tbuckley/cabot-search huggingface dataset:
Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone
Authors: Zhuang Cui, Janet Crane, Hui Xie, Xin Jin, Gehua Zhen, Changjun Li, Liang Xie, Long Wang, Qin Bian, Tao Qiu, Mei Wan, Min Xie, Sheng Ding, Bin Yu, Xu Cao
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Examine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models. Methods 3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone. Results Halofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone. Conclusions Halofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA.
Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma
Authors: G W van Imhoff, B van der Holt, M A MacKenzie, G J Ossenkoppele, P W Wijermans, M H H Kramer, M B van 't Veer, H C Schouten, M van Marwijk Kooy, M H J van Oers, J M M Raemaekers, P Sonneveld, L A M H Meulendijks, P M Kluin, H C Kluin-Nelemans, L F Verdonck
Journal: Leukemia (2005)
Torture: the bright side
Authors: L. Farrell
Journal: BMJ (2010)

“She preferred the timid touchings of the eunuch to the ponderous bollocks of the Roman Emperor,” said Gibbon’s Decline and Fall of the Roman Empire , a metaphor for the empire’s descent from barbarian virility to effete decadence. And we are learning nothing from history, because MI6 recently admitted that it regards torture as illegal and abhorrent, and I’ve been left yearning for those golden days of redneck vigour and bigotry, when Ad extirpanda , a papal bull promulgated in 1252, authorised …
Preferential Association of Human Papillomavirus With High-Grade Histologic Variants of Penile-Invasive Squamous Cell Carcinoma
Authors: L. Gregoire, A. L. Cubilla, V. E. Reuter, G. P. Haas, W. D. Lancaster
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Preferential Association of Human Papillomavirus With High-Grade Histologic Variants of Penile-Invasive Squamous Cell Carcinoma Get access Lucie Gregoire, Lucie Gregoire Department of Obstetrics and Gynecology, Wayne State University School of MedicineDetroit, MI Search for other works by this author on: Oxford Academic PubMed Google Scholar Antonio L. Cubilla, Antonio L. Cubilla Instituto de Anatomía Patológica, Universidad Nacional de AsunciónAsunción, Paraguay Search for other works by this author on: Oxford Academic PubMed Google Scholar Victor E. Reuter, Victor E. Reuter Department of Pathology, Memorial Sloan-Kettering Cancer CenterNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Gabriel P. Haas, Gabriel P. Haas Department of Urology, Wayne State University School of MedicineDetroit, MI Search for other works by this author on: Oxford Academic PubMed Google Scholar Wayne D. Lancaster Wayne D. Lancaster Department of Obstetrics and Gynecology and Center for Molecular Medicine and Genetics, Wayne State University School of MedicineDetroit, MI Wayne D. Lancaster, Ph.D., Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 East Canfield Ave., Detroit, MI 48201. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 22, 15 November 1995, Pages 1705–1709, https://doi.org/10.1093/jnci/87.22.1705 Published: 15 November 1995 Article history Received: 20 April 1995 Revision received: 23 August 1995 Accepted: 31 August 1995 Published: 15 November 1995
Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers
Authors: J H J Vernooy, N E A Drummen, R J van Suylen, R H E Cloots, G M Moller, K R Bracke, S Zuyderduyn, M A Dentener, G G Brusselle, P S Hiemstra, E F M Wouters
Journal: Thorax (2008)

<h3>Background:</h3> Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory reaction of the lungs involving activation of epithelial cells. Leptin is a pleiotropic cytokine important in the regulation of immune responses via its functional receptor Ob-Rb. This study was undertaken to test the hypothesis that severe COPD is associated with increased leptin expression in epithelial cells. <h3>Methods:</h3> Immunohistochemistry for leptin was performed on peripheral lung specimens from 20 patients with COPD (GOLD stage 4), 14 asymptomatic ex-smokers and 13 never smokers. Leptin and Ob-Rb mRNA expression were determined by rtPCR in cultured primary bronchial epithelial cells and primary type II pneumocytes. NCI-H292 and A549 cell lines were used to study functional activation of leptin signalling. <h3>Results:</h3> Leptin immunoreactivity in lung tissue was observed in bronchial epithelial cells, type II pneumocytes, macrophages (tissue/alveolar) and interstitial lymphocytic infiltrates. rtPCR analysis confirmed pulmonary leptin and Ob-Rb mRNA expression in primary bronchial epithelial cells and pneumocytes. Leptin-expressing bronchial epithelial cells and alveolar macrophages were markedly higher in patients with severe COPD and ex-smokers than in never smokers (p&lt;0.02). Exposure of cultured primary bronchial epithelial cells to smoke resulted in increased expression of both leptin and Ob-Rb (p&lt;0.05). Leptin induced phosphorylation of STAT3 in both NCI-H292 and A549 cells. <h3>Conclusions:</h3> Leptin expression is increased in bronchial epithelial cells and alveolar macrophages of ex-smokers with or without severe COPD compared with never smokers. A functional leptin signalling pathway is present in lung epithelial cells.
Expression and function of hypoxia inducible factor-1 alpha in human melanoma under non-hypoxic conditions
Authors: Caroline N Mills, Sandeep S Joshi, Richard M Niles
Journal: Molecular Cancer (2009)

