tbuckley/cabot-search huggingface dataset:
Mechanisms of Neointima Formation and Remodeling in the Porcine Coronary Artery
Authors: Thomas Christen, Vitali Verin, Marie-Luce Bochaton-Piallat, Youri Popowski, Frans Ramaekers, Philippe Debruyne, Edoardo Camenzind, Guillaume van Eys, Giulio Gabbiani
Journal: Circulation (2001)

Background —To characterize the cells responsible for neointima formation after porcine coronary artery wall injury, we studied the expression of smooth muscle cell (SMC) differentiation markers in 2 models: (1) self-expanding stent implantation resulting in no or little interruption of internal elastic lamina and (2) percutaneous transluminal coronary angioplasty (PTCA) resulting in complete medial rupture and exposure of adventitia to blood components. Methods and Results —The expression of α-smooth muscle (SM) actin, SM myosin heavy chain isoforms 1 and 2, desmin, and smoothelin was investigated by means of immunohistochemistry and Western blots in tissues of the arterial wall collected at different time points and in cell populations cultured from these tissues. The expression of smoothelin, a marker of late SMC differentiation, was used to discriminate between SMCs and myofibroblasts. Both stent- and PTCA-induced neointimal tissues and their cultured cell populations expressed all 4 markers. The adventitial tissue underlying PTCA-induced lesions temporarily expressed α-SM actin, desmin, and SM myosin heavy chain isoforms, but not smoothelin. When placed in culture, adventitial cells expressed only α-SM actin. Conclusions —Our results suggest that SMCs are the main components of coronary artery neointima after both self-expanding stent implantation and PTCA. The adventitial reaction observed after PTCA evolves with a chronology independent of that of neointima formation and probably corresponds to a myofibroblastic reaction.
Oxymonads Are Closely Related to the Excavate Taxon Trimastix
Authors: Joel B. Dacks, Jeffrey D. Silberman, Alastair G. B. Simpson, Shigeharu Moriya, Toshiaki Kudo, Moriya Ohkuma, Rosemary J. Redfield
Journal: Molecular Biology and Evolution (2001)

Despite intensive study in recent years, large-scale eukaryote phylogeny remains poorly resolved. This is particularly problematic among the groups considered to be potential early branches. In many recent systematic schemes for early eukaryotic evolution, the amitochondriate protists oxymonads and Trimastix have figured prominently, having been suggested as members of many of the putative deep-branching higher taxa. However, they have never before been proposed as close relatives of each other. We amplified, cloned, and sequenced small-subunit ribosomal RNA genes from the oxymonad Pyrsonympha and from several Trimastix isolates. Rigorous phylogenetic analyses indicate that these two protist groups are sister taxa and are not clearly related to any currently established eukaryotic lineages. This surprising result has important implications for our understanding of cellular evolution and high-level eukaryotic phylogeny. Given that Trimastix contains small, electron-dense bodies strongly suspected to be derived mitochondria, this study constitutes the best evidence to date that oxymonads are not primitively amitochondriate. Instead, Trimastix and oxymonads may be useful organisms for investigations into the evolution of the secondary amitochondriate condition. All higher taxa involving either oxymonads or Trimastix may require modification or abandonment. Affected groups include four contemporary taxa given the rank of phylum (Metamonada, Loukozoa, Trichozoa, Percolozoa), and the informal excavate taxa. A new “phylum-level” taxon may be warranted for oxymonads and Trimastix.
Milk Fat Globule Epidermal Growth Factor 8 Attenuates Acute Lung Injury in Mice after Intestinal Ischemia and Reperfusion
Authors: Tianpen Cui, Michael Miksa, Rongqian Wu, Hidefumi Komura, Mian Zhou, Weifeng Dong, Zhimin Wang, Shinya Higuchi, Wayne Chaung, Steven A. Blau, Corrado P. Marini, Thanjavur S. Ravikumar, Ping Wang
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Milk fat globule epidermal growth factor 8 (MFG-E8) is a potent opsonin for the clearance of apoptotic cells and is produced by mononuclear cells of immune competent organs including the spleen and lungs. It attenuates chronic and acute inflammation such as autoimmune glomerulonephritis and bacterial sepsis by enhancing apoptotic cell clearance. Ischemia-reperfusion (I/R) injury of the gut results in severe inflammation, apoptosis, and remote organ damage, including acute lung injury (ALI).To determine whether MFG-E8 attenuates intestinal and pulmonary inflammation after gut I/R.Wild-type (WT) and MFG-E8(-/-) mice underwent superior mesenteric artery occlusion for 90 minutes, followed by reperfusion for 4 hours. A group of WT mice was treated with 0.4 microg/20 g recombinant murine MFG-E8 (rmMFG-E8) at the beginning of reperfusion. Four hours after reperfusion, MFG-E8, cytokines, myeloperoxidase activity, apoptosis, and histopathology were assessed. A 24-hour survival study was conducted in rmMFG-E8- and vehicle-treated WT mice.Mesenteric I/R caused severe widespread injury and inflammation of the small intestines and remote organs, including the lungs. MFG-E8 levels decreased in the spleen and lungs by 50 to 60%, suggesting impaired apoptotic cell clearance. Treatment with rmMFG-E8 significantly suppressed inflammation (TNF-alpha, IL-6, IL-1beta, and myeloperoxidase) and injury of the lungs, liver, and kidneys. MFG-E8-deficient mice suffered from greatly increased inflammation and potentiated ALI, whereas treatment with rmMFG-E8 significantly improved the survival in WT mice.MFG-E8 attenuates inflammation and ALI after gut I/R and may represent a novel therapeutic agent.
The Molecular Pharmacology of Estrogen Receptor Modulators: Implications for the Treatment of Breast Cancer
Authors: Donald P. McDonnell
Journal: Clinical Cancer Research (2005)

