tbuckley/cabot-search huggingface dataset:
Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461
Authors: Sherif S. Farag, Kellie J. Archer, Krzysztof Mrózek, Amy S. Ruppert, Andrew J. Carroll, James W. Vardiman, Mark J. Pettenati, Maria R. Baer, Mazin B. Qumsiyeh, Prasad R. Koduru, Yi Ning, Robert J. Mayer, Richard M. Stone, Richard A. Larson, Clara D. Bloomfield
Journal: Blood (2006)
Distal Protection With a Filter Device During Coronary Stenting in Patients With Stable and Unstable Angina
Authors: Annalisa Angelini, Paolo Rubartelli, Flavio Mistrorigo, Mila Della Barbera, Francesco Abbadessa, Massimo Vischi, Gaetano Thiene, Sergio Chierchia
Journal: Circulation (2004)

Background— Filter protection after percutaneous coronary intervention (PCI) is now available to prevent distal embolization. The aims of this study were (1) to evaluate the microembolization phenomenon during procedures of stent implantation in native coronary arteries of patients with stable and unstable angina, (2) to assess the amount and characteristics of the debris captured by the Angioguard, and (3) to investigate the relation between clinical and angiographic variables and pathological data. Methods and Results— Elective coronary stenting with the use of a protective filter was attempted in 39 consecutive coronary artery lesions with &gt;60% stenosis (mean, 67.6±8.79%). Debris was present in 75.6% of the filters. Particle size ranged from 47.16 to 2503.48 μm (mean, 518.83±319.61 μm) in the major axis. Particles &gt;300 μm were found in 24 of 28 filters with debris (85.7%), and particles &gt;1000 μm were present in 10 of 28 filters (35.7%). Patients with unstable angina had greater particles (mean maximum longitudinal diameter, 1098.33±714.3 μm) than those with stable angina (412.91±453 μm; P &lt;0.001). The presence of unstable angina (OR, 65; CI, 1.2 to 3420; P =0.03) and age &gt;67 years (OR, 42; CI, 1 to 1698; P =0.04) were found to be the only independent predictors of embolic particle size. Conclusions— By limiting embolization, protective devices may prevent a number of potentially unfavorable events, thereby improving outcome. Our data support the use of these devices, especially in lesions with higher embolic potential, such as those occurring in older patients and in those with unstable angina.
Basophils regulate the recruitment of eosinophils in a murine model of irritant contact dermatitis
Authors: Chisa Nakashima, Atsushi Otsuka, Akihiko Kitoh, Tetsuya Honda, Gyohei Egawa, Saeko Nakajima, Satoshi Nakamizo, Makoto Arita, Masato Kubo, Yoshiki Miyachi, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2014)
Evaluation framework for carotid bifurcation lumen segmentation and stenosis grading
Authors: K. Hameeteman, M.A. Zuluaga, M. Freiman, L. Joskowicz, O. Cuisenaire, L. Flórez Valencia, M.A. Gülsün, K. Krissian, J. Mille, W.C.K. Wong, M. Orkisz, H. Tek, M. Hernández Hoyos, F. Benmansour, A.C.S. Chung, S. Rozie, M. van Gils, L. van den Borne, J. Sosna, P. Berman, N. Cohen, P.C. Douek, I. Sánchez, M. Aissat, M. Schaap, C.T. Metz, G.P. Krestin, A. van der Lugt, W.J. Niessen, T. van Walsum
Journal: Medical Image Analysis (2011)
miR-17 deregulates a core RUNX1-miRNA mechanism of CBF acute myeloid leukemia
Authors: John Adams Fischer, Stefano Rossetti, Arani Datta, Kevin Hasegawa Eng, Alessandro Beghini, Nicoletta Sacchi
Journal: Molecular Cancer (2015)

