tbuckley/cabot-search huggingface dataset:
Health Effects on Leaders and Co-Workers of an Art-Based Leadership Development Program
Authors: Julia Romanowska, Gerry Larsson, Maria Eriksson, Britt-Maj Wikström, Hugo Westerlund, Töres Theorell
Journal: Psychotherapy and Psychosomatics (2010)

&lt;i&gt;Background:&lt;/i&gt; There are very few evaluations of the effectiveness of leadership development programs. The purpose of the study was to examine whether an art-based leadership program may have a more beneficial effect than a conventional one on leaders’ and their corresponding subordinates’ mental and biological stress. &lt;i&gt;Methods:&lt;/i&gt;Participating leaders were randomized to 2 year-long leadership programs, 1 art-based and 1 conventional, with follow-up of the leaders and their subordinates at 12 and 18 months. The art-based program built on an experimental theatre form, a collage of literary text and music, followed by writing and discussions focused on existential and ethical problems. &lt;i&gt;Results:&lt;/i&gt; After 18 months a pattern was clearly visible with advantage for the art-based group. In the art group (leaders and their subordinates together as well as for subordinates only) compared to the conventional group, there was a significant improvement of mental health, covert coping and performance-based self-esteem as well as significantly less winter/fall deterioration in the serum concentration of the regenerative/anabolic hormone dehydroepiandrosterone-sulfate. &lt;i&gt;Conclusions:&lt;/i&gt;Our findings indicate a more beneficial long-term health effect of the art-based intervention compared to a conventional approach. Positive results for both standardized questionnaires and biological parameters strengthened the findings. The study provides a rationale for further evaluation of the effectiveness of this alternative educational approach.
Renoprotective Properties of Angiotensin Receptor Blockers beyond Blood Pressure Lowering
Authors: Yuko Izuhara, Masaomi Nangaku, Reiko Inagi, Naoto Tominaga, Toru Aizawa, Kiyoshi Kurokawa, Charles van Ypersele de Strihou, Toshio Miyata
Journal: Journal of the American Society of Nephrology (2005)

Clinical studies have demonstrated that some antihypertensive agents provide renoprotection independent of BP lowering. Recent in vitro and in vivo studies evaluated the mechanisms involved in this protection. First, the in vitro effects of several angiotensin II type 1 receptor blockers (ARB), calcium channel blockers (CCB), and β blockers (BB) on various mediators were compared: Formation of pentosidine (an advanced glycation end product), hydroxyl radical-induced formation of o-tyrosine, and transition metals–induced oxidation of ascorbic acid (the Fenton reaction). All of the six tested ARB but neither the six CCB nor the nine BB inhibited pentosidine formation. ARB, as well as BB but not CCB, inhibited hydroxyl radicals–mediated o-tyrosine formation. ARB but neither BB nor CCB inhibited efficiently transition metals–catalyzed oxidation of ascorbic acid. Second, the in vivo consequences for the kidney of these various in vitro effects were evaluated. Hypertensive, type 2 diabetic rats with nephropathy, SHR/NDmcr-cp, were given for 20 wk either olmesartan (ARB) or nifedipine (CCB), or atenolol (BB). Despite similar BP reduction, only ARB significantly reduced proteinuria and prevented glomerular and tubulointerstitial damage (mesangial activation, podocyte injury, tubulointerstitial injury, and inflammatory cell infiltration). It is interesting that only ARB prevented abnormal iron deposition in the interstitium, corrected chronic hypoxia, reduced expressions of heme oxygenase and p47phox (a subunit of NADPHoxidase), and inhibited pentosidine formation (which correlates well with proteinuria). These observations confirm unique renoprotective properties of ARB, independent of BP lowering but related to decreased oxidative stress (hydroxyl radicals scavenging and inhibition of the Fenton reaction), correction of chronic hypoxia, and inhibition of advanced glycation end product formation and of abnormal iron deposition. These benefits of ARB may contribute to the renoprotection observed beyond BP lowering.
Merlin, a New Superfamily of DNA Transposons Identified in Diverse Animal Genomes and Related to Bacterial IS1016 Insertion Sequences
Authors: Cédric Feschotte
Journal: Molecular Biology and Evolution (2004)