Abstract In addition to physiologic activities in the reproductive, skeletal, and central nervous systems, estrogens have been shown to play important roles in the aberrant cell proliferation observed in breast and reproductive tract cancers. Not surprisingly, pharmaceuticals that target different steps in the estrogen signal transduction pathway have found widespread use in the treatment of a wide variety of estrogen-linked disorders. The goal of this review is to outline what is known about the molecular pharmacology of the estrogen receptor and discuss how this information can be used to guide selection of drugs for a particular therapeutic application, and identify new targets where pharmaceutical exploitation could yield novel therapeutics.
Enhanced Pulmonary Arteriopathy in Simian Immunodeficiency Virus–infected Macaques Exposed to Morphine
Authors: Leslie Spikes, Pranjali Dalvi, Ossama Tawfik, Haihua Gu, Norbert F. Voelkel, Paul Cheney, Amy O’Brien-Ladner, Navneet K. Dhillon
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

HIV-associated pulmonary arterial hypertension (PAH) is likely a more prevalent noninfectious complication of AIDS than previously recognized. Furthermore, the majority of HIV-PAH cases occur in individuals with a history of intravenous drug use. In this study we used a simian immunodeficiency (SIV) macaque model and a primary cell-culture system to investigate the association between drug abuse and HIV infection in HIV-PAH development.
Colonic mucosal bacterial diversity of de novo extensive paediatric ulcerative colitis by next-generation sequencing
Authors: R. Hansen, C. Reiff, R. K. Russell, W. M. Bisset, S. H. Berry, I. Mukhopadhya, J. M. Thomson, E. M. El-Omar, G. L. Hold
Journal: Gut (2011)

