61 results on '"John Cheung"'
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2. Efficacy of Tailored Exercise Therapy on Physical Functioning in Patients With Knee Osteoarthritis and Comorbidity: A Randomized Controlled Trial
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PT Mariëtte de Rooij MSc, Arja Häkkinen, Martin van der Esch, Joost Dekker, Willem F. Lems, PT Leo D. Roorda PhD, Jos W. R. Twisk, Joke A. Vollebregt, Daniel Haverkamp, Marike van der Leeden, and John Cheung
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030203 arthritis & rheumatology ,medicine.medical_specialty ,WOMAC ,Rehabilitation ,business.industry ,Strength training ,medicine.medical_treatment ,Osteoarthritis ,medicine.disease ,Comorbidity ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Randomized controlled trial ,law ,medicine ,Physical therapy ,030212 general & internal medicine ,Exercise physiology ,business ,Body mass index - Abstract
Objective: To evaluate the efficacy on physical functioning and safety of tailored exercise therapy in patients with knee osteoarthritis (OA) and comorbidities. Methods: In a randomized controlled trial, 126 participants were included with a clinical diagnosis of knee OA and at least 1 of the following target comorbidities: coronary disease, heart failure, type 2 diabetes mellitus, chronic obstructive pulmonary disease, or obesity (body mass index ≥30 kg/m2), with severity score ≥2 on the Cumulative Illness Rating Scale. The intervention group received a 20-week, individualized, comorbidity-adapted exercise program consisting of aerobic and strength training and training of daily activities. The control group received their current medical care for knee OA and were placed on a waiting list for exercise therapy. Primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index, subscale physical functioning (WOMAC-pf), and the 6-minute walk test (6MWT). Measurements were performed at baseline, after 20 weeks (directly posttreatment), and at 3 months posttreatment. Results: Statistically significant physical functioning differences over time were found between the intervention and control group (WOMAC: B = −7.43 [95% confidence interval (95% CI) −9.99, −4.87], P < 0.001; and 6MWT: B = 34.16 [95% CI 17.68, 50.64], P < 0.001) in favor of the intervention group. At 3 months followup, the mean improvements in the intervention group were 33% on the WOMAC scale and 15% on the 6MWT. These improvements are of clinical relevance. No serious adverse events occurred during the intervention. Conclusion: This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and safe in patients with knee OA and severe comorbidities.
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- 2017
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3. Optimization of Analgesics for Greater Exercise Therapy Participation Among Patients With Knee Osteoarthritis and Severe Pain: A Feasibility Study
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Wilfred F. Peter, Joyce van Tunen, Willem F. Lems, Martin van der Esch, Marike van der Leeden, Martijn Gerritsen, Joost Dekker, Wouter H Bos, Leo D. Roorda, R.E. Voorneman, John Cheung, and G.J. Tijhuis
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030203 arthritis & rheumatology ,medicine.medical_specialty ,business.industry ,Analgesic ,Osteoarthritis ,medicine.disease ,law.invention ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Knee pain ,Rheumatology ,Randomized controlled trial ,Rating scale ,law ,Severity of illness ,Physical therapy ,Medicine ,030212 general & internal medicine ,medicine.symptom ,Medical prescription ,business - Abstract
Objective Severe pain in patients with knee osteoarthritis (OA) hampers the ability to exercise. A protocol for the standardized optimization of analgesics in combination with exercise therapy was developed. The purpose of this protocol was to reduce pain, thereby allowing the patient to participate in exercise therapy. The objective of the present study was to evaluate the feasibility and outcome of the protocol. Methods Forty-nine patients with knee OA and severe knee pain (numerical rating scale for pain ≥7) were included. Analgesics were prescribed following an incremental protocol. After 6 weeks, a 12-week exercise therapy program was added. Information about analgesic use and exercise therapy content was recorded. Knee pain and activity limitations were assessed at baseline, after 6 weeks, and after 18 weeks. Results Statistically significant improvements in pain and activity limitations were found in intent-to-treat analysis after 6 weeks of analgesic use and after the intervention was completed. Mean improvements from baseline were 30% (P < 0.001) for pain and 17% (P < 0.001) for activity limitations after the intervention was completed. Seventy-eight percent of the patients were able to exercise according to the protocol. In these patients, exercise therapy following 6 weeks of analgesic use resulted in a further improvement of activity limitations of 10% (P = 0.004). Conclusion The combined intervention of standardized analgesic prescription and exercise therapy allows most patients with knee OA and severe pain to participate in exercise therapy, leading to reduction of pain and activity limitations. These promising results need to be confirmed in a randomized controlled trial.
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- 2016
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4. Alzheimer’s Disease: A Hypothesis
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John Cheung Yuen Chan
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0301 basic medicine ,Messenger RNA ,DNA damage ,business.industry ,Neurodegeneration ,Disease ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Huntington's disease ,medicine ,Protein biosynthesis ,Dementia ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
This hypothesis explores Alzheimer’s Disease (AD) from a new perspective. It has been widely observed that AD patients present initially with “recent” memory loss. Recent memories are constantly created and updated, in contrast to “archived” memories, which do not require updating and which AD patients retain longer. Notably, memory creation and updating require the production and synthesis of proteins in neurons; and in AD patients, neurodegeneration is relative to the number of new proteins that the patient has synthesized. In neuronal protein synthesis, DNA transcribes mRNA, which is then translated into proteins in the cytoplasm. During this process, the unzipped DNA double helix is vulnerable to assault and can subsequently enter apoptosis if it is unable to repair itself. A healthy individual can create and update memories without neurodegeneration, and even among dementia patients, not every protein synthesis is subject to assault or neuronal damage. However, the more proteins are synthesized, the greater the probability of assault. I propose here that, consistent with AD being an agerelated disease, AD patients’ immune systems have declined to the point where they are unable to eradicate assault agents and to repair DNA damage sustained from assaults during neuronal protein synthesis.
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- 2018
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5. Anti-inflammatory Therapy after Selective Laser Trabeculoplasty
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Delan Jinapriya, Isabella Irrcher, Hussein Hollands, James Farmer, Todd Urton, Sherif El-Defrawy, Andrew G. Day, Xiaoquin Sun, Mark D’Souza, John Cheung, Robert J. Campbell, and Donald Smallman
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Intraocular pressure ,medicine.medical_specialty ,genetic structures ,business.industry ,medicine.medical_treatment ,Glaucoma ,Placebo ,medicine.disease ,eye diseases ,Confidence interval ,law.invention ,Clinical trial ,Ophthalmology ,Artificial tears ,Randomized controlled trial ,law ,medicine ,sense organs ,Analysis of variance ,business - Abstract
Purpose To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes. Design Randomized, double-masked, placebo-controlled trial. Participants Patients with primary open-angle or pseudo-exfoliation glaucoma. Methods Patients undergoing SLT were randomized to receive placebo (artificial tears), prednisolone acetate 1%, or ketorolac tromethamine 0.5% eye drops 4 times per day for 5 days commencing immediately after SLT. Main Outcome Measures Change in intraocular pressure (IOP) from baseline to the 1-month post-SLT visit. Results Mean change in IOP at the 1-month primary outcome time point, as well as all other time points, was not significantly different among groups ( P = 0.99). Likewise, a repeated-measures, mixed-effects model did not find significant differences in IOP outcome at the 1-month time point ( P = 0.95). The IOP was reduced in all groups at the 1-month post-SLT time point and all other time points, and no significant differences were found between groups using separate unadjusted cross-sectional analyses of variance ( P > 0.15 for analyses at all time points). Treatment failure rates were not different among groups ( P = 0.75), and at 1 year after SLT, the percentage of patients maintaining a 20% IOP reduction ranged from 18% to 22% in the 3 study groups. Conclusions Anti-inflammatory therapy after SLT does not seem to substantially influence the IOP-lowering effect of SLT. In this study of patients with low baseline IOP, SLT showed limited efficacy in achieving a sustained reduction in IOP.
