tbuckley/cabot-search huggingface dataset:
Epithelial to Mesenchymal Transition in Renal Fibrogenesis
Authors: Youhua Liu
Journal: Journal of the American Society of Nephrology (2004)

Mature tubular epithelial cells in adult kidney can undergo epithelial-to-mesenchymal transition (EMT), a phenotypic conversion that is fundamentally linked to the pathogenesis of renal interstitial fibrosis. Emerging evidence indicates that a large proportion of interstitial fibroblasts are actually originated from tubular epithelial cells via EMT in diseased kidney. Moreover, selective blockade of EMT in a mouse genetic model dramatically reduces fibrotic lesions after obstructive injury, underscoring a definite importance of EMT in renal fibrogenesis. Tubular EMT is proposed as an orchestrated, highly regulated process that consists of four key steps: (1) loss of epithelial cell adhesion; (2) de novo alpha-smooth muscle actin expression and actin reorganization; (3) disruption of tubular basement membrane; and (4) enhanced cell migration and invasion. Of the many factors that regulate EMT in different ways, transforming growth factor-beta1 is the most potent inducer that is capable of initiating and completing the entire EMT course, whereas hepatocyte growth factor and bone morphogenetic protein-7 act as EMT inhibitors both in vitro and in vivo. Multiple intracellular signaling pathways have been implicated in mediating EMT, in which Smad/integrin-linked kinase may play a central role. This article attempts to provide a comprehensive review of recent advances on understanding the pathologic significance, molecular mechanism, and therapeutic intervention of EMT in the setting of chronic renal fibrosis.
Assessment of empirical antibiotic therapy optimisation in six hospitals: an observational cohort study
Authors: Nikolay P Braykov, Daniel J Morgan, Marin L Schweizer, Daniel Z Uslan, Theodoros Kelesidis, Scott A Weisenberg, Birgir Johannsson, Heather Young, Joseph Cantey, Arjun Srinivasan, Eli Perencevich, Edward Septimus, Ramanan Laxminarayan
Journal: The Lancet Infectious Diseases (2014)
Time to Adjuvant Chemotherapy for Breast Cancer in National Comprehensive Cancer Network Institutions
Authors: Jonathan L. Vandergrift, Joyce C. Niland, Richard L. Theriault, Stephen B. Edge, Yu-Ning Wong, Loretta S. Loftus, Tara M. Breslin, Clifford A. Hudis, Sara H. Javid, Hope S. Rugo, Samuel M. Silver, Eva M. Lepisto, Jane C. Weeks
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundHigh-quality care must be not only appropriate but also timely. We assessed time to initiation of adjuvant chemotherapy for breast cancer as well as factors associated with delay to help identify targets for future efforts to reduce unnecessary delays.
Transitional Cell Hyperplasia and Carcinomas in Urinary Bladders of Transgenic Mice with Keratin 5 Promoter-Driven Cyclooxygenase-2 Overexpression
Authors: Russell D. Klein, Carolyn S. Van Pelt, Anita L. Sabichi, Jorge dela Cerda, Susan M. Fischer, Gerhard Fürstenberger, Karin Müller-Decker
Journal: Cancer Research (2005)

Abstract The inducible form of cyclooxygenase (COX), COX-2, is up-regulated in many epithelial cancers and its prostaglandin products increase proliferation, enhance angiogenesis, and inhibit apoptosis in several tissues. Pharmacologic inhibition and genetic deletion studies showed a marked reduction of tumor development in colon and skin. COX-2 has also been strongly implicated in urinary bladder cancer primarily by studies with nonselective COX- and COX-2-selective inhibitors. We now show that forced expression of COX-2, under the control of a keratin 5 promoter, is sufficient to cause transitional cell hyperplasia (TCH) in 17% and 75% of the heterozygous and homozygous transgenic lines, respectively, in an age-dependent manner. TCH was strongly associated with inflammation, primarily nodules of B lymphocytes; some T cells and macrophage infiltration were also observed. Additionally, transitional cell carcinoma was observed in ∼10% of the K5.COX-2 transgenic mice; no TCH or transitional cell carcinoma was observed in wild-type bladders. Immunohistochemistry for vascular proliferation and vascular endothelial growth factor showed significant increases above that in wild-type urinary bladders. Our results suggest that overexpression of COX-2 is sufficient to cause hyperplasia and carcinomas in the urinary bladder. Therefore, inhibition of COX-2 should continue to be pursued as a potential chemopreventive and therapeutic strategy.
Pig farmers have signs of bronchial inflammation and increased numbers of lymphocytes and neutrophils in BAL fluid
Authors: B Pedersen, M Iversen, B Bundgaard Larsen, R Dahl
Journal: European Respiratory Journal (1996)

