tbuckley/cabot-search huggingface dataset:
The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants
Authors: D.N. Slater
Journal: British Journal of Dermatology (2005)

Following consensus meetings of the two parent organizations, a new World Health Organization–European Organization for Research and Treatment of Cancer (WHO–EORTC) classification for primary cutaneous lymphomas has recently been published. This important development will now end the ongoing debate as to which of these was the preferred classification. The new classification will facilitate more uniformity in diagnosis, management and treatment of cutaneous lymphomas. In particular, it provides a useful distinction between indolent and more aggressive types of primary cutaneous lymphoma and provides practical advice on preferred management and treatment regimens. This will thereby prevent patients receiving high‐grade treatment for low‐grade biological disease. This review focuses on those diseases which have found new consensus agreement compared with the original WHO and EORTC classifications. In cutaneous T‐cell lymphomas, these include folliculotropic mycosis fungoides, defining features of Sézary syndrome, primary cutaneous CD30+ lymphoproliferative disorders (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline lesions) and subcutaneous panniculitis‐like T‐cell lymphoma. Primary cutaneous CD4+ small/medium‐sized pleomorphic T‐cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ T‐cell lymphoma and cutaneous γ/δ T‐cell lymphoma are allocated provisional entry status and thereby afford better definitions for some cases of currently unspecified primary cutaneous peripheral T‐cell lymphoma. In cutaneous B‐cell lymphomas, diseases which have found new consensus agreement include primary cutaneous marginal zone B‐cell lymphoma, primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B‐cell lymphoma, leg type and primary cutaneous diffuse large B‐cell lymphoma, other. CD4+/CD56+ haematodermic neoplasm (early plasmacytoid dendritic cell leukaemia/lymphoma) now appears as a precursor haematological neoplasm and replaces the previous terminology of blastic NK‐cell lymphoma. Other haematopoietic and lymphoid tumours involving the skin, as part of systemic disease, will appear in the forthcoming WHO publication Tumours of the Skin. The new classification raises interesting new problems and questions about primary cutaneous lymphoma and some of these are discussed in this article. It is, however, a splendid signpost indicating the direction in which research in cutaneous lymphoma needs to go. In the interim, we have an international consensus classification which is clinically meaningful.
Secretory Granule Proteases in Rat Mast Cells. Cloning of 10 Different Serine Proteases and a Carboxypeptidase A from Various Rat Mast Cell Populations
Authors: Claudia Lützelschwab, Gunnar Pejler, Maria Aveskogh, Lars Hellman
Journal: The Journal of Experimental Medicine (1997)

Two of the major rat mast cell proteases, rat mast cell protease 1 (RMCP-1) and RMCP-2, have for many years served as important phenotypic markers for studies of various aspects of mast cell (MC) biology. However, except for these proteases only fragmentary information has been available on the structure and complexity of proteases expressed by different subpopulations of rat MCs. To address these questions, cDNA libraries were constructed from freshly isolated rat peritoneal MCs and from the rat mucosal MC line RBL-1. cDNA clones for 10 different serine proteases (RMCP-1-10), and the MC carboxypeptidase A were isolated and characterized. Six of these proteases have not been isolated previously. Based on their protease content, three separate subpopulations of MCs were identified. Connective tissue MCs (CTMCs) from the ear and peritoneum express the chymases RMCP-1 and -5, the tryptases RMCP-6, and -7 and the carboxypeptidase A. However, based on a large difference in the level of expression of RMCP-7, CTMCs of these two organs may be regarded as two separate subpopulations. RMCP-2 and the three closely related proteases of the RMCP-8 subfamily were identified as the major mucosal MC proteases in rat. In contrast to what has been reported for human MCs, no expression of cathepsin G or cathepsin G-like proteases was detected in any of the rat MC populations. To determine mRNA frequencies for the various proteases expressed by normal tissue MCs, an unamplified peritoneal MC cDNA library was screened with a panel of mono-specific cDNA probes. These results showed that peritoneal MCs are highly specialized effector cells with mRNA frequencies for the major proteases in the range of several percent of the total mRNA pool.
A Randomized Trial of Sertraline as a Cessation Aid for Smokers With a History of Major Depression
Authors: Lirio S Covey, Alexander H Glassman, Fay Stetner, Sarah Rivelli, Kurt Stage
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated. METHOD: The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits. RESULTS: Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed. CONCLUSIONS: Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.
Abstract 4718: Combined Adenosine Stress Perfusion and Coronary Angiography Using 320-Row Detector Dynamic Volume Computed Tomography in Patients with Suspected Coronary Artery Disease
Authors: Richard T George, Kakuya Kitagawa, Katherine Laws, Albert C Lardo, Joao A Lima
Journal: Circulation (2008)