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- 2014
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6. Does hydroxyapatite coating enhance ingrowth and improve longevity of a Zweymuller type stem? A double-blinded randomised RSA trial
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Harm M. van der Vis, Daniel Hoornenborg, Daniel Haverkamp, Lijkele Beimers, Inger N. Sierevelt, Joost A. Spuijbroek, John Cheung, Graduate School, and AMS - Sports & Work
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Male ,medicine.medical_specialty ,Time Factors ,Double blinded ,media_common.quotation_subject ,Arthroplasty, Replacement, Hip ,engineering.material ,Femoral stem ,Radiostereometric Analysis ,03 medical and health sciences ,0302 clinical medicine ,Coating ,Coated Materials, Biocompatible ,Double-Blind Method ,Foreign-Body Migration ,medicine ,Humans ,Orthopedics and Sports Medicine ,030212 general & internal medicine ,Femur ,Prospective Studies ,media_common ,Aged ,030222 orthopedics ,business.industry ,Longevity ,Middle Aged ,Surgery ,Prosthesis Failure ,Durapatite ,Treatment Outcome ,engineering ,Hydroxyapatite coating ,Female ,Hip Prosthesis ,business ,Total hip arthroplasty ,Follow-Up Studies - Abstract
Introduction: An ongoing discussion is whether using a hydroxyapatite coating enhances the ingrowth and longevity of a femoral stem in total hip arthroplasty. The best way to predict speed of ingrowth and long-term outcome is by evaluating micromotion by radiostereometric analysis. To study the effect of hydroxyapatite (HA) coating on the migration of the SL-PLUS hip stem, we performed a prospective double blind randomised controlled trial comparing the early migration of the hydroxyapatite (HA)-coated SL-PLUS stem compared to the Standard (non-coated) SL-PLUS stem. Patients and methods: 51 patients were randomly assigned to receive either an uncoated or a HA-coated femoral component during total hip replacement. RSA images were obtained direct postoperatively and at 6 weeks, 12 weeks, 6 months, 12 months and 24 months. HOOS scores were obtained preoperative and at final follow-up. Results: RSA evaluation demonstrated significant migration up to 3 months postoperatively in both groups. After initial setting no significant migration was observed. There was no significant difference in migration between the HA-coated group and the uncoated group. Both Harris Hip Score (HHS) and HOOS domain scores (pain and ADL) significantly improved compared to baseline at 24 months after surgery in both treatment groups (pConclusions: At 2 years follow-up, the HA-coated and uncoated Zweymuller type, distal fitting stem do not show different migration patterns.
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- 2017
7. Alzheimer’s Disease: A Hypothesis
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Yuen Chan, John Cheung, primary
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- 2018
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8. Efficacy of Tailored Exercise Therapy on Physical Functioning in Patients With Knee Osteoarthritis and Comorbidity: A Randomized Controlled Trial
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Mariëtte, de Rooij, Marike, van der Leeden, John, Cheung, Martin, van der Esch, Arja, Häkkinen, Daniël, Haverkamp, Leo D, Roorda, Jos, Twisk, Joke, Vollebregt, Willem F, Lems, and Joost, Dekker
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Male ,Comorbidity ,Recovery of Function ,Middle Aged ,Osteoarthritis, Knee ,Rehabilitation Centers ,Exercise Therapy ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Humans ,Female ,Single-Blind Method ,Exercise ,Aged - Abstract
To evaluate the efficacy on physical functioning and safety of tailored exercise therapy in patients with knee osteoarthritis (OA) and comorbidities.In a randomized controlled trial, 126 participants were included with a clinical diagnosis of knee OA and at least 1 of the following target comorbidities: coronary disease, heart failure, type 2 diabetes mellitus, chronic obstructive pulmonary disease, or obesity (body mass index ≥30 kg/mStatistically significant physical functioning differences over time were found between the intervention and control group (WOMAC: B = -7.43 [95% confidence interval (95% CI) -9.99, -4.87], P 0.001; and 6MWT: B = 34.16 [95% CI 17.68, 50.64], P 0.001) in favor of the intervention group. At 3 months followup, the mean improvements in the intervention group were 33% on the WOMAC scale and 15% on the 6MWT. These improvements are of clinical relevance. No serious adverse events occurred during the intervention.This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and safe in patients with knee OA and severe comorbidities.
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- 2016
9. High resolution analysis of follicular lymphoma genomes reveals somatic recurrent sites of copy-neutral loss of heterozygosity and copy number alterations that target single genes
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Nathalie A. Johnson, Susana Ben-Neriah, Sohrab P. Shah, Jacquie Schein, Douglas E. Horsman, Adele Telenius, Andrew J. Mungall, Merrill Boyle, Tang Lee, Betty Lai, Randy D. Gascoyne, Joseph M. Connors, Marco A. Marra, Allen Delaney, K-John Cheung, and Dorothy Cheung
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Male ,Chromosomes, Artificial, Bacterial ,Cancer Research ,Gene Dosage ,Follicular lymphoma ,Loss of Heterozygosity ,Biology ,Polymorphism, Single Nucleotide ,Gene dosage ,Loss of heterozygosity ,FHIT ,CDKN2A ,CDKN2B ,Genetics ,medicine ,Humans ,Prospective Studies ,Lymphoma, Follicular ,Oligonucleotide Array Sequence Analysis ,Chromosomes, Human, Pair 12 ,Genome, Human ,Gene Expression Profiling ,Computational Biology ,Middle Aged ,medicine.disease ,Molecular biology ,Neoplasm Proteins ,Cytogenetic Analysis ,Female ,SNP array ,Comparative genomic hybridization - Abstract
A multiplatform approach, including conventional cytogenetic techniques, BAC array comparative genomic hybridization, and Affymetrix 500K SNP arrays, was applied to the study of the tumor genomes of 25 follicular lymphoma biopsy samples with paired normal DNA samples to characterize balanced translocations, copy number imbalances, and copy-neutral loss of heterozygosity (cnLOH). In addition to the t(14;18), eight unique balanced translocations were found. Commonly reported FL-associated copy number regions were revealed including losses of 1p32-36, 6q, and 10q, and gains of 1q, 6p, 7, 12, 18, and X. The most frequent regions affected by copy-neutral loss of heterozygosity were 1p36.33 (28%), 6p21.3 (20%), 12q21.2-q24.33 (16%), and 16p13.3 (24%). We also identified by SNP analysis, 45 aberrant regions that each affected one gene, including CDKN2A, CDKN2B, FHIT, KIT, PEX14, and PTPRD, which were associated with canonical pathways involved in tumor development. This study illustrates the power of using complementary high-resolution platforms on paired tumor/normal specimens and computational analysis to provide potential insights into the significance of single-gene somatic aberrations in FL tumorigenesis.