Abstract Background Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas. Results HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part of the oxygen-dependent regulation domain in WM1366 and WM9 melanoma cells. Over-expression of HIF-1α and its splice variant in the RGP cell line SbCl2 resulted in a small increase in soft agar colony formation and a large increase in matrigel invasion relative to control transfected cells. Knockdown of HIF-1α expression by siRNA in the MET WM9 melanoma cell line resulted in a large decrease in both soft agar colony formation and matrigel invasion relative to cells treated with non-specific siRNA. There is a high level of ERK1/2 phosphorylation in WM9 cells, indicating an activated Ras-Raf-MEK-ERK1/2 MAPK pathway. Treatment of WM9 cells with 30 μM U0126 MEK inhibitor, decreased ERK1/2 phosphorylation and resulted in a decrease in HIF-1α expression. However, a 24 h treatment with 10 μM U0126 totally eliminated Erk1/2 phosphorylation, but did not change HIF-1alpha levels. Furthermore, siRNA knockdown of MEK siRNA did not change HIF-1alpha levels. Conclusion We speculate that metabolic products of U0126 decrease HIF-1alpha expression through "off target" effects. Overall our data suggest that increased HIF-1α expression under normoxic conditions contributes to some of the malignant phenotypes exhibited by human melanoma cells. The expanded role of HIF-1α in melanoma biology increases its importance as a therapeutic target.
Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases
Authors: Patrick M Reeves, Bettina Bommarius, Sarah Lebeis, Shannon McNulty, Jens Christensen, Alyson Swimm, Ann Chahroudi, Rahul Chavan, Mark B Feinberg, Darren Veach, William Bornmann, Melanie Sherman, Daniel Kalman
Journal: Nature Medicine (2005)
Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial
Authors: Mark R Rigby, Linda A DiMeglio, Marc S Rendell, Eric I Felner, Jean M Dostou, Stephen E Gitelman, Chetanbabu M Patel, Kurt J Griffin, Eva Tsalikian, Peter A Gottlieb, Carla J Greenbaum, Nicole A Sherry, Wayne V Moore, Roshanak Monzavi, Steven M Willi, Philip Raskin, Antoinette Moran, William E Russell, Ashley Pinckney, Lynette Keyes-Elstein, Michael Howell, Sudeepta Aggarwal, Noha Lim, Deborah Phippard, Gerald T Nepom, James McNamara, Mario R Ehlers
Journal: The Lancet Diabetes & Endocrinology (2013)
Juvenile dermatomyositis: treatment with intravenous gammaglobulin
Authors: K. COLLET, S. DALAC, B. MAERENS, J.M. COURTOIS, M. IZAC, D. LAMBERT
Journal: British Journal of Dermatology (1994)

High‐dose intravenous gammaglobulin (IVGG) has proved to be effective in the treatment of a number of immune disorders. We report two patients with juvenile dermatomyositis (DM) who improved with IVGG therapy. These patients had become refractory to corticosteroids and had developed unacceptable steroid toxicity. We suggest that IVGG can be useful in the treatment of juvenile DM. by reducing steroid requirements, and replacing immunosuppressive drugs.
Effects of Angiotensin Infusion on Catecholamine Uptake and Reactivity in Blood Vessels
Authors: P. A. KHAIRALLAH, D. DAVILA, N. PAPANICOLAOU, N. M. GLENDE, P. MEYER
Journal: Circulation Research (1971)