Dynamic volume 320-row detector computed tomography (CT), with full cardiac coverage, allows for the combination of non-invasive angiography (CTA) performed at rest with myocardial perfusion imaging (MPI) during adenosine stress. The purpose of this study was to test the accuracy of combined CTA and MPI using dynamic volume 320-row detector CT to identify atherosclerosis causing territorial ischemia. Eighteen patients with chest pain and intermediate to high pre-test likelihood of coronary artery disease (CAD) underwent rest CTA and stress CT-MPI following radionuclide MPI using the following prospective ECG-gated protocol: Rest CTA: 320 × 0.5mm, 120 kV, 400 mA, 70 – 80% R-R interval followed by Stress CT-MPI: adenosine (140μg/kg/min), 320 × 0.5mm, 120 kV, 400 mA, 70 – 80% R-R interval. CT-MPI images were reconstructed in the short axis with a 3 mm slice thickness. The transmural perfusion ratio (TPR) was calculated by dividing the endocardial attenuation density (AD) by the epicardial AD in each sector. Ischemia was defined as a TPR &lt;0.99 on adenosine stress CT-MPI that normalized on the rest CTA images. CTA was analyzed for stenoses ≥50% and radionuclide MPI was analyzed for fixed and reversible perfusion abnormalities. Using a 17-segment model in a territory/vessel based analysis, the combination of CTA + CT-MPI was compared with CTA 3 radionuclide MPI (gold standard) for its ability to detect atherosclerosis causing territorial ischemia. Mean TPRs in ischemic and normal territories were 0.90±0.09 and 1.13±0.10, respectively (p&lt;0.001). The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) for CTA + CT-MPI were 86%, 85%, 67, and 94% compared with the gold standard; respectively. However, when adjusting for balanced multivessel disease the sensitivity, specificity, PPV, and NPV were 89%, 94%, 89%, and 94%; respectively. Mean effective radiation dose for the combined rest (4.9±0 mSv) and stress (8.5±0.5mSv) protocols was 13.4±0.5 mSv. The combination of CTA and CT -MPI, using 320-row detector dynamic volume CT, is capable of accurately identifying myocardial ischemia in the presence of obstructive atherosclerosis and compares well with CTA/radionuclide MPI.
Prolonged antigen presentation by immune complex–binding dendritic cells programs the proliferative capacity of memory CD8 T cells
Authors: Beatriz León, André Ballesteros-Tato, Troy D. Randall, Frances E. Lund
Journal: The Journal of Experimental Medicine (2014)

The commitment of naive CD8 T cells to effector or memory cell fates can occur after a single day of antigenic stimulation even though virus-derived antigens (Ags) are still presented by DCs long after acute infection is resolved. However, the effects of extended Ag presentation on CD8 T cells are undefined and the mechanisms that regulate prolonged Ag presentation are unknown. We showed that the sustained presentation of two different epitopes from influenza virus by DCs prevented the premature contraction of the primary virus-specific CD8 T cell response. Although prolonged Ag presentation did not alter the number of memory CD8 T cells that developed, it was essential for programming the capacity of these cells to proliferate, produce cytokines, and protect the host after secondary challenge. Importantly, prolonged Ag presentation by DCs was dependent on virus-specific, isotype-switched antibodies (Abs) that facilitated the capture and cross-presentation of viral Ags by FcγR-expressing DCs. Collectively, our results demonstrate that B cells and Abs can regulate the quality and functionality of a subset of antiviral CD8 T cell memory responses and do so by promoting sustained Ag presentation by DCs during the contraction phase of the primary T cell response.
Antibiofilm activity of a monolayer of silver nanoparticles anchored to an amino-silanized glass surface
Authors: Angelo Taglietti, Carla Renata Arciola, Agnese D'Agostino, Giacomo Dacarro, Lucio Montanaro, Davide Campoccia, Lucia Cucca, Marco Vercellino, Alessandro Poggi, Piersandro Pallavicini, Livia Visai
Journal: Biomaterials (2013)
Targeting Cdc37 Inhibits Multiple Signaling Pathways and Induces Growth Arrest in Prostate Cancer Cells
Authors: Phillip J. Gray, Mary Ann Stevenson, Stuart K. Calderwood
Journal: Cancer Research (2007)