Core Binding Factor acute myeloid leukemia (CBF-AML) with t(8;21) RUNX1-MTG8 or inv(16) CBFB-MYH11 fusion proteins often show upregulation of wild type or mutated KIT receptor. However, also non-CBF-AML frequently displays upregulated KIT expression. In the first part of this study we show that KIT expression can be also upregulated by miR-17, a regulator of RUNX1, the gene encoding a CBF subunit. Interestingly, both CBF leukemia fusion proteins and miR-17, which targets RUNX1-3′UTR, negatively affect a common core RUNX1-miRNA mechanism that forces myeloid cells into an undifferentiated, KIT-induced, proliferating state. In the second part of this study we took advantage of the conservation of the core RUNX1-miRNA mechanism in mouse and human, to mechanistically demonstrate in a mouse myeloid cell model that increased KIT-induced proliferation is per se a mechanism sufficient to delay myeloid differentiation. Human (U937) or mouse (32D) myeloid clonal lines were used, respectively, to test: 1) the effect of RUNX1-MTG8 and CBFB-MYH11 fusion proteins, or upregulation of miR-17, on KIT-induced proliferation and myeloid differentiation, and 2) the effect of upregulation of KIT-induced proliferation per se on myeloid cell differentiation. In the first part of this study we found that stable miR-17 upregulation affects, like the CBF-AML fusion proteins (RUNX1-MTG8 or CBFB-MYH11), a core RUNX1-miRNA mechanism leading to KIT-induced proliferation of differentiation-arrested U937 myeloid cells. In the second part of the study we harnessed the conservation of this core mechanism in human and mouse to demonstrate that the extent of KIT upregulation in 32D mouse myeloid cells with wild type RUNX1 can per se delay G-CSF-induced differentiation. The integrated information gathered from the two myeloid cell models shows that RUNX1 regulates myeloid differentiation not only by direct transcriptional regulation of coding and non-coding myeloid differentiation functions (e.g. miR-223), but also by modulating KIT-induced proliferation via non-coding miRNAs (e.g. miR-221). The novelty of this study is dual. On the one hand, miRNAs (e.g. miR-17) can mimic the effects of CBF-AML fusion proteins by affecting a core RUNX1-miRNA mechanism of KIT-induced proliferation of undifferentiated myeloid cells. On the other hand, the extent of KIT-induced proliferation itself can modulate myeloid differentiation of cells with wild type RUNX1 function.
Peroxisome proliferator–activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor–deficient mice
Authors: Andrew C. Li, Kathleen K. Brown, Mercedes J. Silvestre, Timothy M. Willson, Wulf Palinski, Christopher K. Glass
Journal: Journal of Clinical Investigation (2000)

The peroxisome proliferator–activated receptor γ (PPARγ) is a nuclear receptor that regulates fat-cell development and glucose homeostasis and is the molecular target of a class of insulin-sensitizing agents used for the management of type 2 diabetes mellitus. PPARγ is highly expressed in macrophage foam cells of atherosclerotic lesions and has been demonstrated in cultured macrophages to both positively and negatively regulate genes implicated in the development of atherosclerosis. We report here that the PPARγ-specific agonists rosiglitazone and GW7845 strongly inhibited the development of atherosclerosis in LDL receptor–deficient male mice, despite increased expression of the CD36 scavenger receptor in the arterial wall. The antiatherogenic effect in male mice was correlated with improved insulin sensitivity and decreased tissue expression of TNF-α and gelatinase B, indicating both systemic and local actions of PPARγ. These findings suggest that PPARγ agonists may exert antiatherogenic effects in diabetic patients and provide impetus for efforts to develop PPARγ ligands that separate proatherogenic activities from antidiabetic and antiatherogenic activities.
Psychodynamic Considerations of Aging and the Aged: An Overview
Authors: MARTIN A. BEREZIN
Journal: American Journal of Psychiatry (1972)

Until recently aging and the aged tended not only to be neglected but to be subject to misconceptions and myths. In this overview the author points out that most of the elderly are emotionally healthy persons who retain the same drives and ego operations that served them earlier. However, old age does precipitate special problems, which the author describes. He discusses psychotherapy and somatic therapies as they apply to the aged, as well as death and dying and the problems faced by the families of elderly persons.
Nutritional Needs of Athletes
Authors: Jane Griffin
Journal: British Journal of Sports Medicine (1995)

Book reviews and the clinician then comes to the key chapters on fatigue, muscle damage and pain, with a final review of the changes occurring in muscle diseases.This text is based on undergraduate and postgraduate courses and will be of interest to scientists and physiologists as well as clinicians.I have found this book both fascinating and useful, but part of the fascination is that some of our practical sports medicine problems, such as severe post-exertional muscle pain, are not yet fully explicable.This book encourages both dipping and further study in pursuit of clinical answers and is highly recommended.
Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study
Authors: M Sebastiani, A Manfredi, G Vukatana, S Moscatelli, L Riato, M Bocci, M Iudici, A Principato, S Mazzuca, P Del Medico, R De Angelis, R D'Amico, R Vicini, M Colaci, C Ferri
Journal: Annals of the Rheumatic Diseases (2011)