Several new families of DNA transposons were identified by computer-assisted searches in a wide range of animal species that includes nematodes, flat worms, mosquitoes, sea squirt, zebrafish, and humans. Many of these elements have coding capacity for transposases, which are related to each other and to those encoded by the IS1016 group of bacterial insertion sequences. Although these transposases display a motif similar to the DDE motif found in many transposases and integrases, they cannot be directly allied to any of the previously described eukaryotic transposases. Other common features of the new eukaryotic and bacterial transposons include similarities in their terminal inverted repeats and 8-bp or 9-bp target-site duplications. Together, these data indicate that these elements belong to a new superfamily of DNA transposons, called Merlin/IS1016, which is common in many eubacterial and animal genomes. We also present evidence that these transposons have been recently active in several animal species. This evidence is particularly strong in the parasitic blood fluke Schistosoma mansoni, in which Merlin is also the first described DNA transposon family.
Oncogenic Serine-Threonine Kinase Receptor-Associated Protein Modulates the Function of Ewing Sarcoma Protein through a Novel Mechanism
Authors: Govindaraj Anumanthan, Sunil K. Halder, David B. Friedman, Pran K. Datta
Journal: Cancer Research (2006)

Abstract Although much is known about the oncogenic functions of chimeric Ewing sarcoma (EWS) fusion proteins that result from chromosomal translocations, the cellular role of the normal EWS protein is not well characterized. We have previously identified a WD domain–containing protein, serine-threonine kinase receptor-associated protein (STRAP), which inhibits transforming growth factor β (TGF-β) signaling through interaction with receptors and Smad7 and promotes growth and enhances tumorigenicity. Here, we report the interaction between STRAP and EWS using matrix-assisted laser desorption/ionization, time-of-flight and tandem mass spectrometry. Although STRAP is localized in both cytoplasm and nucleus, nuclear STRAP colocalizes and associates specifically with EWS in the nucleus through its NH2 and COOH termini. We have found that normal EWS protein is up-regulated in human cancers, which correlates with the up-regulation of STRAP in 71% of colorectal cancers and 54% of lung cancers, suggesting a cooperative role of these two proteins in human cancers. TGF-β has no effect on STRAP and EWS interaction. However, EWS, like STRAP, attenuates TGF-β-dependent transcription. STRAP inhibits EWS-dependent p300-mediated transactivation of EWS target genes, such as ApoCIII and c-fos, in a TGF-β-independent manner. Interestingly, we have shown that STRAP blocks the interaction between EWS and p300, whereas the complex formation between STRAP and EWS is not affected by p300. These results suggest that STRAP inhibits the transactivation function of EWS by displacing p300 from the functional transcriptional complex. Thus, this study provides a novel TGF-β-independent function of STRAP and describes a mechanism by which STRAP regulates the function of oncogenic EWS protein. (Cancer Res 2006; 66(22): 10824-32)
Adenosine A <sub>3</sub> Receptor Activation Modulates the Capillary Endothelial Glycocalyx
Authors: Steven H. Platts, Brian R. Duling
Journal: Circulation Research (2003)

The endothelial glycocalyx is a dynamic extracellular matrix composed of cell surface proteoglycans, glycoproteins, and adsorbed serum proteins that has been implicated in the regulation and modulation of capillary tube hematocrit, permeability, and hemostasis. High tissue adenosine levels have been shown to adversely affect microvascular function and tissue survival after an ischemic episode, and previous work in this laboratory has shown that adenosine causes arteriolar constriction and degranulation of mast cells via the A3 receptor (A3AR). We hypothesized that adenosine exerts at least part of its effect through modification of the glycocalyx via the A3AR. We used an in vivo cremaster model (hamster and mouse) in which circulating plasma was labeled with a 70-kDa FITC-dextran, and the capillaries were examined before and after superfusion with varying concentrations of adenosine (or other vasoactive molecules). Measurements of the dextran exclusion from an endothelial cell surface layer and red cell separation from the endothelial cell surface were made for up to 30 minutes. Our data indicate that adenosine causes a rapid and profound decrease in the ability of the glycocalyx to exclude dextran but only affects red blood cell exclusion at pharmacological levels. Knockout mice deficient in the A3AR were completely protected from glycocalyx changes attributable to adenosine. These data show a potential link between a known vasoactive tissue metabolite, adenosine, and regulation of the glycocalyx, which may be important during (patho)physiological changes in microvascular function during inflammatory insults.
RETINAL WAVES AND VISUAL SYSTEM DEVELOPMENT
Authors: Rachel O. L. Wong
Journal: Annual Review of Neuroscience (1999)