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- 2010
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10. Analysis of Oxford medial unicompartmental knee replacement using the minimally invasive technique in patients aged 60 and above
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John Cheung, Robbie Deutman, Nanne P. Kort, Casper Jolink, and Jos J. A. M. van Raay
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Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,knee ,Osteoarthritis ,medicine.disease_cause ,replacement ,Prosthesis ,Weight-bearing ,Weight-Bearing ,Humans ,Minimally Invasive Surgical Procedures ,Medicine ,Orthopedics and Sports Medicine ,Prospective Studies ,Range of Motion, Articular ,ARTHROPLASTY ,Arthroplasty, Replacement, Knee ,Prospective cohort study ,Survival rate ,Aged ,Aged, 80 and over ,business.industry ,Age Factors ,Middle Aged ,Osteoarthritis, Knee ,unicompartmental ,medicine.disease ,Arthroplasty ,Surgery ,mobile bearing ,Treatment Outcome ,Orthopedic surgery ,SURVIVAL ,Female ,Knee Prosthesis ,business ,Range of motion ,Follow-Up Studies - Abstract
We present the outcome of an independent prospective series of phase-3 Oxford medial mobile-bearing unicompartmental knee replacement surgery. Eight surgeons performed the 154 procedures in a community-based hospital between 1998 and 2003 for patients aged 60 and above. Seventeen knees were revised; in 14 cases a total knee replacement was performed, in 3 cases a component of the unicompartmental knee prosthesis was revised, resulting in a survival rate of 89% during these 2-7 years follow-up interval. This study shows that mobile-bearing unicompartmental knee replacement using a minimally invasive technique is a demanding procedure. The study emphasises the importance of routine in surgical management and strict adherence to indications and operation technique used to reduce outcome failure.
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- 2007
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11. Pilus-mediated epithelial cell death in response to infection with Burkholderia cenocepacia
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Joanna B. Goldberg, Gang Li, Teresa A. Urban, K-John Cheung, Fuqu Lu, Jane L. Burns, and Adam Griffith
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Programmed cell death ,Cystic Fibrosis ,Burkholderia cenocepacia ,Cell Survival ,Blotting, Western ,Immunology ,Virulence ,Apoptosis ,DNA Fragmentation ,Microbiology ,Pilus ,Cell Line ,Type three secretion system ,Humans ,Annexin A5 ,A549 cell ,biology ,Burkholderia cepacia complex ,Burkholderia Infections ,Epithelial Cells ,Flow Cytometry ,biology.organism_classification ,Infectious Diseases ,Burkholderia ,Microscopy, Fluorescence ,Caspases ,Fimbriae, Bacterial ,Propidium - Abstract
Burkholderia cenocepacia is an opportunistic pathogen that can cause serious infections in cystic fibrosis (CF) patients. The ET12 lineage appears particularly virulent in CF; however, its pathogenesis is poorly understood and may be associated with host response. To help characterize this response, the ability of B. cenocepacia to induce cytotoxicity and apoptosis in an epithelial cell model was examined. Upon infection with B. cenocepacia strain K56-2, A549 human lung epithelial cells underwent significant cell death; propidium iodine staining and DNA fragmentation assays suggested apoptosis. Initiation of cell death was independent of the type III secretion system, biofilm formation, and secreted bacterial cytotoxins. However, the frequency of cell death was lower in cells infected with a non-piliated mutant, K56-2 cblA::Tp. Furthermore, purified cbl pili were found to directly induce cytotoxicity in A549 cells and activate caspase-9, -8, -7, and -3, the major cysteine proteinases involved in apoptosis. It appears that B. cenocepacia cbl pili, which are a distinctive feature of the ET12 lineage, act as an initiator of cytotoxicity and apoptosis. Understanding the role of cbl pili in the pathogenesis of B. cenocepacia infections offers the potential for decreasing the virulence of these potentially life-threatening organisms in CF patients.
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- 2007
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12. Reliability, Validity, and Responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index for Elderly Patients with a Femoral Neck Fracture
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Paul T.P.W. Burgers, Rudolf W Poolman, Theodorus MJ Van Bakel, Wim E Tuinebreijer, Stephanie M Zielinski, Mohit Bhandari, Peter Patka, Esther MM Van Lieshout, P J Devereaux, Gordon H Guyatt, Thomas A Einhorn, Lehana Thabane, Emil H Schemitsch, Kenneth J Koval, Frede Frihagen, Kevin Tetsworth, Ernesto Guerra-Farfan, Stephen D Walter, Sheila Sprague, Marilyn Swinton, Taryn Scott, Paula McKay, Kim Madden, Diane Heels-Ansdell, Lisa Buckingham, Aravin Duraikannan, Heather Silva, Martin J Heetveld, Robert D Zura, Victoria Avram, Ajay Manjoo, Dale Williams, John Antoniou, Tim Ramsay, Earl R Bogoch, Andrew Trenholm, Stephen Lyman, Madhu Mazumdar, Kevin J Bozic, Mark Luborsky, Stuart Goodman, Susan Muray, Rob Korley, Richard Buckley, Paul Duffy, Shannon Puloski, Kimberly Carcary, Melissa Lorenzo, Michael D McKee, Jeremy A Hall, Aaron Nauth, Daniel Whelan, Timothy R Daniels, James P Waddell, Henry Ahn, Milena R Vicente, Jennifer T Hidy, Melanie T MacNevin, Hans Kreder, Terry Axelrod, Richard Jenkinson, Markku Nousiainen, David Stephen, Veronica Wadey, Monica Kunz, Katrine Milner, Ria Cagaanan, Melanie MacNevin, Peter J O’Brien, Piotr A Blachut, Henry M Broekhuyse, Pierre Guy, Kelly A Lefaivre, Gerard P Slobogean, Raman Johal, Irene Leung, Chad Coles, Ross Leighton, C. Glen Richardson, Michael