Abstract Members of the 90-kDa heat shock protein (HSP90) family are known to bind and stabilize intermediates in a wide variety of cell signaling pathways and contribute to their dysregulation in cancer. An important intracellular cofactor for HSP90 is Cdc37, a protein with a broad role in fostering the activities of protein kinases. By targeting Cdc37 using RNA interference, we have shown that the loss of Cdc37 function induces irreversible growth arrest in androgen receptor-positive and -negative prostate carcinoma cells. In contrast to HSP90-directed agents, Cdc37 targeting seems to affect cancer cells through a distinct mechanism and does not significantly deplete the intracellular levels of most known HSP90 client proteins. Instead, Cdc37 depletion inhibits cellular kinase activity and flux through growth-promoting signal transduction cascades. We show that the loss of Cdc37 leads to reduced activity of the Erk, Akt, mTOR, and androgen-induced pathways. We have also discovered synergistic interactions between Cdc37 inactivation and the HSP90-inhibitory anticancer drug 17-(allylamino)-17-demethoxygeldanamycin (17AAG). These interactions involve enhanced degradation of proteins essential for growth and inhibition of 17AAG-induced expression of the antiapoptotic HSP70. Thus, Cdc37 is essential for maintaining prostate tumor cell growth and may represent a novel target in the search for multitargeted therapies based on the HSP90 chaperone system. [Cancer Res 2007;67(24):11942–50]
Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup phase III BIG 02-98 trial
Authors: B.C. Pestalozzi, P. Francis, E. Quinaux, S. Dolci, E. Azambuja, R.D. Gelber, G. Viale, A. Balil, M. Andersson, B. Nordenskjöld, M. Gnant, J. Gutierrez, I. Láng, J.P.A. Crown, M. Piccart-Gebhart
Journal: Annals of Oncology (2008)
Quantification of thioguanine-resistant lymphocytes from mice irradiated in vivo.
Authors: R Lorenz, T Göllner, K Hempel
Journal: Environmental Health Perspectives (1990)

Adult mice were Co-60 gamma irradiated, and 7 months later splenocytes were isolated, cultured in microwells, and the frequency of hprt-deficient mutants was determined by measuring the cloning efficiency in media with 6-thioguanine. The mutant frequency at 2, 4, and 6 Gy was 1.6 x 10(-5), 4.4 x 10(-5), and 12.7 x 10(-5), respectively. The frequency of spontaneous mutants was 2.5 x 10(-6). The effect of metabolic cooperation on the cloning efficiency of thioguanine-resistant T-cells in selective medium was evaluated in co-cultures with wild-type T-cells. We found that the growth of hprt-deficient T-cells is supported in the presence of thioguanine-inactivated wild-type splenocytes up to a cell density of 5 x 10(5) cells per well. When cell density was higher, cell growth was inhibited. Possibilities and limitations of cloned lymphocytes for the analysis of somatic mutations that occur in vivo are discussed.
Ibufenac (4-isobutylphenyl Acetic Acid)
Authors: F. D. Hart, P. L. Boardman
Journal: Annals of the Rheumatic Diseases (1965)