<h3>Introduction</h3> Dysbiosis may contribute to inflammatory bowel disease (IBD) pathogenesis along with a reduced bacterial diversity. Limited bacterial diversity studies have been performed at the onset of disease in adults but rarely in children. High-throughput, parallel sequencing technology (next-generation sequencing) provides the means of assessing microbial diversity in samples from diverse ecosystems such as the colonic mucosa. <h3>Methods</h3> Paediatric patients undergoing colonoscopy were recruited to two groups: those with a new diagnosis of IBD at their first presentation and controls with a macroscopically normal colon and no evidence of IBD on biopsy. All subjects were free from systemic antibiotics, steroids and immunosuppression for 3 months. 5 extensive UC patients (E3) by Montreal criteria and 5 controls with macroscopically/microscopically normal colons were selected for assessment. The median age was 11.5 years in the UC group and 10.7 years in the controls. All patients were male. Colonic mucosal biopsies were taken from the rectum/sigmoid. DNA extraction was performed by a modified Qiagen QiAMP mini-kit method. The presence of bacteria was confirmed by universal eubacterial primers before next-generation PCR utilising V3 Forward/V6 Reverse primers. Bacterial diversity was assessed by 454 Titanium sequencing. Sequencing data was filtered, chimera and error checked and denoised before rarefaction to 13 000 reads per sample. Statistical comparisons were made by Mann–Whitney U tests using Sigma Plot 11. <h3>Results</h3> All biopsies were positive for bacterial DNA with universal eubacterial primers. The most commonly identified bacterial phyla (comprising 95.4% of sequence reads) were <i>Bacteroidetes</i> (45.3%), <i>Firmicutes</i> (40.5%) and <i>Proteobacteria</i> (9.7%). <i>Bacteroidetes</i> were significantly more common in the control colon than in UC (7641 median reads versus 4062, p=0.032) whereas <i>Firmicutes</i> were significantly more common in the UC colon than in controls (5471 median reads versus 3892, p=0.016). The difference between <i>Proteobacteria</i> was not significant (p=0.421). Bacterial diversity assessed by the Shannon index was similar in both groups (Medians of 6.1 in UC and 6.5 in controls, p=0.841). <h3>Conclusion</h3> Colonic mucosal bacteria differ between paediatric patients with extensive UC at diagnosis and controls. UC microbiota was typified by a reduction in <i>Bacteroidetes</i> and an increase in <i>Clostridia</i>. Surprisingly, a reduction in bacterial diversity is not present in extensive UC at diagnosis. This is contrary to findings from previous studies in established disease and warrants further investigation.
From the Museum: the Art of Thinking. Part Two: Knowing
Authors: Tom Kotsimbos
Journal: European Respiratory Journal (2014)

The Ambassadors is a signature double portrait combined with meticulous still life painting and masterful symbolic referencing that creates many levels of meaning. It relates specifically to a tumultuous period in history and more generally to how we know our world and the different ways that we can paint our "bigger picture". This work is in the tradition of coupling learned men with the tools of their trade – scientific instruments and academic/religious books. The portrait of two childhood friends with different life paths – Jean de Dinteville, a landowner and French Ambassador to England in 1533, and his friend, George de Selve, the Bishop of Lavaur – also contains overtones of early 16th century politics (especially Anglo-French relations), the conflict between secular and religious authorities, and medieval-reformation theology. In addition, a lute with a broken string (discord) and a Lutheran hymn book suggests strife between scholars and clergy and a plea for Christian harmony.
BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models
Authors: C. Capalbo, E. Ricevuto, A. Vestri, E. Ristori, T. Sidoni, O. Buffone, B. Adamo, E. Cortesi, P. Marchetti, G. Scambia, S. Tomao, C. Rinaldi, M. Zani, S. Ferraro, L. Frati, I. Screpanti, A. Gulino, G. Giannini
Journal: Annals of Oncology (2006)
Observations on the Interpretation of Clinical Trials in Early Ovarian Cancer
Authors: Ann Marie C. Swart, Mahesh K.B. Parmar
Journal: Journal of Clinical Oncology (2005)