Biddulph, Michael Gross, Michael Dunbar, J. David Amirault, David Alexander, Catherine Coady, Mark Glazebrook, David Johnston, William Oxner, Gerald Reardon, Ivan Wong, Kelly Trask, Shelley MacDonald, Andrew Furey, Craig Stone, Minnie Parsons, Trevor Stone, Mauri Zomar, Robert McCormack, Kelly Apostle, Dory Boyer, Farhad Moola, Bertrand Perey, Darius Viskontas, Karyn Moon, Raely Moon, Yves Laflamme, Benoit Benoit, Pierre Ranger, Michel Malo, Julio Fernandes, Karine Tardif, Julie Fournier, Pascal André Vendittoli, Vincent Massé, Alain G Roy, Martin Lavigne, Daniel Lusignan, Craig Davis, Philip Stull, Stewart Weinerman, Peter Weingarten, Steven Lindenbaum, Michael Hewitt, Rebecca Danielwicz, Janell Baker, Michael Mont, Donald E Delanois, Bhaveen Kapadia, Kimona Issa, Marylou Mullen, Andrew Sems, Barb Foreman, Javad Parvizi, Tiffany Morrison, Courtland Lewis, Stephanie Caminiti, Paul Tornetta, William R Creevy, Michelle J Lespasio, Hope Carlisle, Andrew Marcantonio, Michael Kain, Lawrence Specht, John Tilzey, John Garfi, Samir Mehta, John L Esterhai, Jaimo Ahn, Derek Donegan, Annamarie Horan, Kelly McGinnis, James Roberson, Thomas Bradbury, Greg Erens, Kyle Webb, Brian Mullis, Karl Shively, Andrew Parr, Janos Ertl, Ripley Worman, Mark Webster, Judd Cummings, Valda Frizzell, Molly Moore, Clifford B Jones, James R Ringler, Debra L Sietsema, Jane E Walker, Enes Kanlic, Amr Abdelgawad, Juan Shunia, Charles DePaolo, Susan Sutherland, Rachel Alosky, Robert Zura, Maria Manson, Gregg Strathy, Kathleen Peter, Paul Johnson, Meaghan Morton, James Shaer, Tyson Schrickel, Barbara Hileman, Marina Hanes, Elisha Chance, E. Matthew Heinrich, David Dodgin, Michele LaBadie, David Zamorano, Martin Tynan, Ran Schwarzkopf, John A Scolaro, Ranjan Gupta, Samuel Bederman, Nitin Bhatia, Bang Hoang, Douglas Kiester, Neil Jones, Gregory Rafijah, Damon Alavekios, Jason Lee, Akshay Mehta, Steven Schroder, Tom Chao, Vincent Colin, Phuc (Phil) Dang, Stephen Keun Heng, Gregory Lopez, Samuel Galle, Sohrab Pahlavan, Duy L Phan, Minal Tapadia, Christopher Bui, Nickul Jain, Tyler Moore, Nathan Moroski, Deeba Pourmand, Erik N Kubiak, Jeremy Gililland, David Rothberg, Christopher Peters, Christopher Pelt, Ami R Stuart, Kirby Corbey, Franklin D Shuler, James Day, Tigran Garabekyan, Felix Cheung, Ali Oliashirazi, Jonathon Salava, Linda Morgan, Timothy Wilson-Byrne, Mary Beth Cordle, Leon H.G.J. Elmans, Joost A.A.M. van den Hout, Adrianus JP Joosten, Ad FA van Beurden, Stefan BT Bolder, Denise Eygendaal, Adrianus F.C.M. Moonen, Rutger CI van Geenen, Eric A Hoebink, Robert Wagenmakers, Wouter van Helden, Hans-Peter W van Jonbergen, Herbert Roerdink, Joost M Reuver, Alexander FW Barnaart, Elvira R Flikweert, Rover Krips, J. Bernard Mullers, Hans Schüller, Mark LM Falke, Frans J Kurek, Adrianus CH Slingerland, Jan P van Dijk, Wouter H van Helden, Hugo W Bolhuis, Pieter HJ Bullens, Mike Hogervorst, Karin E de Kroon, Rob H Jansen, Ferry Steenstra, Eric EJ Raven, W. Peter J Fontijne, Saskia C Wiersma, Bastiaan Boetes, Edgar JT ten Holder, Huub JL van der Heide, Jochem Nagels, Enrike H.M.J. van der Linden-van der Zwaag, Stefan B Keizer, Jan-Willem A Swen, Peter HC den Hollander, Bregje JW Thomassen, Willem Jan Kleyn Molekamp, Frank R.A.J. de Meulemeester, Arthur EB Kleipool, Robert Haverlag, Maarten P Simons, Eduard L.A.R. Mutsaerts, Rob Kooijman, Roelf R Postema, René J.T.M. Bleker, Harald IH Lampe, Lein Schuman, John Cheung, Frank van Bommel, W. Paul Winia, Daniel Haverkamp, Harm van der Vis, Peter A Nolte, Michel PJ van den Bekerom, Tjitte de Jong, Arthur van Noort, Diederik A Vergroesen, Bernard G Schutte, Harm M van der Vis, Lijkele Beimers, Jasper de Vries, Arthur W Zurcher, G.H. Rob Albers, Maarten Rademakers, Stefan Breugem, Ibo van der Haven, Pieter Jan Damen, Gythe H Bulstra, Martin M Campo, Mathijs P Somford, Daniël Haverkamp, Susan Liew, Harvinder Bedi, Ashley Carr, Andrew Chia, Steve Csongvay, Craig Donohue, Stephen Doig, Elton Edwards, Max Esser, Richard Freeman, Andrew Gong, Doug Li, Russell Miller, Lu Ton, Otis Wang, Ian Young, Adam Dowrick, Zoe Murdoch, Claire Sage, Richard Page, David Bainbridge, Richard Angliss, Ben Miller, Andrew Thomson, Graeme Brown, Simon Williams, Kevin Eng, David Bowyer, John Skelley, Chatar Goyal, Sally Beattie, Enrique Guerado, Encarnacion Cruz, Juan Ramon Cano, Miguel Angel Froufe, Lluis Marull Serra, Samer Al-dirra, Cristina Martinez, Francisco José Tarazona Santabalbina, Jordi Teixidor Serra, Jordi Tomas Hernandez, Marc Aguilar Garcia, Vicente Molero Garcia, Sergi Barrera, Miriam Garrido, Lars Nordsletten, John Clarke-Jenssen, Geir Hjorthaug, Anne Christine Brekke, Elise Berg Vesterhus, Ingunn Skaugrud, Pradeep Tripathi, Sandesh Katiyar, Preksha Shukla, Marc Swiontkowski, Gordon Guyatt, Kyle Jeray, Stephen Walter, Helena Viveiros, Victoria Truong, Kaitlin Koo, Qi Zhou, Deborah Maddock, Nicole Simunovic, Julie Agel, Amar Rangan, Birgit C Hanusch, Lucksy Kottam, Rachel Clarkson, Gregory J Della Rocca, Gerard Slobogean, Jeffrey Katz, Brenda Gillespie, Gail A Greendale, Curtis Hartman, Craig Rubin, James Waddell, H. Michael Lemke, Amber Oatt, Richard E Buckley, Robert Korley, Kelly Johnston, James Powell, David Sanders, Abdel Lawendy, Christina Tieszer, John Murnaghan, Diane Nam, Albert Yee, Daniel B Whelan, Lisa M Wild, Ryan M Khan, Cathy Coady, David Amirault, Glen Richardson, Gwen Dobbin, Ryan Bicknell, Jeff Yach, Davide Bardana, Gavin Wood, Mark Harrison, David Yen, Sue Lambert, Fiona Howells, Angela Ward, Paul Zalzal, Heather Brien, V Naumetz, Brad Weening, Eugene K Wai, Steve Papp, Wade T Gofton, Stephen P Kingwell, Garth Johnson, Joseph O’Neil, Darren M Roffey, Vivian Borsella, Todd M Oliver, Vicki Jones, Terrence J Endres, Samuel G Agnew, Kyle J Jeray, J. Scott Broderick, David R Goetz, Thomas B Pace, Thomas