The interrelations between angiotensin and catecholamine uptake have been studied in rats. Angiotensin was infused for either 5, 30, or 120 minutes at three dose levels: 1, 12, and 45 ng/kg/min. With short exposures to angiotensin, effects were seen in kidney, uterus, and adrenal gland. These organs had been previously shown to bind the greatest amount of tritiated peptide administered intravenously. In the 5- and 30-minute experiments angiotensin inhibited uptake of either metaraminol or norepinephrine in most tissues, especially at the higher dose levels, with the exception of the adrenal gland where uptake was increased. After the two-hour infusion inhibition of uptake was seen in most organs. When high titer angiotensin II antibodies were administered intravenously, responses to iv angiotensin were abolished. At this stage the uptake of tritiated norepinephrine was increased in kidney, heart, spleen, and vas deferens, while it was decreased in the adrenal gland. To see whether these biochemical findings are related to a physiological role, contractile responses of isolated perfused arteries of rabbits were studied. Angiotensin potentiated the increase in perfusion pressure after the infusion of norepinephrine, while angiotensin II antibodies decreased this response. Thus, it is concluded that angiotensin can modify the uptake and, hence, the inactivation of the sympathetic neurotransmitter and possibly by this mechanism alter the physiological response to norepinephrine and sympathetic stimulation.
Systematic reviews of public health in developing countries are in train
Authors: Elizabeth Waters, Jodie Doyle
Journal: BMJ (2004)

EDITOR—The Cochrane Collaboration's health promotion and public health field, in collaboration with an international taskforce comprising the World Health Organization, the Global Health Council, the International Union for Health Promotion and Education, the South African Medical Research Council, the Burnet Institute for International and Public Health, and the US Centers for Disease Control and Prevention, has recently completed …
The <i>Plasmodium</i> eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands
Authors: Min Zhang, Clare Fennell, Lisa Ranford-Cartwright, Ramanavelan Sakthivel, Pascale Gueirard, Stephan Meister, Anat Caspi, Christian Doerig, Ruth S. Nussenzweig, Renu Tuteja, William J. Sullivan, David S. Roos, Beatriz M.A. Fontoura, Robert Ménard, Elizabeth A. Winzeler, Victor Nussenzweig
Journal: The Journal of Experimental Medicine (2010)

Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2α (eIF2α) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells.
The Colour Atlas of Bone Disease
Authors: A K Bhalla
Journal: Annals of the Rheumatic Diseases (1990)

This is a handbook for patients, actual and potential, and for all lay readers with an interest in osteoporosis.It is written jointly by three American doctors, one a specialist, who share a Florida practice, and by one professional writer.Within its context it provides a comprehensive account of osteoporosis-what it is, how it should be managed, its risk factors, signs and symptoms, and plans for prevention and treatment from childhood to old age.It is profusely but clearly illustrated, readable, and informative.It might be argued that the benefits of high calcium intake and calcium supplementation are less well proved than the authors uncritically maintain.The minute details given of the calcium content of everything we eat might, therefore, lead to unnecessary obsessions on the patients' part.Nevertheless, the book is judicious in its recommendations for therapy and treads a fair line between accepted and experimental treatment.Other details include a simple description of quantitative computed tomography and even the exact calcium content of every 'dish' available at McDonalds and Burger King!The flavour is therefore transatlantic, and one disadvantage to British readers is the limitation of all drug names to American proprietary preparations.Despite this, it
In vivo hypoxic exposure impairs metabolic adaptations to a 48 hour fast in rats
Authors: CM Pison, C Chauvin, H Perrault, C Schwebel, JL Lafond, C Boujet, XM Leverve
Journal: European Respiratory Journal (1998)

Hypoxia is well known to affect carbohydrate metabolism through its action on liver function and thus on glucose homeostasis. The aim of this study was to examine the carbohydrate, lipid and protein metabolic responses to 48 h of hypoxia, as well as the hormonal adaptations using both normoxic controls and hypoxic animals in the fasted state to standardize for the marked hypophagia observed in response to hypoxia. Hypoxia exposure (inspiratory oxygen fraction (FI,O2) = 0.1) resulted in a greater weight loss (-23 +/- 3.6% versus -16 +/- 2% in controls, p&lt;0.001). Hypoxia plus fasting led to a significant increase in plasma glucose, lactate, insulin and catecholamine concentrations, while the increase in free fatty acid and beta-hydroxybutyrate was abolished. Changes in plasma amino acid patterns were not affected by hypoxia. Liver glycogen depletion was significantly less pronounced in the hypoxic group, while phosphoenolpyruvate carboxykinase (a key enzyme of liver gluconeogenesis) activity and transcription enhancements were abolished by hypoxia. Overall, hypoxic exposure in rats fasted for 48 h resulted in a unique pattern that differed from responses to injury or fasting per se. Oxygen seems to play a central role in the metabolic adaptation to fasting, from gene expression to weight loss. Since hypoxaemia associated with fasting has detrimental effects on nutritional balance, the present observations may be clinically relevant in the setting of acute exacerbation with hypoxaemia for chronic respiratory disease.
Matched Pair Analysis Comparing Surgery Followed By Radiotherapy and Radiotherapy Alone for Metastatic Spinal Cord Compression
Authors: Dirk Rades, Stefan Huttenlocher, Juergen Dunst, Amira Bajrovic, Johann H. Karstens, Volker Rudat, Steven E. Schild
Journal: Journal of Clinical Oncology (2010)