Many pathways in the developing visual system are restructured and become highly organized even before vision occurs. Yet the developmental processes underlying the remodeling of visual connectivity are crucially dependent on retinal activity. Surprisingly, the immature and light-insensitive retina spontaneously generates a pattern of rhythmic bursting activity during the period when the connectivity patterns of retinal ganglion cells are shaped. Spatially, the activity is seen to spread across the retina in the form of waves that bring into synchrony the bursts of neighboring cells. Waves are present in the developing retina of higher and lower vertebrates, which suggests that this form of activity may be a common and fundamental mechanism employed in the activity-dependent refinement of early patterns of visual connections. Unraveling the cues encoded by the waves promises to provide important insights into how interactions driven by specific patterns of activity could lead to the modification of connectivity during development.
Validation of Met as a Therapeutic Target in Alveolar and Embryonal Rhabdomyosarcoma
Authors: Riccardo Taulli, Claudio Scuoppo, Francesca Bersani, Paolo Accornero, Paolo E. Forni, Silvia Miretti, Alberto Grinza, Paola Allegra, Michel Schmitt-Ney, Tiziana Crepaldi, Carola Ponzetto
Journal: Cancer Research (2006)

Abstract Rhabdomyosarcoma (RMS) is a highly malignant soft-tissue tumor of childhood deriving from skeletal muscle cells. RMS can be classified in two major histologic subtypes: embryonal (ERMS) and alveolar (ARMS), the latter being characterized by the PAX3/7-FKHR translocation. Here we first investigated whether the Met receptor, a transcriptional target of PAX3 and PAX7, has a role in PAX3-FKHR–mediated transformation. Following PAX3-FKHR transduction, Met was up-regulated in mouse embryonal fibroblasts (MEF), NIH 3T3 and C2C12 cells, and they all acquired anchorage independence. This property was lost in low serum but addition of hepatocyte growth factor/scatter factor (HGF/SF) rescued soft-agar growth. Genetic proof that Met is necessary for this PAX3-FKHR–mediated effect was obtained by transducing with PAX3-FKHR MEFs derived from Met mutant (MetD/D) and wild-type (Met+/+) embryos. Only Met+/+ MEFs acquired anchorage-independent growth whereas PAX3-FKHR–transduced MetD/D cells were unable to form colonies in soft agar. To verify if Met had a role in RMS maintenance, we silenced the receptor by transducing ERMS and ARMS cell lines with an inducible lentivirus expressing an anti-Met short hairpin RNA (shRNA). Met down-regulation significantly affected RMS cells proliferation, survival, invasiveness, and anchorage-independent growth. Finally, induction of the Met-directed shRNA promoted a dramatic reduction of tumor mass in a xenograft model of RMS. Our data show that both ARMS- and ERMS-derived cell lines, in spite of the genetic drift which may have occurred in years of culture, seem to have retained an “addiction” to the Met oncogene and suggest that Met may represent a target of choice to develop novel therapeutic strategies for ARMS. (Cancer Res 2006; 66(9): 4742-9)
New Potential Targets for Treating Myeloma Bone Disease
Authors: G. David Roodman
Journal: Clinical Cancer Research (2006)

