HEK293 cells, we show that MRP5 transports both MTX (KM = 1.3 mmol/L and VMAX = 780 pmol per mg protein per minute) and folic acid (KM = 1.0 mmol/L and VMAX = 875 pmol per mg protein per minute). MRP5 also transports MTX-glu2 (KM = 0.7 mmol/L and VMAX = 450 pmol per mg protein per minute) but not MTX-glu3. (b) Both accumulation of total [3H]MTX and of MTX polyglutamates were significantly reduced in MRP5 overexpressing cells. (c) Cell growth inhibition studies with MRP5 transfected HEK293 cells showed that MRP5 conferred high-level resistance (&amp;gt;160-fold) against the antifolates MTX, GW1843, and ZD1694 (raltitrexed) in short-term (4 hours) incubations with high drug concentrations; this resistance was proportional to the MRP5 level. (d) MRP5-mediated resistance (8.5- and 2.1-fold) was also found in standard long-term incubations (72 hours) at low concentrations of ZD1694 and GW1843. These results show the potential of MRP5 to mediate transport of (anti)folates and contribute to resistance against antifolate drugs.
A Potent Thioxanthone which Induces Autophagy and Cell Death in a Melanoma Cell Line
Authors: R.T. Lima, D. Sousa, K. Choosang, P. Pakkong, A. Palmeira, A.M. Paiva, H. Seca, F. Cerqueira, M. Pedro, M.M. Pinto, E. Sousa, M.H. Vasconcelos
Journal: Annals of Oncology (2013)
Combined Gene Expression Profiling and RNAi Screening in Clear Cell Renal Cell Carcinoma Identify PLK1 and Other Therapeutic Kinase Targets
Authors: Yan Ding, Dan Huang, Zhongfa Zhang, Josh Smith, David Petillo, Brendan D. Looyenga, Kristin Feenstra, Jeffrey P. MacKeigan, Kyle A. Furge, Bin T. Teh
Journal: Cancer Research (2011)

In recent years, several molecularly targeted therapies have been approved for clear cell renal cell carcinoma (ccRCC), a highly aggressive cancer. Although these therapies significantly extend overall survival, nearly all patients with advanced ccRCC eventually succumb to the disease. To identify other molecular targets, we profiled gene expression in 90 ccRCC patient specimens for which tumor grade information was available. Gene set enrichment analysis indicated that cell-cycle-related genes, in particular, Polo-like kinase 1 (PLK1), were associated with disease aggressiveness. We also carried out RNAi screening to identify kinases and phosphatases that when inhibited could prevent cell proliferation. As expected, RNAi-mediated knockdown of PLK1 and other cell-cycle kinases was sufficient to suppress ccRCC cell proliferation. The association of PLK1 in both disease aggression and in vitro growth prompted us to examine the effects of a small-molecule inhibitor of PLK1, BI 2536, in ccRCC cell lines. BI 2536 inhibited the proliferation of ccRCC cell lines at concentrations required to inhibit PLK1 kinase activity, and sustained inhibition of PLK1 by BI 2536 led to dramatic regression of ccRCC xenograft tumors in vivo. Taken together, these findings highlight PLK1 as a rational therapeutic target for ccRCC.
Circulating Estrone Levels Are Associated Prospectively With Diabetes Risk in Men of the Framingham Heart Study
Authors: Guneet Kaur Jasuja, Thomas G. Travison, Maithili Davda, Adam J. Rose, Anqi Zhang, Mark M. Kushnir, Alan L. Rockwood, Wayne Meikle, Andrea D. Coviello, Ralph D’Agostino, Ramachandran S. Vasan, Shalender Bhasin
Journal: Diabetes Care (2013)