M Schaller, Scott E Porter, Stephanie L Tanner, Rebecca G Snider, Lauren A Nastoff, Shea A Bielby, Julie A Switzer, Peter A Cole, Sarah A Anderson, Paul M Lafferty, Mengnai Li, Thuan V Ly, Scott B Marston, Amy L Foley, Sandy Vang, David M Wright, Andrew J Marcantonio, Michael SH Kain, Richard Iorio, Lawrence M Specht, John F Tilzey, Margaret J Lobo, John S Garfi, Heather A Vallier, Andrea Dolenc, Chalitha Robinson, Michael J Prayson, Richard Laughlin, L. Joseph Rubino, Jedediah May, Geoffrey Ryan Rieser, Liz Dulaney-Cripe, Chris Gayton, John T Gorczyca, Jonathan M Gross, Catherine A Humphrey, Stephen Kates, Krista Noble, Allison W McIntyre, Kaili Pecorella, Craig A Davis, Stephen Lindenbaum, John Schwappach, Janell K Baker, Tori Rutherford, Heike Newman, Shane Lieberman, Erin Finn, Kristin Robbins, Meghan Hurley, Lindsey Lyle, Khalis Mitchell, Kieran Browner, Erica Whatley, Krystal Payton, Christina Reeves, Lisa K Cannada, David Karges, Leslie Hill, John Esterhai, Annamarie D Horan, Christine A Kaminski, Brynn N Kowalski, Jonathan P Keeve, Christopher G Anderson, Michael D McDonald, Jodi M Hoffman, Ivan Tarkin, Peter Siska, Gary Gruen, Andrew Evans, Dana J Farrell, James Irrgang, Arlene Luther, William W Cross, Joseph R Cass, Stephen A Sems, Michael E Torchia, Tyson Scrabeck, Mark Jenkins, Jules Dumais, Amanda W Romero, Carlos A Sagebien, Mark S Butler, James T Monica, Patricia Seuffert, Joseph R Hsu, James Ficke, Michael Charlton, Matthew Napierala, Mary Fan, Chadi Tannoury, Michael Archdeacon, Ryan Finnan, Toan Le, John Wyrick, Shelley Hess, Michael L Brennan, Robert Probe, Evelyn Kile, Kelli Mills, Lydia Clipper, Michelle Yu, Katie Erwin, Daniel Horwitz, Kent Strohecker, Teresa K Swenson, Andrew H Schmidt, Jerald R Westberg, Kamran Aurang, Gary Zohman, Brett Peterson, Roger B Huff, Joseph Baele, Timothy Weber, Matt Edison, Jessica McBeth, Janos P Ertl, J. Andrew Parr, Molly M Moore, Erin Tobias, Emily Thomas, Charles J DePaolo, Leslie E Shell, Lynne Hampton, Stephanie Shepard, Tracy Nanney, Claudine Cuento, Robert V Cantu, Eric R Henderson, Linda S Eickhoff, E. Mark Hammerberg, Philip Stahel, David Hak, Cyril Mauffrey, Douglas Gibula, Hannah Gissel, Corey Henderson, David P Zamorano, Martin C Tynan, Deanna Lawson, Brett D Crist, Yvonne M Murtha, Linda K Anderson, Colleen Linehan, Lindsey Pilling, Courtland G Lewis, Raymond J Sullivan, Elizabeth Roper, William Obremskey, Philip Kregor, Justin E Richards, Kenya Stringfellow, Michael P Dohm, Abby Zellar, Michiel JM Segers, Jacco AC Zijl, Bart Verhoeven, Anke B Smits, Jean Paul PM de Vries, Bram Fioole, Henk van der Hoeven, Evert BM Theunissen, Tammo S de Vries Reilingh, Lonneke Govaert, Philippe Wittich, Maurits de Brauw, Jan Wille, Peter M.N.Y.M. Go, Ewan D Ritchie, Ronald N Wessel, Eric R Hammacher, Gijs A Visser, Heyn Stockmann, Rob Silvis, Jaap P Snellen, Bram Rijbroek, Joris JG Scheepers, Erik GJ Vermeulen, Michiel PC Siroen, Ronald Vuylsteke, Hans LF Brom, Herman Rijna, Piet AR de Rijcke, Cees L Koppert, Steven E Buijk, Richard PR Groenendijk, Imro Dawson, Geert WM Tetteroo, Milko MM Bruijninckx, Pascal G Doornebosch, Eelco JR de Graaf, Maarten van der Elst, Carmen C van der Pol, Martijne van’t Riet, Tom M Karsten, Mark R de Vries, Laurents PS Stassen, Niels WL Schep, G Ben Schmidt, W H Hoffman, Frank H.W.M. van der Heijden, W. Jaap Willems, Cor P van der Hart, Kahn Turckan, Sebastiaan Festen, Frank de Nies, Nico JM Out, Jan Bosma, Albert van Kampen, Jan Biert, Arie B van Vugt, Michael JR Edwards, Taco J Blokhuis, Jan Paul M Frölke, Leo MG Geeraedts, Jean WM Gardeniers, Edward T.C.H. Tan, Lodewijk M.S.J. Poelhekke, Maarten C de Waal Malefijt, Bart Schreurs, Gert R Roukema, Hong A Josaputra, Paul Keller, Peter D de Rooij, Hans Kuiken, Han Boxma, Berry I Cleffken, Ronald Liem, Steven J Rhemrev, Coks HR Bosman, Alexander de Mol van Otterloo, Jochem Hoogendoorn, Alexander C de Vries, Sven AG Meylaerts, Michiel HJ Verhofstad, Joost Meijer, Teun van Egmond, Igor van der Brand, Martin G Eversdijk, Rolf Peters, Dennis Den Hartog, Oscar JF Van Waes, Pim Oprel, Martin Campo, Ronald Verhagen, G.H. Robert Albers, Rogier KJ Simmermacher, Jeroen van Mulken, Karlijn van Wessem, Steven M van Gaalen, Luke PH Leenen, Maarten W.G.A. Bronkhorst, Onno R Guicherit, J. Carel Goslings, Kees Jan Ponsen, Mahesh Bhatia, Vinod Arora, Vivek Tyagi, Ajay Gupta, Neeraj Jain, Farah Khan, Ateet Sharma, Amir Sanghavi, Mittal Trivedi, Anil Rai, null Subash, Kamal Rai, Vineet Yadav, Sanjay Singh, Amal Shankar Prasad, Vimlesh Mishra, D C Sundaresh, Angshuman Khanna, Joe Joseph Cherian, Davy J Olakkengil, Gaurav Sharma, Akhil Dadi, Naveen Palla, Utsav Ganguly, B. Sachidananda Rai, Janakiraman Rajakumar, Peter Hull, Sophie Lewis, Simone Evans, Rajesh Nanda, Rajanikanth Logishetty, Sanjeev Anand, Carol Bowler, Andrew Jennings, Graham Chuter, Glynis Rose, Gillian Horner, Callum Clark, Kate Eke, Mike Reed, Chris Herriott, Christine Dobb, Hamish Curry, Greg Etherington, Arvind Jain, Ash Moaveni, Matthias Russ, Geoff Donald, Patrick Weinrauch, Paul Pincus, Steven Yang, Brett Halliday, Trevor Gervais, Michael Holt, Annette Flynn, Marinis Pirpiris, David Love, Andrew Bucknill, Richard J Farrugia, Torben Ianssen, Asgeir Amundsen, Jan Egil Brattgjerd, Tor Borch, Berthe Bøe, Bernhard Flatøy, Sondre Hasselund, Knut Jørgen Haug, Kim Hemlock, Tor Magne Hoseth, Geir Jomaas, Thomas Kibsgård, Tarjei Lona, Gilbert Moatshe, Oliver Müller, Marius Molund, Tor Nicolaisen, Fredrik Nilsen, Jonas Rydinge, Morten Smedsrud, Are Stødle, Axel Trommer, Stein Ugland, Anders Karlsten, Guri Ekås, Hans-Christoph Pape, Matthias Knobe, Roman Pfeifer, Orthopedic Surgery and Sports Medicine, Graduate School, Other departments, Surgery, Other Research, Amsterdam Movement Sciences, Cardiothoracic Surgery, and Emergency Medicine