Adams,Cliffe, Lessel, andNicholson (1963) reported* thebiological properties ofa newsubstance, 4-isobutylphenyl acetic acid(Ibufenac). As assessed bytheultra-violet erythema test inguineapigs (AdamsandCobb,1958), itproved tohavetwo tofourtimes theanti-inflammatory effect ofaspirin, andits analgesic activity asmeasured byamodificationofthemethodofRandall andSelitto (1957) wasofthesameorder.Their worksuggested that thissubstance mightbea useful substitute for acetylsalicylic acid.Inhumansubjects, after doses of640mg.bymouth,detectable amountswere present inthebloodwithin 30to60minutes, rising toamaximumof2to4mg./100 ml.in2to4hours, andsmall butdetectable amountswerestill present 8hoursafter ingestion ofthedose(Adams, 1963). Chalmers (1963) reported thatIbufenac indoses of 30gr.daily appeared tobeaseffective asaspirin in doses of60gr.daily inthecontrol ofsymptoms in patients withrheumatoid arthritis, side-effects being fewer withIbufenac thanwithacetylsalicylic acid. Tudhope (1964), using the51chromium technique previously employed byScott, Porter, Lewis, and Dixon(1961) andWood,Harvey-Smith, andDixon (1962) withsalicylates, foundIbufenac considerably lessproductive ofgastro-intestina l haemorrhage,
CXCR4 Regulates Migration and Development of Human Acute Myelogenous Leukemia Stem Cells in Transplanted NOD/SCID Mice
Authors: Sigal Tavor, Isabelle Petit, Svetlana Porozov, Abraham Avigdor, Ayelet Dar, Leonor Leider-Trejo, Noga Shemtov, Varda Deutsch, Ella Naparstek, Arnon Nagler, Tsvee Lapidot
Journal: Cancer Research (2004)

Abstract The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 participate in the retention of normal hematopoietic stem cells within the bone marrow (BM) and their release into the circulation. Homing and engraftment of human stem cells in immunodeficient mice are dependent on cell surface CXCR4 expression and the production of BM SDF-1, which acts also as a survival factor for both human and murine stem cells. However, the role of SDF-1/CXCR4 interactions in the control of human acute myelogenous leukemia (AML) cell trafficking and disease progression is poorly understood. In this study, we report that although some AML cells do not express surface CXCR4, all AML cells tested express internal CXCR4 and SDF-1. Culture of AML cells with SDF-1 promoted their survival, whereas addition of neutralizing CXCR4 antibodies, SDF-1 antibodies, or AMD3100 significantly decreased it. Pretreatment of primary human AML cells with neutralizing CXCR4 antibodies blocked their homing into the BM and spleen of transplanted NOD/SCID/B2mnull mice. Furthermore, weekly administrations of antihuman CXCR4 to mice previously engrafted with primary AML cells led to a dramatic decrease in the levels of human AML cells in the BM, blood, and spleen in a dose- and time-dependent manner. Interestingly, the same treatment did not affect significantly the levels of normal human progenitors engrafted into NOD/SCID mice. Taken together, our findings demonstrated the importance of the SDF-1/CXCR4 axis in the regulation of in vivo motility and development of human AML stem cells and identified CXCR4 neutralization as a potential treatment for AML.
Rhabdomyolysis Associated With 2009 Influenza A(H1N1)
Authors: Estela Ayala
Journal: JAMA (2009)