OBJECTIVE In postmenopausal women and preclinical murine models, estrogen administration reduces diabetes risk; however, the relationship of estradiol and estrone to diabetes in men is poorly understood. We determined the relationship between circulating estradiol and estrone levels and diabetes risk in community-dwelling men of the Framingham Heart Study (FHS). RESEARCH DESIGN AND METHODS Cross-sectional relationships of estradiol and estrone levels with diabetes were assessed at examination 7 (1998–2001) in FHS generation 2 men (n = 1,458); prospective associations between hormone levels at examination 7 and incident diabetes were assessed 6.8 years later at examination 8. Type 2 diabetes mellitus was defined as fasting glucose &amp;gt;125 mg/dL, medication use, or both. Estradiol, estrone, and testosterone levels were measured with liquid chromatography–tandem mass spectrometry, and free estradiol and estrone were calculated. RESULTS In cross-sectional models, men with elevated estrone and estradiol had 40% and 62% increased likelihoods of existing diabetes per cross-sectional doubling of estrone and estradiol levels, respectively. Free estrone (cross-sectional odds ratio 1.28 [95% CI 1.02–1.62], P = 0.04) was associated with impaired fasting glucose at examination 7. There was an increase in risk of existing diabetes with increasing quartiles of total and free estrone and estradiol and an increase in risk of incident diabetes with increasing quartiles of estrone levels. In multivariate longitudinal analyses, a twofold increase in total or free estrone levels at examination 7 was associated with 77 and 93% increases, respectively, in odds of incident diabetes at examination 8. CONCLUSIONS Although both estradiol and estrone exhibit cross-sectional associations with diabetes in men, in longitudinal analyses estrone is a more sensitive marker of diabetes risk than is estradiol.
Leisure-time aerobic physical activity, muscle-strengthening activity and mortality risks among US adults: the NHANES linked mortality study
Authors: Guixiang Zhao, Chaoyang Li, Earl S Ford, Janet E Fulton, Susan A Carlson, Catherine A Okoro, Xiao Jun Wen, Lina S Balluz
Journal: British Journal of Sports Medicine (2013)

Background Regular physical activity elicits multiple health benefits in the prevention and management of chronic diseases. We examined the mortality risks associated with levels of leisure-time aerobic physical activity and muscle-strengthening activity based on the 2008 Physical Activity Guidelines for Americans among US adults. Methods We analysed data from the 1999 to 2004 National Health and Nutrition Examination Survey with linked mortality data obtained through 2006. Cox proportional HRs with 95% CIs were estimated to assess risks for all-causes and cardiovascular disease (CVD) mortality associated with aerobic physical activity and muscle-strengthening activity. Results Of 10 535 participants, 665 died (233 deaths from CVD) during an average of 4.8-year follow-up. Compared with participants who were physically inactive, the adjusted HR for all-cause mortality was 0.64 (95% CI 0.52 to 0.79) among those who were physically active (engaging in ≥150 min/week of the equivalent moderate-intensity physical activity) and 0.72 (95% CI 0.54 to 0.97) among those who were insufficiently active (engaging in &gt;0 to &lt;150 min/week of the equivalent moderate-intensity physical activity). The adjusted HR for CVD mortality was 0.57 (95% CI 0.34 to 0.97) among participants who were insufficiently active and 0.69 (95% CI 0.43 to 1.12) among those who were physically active. Among adults who were insufficiently active, the adjusted HR for all-cause mortality was 44% lower by engaging in muscle-strengthening activity ≥2 times/week. Conclusions Engaging in aerobic physical activity ranging from insufficient activity to meeting the 2008 Guidelines reduces the risk of premature mortality among US adults. Engaging in muscle-strengthening activity ≥2 times/week may provide additional benefits among insufficiently active adults.
Amyloidosis and the respiratory tract
Authors: J. D Gillmore, P. N Hawkins
Journal: Thorax (1999)

Amyloidosis is a generic term for a heterogeneous group of disorders associated with deposition of protein in an abnormal fibrillar form.1 The diverse spectrum of amyloid related diseases is now recognised to include Alzheimer’s disease, type II diabetes, and the transmissible spongiform encephalopathies. Amyloidosis can be hereditary or acquired, localised or systemic, and potentially lethal or merely an incidental finding.