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Male ,medicine.medical_specialty ,WOMAC ,Abstracting and Indexing ,Osteoarthritis ,Cronbach's alpha ,Surveys and Questionnaires ,medicine ,Humans ,Orthopedics and Sports Medicine ,Clinical significance ,Femoral neck ,Aged, 80 and over ,Ontario ,business.industry ,Reproducibility of Results ,Construct validity ,General Medicine ,medicine.disease ,RELIABILITY VALIDITY ,Femoral Neck Fractures ,Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,Clinical trial ,Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] ,medicine.anatomical_structure ,Physical therapy ,Female ,Surgery ,business - Abstract
Item does not contain fulltext BACKGROUND: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been extensively evaluated in groups of patients with osteoarthritis, yet not in patients with a femoral neck fracture. This study aimed to determine the reliability, construct validity, and responsiveness of the WOMAC compared with the Short Form-12 (SF-12) and the EuroQol 5D (EQ-5D) questionnaires for the assessment of elderly patients with a femoral neck fracture. METHODS: Reliability was tested by assessing the Cronbach alpha. Construct validity was determined with the Pearson correlation coefficient. Change scores were calculated from ten weeks to twelve months of follow-up. Standardized response means and floor and ceiling effects were determined. Analyses were performed to compare the results for patients less than eighty years old with those for patients eighty years of age or older. RESULTS: The mean WOMAC total score was 89 points before the fracture in the younger patients and increased from 70 points at ten weeks to 81 points at two years postoperatively. In the older age group, these scores were 86, 75, and 78 points. The mean WOMAC pain scores before the fracture and at ten weeks and two years postoperatively were 92, 76, and 87 points, respectively, in the younger age group and 92, 84, and 93 points in the older age group. Function scores were 89, 68, and 79 points for the younger age group and 84, 71, and 73 points for the older age group. The Cronbach alpha for pain, stiffness, function, and the total scale ranged from 0.83 to 0.98 for the younger age group and from 0.79 to 0.97 for the older age group. Construct validity was good, with 82% and 79% of predefined hypotheses confirmed in the younger and older age groups, respectively. Responsiveness was moderate. No floor effects were found. Moderate to large ceiling effects were found for pain and stiffness scales at ten weeks and twelve months in younger patients (18% to 36%) and in the older age group (38% to 53%). CONCLUSIONS: The WOMAC showed good reliability, construct validity, and responsiveness in both age groups of elderly patients with a femoral neck fracture who had been physically and mentally fit before the fracture. The instrument is suitable for use in future clinical studies in these populations. CLINICAL RELEVANCE: The results are based on two clinical trials. The questionnaires used concern pure, clinically relevant issues (ability to walk, climb stairs, etc.). Moreover, the results can be used for future research comparing clinical outcomes (or treatments) for populations with a femoral neck fracture.
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- 2015
13. Optimization of Analgesics for Greater Exercise Therapy Participation Among Patients With Knee Osteoarthritis and Severe Pain: A Feasibility Study
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Joyce A C, van Tunen, Marike, van der Leeden, Wouter H, Bos, John, Cheung, Martin, van der Esch, Martijn, Gerritsen, Wilfred F, Peter, Leo D, Roorda, Gerard J, Tijhuis, Ramon E, Voorneman, Willem F, Lems, and Joost, Dekker
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Male ,Analgesics ,Time Factors ,Recovery of Function ,Middle Aged ,Osteoarthritis, Knee ,Arthralgia ,Severity of Illness Index ,Exercise Therapy ,Disability Evaluation ,Treatment Outcome ,Feasibility Studies ,Humans ,Pain Management ,Patient Compliance ,Female ,Aged ,Netherlands ,Pain Measurement - Abstract
Severe pain in patients with knee osteoarthritis (OA) hampers the ability to exercise. A protocol for the standardized optimization of analgesics in combination with exercise therapy was developed. The purpose of this protocol was to reduce pain, thereby allowing the patient to participate in exercise therapy. The objective of the present study was to evaluate the feasibility and outcome of the protocol.Forty-nine patients with knee OA and severe knee pain (numerical rating scale for pain ≥7) were included. Analgesics were prescribed following an incremental protocol. After 6 weeks, a 12-week exercise therapy program was added. Information about analgesic use and exercise therapy content was recorded. Knee pain and activity limitations were assessed at baseline, after 6 weeks, and after 18 weeks.Statistically significant improvements in pain and activity limitations were found in intent-to-treat analysis after 6 weeks of analgesic use and after the intervention was completed. Mean improvements from baseline were 30% (P0.001) for pain and 17% (P0.001) for activity limitations after the intervention was completed. Seventy-eight percent of the patients were able to exercise according to the protocol. In these patients, exercise therapy following 6 weeks of analgesic use resulted in a further improvement of activity limitations of 10% (P = 0.004).The combined intervention of standardized analgesic prescription and exercise therapy allows most patients with knee OA and severe pain to participate in exercise therapy, leading to reduction of pain and activity limitations. These promising results need to be confirmed in a randomized controlled trial.