Introduction The early detection of systemic sclerosis (SSc) patients at high risk of developing digital ulcers could allow preventive treatment, with a reduction of morbidity and social costs. In 2009, a quantitative score, the capillaroscopic skin ulcer risk index (CSURI), calculated according to the formula ‘D×M/N 2’ , was proposed, which was highly predictive of the appearance of scleroderma digital ulcers within 3 months of capillaroscopic evaluation. Objectives This multicentre study aims to validate the predictive value and reproducibility of CSURI in a large population of SSc patients. Methods CSURI was analysed in 229 unselected SSc patients by nailfold videocapillaroscopy (NVC). All patients were re-evaluated 3 months later with regard to the persistence and/or appearance of new digital ulcers. Results 57 of 229 patients presented with digital ulcers after 3 months. The receiver operating characteristic curve analysis showed an area under the curve of 0.884 (95% CI 0.835 to 0.922), with specificity and sensitivity of 81.4% (95% CI 74.8 to 86.89) and 92.98% (95% CI 83.0 to 98.0), respectively, at the cut-off value of 2.96. The reproducibility of CSURI was validated on a random sample of 81 patients, with a κ-statistic measure of interrater agreement of 0.8514. Conclusions The role of CSURI was confirmed in detecting scleroderma patients with a significantly high risk of developing digital ulcers within the first 3 months from NVC evaluation. CSURI is the only method validated to predict the appearance of digital ulcers and its introduction into routine clinical practice might help optimise the therapeutic strategy of these harmful SSc complications.
Potent Anticarcinoma Activity of the Humanized Anti-CD70 Antibody h1F6 Conjugated to the Tubulin Inhibitor Auristatin via an Uncleavable Linker
Authors: Ezogelin Oflazoglu, Ivan J. Stone, Kristine Gordon, Christopher G. Wood, Elizabeth A. Repasky, Iqbal S. Grewal, Che-Leung Law, Hans-Peter Gerber
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The antitubulin agent monomethyl auristatin F (MMAF) induces potent antitumor effects when conjugated via protease cleavable linkers to antibodies targeting internalizing, tumor-specific cell surface antigens. Humanized 1F6 (h1F6) is a humanized monoclonal antibody targeting CD70, a member of the tumor necrosis factor family that is expressed on hematologic malignancies and carcinomas. Here, we tested h1F6–maleimidocaproyl (mc) MMAF conjugates, consisting of an uncleavable mc linker, for their ability to interfere with the growth of CD70-positive carcinomas. Experimental Design: To evaluate the optimal drug per antibody ratio, we conjugated either four or eight MMAF molecules to the cysteines that comprise the interchain disulfides of h1F6 and determined antitumor activities in vitro and in xenografted mice. The tumor types tested included glioblastoma, patient-derived renal cell carcinoma (RCC) cell isolates, and standard RCC tumor cell lines. Results: All h1F6-mcMMAF conjugates potently interfered with the growth of all carcinomas in vitro and resulted in complete responses of RCC tumors implanted orthotopically or s.c. in mice. In vitro, h1F6-mcMMAF(8) was generally more potent than h1F6-mcMMAF(4). However, h1F6-mcMMAF(4) displayed equal or better efficacy than h1F6-mcMMAF(8) when administered to tumor-bearing mice. Conclusions: We showed that h1F6-mcMMAF conjugates inhibited the growth of human carcinomas and that increased drug loading, while improving potency in vitro, did not substantially affect the pharmacodynamic and pharmacokinetic properties in vivo. Based on these findings, h1F6-mcMMAF(4), designated SGN-75, has been identified as a potential antibody-drug conjugate for clinical development.
Influence of Smoking on the Pharmacokinetics and Toxicity Profiles of Taxane Therapy
Authors: Anne-Joy M. de Graan, Walter J. Loos, Lena E. Friberg, Sharyn D. Baker, Jessica M. van der Bol, Leni van Doorn, Erik A.C. Wiemer, Bronno van der Holt, Jaap Verweij, Ron H.J. Mathijssen
Journal: Clinical Cancer Research (2012)