Amyloid deposits consist mainly of protein fibrils, the varying peptide subunits of which constitute the basis for its classification (table1).2 Despite much heterogeneity among their respective precursor proteins, all amyloid fibrils have a remarkably similar adopted ultrastructure and share many physicochemical properties attributable to their acquired rich β-sheet content.3Certain glycosaminoglycans (GAGs) are invariably associated with the fibrils and, in addition, all amyloid deposits contain the normal plasma protein serum amyloid P component (SAP). The specific binding interaction between SAP and all amyloid fibrils is the basis for our development of radiolabelled SAP as a diagnostic nuclear medicine tracer.4 5

View this table:

Table 1 
Classification of the more common types of amyloid and amyloidosis



There have been many recent advances in amyloidosis including elucidation of the structure and properties of amyloid fibrils, the role of GAGs and SAP, and substantial improvements in clinical diagnosis and management. Although a specific generic treatment for the disease is not yet available, compelling evidence that amyloid deposits frequently regress when the supply of the respective fibril precursor protein is reduced has encouraged a much more positive approach to patient care.5 

Amyloidosis is a disorder of protein folding which breaks the traditional dogma that amino acid sequence is the sole determinant of a protein’s tertiary form. Amyloid fibril proteins can evidently exist as two radically different stable structures—a normal soluble form and the highly abnormal fibril conformation.

The pathogenesis of amyloidosis thus …
Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial
Authors: Maja Stulemeijer, Lieke W A M de Jong, Theo J W Fiselier, Sigrid W B Hoogveld, Gijs Bleijenberg
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To evaluate the efficacy of cognitive behaviour therapy for adolescents aged 10-17 years with chronic fatigue syndrome. <b>Design</b> Randomised controlled trial. <b>Setting</b> Department of child psychology. <b>Participants</b> 71 consecutively referred patients with chronic fatigue syndrome; 36 were randomly assigned to immediate cognitive behaviour therapy and 35 to the waiting list for therapy. <b>Intervention</b> 10 sessions of therapy over five months. Treatment protocols depended on the type of activity pattern (relatively active or passive). All participants were assessed again after five months. <b>Main outcome measures</b> Fatigue severity (checklist individual strength), functional impairment (SF-36 physical functioning), and school attendance. <b>Results</b> 62 patients had complete data at five months (29 in the immediate therapy group and 33 on the waiting list). Patients in the therapy group reported significantly greater decrease in fatigue severity (difference in decrease on checklist individual strength was 14.5, 95% confidence interval 7.4 to 21.6) and functional impairment (difference in increase on SF-36 physical functioning was 17.3, 6.2 to 28.4) and their attendance at school increased significantly (difference in increase in percentage school attendance was 18.2, 0.8 to 35.5). They also reported a significant reduction in several accompanying symptoms. Self reported improvement was largest in the therapy group. <b>Conclusion</b> Cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome in adolescents.
Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis
Authors: Wanhong Ding, Stefan Beissert, Liang Deng, Edward Miranda, Christopher Cassetty, Kristina Seiffert, Kristina L. Campton, Zhengmin Yan, George F. Murphy, Jeffrey A. Bluestone, Richard D. Granstein
Journal: Journal of Clinical Investigation (2003)

IL-10 is a pleiotropic cytokine that inhibits several immune parameters, including Th1 cell–mediated immune responses, antigen presentation, and antigen-specific T cell proliferation. Recent data implicate IL-10 as a mediator of suppression of cell-mediated immunity induced by exposure to UVB radiation (280–320 nm). To investigate the effects of IL-10 on the cutaneous immune system, we engineered transgenic mice that overexpress viral IL-10 (vIL-10) in the epidermis. vIL-10 transgenic mice demonstrated a reduced number of I-A+ epidermal and dermal cells and fewer I-A+ hapten-bearing cells in regional lymph nodes after hapten painting of the skin. Reduced CD80 and CD86 expression by I-A+ epidermal cells was also observed. vIL-10 transgenic mice demonstrated a smaller delayed-type hypersensitivity response to allogeneic cells upon challenge but had normal contact hypersensitivity to an epicutaneously applied hapten. Fresh epidermal cells from vIL-10 transgenic mice showed a decreased ability to stimulate allogeneic T cell proliferation, as did splenocytes. Additionally, chronic exposure of mice to UVB radiation led to the development of fewer skin tumors in vIL-10 mice than in WT controls, and vIL-10 transgenic mice had increased splenic NK cell activity against YAC-1targets. These findings support the concept that IL-10 is an important regulator of cutaneous immune function.
Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial
Authors: Kishore M Gadde, David B Allison, Donna H Ryan, Craig A Peterson, Barbara Troupin, Michael L Schwiers, Wesley W Day
Journal: The Lancet (2011)
Comparison of the Appropriateness of Coronary Angiography and Coronary Artery Bypass Graft Surgery Between Canada and New York State
Authors: E A McGlynn, C D Naylor, G M Anderson, L L Leape, R E Park, L H Hilborne, S J Bernstein, B S Goldman, P W Armstrong, J W Keesey
Journal: JAMA (1994)