The purpose of this study was to investigate whether pig farmers had inflammation of the bronchial mucosa and activation of bronchoalveolar lavage (BAL) cells. Pig farmers are exposed to high dust levels and have a prevalence of work-related respiratory symptoms. Bronchoscopy and BAL were performed in 27 young large-scale pig farmers, who had never smoked. Fifty three lifetime nonsmoking healthy students participated as controls. All farmers and controls had normal lung function (forced expiratory volume in one second (FEV1) 109 and 105% predicted respectively. Estimation of macroscopic signs of inflammation in the bronchi (erythema, oedema, secretion and friability) showed that pig farmers had significantly increased signs of inflammation. The median score was 3 (range 0-6) compared to a median score of 0 (range 0-3) in controls. More pig farmers than controls (41 versus 25%) had a positive histamine challenge (provocative dose producing a 20% fall in FEV1 (PC20) < or = 32 mg.mL-1) but the difference was not significant. The cell concentration in BAL fluid was identical in the two groups. Pig farmers had a significantly increased percentage of lymphocytes (median 7, range 1-27 versus median 2, range 0-7) and neutrophils (median 2, range 0-30 versus median 1, range 0-4) compared to controls. Spontaneous migration (19.8 versus 5.5 microns) and chemotaxis (62.6 versus 11.2 microns) was significantly increased in pig farmers compared to controls. After stimulation with zymosan and phorbol myristrate acetate (PMA), the reactive oxygen radical generation of purified alveolar macrophages was also significantly increased in pig farmers. Lifetime nonsmoking pig farmers with normal lung function have macroscopic signs of bronchial inflammation and an increased number of neutrophils in bronchoalveolar lavage. Their alveolar macrophages showed biological signs of activation. The inflammation of pig farmers bronchi may be early signs of bronchitis.
Expression of Epstein–Barr Virus–Encoded Small RNA (by the EBER-1 Gene) in Liver Specimens from Transplant Recipients with Post-Transplantation Lymphoproliferative Disease
Authors: Parmjeet S. Randhawa, Ronald Jaffe, Anthony J. Demetris, Michael Nalesnik, Thomas E. Starzl, Yuan Yuan Chen, Lawrence M. Weiss
Journal: New England Journal of Medicine (1992)

Epstein-Barr virus (EBV)—associated post-transplantation lymphoproliferative disease (PTLD) develops in 1 to 10 percent of transplant recipients, in whom it can be treated by a reduction in the level of immunosuppression. We postulated that the tissue expression of the small RNA transcribed by the EBER-1 gene during latent EBV infection would identify patients at risk for PTLD.
Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease
Authors: Dominik Hartl, Philipp Latzin, Peter Hordijk, Veronica Marcos, Carsten Rudolph, Markus Woischnik, Susanne Krauss-Etschmann, Barbara Koller, Dietrich Reinhardt, Adelbert A Roscher, Dirk Roos, Matthias Griese
Journal: Nature Medicine (2007)
The biologic significance of alloreactivity. The ontogeny of T-cell sets specific for alloantigens or modified self antigens
Authors: SJ Burakoff, R Finberg, L Glimcher, F Lemonnier, B Benacerraf, H Cantor
Journal: The Journal of Experimental Medicine (1978)