Cigarette smoke is known to interact with the metabolism of several anticancer drugs. It may also affect the incidence and severity of adverse events and efficacy of chemotherapy. The main objective of this study was to examine the effects of smoking on the pharmacokinetics and toxicities of patients treated with docetaxel or paclitaxel.Smoking status, toxicity profiles, and pharmacokinetic parameters (calculated by nonlinear mixed-effect modeling population analysis) were determined in 566 patients (429 nonsmokers and 137 smokers) treated with docetaxel or paclitaxel.Smokers treated with docetaxel showed less grade IV neutropenia (35% vs. 52%; P = 0.01) than nonsmokers. Smokers treated with paclitaxel had less grade III-IV leukopenia than nonsmokers (12% vs. 25%; P = 0.03), and the white blood cell (WBC) nadir was lower in nonsmokers (median, 2.7 × 10(9)/L; range, 0.05 × 10(9) to 11.6 × 10(9)/L) than in smokers (median, 3.3 × 10(9)/L; range 0.8 × 10(9) to 10.2 × 10(9)/L; P = 0.02). Of interest, significantly lower WBC counts and absolute neutrophil counts at baseline were seen in nonsmoking patients treated with paclitaxel (P = 0.0001). Pharmacokinetic parameters were similar in smokers and nonsmokers for both taxanes.Cigarette smoking does not alter the pharmacokinetic determinants of docetaxel and paclitaxel. Smokers treated with docetaxel and paclitaxel have less neutropenia and leukopenia, but further research is warranted to elucidate this potential protective effect.
Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche
Authors: Janine T. Erler, Kevin L. Bennewith, Thomas R. Cox, Georgina Lang, Demelza Bird, Albert Koong, Quynh-Thu Le, Amato J. Giaccia
Journal: Cancer Cell (2009)
Helicobacter pylori induced transactivation of SRE and AP-1 through the ERK signalling pathway in gastric cancer cells
Authors: Y Mitsuno
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> Helicobacter pylori infection induces expression of proinflammatory cytokines such as interleukin (IL)-8 and tumour necrosis factor α (TNF-α) in gastric mucosa, and their genes have AP-1 binding sites in the promoter region. c-Fos is important for transactivation of AP-1 which has SRE in the promoter region. We conducted this study to confirm <i>H pylori</i> induced transactivation of these binding sites. <h3>METHODS</h3> Transactivation of SRE and AP-1 was evaluated in human gastric cancer cells TMK1 and MKN45 by luciferase reporter assay in transient transfection. We compared the effects of coculture with four <i>H pylori</i> strains, a <i>cag</i> pathogenicity island (PAI) positive strain TN2, its isogenic<i>vacA</i> negative (TN2-Δ<i>vacA</i>) or<i>cagE</i> negative (TN2-Δ<i>cagE</i>) mutants, and a<i>cag</i> PAI negative clinical isolate T68. Phosphorylation of ERK1/2, JNK, and c-Jun was measured by immunoblot, induction of IL-8 secretion by ELISA, and the effects of MEK by inhibitor U0126. <h3>RESULTS</h3> Both SRE and AP-1 were transactivated by coculture with TN2. Although TN2-Δ<i>vacA</i> induced comparable transactivation, TN2-Δ<i>cagE</i> and T68 showed decreased transactivation of SRE (65% and 51%) and AP-1 (71% and 54%, respectively, of TN2). Heat killed TN2 or indirect contact using a permeable membrane inhibited transactivation. Levels of phosphorylated ERK1/2, JNK, and c-Jun were increased by coculture with TN2. MEK inhibitor U0126 reduced TN2 induced transactivation of SRE and AP1, as well as secretion of IL-8, by 83%, 87%, and 53%, respectively, of TN2. <h3>CONCLUSIONS</h3> Transactivation of SRE and AP-1, through ERK/MAPK and JNK/SAPK cascades, respectively, was found in gastric cancer cells cocultured with <i>H pylori</i>. Direct contact with viable bacteria possessing intact<i>cag</i> PAI is a prerequisite for the onset of intracellular signalling leading to AP-1 transactivation.
Positive and negative selection of T cell receptor V beta domains controlled by distinct cell populations in the thymus.
Authors: D E Speiser, R K Lees, H Hengartner, R M Zinkernagel, H R MacDonald
Journal: The Journal of Experimental Medicine (1989)

The role of thymic MHC class II-bearing cells in the selection of the TCR repertoire has been investigated in allogeneic radiation bone marrow chimeras. Positive selection of mature CD4+ T lymphocytes expressing the V beta 6+ TCR domain was found to depend upon radioresistant (presumably epithelial) I-E+ thymic cells. On the other hand, negative selection of CD4+ V beta 6+ cells (which was additionally dependent upon expression of the Mls-1a gene product) was controlled by a radiosensitive I-E+ thymic component (most likely dendritic cells). These data argue in favor of a compartmentalization of positive and negative selection events during T cell development.
THE SPECIFICITY OF KERATINS
Authors: L. Pillemer, E. E. Ecker, J. R. Wells
Journal: The Journal of Experimental Medicine (1939)