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- 2015
14. p33ING1 Enhances UVB-Induced Apoptosis in Melanoma Cells
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Gang Li and K-John Cheung
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Programmed cell death ,Cell cycle checkpoint ,Ultraviolet Rays ,DNA repair ,Apoptosis ,Cell Cycle Proteins ,Endogeny ,Membrane Potentials ,Proto-Oncogene Proteins ,Tumor Cells, Cultured ,medicine ,Humans ,Genes, Tumor Suppressor ,Melanoma ,bcl-2-Associated X Protein ,biology ,Tumor Suppressor Proteins ,Intracellular Signaling Peptides and Proteins ,Nuclear Proteins ,Proteins ,Cell Biology ,medicine.disease ,Growth Inhibitors ,Mitochondria ,Proliferating cell nuclear antigen ,Cell biology ,DNA-Binding Proteins ,Proto-Oncogene Proteins c-bcl-2 ,UVB-induced apoptosis ,biology.protein ,Cancer research ,Female ,Tumor Suppressor Protein p53 ,Inhibitor of Growth Protein 1 - Abstract
The biological functions of the tumor suppressor ING1 have been studied extensively in the past few years since it was cloned. It shares many biological functions with p53 and has been reported to mediate growth arrest, senescence, apoptosis, anchorage-dependent growth, chemosensitivity, and DNA repair. Some of these functions, such as cell cycle arrest and apoptosis, have been shown to be dependent on the activity of both ING1 and p53 proteins. Two recent reports by Scott and colleagues demonstrate that p33(ING1) (one of the ING1 isoforms) translocates to the nucleus and binds to PCNA upon UV irradiation. Here we report that p33(ING1) mediates UV-induced cell death in melanoma cells. We found that overexpression of p33(ING1) increased while the introduction of an antisense p33(ING1) plasmid reduced the apoptosis rate in melanoma cells after UVB irradiation. We also demonstrated that enhancement of UV-induced apoptosis by p33(ING1) required the presence of p53. Moreover, we found that p33(ING1) enhanced the expression of endogenous Bax and altered the mitochondrial membrane potential. Taken together, these observations strongly suggest that p33(ING1) cooperates with p53 in UVB-induced apoptosis via the mitochondrial cell death pathway in melanoma cells.
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- 2002
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15. Perception of vertical and horizontal orientation in children with scoliosis
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Wim J. Sluiter, John Cheung, Jim R. van Horn, Albert G. Veldhuizen, and J.C. Cool
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Horizontal and vertical ,media_common.quotation_subject ,Posture ,Scoliosis ,Severity of Illness Index ,BRAIN-STEM ,RATS ,Postural control ,Diagnosis, Differential ,Physical medicine and rehabilitation ,Reference Values ,Orientation ,Orientation (geometry) ,Perception ,Body Image ,medicine ,Deformity ,Humans ,Contrast (vision) ,Orthopedics and Sports Medicine ,Child ,Projection (set theory) ,media_common ,ADOLESCENT IDIOPATHIC SCOLIOSIS ,business.industry ,Lasers ,medicine.disease ,Self Concept ,Radiography ,POSTURAL EQUILIBRIUM ,Child, Preschool ,Female ,medicine.symptom ,business - Abstract
To determine whether the perception of body posture is altered in idiopathic scoliosis, a simple neurophysiologic experiment through laser line projection was conducted to test this hypothesis in three groups of individuals: 89 children with idiopathic scoliosis (IS). 50 children with congenital scoliosis (CS) and 45 controls without scoliosis. The subjects were instructed to adjust a laser line projection to the direction of gravity in vertical and in horizontal projections in a dark environment. The performance, expressed as the deviation from the earth vertical (measured in degrees). was calculated by a computer. The three groups fulfilled the vertical and horizontal adjustments within the same accuracy. No relation with age. sex or severity of scoliotic deformity was found. Yet, the angle between vertical and horizontal laser lines was significantly related with the severity of scoliosis, both in IS and CS. In contrast to our hypothesis, it A as concluded that perception Of Postural control in IS is not altered. Therefore, this study indicates that IS is not likely to be caused by a dysfunction of postural control. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
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- 2002
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16. Hypotheses of cancer weakening and origin
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John Cheung Yuen Chan
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Genetics ,Evolution of cells ,GMO ,Endogenous retrovirus ,Cancer ,Biology ,medicine.disease ,Genome ,Cancer origin ,Genetically modified organism ,Oncology ,Viral genes ,Horizontal gene transfer ,Cancer cell ,medicine ,Commentary ,Nanoparticles ,Gene - Abstract
Approximately 2.7 billion years ago, cyanobacteria began producing oxygen by photosynthesis. Any free oxygen they produced was chemically captured by dissolved iron or organic matter. There was no ozone layer to protect living species against the radiation from space. Eukaryotic cells lived in water, under hypoxic environments, and metabolized glucose by fermentation. The Great Oxygenation Event (GOE) describes the point when oxygen sinks became saturated. This massive oxygenation of the Earth occurred approximately half a billion years ago. Species that evolved after the GOE are characterized by aerobic metabolism. Mammals evolved approximately a few hundred million years ago, with the ancient eukaryotic genes deeply embedded in their genome. Many genes have been exchanged by horizontal gene transfer (HGT) throughout the history of cellular evolution. Mammals have been invaded by viruses, and while viral genetic relics are embedded in mammalian junk genes, not all junk genes are genetic relics of viruses. These viral relics have been inactivated through evolution and have little impact on mammalian life. However, there is evidence to suggest that these viral genetic relics are linked to cancer. This hypothesis states that cancer develops when cell reproduction becomes defective because of the active involvement of viral genes, in a process similar to genetic engineering. Cancer cells are amalgamations of genetically modified organisms (GMOs). There are two main groups in cancer development. One group of cells arises by genetic engineering of a viral genetic relic, such as endogenous retroviruses (ERVs), which evolved after oxygenation of the atmosphere. This group is referred to here as genetically modified organisms from viral genes (GMOV). GMOVs may be inhibited by anticancer drugs. The second group arises by engineering of the genes of ancient eukaryotes, which existed prior to the oxygenation of the Earth. This second group is referred to as genetically modified organisms from ancient eukaryotic genes (GMOE). The GMOE group lives in hypoxic environments and metabolizes glucose by fermentation. GMOEs represent advanced cancer, which proliferate aggressively and are resistant to DNA damage. It has been demonstrated that as an ERV becomes more prevalent in a mammalian genome, the possibility that the mammal will develop cancer increases. The hypothesis also states that most cancers have their origins in GMOV by the incorporation of viral genes from junk genes. As the cancer progresses, further subgroups of cancer GMOs will develop. If the cancer advances even further, the GMOE could eventually develop prior to late-stage cancer. Because the genes of ancient eukaryotes have enhanced innate immunity, GMOE will eventually prevail over the weaker GMOV during cancer subgroup competition. Hence, cancer development is mainly determined by genes in the mammalian genome. An inherent weakness of cancer cells is their dependence on glucose and iron. Furthermore, they cannot tolerate physical disturbance. Ancient gene GMOs can be treated with a combination of mechanical vibration using glucose-coated magnetic nanoparticles and strengthening of the immune system. Herein, I suggest trials for verifying this hypothesis.