Myeloma bone disease results in severe pain and pathologic fractures in >80% of patients. Myeloma bone disease is characterized by both increased osteoclast activity and suppressed new bone formation. The basis for both the increased bone destruction and decreased bone formation has been a topic of extensive investigation during the last several years.Marrow samples from patients with myeloma were screened by both molecular biological and gene expression profiling techniques to identify factors that may be responsible for the enhanced bone destruction and suppressed bone formation in patients with the disease.Several novel factors have been identified that directly stimulate osteoclastic bone destruction in myeloma. These include receptor activator of NF-kappaB ligand, macrophage inflammatory peptide 1alpha, and interleukin (IL)-3. All of these factors are increased in most patients with myeloma. Furthermore, osteoprotegerin levels are markedly suppressed, further driving osteoclast formation. In addition, four novel inhibitors of osteoblast differentiation or activity have been identified. These include two inhibitors of the Wnt signaling pathway, DKK1 and soluble frizzled protein 2. The Wnt signaling pathway is critical for osteoblast differentiation. Two cytokines, IL-3 and IL-7, have also been reported that directly or indirectly inhibit osteoblast differentiation in patients with myeloma. Interestingly, increased macrophage inflammatory peptide 1alpha, IL-3, and IL-7 result from abnormal transcriptional regulation of these genes by increased levels of acute myelogenous leukemia-1 to acute myelogenous leukemia-1B transcription factors.The recent identification of novel stimulators of osteoclast activity and inhibitors of osteoblast differentiation provide new therapeutic targets for treating this devastating bone disease in patients with myeloma.
A Field Synopsis on Low-Penetrance Variants in DNA Repair Genes and Cancer Susceptibility
Authors: Paolo Vineis, Maurizio Manuguerra, Fotini K. Kavvoura, Simonetta Guarrera, Alessandra Allione, Fabio Rosa, Alessandra Di Gregorio, Silvia Polidoro, Federica Saletta, John P. A. Ioannidis, Giuseppe Matullo
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundSeveral genes encoding for DNA repair molecules implicated in maintaining genomic integrity have been proposed as cancer-susceptibility genes. Although efforts have been made to create synopses for specific fields that summarize the data from genetic association studies, such an overview is not available for genes involved in DNA repair.
A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg–Strauss, EGPA): monocentric experiences in 150 patients
Authors: Frank Moosig, Jan Phillip Bremer, Bernhard Hellmich, Julia Ulrike Holle, Konstanze Holl-Ulrich, Martin Laudien, Christine Matthis, Claudia Metzler, Bernhard Nölle, Gert Richardt, Wolfgang L Gross
Journal: Annals of the Rheumatic Diseases (2012)

To evaluate a vasculitis centre based management strategy for eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA).A retrospective cohort study at a vasculitis referral centre was performed. All EGPA patients admitted from 1990 to 2009 were included. A structured interdisciplinary work-up for proof of diagnosis, Disease Extent Index and Birmingham Vasculitis Activity Score was performed. Immunosuppressive therapy was initiated and regularly adapted. Treatment targets were induction and maintenance of remission according to definitions given by the European League Against Rheumatism and the European Vasculitis Study Group. Outcomes were mortality, rate of remission, relapses, adverse events and prednisolone-dose.Out of 269 patients with suspected EGPA 150 fulfilled the inclusion criteria. Of those, 104 had more than one follow-up visit resulting in a mean follow up of 53±4.9 months. By using additional data sources the follow-up concerning survival was extended to 92±5 month. Severe organ manifestations occurred at heart (46%), kidney (18%) and lungs (10%). Cyclophosphamide was used in 107 patients (71%). The prednisolone-doses of all patients were within the targeted range (i.e. ≤7.5 mg) in 69% of the total follow-up time; the median dose at end of follow-up was 5mg/d. The 10-year survival rate was 89% resulting in mortality comparable to the general population (SMR 1.29). Only patients with cardiac failure associated with EGPA had an increased mortality (SMR 3.06).Regular re-evaluation and target-orientated adaption of therapy may lead to normalization of life expectancy and attenuation of disease progression. Continued centre based interdisciplinary treatment should be standard of care.
Intraperitoneal Hyperthermic Chemotherapy As Treatment of Peritoneal Carcinomatosis of Colorectal Cancer
Authors: Maurie Markman
Journal: Journal of Clinical Oncology (2004)