Kerateine and metakeratin were prepared from wool, chicken feathers and human hair. Chemical analyses revealed that the compounds are closely related. The results of serological studies disclose that species specificity is an individual characteristic of the keratins employed and that the specificity observed is dependent on the redox state of the sulfhydryl groupings in the protein molecule.
Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice
Authors: Eric J. Marrotte, Dan-Dan Chen, Jeffrey S. Hakim, Alex F. Chen
Journal: Journal of Clinical Investigation (2010)

Amputation as a result of impaired wound healing is a serious complication of diabetes. Inadequate angiogenesis contributes to poor wound healing in diabetic patients. Endothelial progenitor cells (EPCs) normally augment angiogenesis and wound repair but are functionally impaired in diabetics. Here we report that decreased expression of manganese superoxide dismutase (MnSOD) in EPCs contributes to impaired would healing in a mouse model of type 2 diabetes. A decreased frequency of circulating EPCs was detected in type 2 diabetic (db/db) mice, and when isolated, these cells exhibited decreased expression and activity of MnSOD. Wound healing and angiogenesis were markedly delayed in diabetic mice compared with normal controls. For cell therapy, topical transplantation of EPCs onto excisional wounds in diabetic mice demonstrated that diabetic EPCs were less effective than normal EPCs at accelerating wound closure. Transplantation of diabetic EPCs after MnSOD gene therapy restored their ability to mediate angiogenesis and wound repair. Conversely, siRNA-mediated knockdown of MnSOD in normal EPCs reduced their activity in diabetic wound healing assays. Increasing the number of transplanted diabetic EPCs also improved the rate of wound closure. Our findings demonstrate that cell therapy using diabetic EPCs after ex vivo MnSOD gene transfer accelerates their ability to heal wounds in a mouse model of type 2 diabetes.
Parental Smoking Modifies Effects Of Genetic Variation In Tumor Necrosis Factor-α On Childhood Asthma
Authors: H. Wu, I. Romieu, J. Sienra-Monge, B. Rio-Navarro, D.M. Anderson, E.W. Dunn, L.L. Steiner, I. Lara-Sanchez, S. London
Journal: Journal of Allergy and Clinical Immunology (2007)
Alterations in intestinal permeability
Authors: M C Arrieta
Journal: Gut (2006)

he goal of this review is to describe barrier function of the intestine, the structure of the tight junction, methods to evaluate intestinal permeability, and most importantly the relevance of abnormal permeability to disease.In this context, we will also present an emerging paradigm regarding the genesis of autoimmune diseases and describe the data that supports this from the perspective of both human disease and animal models.While this is a complicated area there are several points worth remembering: c epithelial permeability of the gastrointestinal tract can be evaluated in a site specific manner; c increased intestinal permeability is observed in association with several autoimmune diseases.It is observed prior to disease and appears to be involved in disease pathogenesis; c there are new and novel therapies directed at altering abnormally increased intestinal permeability and these may play a role in treating or preventing these diseases. BARRIER FUNCTION cFrom the lower oesophageal sphincter to the anus, the gastrointestinal tract has a single contiguous layer of cells that separates the inside of the body from the external environment.Separation is important as there are a wide variety of environmental agents in the lumen of the bowel that can initiate or perpetuate mucosal inflammation if they cross the epithelial barrier.While the epithelial lining of the intestine plays a critical role in preventing access of these agents, it is not the only component of what is termed barrier function.Also important are secreted products such as immunoglobulin, mucous, defensins, and other antimicrobial products.The importance of epithelial barrier function in normal homeostasis can be appreciated from experiments performed in the early 1990s where cell wall extracts from luminal bacteria were injected into the colonic wall of rats. 1 This simple manoeuvre of bypassing the epithelial barrier and placing luminal compounds directly into the colonic wall initiated an inflammatory disease that was characterised by granulomatous reactions both in the bowel and, importantly, as a systemic inflammatory process.Similar results were also observed by variably expressing a dominant negative N-cadherin mutant in epithelial cells along the crypt-villus axis.This induced abnormal function of intercellular junctions and initiated a mucosal inflammatory disorder that resembled Crohn's disease. 2 The important concept that emerges from these experiments is that by simply abrogating epithelial barrier function, inflammatory disease can be induced in a susceptible host with features that are expressed both locally and systemically.