<h3>Objective.</h3> —To compare the appropriateness of coronary angiography and coronary artery bypass graft (CABG) use between the United States and Canada. <h3>Design.</h3> —Retrospective randomized medical record review. <h3>Setting.</h3> —All hospitals performing coronary angiography and/or CABG surgery in two Canadian provinces (Ontario and British Columbia); in New York State, 15 randomly selected hospitals that provide coronary angiography and 15 randomly selected hospitals that provide CABG surgery. <h3>Patients.</h3> —All patients were randomly selected. For coronary angiography, 533 patients in Canada and 1333 patients in New York were selected; for CABG, 556 patients in Canada and 1336 patients in New York were selected. <h3>Main Outcome Measures.</h3> —Percentage of patients in each country who had coronary angiography or CABG for necessary, appropriate, uncertain, or inappropriate indications as rated by criteria developed separately in each country and the complications of those procedures. <h3>Results.</h3> —For coronary angiography, 9% of Canadian cases and 10% of New York cases were rated inappropriate using Canadian criteria compared with 5% and 4%, respectively, using US criteria. For CABG, 4% of Canadian cases and 6% of New York cases were rated inappropriate by Canadian criteria compared with 3% and 2%, respectively, using US criteria. A lower proportion of procedures were performed on persons aged 75 years or older in Canada than in New York for both coronary angiography (5% vs 11%;<i>P</i>&lt;.001) and CABG (6% vs 14%;<i>P</i>&lt;.001). Women were also represented in lower proportions among angiography cases in Canada than in New York (28% vs 35%;<i>P</i>=.023). Canadian patients with left main coronary disease waited significantly longer between angiography and CABG than did New York patients (<i>P</i>&lt;.0001). <h3>Conclusions.</h3> —Rates of inappropriate use of cardiac procedures were low in Canada and New York, which suggests that the regionalization of cardiac procedures that characterizes both health care systems contributes to better clinical decision making. Differences in the use of cardiac procedures among the elderly in the two countries merits further comparative examination. (<i>JAMA</i>. 1994;272:934-940)
Sublethal Irradiation of Human Tumor Cells Modulates Phenotype Resulting in Enhanced Killing by Cytotoxic T Lymphocytes
Authors: Charlie T. Garnett, Claudia Palena, Mala Chakarborty, Kwong-Yok Tsang, Jeffrey Schlom, James W. Hodge
Journal: Cancer Research (2004)

Abstract Local radiation of tumor masses is an established modality for the therapy of a range of human tumors. It has recently been recognized that doses of radiation, lower than or equal to those that cause direct cytolysis, may alter the phenotype of target tissue by up-regulating gene products that may make tumor cells more susceptible to T-cell–mediated immune attack. Previously, we demonstrated that radiation increased Fas (CD95) gene expression in carcinoembryonic antigen (CEA)-expressing murine tumor cells, which consequently enhanced their susceptibility to CEA-specific CTL-mediated killing. The present study was designed to determine whether these phenomena also occur with human tumor cells. Here, 23 human carcinoma cell lines (12 colon, 7 lung, and 4 prostate) were examined for their response to nonlytic doses of radiation (10 or 20 Gy). Seventy-two hours postirradiation, changes in surface expression of Fas (CD95), as well as expression of other surface molecules involved in T-cell–mediated immune attack such as intercellular adhesion molecule 1, mucin-1, CEA, and MHC class I, were examined. Twenty-one of the 23 (91%) cell lines up-regulated one or more of these surface molecules postirradiation. Furthermore, five of five irradiated CEA+/A2+ colon tumor cells lines demonstrated significantly enhanced killing by CEA-specific HLA-A2–restricted CD8+ CTLs compared with nonirradiated counterparts. We then used microarray analysis to broaden the scope of observed changes in gene expression after radiation and found that many additional genes had been modulated. These up-regulated gene products may additionally enhance the tumor cells’ susceptibility to T-cell–mediated immune attack or serve as additional targets for immunotherapy. Overall, the results of this study suggest that nonlethal doses of radiation can be used to make human tumors more amenable to immune system recognition and attack and form the rational basis for the combinatorial use of cancer vaccines and local tumor irradiation.
Impaired Fasting Plasma Glucose and Type 2 Diabetes Are Related to the Risk of Out-of-Hospital Sudden Cardiac Death and All-Cause Mortality
Authors: Jari A. Laukkanen, Timo H. Mäkikallio, Kimmo Ronkainen, Jouni Karppi, Sudhir Kurl
Journal: Diabetes Care (2012)