Zhou et al state that "recent evidence-based recommendations for the management of patients with herpes zoster recommend using antiviral therapy to decrease the incidence of PHN," citing an article for which I am a coauthor. 4This article stated that antiviral therapy should be used to treat patients with herpes zoster and that it had an impact on acute neuritis.Although the guidelines concluded that the use of antiviral therapy may have an effect on "chronic pain," this therapy was not sufficient to uniformly prevent PHN.As noted here, the FDA reached a similar conclusion.The goal of management of herpes zoster is to accelerate healing, prevent complications, and decrease pain-both acute pain and PHN.With the evidence available from existing antiviral studies, these end points have been achieved with the exception of prevention of PHN.The management of PHN is of critical importance for individuals who have herpes zoster.Consideration of combination therapy at the onset of disease, particularly in patients with severe acute pain, needs to be further evaluated. 4Future treatment strategies may prevent or provide more significant relief for this potentially devastating complication.
Two Gene Fragments that Direct Podocyte-Specific Expression in Transgenic Mice
Authors: Marcus J Moeller, Silja K Sanden, Abdulsalam Soofi, Roger C Wiggins, Lawrence B Holzman
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Transgenic manipulation of the glomerular visceral epithelial cell offers a powerful approach for studying the biology of this morphologically complex cell type. It has been previously demonstrated that an 8.3-kb and a 5.4-kb fragment of the murine Nphs1 (nephrin) promoter-enhancer drives lacZ expression in podocytes, brain, and pancreas of transgenic mice, recapitulating the expression pattern of the endogenous nephrin gene. In this present study, two truly podocyte-specific promoters were identified that drive transgene expression in podocytes without expression in extrarenal tissues in adult or embryonic mice. A 1.25-kb fragment driving a lacZ reporter gene (p1.25N-nlacF) was derived from murine Nphs1 promoter similar to a human NPHS1 promoter fragment previously reported. Transgenic mice were generated and beta-galactosidase (beta-gal) expression was analyzed. Four of twelve founder mice were found to express beta-gal in podocytes (33% penetrance). Expression in brain and pancreas was absent in all animals, suggesting that nephrin expression in these organs might be driven by distinct cis-regulatory elements that can be removed to obtain podocyte-specific expression. A 2.5-kb fragment derived from the human NPHS2 (podocin) gene was designed in a similar fashion to drive lacZ expression in transgenic mice (p2.5P-nlacF). Twelve of twlve NPHS2 mouse founder lines expressed beta-gal exclusively in podocytes (100% penetrance). Beta-gal activity was not observed extrinsic to the kidney in p1.25N-nlacF or p2.5P-nlacF mouse embryos at gestational time points between 8.5 d post coitus and birth. In conclusion, the 2.5-kb NPHS2 promoter fragment may be useful for podocyte-specific transgenic expression when extrarenal expression of a transgene is problematic.
Effect of <i>Pseudomonas</i> Infection on Weight Loss, Lung Mechanics, and Cytokines in Mice
Authors: ANNA M. van HEECKEREN, JAMSAK TSCHEIKUNA, RONALD W. WALENGA, MICHAEL W. KONSTAN, PAMELA B. DAVIS, BERNIE EROKWU, MUSA A. HAXHIU, THOMAS W. FERKOL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Poor growth, Pseudomonas aeruginosa endobronchitis, pulmonary inflammation, and decline of lung function are hallmarks of cystic fibrosis (CF), yet the relationship between these features is poorly understood. Because animal models of chronic bronchopulmonary infection with P. aeruginosa used to study pulmonary inflammation in CF have also been associated with weight loss, we sought to determine whether this weight loss was due to the inflammatory process and/or to changes in lung function. P. aeruginosa-laden agarose beads were instilled into the lungs of mice. Weight loss was greatest 3 d after Pseudomonas infection. Infected mice had a rapid though transient rise in absolute neutrophil counts, mTNF- α , mIL-1 β , mIL-6, mip-2, and KC in bronchoalveolar lavage fluid. There was no difference in lung resistance or lung compliance measured by body plethysmography between infected and control mice. Weight loss did correlate with the concentration of proinflammatory cytokine levels 3 d after inoculation of mice with Pseudomonas, and body composition analysis revealed loss of skeletal muscle mass. These results suggest that weight loss in P. aeruginosa-infected mice was associated with the inflammatory process and not with altered pulmonary responsiveness. These findings may provide insights into the cause of cachexia and weight loss seen in patients with CF. van Heeckeren AM, Tscheikuna J, Walenga RW, Konstan MW, Davis PB, Erokwu B, Haxhiu MA, Ferkol TW. Effect of Pseudomonas infection on weight loss, lung mechanics, and cytokines in mice.
Survey of informed consent for registration of congenital anomalies in Europe
Authors: Araceli Busby, Annukka Ritvanen, Helen Dolk, Nicola Armstrong, Hermien De Walle, Isolina Riaño-Galán, Miriam Gatt, Robert McDonnell, Vera Nelen, David Stone
Journal: BMJ (2005)

Eurocat is a network of population based registers of congenital anomalies in Europe covering about a quarter of the birth population in 19 countries (www.eurocat.