Ovarian cancer is a relatively rare disease, and patients are infrequently diagnosed with early stages of the disease.Among those with high-risk stage I disease, the probability of disease recurrence within 10 years is approximately 27%, and for those with stage II disease, 44%. 1 Most
The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue–resident regulatory T cells
Authors: Ajithkumar Vasanthakumar, Kazuyo Moro, Annie Xin, Yang Liao, Renee Gloury, Shimpei Kawamoto, Sidonia Fagarasan, Lisa A Mielke, Shoukat Afshar-Sterle, Seth L Masters, Susumu Nakae, Hirohisa Saito, John M Wentworth, Peng Li, Wei Liao, Warren J Leonard, Gordon K Smyth, Wei Shi, Stephen L Nutt, Shigeo Koyasu, Axel Kallies
Journal: Nature Immunology (2015)
Chronic synovitis with early cartilage destruction in sickle cell disease.
Authors: H R Schumacher, B B Dorwart, J Bond, A Alavi, W Miller
Journal: Annals of the Rheumatic Diseases (1977)

Two patients with sickle cell disease presented with joint pain and early x-ray evidence of articular cartilage loss. Both later developed increasingly destructive arthritis with chronic synovitis identified in synovial biopsies. One patient developed demonstrable aseptic necrosis. Destructive arthropathy is much less common than the frequent transient effusions in sickle cell disease.
Rheumatology in General Practice
Authors: R. Grahame
Journal: Annals of the Rheumatic Diseases (1983)

He had just run successfully the Australasian Congress of Rheumatology in Rotorua, 1982, and had come over with his wife to England to participate in meetings in London at Hammersmith and the Heberden Society, of which he was one of the most respected Antipodean members, and finally in Am- sterdam.We in England first knew him in the 1950s, a vigorous, energetic physician full of common sense
SENP1 deSUMOylates and Regulates Pin1 Protein Activity and Cellular Function
Authors: Chun-Hau Chen, Che-Chang Chang, Tae Ho Lee, ManLi Luo, Pengyu Huang, Pei-Hsin Liao, Shuo Wei, Fu-An Li, Ruey-Hwa Chen, Xiao Zhen Zhou, Hsiu-Ming Shih, Kun Ping Lu
Journal: Cancer Research (2013)

Abstract The Pin1 prolyl isomerase regulates phosphorylation signaling by controlling protein conformation after phosphorylation, and its upregulation promotes oncogenesis via acting on numerous oncogenic molecules. SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in cancers. However, nothing is known about the role of SUMOylation in regulating Pin1 function. Here, we show that Pin1 is SUMOylated on Lys6 in the WW domain and on Lys63 in the PPIase domain. Pin1 SUMOylation inhibits its protein activity and oncogenic function. We further identify that SENP1 binds to and deSUMOylates Pin1. Importantly, either overexpression of SENP1 or disruption of Pin1 SUMOylation promotes the ability of Pin1 to induce centrosome amplification and cell transformation. Moreover, SENP1 also increases Pin1 protein stability in cell cultures, and Pin1 levels are positively correlated with SENP1 levels in human breast cancer specimens. These results not only uncover Pin1 SUMOylation on Lys6/63 as a novel mechanism to inhibit its activity and function but also identify a critical role for SENP1-mediated deSUMOylation in promoting Pin1 function during tumorigenesis. Cancer Res; 73(13); 3951–62. ©2013 AACR.
Differential Requirement for TANK-binding Kinase-1 in Type I Interferon Responses to Toll-like Receptor Activation and Viral Infection
Authors: Andrea K. Perry, Edward K. Chow, Julia B. Goodnough, Wen-Chen Yeh, Genhong Cheng
Journal: The Journal of Experimental Medicine (2004)

TANK-binding kinase-1 (TBK1) and the inducible IκB kinase (IKK-i) have been shown recently to activate interferon (IFN) regulatory factor-3 (IRF3), the primary transcription factor regulating induction of type I IFNs. Here, we have compared the role and specificity of TBK1 in the type I IFN response to lipopolysaccharide (LPS), polyI:C, and viral challenge by examining IRF3 nuclear translocation, signal transducer and activator of transcription 1 phosphorylation, and induction of IFN-regulated genes. The LPS and polyI:C-induced IFN responses were abolished and delayed, respectively, in macrophages from mice with a targeted disruption of the TBK1 gene. When challenged with Sendai virus, the IFN response was normal in TBK1−/− macrophages, but defective in TBK1−/− embryonic fibroblasts. Although both TBK1 and IKK-i are expressed in macrophages, only TBK1 but not IKK-i was detected in embryonic fibroblasts by Northern blotting analysis. Furthermore, the IFN response in TBK1−/− embryonic fibroblasts can be restored by reconstitution with wild-type IKK-i but not a mutant IKK-i lacking kinase activity. Thus, our studies suggest that TBK1 plays an important role in the Toll-like receptor–mediated IFN response and is redundant with IKK-i in the response of certain cell types to viral infection.
Subungual fixed drug eruption
Authors: E. C. Benton, D. McGibbon
Journal: British Journal of Dermatology (2010)