The aim of the study was to determine whether impaired fasting plasma glucose (FPG) and type 2 diabetes may be risk factors for sudden cardiac death (SCD).This prospective study was based on 2,641 middle-aged men 42-60 years of age at baseline. Impaired FPG level (≥5.6 mmol/L) among nondiabetic subjects (501 men) was defined according to the established guidelines, and the group with type 2 diabetes included subjects (159 men) who were treated with oral hypoglycemic agents, insulin therapy, and/or diet.During the 19-year follow-up, a total of 190 SCDs occurred. The relative risk (RR) for SCD was 1.51-fold (95% CI 1.07-2.14, P = 0.020) for nondiabetic men with impaired FPG and 2.86-fold (1.87-4.38, P < 0.001) for men with type 2 diabetes as compared with men with normal FPG levels, after adjustment for age, BMI, systolic blood pressure, serum LDL cholesterol, smoking, prevalent coronary heart disease (CHD), and family history of CHD. The respective RRs for out-of-hospital SCDs (157 deaths) were 1.79-fold (1.24-2.58, P = 0.001) for nondiabetic men with impaired FPG and 2.26-fold (1.34-3.77, P < 0.001) for men with type 2 diabetes. Impaired FPG and type 2 diabetes were associated with the risk of all-cause death. As a continuous variable, a 1 mmol/L increment in FPG was related to an increase of 10% in the risk of SCD (1.10 [1.04-1.20], P = 0.001).Impaired FPG and type 2 diabetes represent risk factors for SCD.
Tissue Doppler Imaging Consistently Detects Myocardial Abnormalities in Patients With Hypertrophic Cardiomyopathy and Provides a Novel Means for an Early Diagnosis Before and Independently of Hypertrophy
Authors: Sherif F. Nagueh, Linda L. Bachinski, Denise Meyer, Rita Hill, William A. Zoghbi, James W. Tam, Miguel A. Quiñones, Robert Roberts, A.J. Marian
Journal: Circulation (2001)

Background — Left ventricular hypertrophy (LVH), the clinical hallmark of familial hypertrophic cardiomyopathy (FHCM), is absent in a significant number of subjects with causal mutations. In transgenic rabbits that fully recapitulate the FHCM phenotype, reduced myocardial tissue Doppler (TD) velocities accurately identified the mutant rabbits, even in the absence of LVH. We tested whether humans with FHCM also consistently showed reduced myocardial TD velocities, irrespective of LVH. Methods and Results — We performed 2D and Doppler echocardiography and TD imaging in 30 subjects with FHCM, 13 subjects who were positive for various mutations but did not have LVH, and 30 age- and sex-matched controls (all adults; 77% women). LV wall thickness and mass were significantly greater in FHCM subjects ( P &lt;0.01 versus those without LVH and controls). There were no significant differences in 2D echocardiographic, mitral, and pulmonary venous flow indices between mutation-positives without LVH and controls. In contrast, systolic and early diastolic TD velocities were significantly lower in both mutation-positives without LVH and in FHCM patients than in controls ( P &lt;0.001). Reduced TD velocities had a sensitivity of 100% and a specificity of 93% for identifying mutation-positives without LVH. Conclusions — Myocardial contraction and relaxation velocities, detected by TD imaging, are reduced in FHCM, including in those without LVH. Before and independently of LVH, TD imaging is an accurate and sensitive method for identifying subjects who are positive for FHCM mutations.