The appropriate treatment for MSCC is controversial. A small randomized trial showed that decompressive surgery followed by radiotherapy was superior to radiotherapy alone. That study was limited to highly selected patients. Additional studies comparing surgery plus radiotherapy to radiotherapy could better clarify the role of surgery.Data from 108 patients receiving surgery plus radiotherapy were matched to 216 patients (1:2) receiving radiotherapy alone. Groups were matched for 11 potential prognostic factors and compared for post-treatment motor function, ambulatory status, regaining ambulatory status, local control, and survival. Subgroup analyses were performed for patients receiving adequate surgery (direct decompressive surgery plus stabilization of involved vertebrae), patients receiving laminectomy, patients with solid tumors, patients with solid tumors receiving adequate surgery, and patients with solid tumors receiving laminectomy.Improvement of motor function occurred in 27% of patients after surgery plus radiotherapy and 26% after radiotherapy alone (P = .92). Post-treatment ambulatory rates were 69% after surgery plus radiotherapy and 68% after radiotherapy alone (P = .99). Of the nonambulatory patients, 30% and 26%, respectively, (P = .86) regained ambulatory status after treatment. One-year local control rates were 90% after surgery plus radiotherapy and 91% after radiotherapy alone (P = .48). One-year overall survival rates were 47% and 40%, respectively (P = .50). The subgroup analyses did not show significant differences between both groups. Surgery-related complications occurred in 11% of patients.In this study, the outcomes of the end points evaluated after radiotherapy alone appeared similar to those of surgery plus radiotherapy. A new randomized trial comparing both treatments is justified.
Neuregulin 1 Sustains the Gene Regulatory Network in Both Trabecular and Nontrabecular Myocardium
Authors: Donna Lai, Xifu Liu, Ariel Forrai, Orit Wolstein, Jan Michalicek, Ishtiaq Ahmed, Alistair N. Garratt, Carmen Birchmeier, Mingdong Zhou, Lynne Hartley, Lorraine Robb, Michael P. Feneley, Diane Fatkin, Richard P. Harvey
Journal: Circulation Research (2010)

The cardiac gene regulatory network (GRN) is controlled by transcription factors and signaling inputs, but network logic in development and it unraveling in disease is poorly understood. In development, the membrane-tethered signaling ligand Neuregulin (Nrg)1, expressed in endocardium, is essential for ventricular morphogenesis. In adults, Nrg1 protects against heart failure and can induce cardiomyocytes to divide.To understand the role of Nrg1 in heart development through analysis of null and hypomorphic Nrg1 mutant mice.Chamber domains were correctly specified in Nrg1 mutants, although chamber-restricted genes Hand1 and Cited1 failed to be activated. The chamber GRN subsequently decayed with individual genes exhibiting decay patterns unrelated to known patterning boundaries. Both trabecular and nontrabecular myocardium were affected. Network demise was spatiotemporally dynamic, the most sensitive region being the central part of the left ventricle, in which the GRN underwent complete collapse. Other regions were partially affected with graded sensitivity. In vitro, Nrg1 promoted phospho-Erk1/2-dependent transcription factor expression, cardiomyocyte maturation and cell cycle inhibition. We monitored cardiac pErk1/2 in embryos and found that expression was Nrg1-dependent and levels correlated with cardiac GRN sensitivity in mutants.The chamber GRN is fundamentally labile and dependent on signaling from extracardiac sources. Nrg1-ErbB1/4-Erk1/2 signaling critically sustains elements of the GRN in trabecular and nontrabecular myocardium, challenging our understanding of Nrg1 function. Transcriptional decay patterns induced by reduced Nrg1 suggest a novel mechanism for cardiac transcriptional regulation and dysfunction in disease, potentially linking biomechanical feedback to molecular pathways for growth and differentiation.