Journal Article Subungual fixed drug eruption Get access E. C. Benton, E. C. Benton Department of Dermatology, St John’s Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. E‐mail: emma.benton@gstt.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar D. McGibbon D. McGibbon Department of Dermatology, St John’s Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 6, 1 June 2010, Pages 1397–1398, https://doi.org/10.1111/j.1365-2133.2010.09695.x Published: 01 June 2010
Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial
Authors: Drahomir Aujesky, Pierre-Marie Roy, Franck Verschuren, Marc Righini, Joseph Osterwalder, Michael Egloff, Bertrand Renaud, Peter Verhamme, Roslyn A Stone, Catherine Legall, Olivier Sanchez, Nathan A Pugh, Alfred N'gako, Jacques Cornuz, Olivier Hugli, Hans-Jürg Beer, Arnaud Perrier, Michael J Fine, Donald M Yealy
Journal: The Lancet (2011)
Synergistic Adaptations to Exercise in the Systemic and Coronary Circulations That Underlie the Warm-Up Angina Phenomenon
Authors: Timothy P.E. Lockie, M. Cristina Rolandi, Antoine Guilcher, Divaka Perera, Kalpa De Silva, Rupert Williams, Kaleab N. Asrress, Kiran Patel, Sven Plein, Phil Chowienczyk, Maria Siebes, Simon R. Redwood, Michael S. Marber
Journal: Circulation (2012)

Background— The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise. Methods and Results— Sixteen patients (15 male, 61±4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 ( P &lt;0.01). A 33% decline in aortic pressure augmentation in Ex2 ( P &lt;0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload ( P &lt;0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both P &lt;0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise ( P &lt;0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation. Conclusions— On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular–ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon.
Identification of valid endogenous control genes for determining gene expression in human glioma
Authors: S. Kreth, J. Heyn, S. Grau, H. A. Kretzschmar, R. Egensperger, F. W. Kreth
Journal: Neuro-Oncology (2010)

In human glioma, quantitative real-time reverse-transcription PCR (qPCR) is a frequently used research tool. However, no systematic analysis of suitable reference genes for reliable gene expression analysis has been performed so far. In the current study, we tested 19 commonly used reference genes for their expression stability in human astrocytoma WHO Grade II, astrocytoma WHO Grade III, and glioblastoma (WHO Grade IV) both alone and compared with normal brain. First, equivalence tests for equal expression of candidate genes were applied, and those genes showing differential expression were ruled out from further analyses. Second, expression stability of the remaining candidate genes was determined by the NormFinder software. Generally, glioblastoma exhibited the highest expression levels and largest variability of candidate genes, whereas the opposite was true for normal brain. Even though Normfinder analyses revealed a large number of genes suitable for normalization in each of the tumor subgroups and across these groups, this number was drastically reduced after inclusion of normal brain into the analyses: Only GAPDH, IPO8, RPL13A, SDHA, and TBP were expected not to be differentially expressed; NormFinder analysis indicated favorable stability values for all of these genes, with TBP and IPO8 being the most stable ones. These 5 genes represent different physiological pathways and may be regarded as universal reference genes applicable for accurate normalization of gene expression in human astrocytomas of different grades (WHO Grades II–IV) alone and compared with normal brain, thereby enabling longitudinally designed studies (eg, in astrocytoma before and after malignant transformation).