We have analyzed the cellular basis of T-cell reactivity against lymphocytes expressing major histocompatibility complex (MHC) products that are foreign by virtue of polymorphism (alloantigens) or because of modification by chemicals or viruses. We find that early in ontogeny, prekiller activity against both trinitrophenyl (TNP)-coupled autologous MHC products and allogeneic MHC products resides in the same (Ly123(+)) T-cell pool; later in ontogeny alloreactivity is invested in Ly23 cells which, when activated, lyse TNP-coupled autologous cells as well as appropriate allogeneic target cells. We demonstrate that stimulation of Ly123(+) T cells in vitro by autologous cells coated with chemically-inactivated Sendai virus results in the formation of Ly23(+) cytolytic T lymphocytes (CTL) that specifically lyse both virus modified autologous target cells and unmodified allogeneic target cells. These results suggest the following model to account for the presence of large numbers of alloreactive T-cell clones in adult animals: continuous stimulation of Ly123 cells by autologous MHC antigens associated with foreign materials such as a virus results in the formation of Ly23 memory progeny carrying receptors that recognize MHC products that are foreign due to genetic polymorphism (alloantigens). In general, these studies indicate that alloaggression (as manifest by Ly23 cells in the CTL response) reflects a high degree of cross stimulation between physiologically relevant antigens, e.g., viral determinants associated with self MHC products, and biologically irrelevant allelic variants of the MHC.
Freedom From Atrial Tachyarrhythmias After Catheter Ablation of Atrial Fibrillation
Authors: Martin R. Karch, Bernhard Zrenner, Isabel Deisenhofer, Jürgen Schreieck, Gjin Ndrepepa, Jun Dong, Katrin Lamprecht, Petra Barthel, Etienne Luciani, Albert Schömig, Claus Schmitt
Journal: Circulation (2005)

Data on the comparative value of the circumferential pulmonary vein and the segmental pulmonary vein ablation for interventional treatment of atrial fibrillation are limited. We hypothesized that the circumferential pulmonary vein ablation approach was superior to the segmental pulmonary vein ablation approach.One hundred patients with highly symptomatic atrial fibrillation were randomly assigned to undergo either circumferential (n=50) or segmental pulmonary vein ablation (n=50). Freedom from atrial tachyarrhythmias in a 7-day Holter monitoring at 6 months was the primary end point. Secondary end points were freedom of arrhythmia-related symptoms and a composite of pericardial tamponade, thromboembolic complications, and pulmonary vein stenosis (safety end point). On the basis of the results of the 7-day Holter monitoring at 6 months, 21 patients (42%) after circumferential pulmonary vein ablation and 33 patients (66%) after segmental pulmonary vein ablation (P=0.02) were free of atrial tachyarrhythmia episodes. During the 6-month follow-up period, 27 patients (54%) after circumferential pulmonary vein ablation and 41 patients (82%) after segmental pulmonary vein ablation remained free of arrhythmia-related symptoms (P<0.01). No significant difference was found in the safety end point (6 versus 7 events; P=0.77) in the circumferential versus segmental pulmonary vein ablation group, respectively.This study demonstrates no superiority of the circumferential pulmonary vein ablation over segmental pulmonary vein ablation for treatment of atrial fibrillation in terms of efficacy and safety.
Phase III Clinical Trial of Thalidomide Plus Dexamethasone Compared With Dexamethasone Alone in Newly Diagnosed Multiple Myeloma: A Clinical Trial Coordinated by the Eastern Cooperative Oncology Group
Authors: S. Vincent Rajkumar, Emily Blood, David Vesole, Rafael Fonseca, Philip R. Greipp
Journal: Journal of Clinical Oncology (2005)

To determine if thalidomide plus dexamethasone yields superior response rates compared with dexamethasone alone as induction therapy for newly diagnosed multiple myeloma.Patients were randomly assigned to receive thalidomide plus dexamethasone or dexamethasone alone. Patients in arm A received thalidomide 200 mg orally for 4 weeks; dexamethasone was administered at a dose of 40 mg orally on days 1 to 4, 9 to 12, and 17 to 20. Cycles were repeated every 4 weeks. Patients in arm B received dexamethasone alone at the same schedule as in arm A.Two hundred seven patients were enrolled: 103 were randomly assigned to thalidomide plus dexamethasone and 104 were randomly assigned to dexamethasone alone; eight patients were ineligible. The response rate with thalidomide plus dexamethasone was significantly higher than with dexamethasone alone (63% v 41%, respectively; P = .0017). The response rate allowing for use of serum monoclonal protein levels when a measurable urine monoclonal protein was unavailable at follow-up was 72% v 50%, respectively. The incidence rates of grade 3 or higher deep vein thrombosis (DVT), rash, bradycardia, neuropathy, and any grade 4 to 5 toxicity in the first 4 months were significantly higher with thalidomide plus dexamethasone compared with dexamethasone alone (45% v 21%, respectively; P < .001). DVT was more frequent in arm A than in arm B (17% v 3%); grade 3 or higher peripheral neuropathy was also more frequent (7% v 4%, respectively).Thalidomide plus dexamethasone demonstrates significantly superior response rates in newly diagnosed myeloma compared with dexamethasone alone. However, this must be balanced against the greater toxicity seen with the combination.
Primary cutaneous anaplastic large-cell lymphoma with a prolonged erythrodermic prodrome
Authors: K. DENTON, C.L. WILSON, V.A. VENNING
Journal: British Journal of Dermatology (1992)