TO THE EDITOR: Verwaal et al are to be congratulated for their efforts to evaluate in a phase III randomized trial the clinical utility of “aggressive surgical cytoreduction” followed by hyperthermic intraperitoneal chemotherapy (HIPEC) as a management strategy for peritoneal carcinomatosis resulting from a colorectal malignancy. Unfortunately, a major conceptual flaw in the study’s design prevents any meaningful conclusions to be drawn from the results of this otherwise interesting study. The investigators elected to compare a strategy that combined aggressive surgery with HIPEC versus standard intravenous chemotherapy plus palliative surgery (if necessary). However, if the aim of the study was to evaluate the highly experimental, complex, costly, and potentially very morbid regional chemotherapy strategy, this trial has failed to address this important question. A more appropriate trial design would have been to randomly assign patients with peritoneal carcinomatosis to aggressive surgical cytoreduction with or without HIPEC. With the present study design, the demonstrated survival benefit may have been due principally, if not totally, to the extensive surgery, with the regional chemotherapy only adding toxicity. The favorable impact on survival associated with an attempt at “interval surgical cytoreduction” (without the subsequent administration of intraperitoneal chemotherapy) has been documented in ovarian cancer, and the major influence of the volume of residual disease on survival has been clearly shown in the current study (median survival of 20 months v 5 months for patients with “limited” versus “extensive” residual cancer, respectively). As appropriately noted by the authors: “... it cannot be excluded that the observed effect was exclusively or mainly caused by the aggressive cytoreduction alone.” In sum, this study fails to provide any support for the routine (as opposed to investigative) use of HIPEC in this clinical setting. It is hoped that these investigators will follow their important initial efforts with a phase III randomized trial that directly addresses the unique contribution (if any) of the regional chemotherapy component of this intensive management strategy.
Accuracy of cell typing in nonsmall cell lung cancer by EBUS/EUS-FNA cytological samples
Authors: W.A.H. Wallace, D.M. Rassl
Journal: European Respiratory Journal (2011)

Endoscopic ultrasound-guided transbronchial or transoesophageal lymph node aspiration is increasingly used as a method of diagnosing nonsmall cell carcinoma. Data validating the accuracy of cell typing of nonsmall cell carcinoma using these cytological samples has not been assessed. 23 samples were identified in Edinburgh, UK and a further 25 in Cambridge, UK, with matching histological samples. The morphological cell type, as assessed on the cytological preparations and cell blocks, was recorded and immunohistochemical staining was performed, where possible, as an adjunct. The final cell type, as assessed by morphology with or without immunohistochemistry, was correlated with that reported in the paired histological samples. Cell blocks with tumour were available in 39 out of 48 cases. The accuracy of cell typing when no cell block was available was four out of nine cases. This increased to 25 out of 39 when a cell block was available, increasing to 33 out of 39 with the addition of immunohistochemistry. The overall accuracy of classification was 37 out of 48 cases. Accurate cell typing of nonsmall cell carcinomas can be performed using endoscopically derived fine-needle aspirates. The importance of obtaining sufficient material for the production of cell blocks is critical in allowing optimal assessment.
Alan Aderem: From molecules to megabytes
Authors: Nicole LeBrasseur
Journal: The Journal of Experimental Medicine (2008)

The matter of immunology often conjures images of the minute: tiny cells on guard against tiny invaders. Many immunologists, not unreasonably, think in microscopic terms—molecular events in disease and resistance. Alan Aderem has likewise studied the infinitesimal. His early work dissected the molecular signaling pathways that are activated within macrophages when these white blood cells sense bacterial intruders (1, 2).




Figure 1





Alan Aderem




Later, Aderem's view expanded somewhat. He studied the events that lead macrophages to engulf pathogens (3). He also became interested in a large family of immune cell receptors, known as the Toll family, that allows the host to distinguish between various types of pathogens (4, 5).

Now, as cofounder and director of the Institute for Systems Biology (ISB) in Seattle, WA, Aderem deals with the immense. His researchers collect vast amounts of data on a daily basis. He now spends his days organizing and analyzing this enormous load.
Annular elastolytic giant cell granuloma: a prodromal stage of mid-dermal elastolysis?
Authors: F.B. Müller, W. Groth
Journal: British Journal of Dermatology (2007)

Journal Article Annular elastolytic giant cell granuloma: a prodromal stage of mid‐dermal elastolysis? Get access F.B. Müller, F.B. Müller Department of Dermatology and Venereology, University of Cologne, 50924 Cologne, Germany E‐mail: f.mueller@dermatologie‐frechen.de Search for other works by this author on: Oxford Academic Google Scholar W. Groth W. Groth Department of Dermatology and Venereology, University of Cologne, 50924 Cologne, Germany E‐mail: f.mueller@dermatologie‐frechen.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 6, 1 June 2007, Pages 1377–1378, https://doi.org/10.1111/j.1365-2133.2007.07902.x Published: 01 June 2007