Anaplastic large cell lymphoma (ALCL) is a high grade non-Hodgkins lymphoma recognized by the expression of the CD30 marker and by its morphology. We report a patient with a 6-year history of a non-specific erythroderma in whom ALCL developed with rapid and fatal dissemination to the lymph nodes and internal organs.
Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis†
Authors: Alexander S. Petrides, Christoph Vogt, Dirk Schulze-Berge, Dwight Matthews, Georg Strohmeyer
Journal: Hepatology (1994)

Glucose intolerance and diabetes mellitus are both prevalent in cirrhosis, yet the pathogenesis of impaired glucose metabolism remains unknown. Therefore insulin secretion (hyperglycemic clamp, +125 mg/dl), insulin sensitivity (euglycemic hyperinsulinemic insulin clamp, +10 μU/ml and +50 μ/ml), whole-body glucose oxidation (indirect calorimetry) and glucose turnover ([6,6- 2 H 2 ]glucose isotope dilution) were evaluated in a homogenous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 6). The results were compared with those obtained in control subjects (n = 8). In glucose-intolerant patients, whole-body glucose uptake (mainly reflecting glucose utilization by muscle) was significantly impaired in patients during both insulin infusions as a result of decreased stimulation of the two major intracellular pathways of glucose disposal-nonoxidative glucose disposal (i.e., glycogen synthesis) and glucose oxidation. Hepatic glucose production was normal in the basal state and was normally suppressed during stepwise insulin infusion (by 65% and 85%, respectively, p = NS vs. controls). Hyperglycemia-induced increases of plasma C-peptide concentrations were comparable to those in controls (p = NS). In diabetic patients, insulin-mediated glucose uptake was significantly reduced, mainly because of impaired non-oxidative glucose disposal. Glucose oxidation appeared to be reduced, too. Hepatic glucose production was significantly increased in the basal state (3.03 ± 0.24 vs. 2.34 ± 0.10 mg/kg min, p &lt; 0.02) and during insulin infusion ( +50 μ/ml: 0.67 ± 0.17 vs. 0.13 ± 0.08 mg/kg min, p &lt; 0.05) compared with that in controls. Both the first and second phases of β-cell secretion were significantly reduced in response to steady-state hyperglycemia (both p &lt; 0.01 vs. control values). In conclusion, glucose intolerance in cirrhosis results from two abnormalities that occur simultaneously: (a) insulin resistance of muscle and (b) an inadequate response (even when comparable to that of controls) of the β-cells to appropriately secrete insulin to overcome the defect in insulin action. Diabetes mellitus in insulinresistant cirrhotic patients develops as the result of progressive impairment in insulin secretion together with the development of hepatic insulin resistance leading to fasting hyperglycemia and a diabetic glucose tolerance profile. (Hepatology 1994;19:616-627).
Renal failure after upper gastrointestinal bleeding in cirrhosis. Incidence, clinical course, predictive factors and short-term prognosis
Authors: A. Cardenas, P. Ginès, J. Uriz, X. Bessa, J.M. Salmerón, A. Mas, R. Ortega, B. Calahorra, D. de las Heras, J. Bosch, V. Arroyo, J. Rodés
Journal: Journal of Hepatology (2001)
Severe lipoid pneumonia following attempted suicide by mineral oil immersion.
Authors: I R Hussain, F P Edenborough, R S Wilson, D E Stableforth
Journal: Thorax (1996)

Following an attempted suicide by drowning in a vat of mineral oil, a previously fit man survived the usually fatal lipoid pneumonia resulting from total immersion after intensive support and prolonged steroid therapy with recovery of chest radiography and pulmonary function at one year.
Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis
Authors: Y. T Konttinen, M. Ainola, H. Valleala, J. Ma, H. Ida, J. Mandelin, R. W Kinne, S. Santavirta, T. Sorsa, C. Lopez-Otin, M. Takagi
Journal: Annals of the Rheumatic Diseases (1999)

To define the pattern of mRNA expression of all human matrix metalloproteinases (MMPs) described to date in rheumatoid arthritis (RA) and traumatic synovial membrane, in order to differentiate between a physiological tissue remodelling pattern and that associated with inflammatory tissue destruction.Analysis of SwissProt protein and EMBL/GenBank nucleotide sequence banks, protein sequence alignment, reverse transcriptase-polymerase chain reaction and nucleotide sequencing were used.MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-11 (stromelysin-3) and MMP-19 were constitutively expressed. MMP-1 (fibroblast type collagenase), MMP-9 (gelatinase B) and MMP-14 (MT1-MMP) were expressed in all RA, but only in 55-80% of trauma samples. MMP-13 (collagenase-3) and MMP-15 (MT2-MMP) were expressed exclusively in RA (80-90% of the samples). MMP-20 (enamelysin) was absent and MMP-8 (collagenase-2) was rarely found in RA or trauma. All other MMPs (-7, -10, -12, -16, -17) had an intermediate pattern of expression.Some MMPs without interstitial collagenase activity seem to have a constitutive pattern of expression and probably participate in physiological synovial tissue remodelling. Some MMPs are exclusively associated to RA synovitis, for example, MMP-13, which preferentially degrades type II collagen and aggrecan, and MMP-15, which activates proMMP-2 and proMMP-13 and is involved in tumour necrosis factor alpha processing. This clear cut rheumatoid/inflammatory MMP profile, more complex than has been previously appreciated, may facilitate inflammatory tissue destruction in RA.
An Address ON THE HOUR-GLASS STOMACH
Authors: C. T. Holland
Journal: BMJ (1921)

MEDICALEI OLJUAA not invariably, associated witlh a curious but indescribable, often disagreeable, smell.To suclh cases Dr. Jackson applied the name "uncinate epilepsy," because in some cases in wljich such an aura was associated with convulsions, or at least with loss of consciousness, a lesion was found in the uncinate gyrus of the temporo-splienoidal lobe.In some cases the lesion was a tumour, in one case a smuall non-malignant cyst.In the case4 in which the cyst was found by Dr. Walter S. Colman the patient was a medical man who lhad been subject for maniv years to recurrent attacks uslhered in with the "dreamy state."In this case the cyst was probably tlle resalt of some early, probably vascular, lesion, tlhe effect of wlicih was to pro.Cluce a small area of unstab!e cells in tllat particular region.Here was a case clharacterized by recurrent con- vulsions of a particular kind, only differing from other
An evidence-driven approach to scrum law modifications in amateur rugby played in South Africa
Authors: Sharief Hendricks, Mike I Lambert, James C Brown, Clint Readhead, Wayne Viljoen
Journal: British Journal of Sports Medicine (2014)

In 2012, the South African Rugby Union (SARU) approved a new set of scrum laws for amateur rugby played in the country, to be implemented at the start of the 2013 rugby season. These law changes were primarily based on the relatively high proportion of scrum-related catastrophic injury data collected as part of the BokSmart National Rugby Safety Programme (BokSmart) over the preceding 4 years (2008-2011).To describe the scrum-related catastrophic injury data in South Africa over the past 5 years (2008-2012), and to discuss how this evidence justifies the change in the Amateur Scrum Laws to make this aspect of the game safer in South Africa.Catastrophic injury data were collected through BokSmart at amateur and professional levels, during training and matches over 5 years (2008-2012).The scrum phase accounted for 33% (n=20 of 60) of all catastrophic injuries between 2008 and 2012. Eighteen of the 20 scrum injuries (90%) were confirmed as acute spinal cord injuries, with 13 of these being permanent injuries. For the scrum injury mechanisms that were provided (n=19), 'impact on the engagement' was the most frequently reported (n=11 of 19, 58%), followed by 'collapsed scrum' (n=7 of 19, 37%) and 'popping out' (n=1 of 19, 5%).Based on these scrum-related catastrophic injury data, a change in the Amateur Scrum Laws of South African Rugby was justified. The main purpose of these scrum law changes is to reduce the number of scrum-related catastrophic injuries in the country, by minimising the opportunity for impact injury and subsequent scrum collapse in amateur rugby in South Africa, thereby making this aspect of the game of rugby safer.
A prognostic scoring system based on clinical features of intrahepatic cholangiocarcinoma: the Fudan score
Authors: W. Jiang, Z.-C. Zeng, Z.- Y. Tang, J. Fan, H.-C. Sun, J. Zhou, M.-S. Zeng, B.-H. Zhang, Y. Ji, Y.-X. Chen
Journal: Annals of Oncology (2011)