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- 2014
17. Tissue-Specific Regulation of Chk1 Expression by p53
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Gang Li and K.-John Cheung
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Male ,Tumor suppressor gene ,Biopsy ,Blotting, Western ,Clinical Biochemistry ,Thymus Gland ,Biology ,Cell Line ,Pathology and Forensic Medicine ,Immunoenzyme Techniques ,Mice ,Downregulation and upregulation ,Western blot ,Gene expression ,medicine ,Animals ,Protein kinase A ,Lung ,Molecular Biology ,Skin ,Mice, Knockout ,medicine.diagnostic_test ,Brain ,Fibroblasts ,Cell cycle ,Molecular biology ,Mice, Inbred C57BL ,Liver ,Checkpoint Kinase 1 ,Knockout mouse ,Immunohistochemistry ,Tumor Suppressor Protein p53 ,Protein Kinases ,Spleen - Abstract
The regulation of Chk1, a critical protein kinase involved in G 2 phase arrest, has been a subject of recent research. Chk1 phosphorylates tumor suppressor p53 at multiple sites, while p53 has been shown to downregulate Chk1 expression under stress conditions in vitro , suggesting negative feedback between the two checkpoint proteins. Using the p53 knockout mouse model, we demonstrate by Western blot and immunohistochemistry that mChk1 expression is induced in spleen, thymus, and dermal fibroblasts and is reduced in lung and testis in p53 −/− mice compared to p53 +/+ controls. The mChk1 protein was undetectable in heart, kidney, and skin, whereas abundant expression was observed in brain and liver in both p53 +/+ and p53 −/− mice. These data indicate that p53 regulates Chk1 expression in a tissue-specific manner.
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- 2001
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18. The Tumor Suppressor ING1: Structure and Function
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Gang Li and K-John Cheung
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Gene isoform ,Senescence ,Cell Cycle Proteins ,Biology ,DNA-binding protein ,Mice ,Neoplasms ,Animals ,Humans ,Protein Isoforms ,Genes, Tumor Suppressor ,RNA, Messenger ,Nuclear protein ,Cell Cycle Protein ,Gene ,Cloning ,Sequence Homology, Amino Acid ,Tumor Suppressor Proteins ,Alternative splicing ,Intracellular Signaling Peptides and Proteins ,Nuclear Proteins ,Proteins ,Cell Biology ,Growth Inhibitors ,Cell biology ,DNA-Binding Proteins ,Alternative Splicing ,Organ Specificity ,Multigene Family ,Inhibitor of Growth Protein 1 - Abstract
The biological functions of the tumor suppressor ING1 have been studied extensively in the past 5 years since it was cloned. Of the three alternatively spliced forms of ING1, p24(ING1) has been the focus of much of past research. Information on the other currently known isoforms, p47(ING1), p32(ING1), and p27(ING1), has been lacking. ING1 shares many biological functions with p53. It has been reported to mediate growth arrest, senescence, apoptosis, anchorage-dependent growth, and chemosensitivity. Some of these functions, such as cell-cycle arrest and apoptosis, have been shown to be dependent on the activity of both ING1 and p53 proteins. In this review, we will examine what is known about ING1 up to this point and clarify the cloning errors originating from the isolation of this gene.
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- 2001
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19. Increased genetic damage in oral leukoplakia from high risk sites
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Lewei Zhang, Miriam P. Rosin, Joel B. Epstein, Catherine F. Poh, Nhu D. Le, Robert W. Priddy, K-John Cheung, Xing Cheng, and Wan L. Lam
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Cancer Research ,medicine.medical_specialty ,Pathology ,Epithelial dysplasia ,business.industry ,Carcinoma in situ ,Cytogenetics ,Cancer ,medicine.disease ,Gastroenterology ,Lesion ,Loss of heterozygosity ,medicine.anatomical_structure ,Oncology ,Tongue ,Dysplasia ,Internal medicine ,medicine ,medicine.symptom ,business - Abstract
BACKGROUND Two staging systems for oral leukoplakias have been proposed to better predict prognosis. Although one system includes site as an independent determinant, its use is controversial. METHODS Recent studies have shown that loss of heterozygosity (LOH) in oral premalignancies is associated with risk of progression. The authors analyzed 127 oral dysplasias for LOH on 3 chromosome arms (3p, 9p, and 17p). The lesions included 71 from the floor of mouth, ventrolateral tongue, and soft palate complex (designated high risk [HR] sites) and 56 from the rest of the oral cavity (low risk [LR] sites). RESULTS Dysplasias from HR sites contained significantly higher LOH frequencies than LR sites (percentage with any loss, P = 0.0004; percentage with multiple losses, P = 0.0001; percentage loss on each of the arms, P < 0.05). Loss on 3p and/or 9p, a pattern associated with a 24-fold increased risk of progression (Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, Lovas J, et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res 2000;6:357–62) was more frequent among HR lesions (P = 0.0005). Loss of heterozygosity frequencies were elevated at HR sites among both genders and among smokers and nonsmokers. For different histologic groups, LOH frequencies were elevated for HR sites in mild dysplasias (P < 0.05) and moderate dysplasias (marginal significance, P = 0.06), but not in severe dysplasias/carcinoma in situ. CONCLUSIONS Anatomic location of mild and moderate oral dysplasias in Western populations may be an important diagnostic indicator because lesions at HR sites have a greater tendency to include genetic alterations associated with elevated risk of progression. Cancer 2001;91:2148–55. © 2001 American Cancer Society.
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- 2001
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20. Outcome assessment of a community based model of general practitioner care of diabetes patients
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Rohan Jayasuriya, Rhonda Griffiths, and John Cheung
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Community based ,medicine.medical_specialty ,Shared care ,business.industry ,Endocrinology, Diabetes and Metabolism ,Impact evaluation ,Psychological intervention ,Variance (accounting) ,medicine.disease ,Nursing ,Intervention (counseling) ,Diabetes mellitus ,Internal Medicine ,Physical therapy ,Medicine ,Analysis of variance ,business - Abstract
The objective of this study was to determine the impact of a community based model of care for diabetes patients in general practice settings. Using a quasi-experimental study design the effects of two interventions, individual dietetic counselling and group counselling, were assessed using glycosylated haemoglobin (HbA1c) as the outcome measure. Clients were referred by 78 of the 136 members of a Division of General Practice in New South Wales, Australia. This project was designed to replicate decision making in the practice setting rather than follow strict protocols and criteria for interventions associated with controlled trials. When the intervention groups were compared, there was no significant difference with respect to age, gender, diagnosis, exercise level, therapy or initial level of HbA1c .A significant difference in the pre- and post-intervention level of HbA1c was found for those patients who attended individual education ( p=0.03), which was in contrast to those provided a group intervention, where there was no significant difference ( p=0.84). The ‘best fit’ model for the individual intervention explained 60% of the variance. The analysis of variance indicates that initial HbA1c ( p
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- 2000
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21. Optimization of analgesics allows patients with knee osteoarthritis and severe pain to participate in exercise therapy
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M. van der Leeden, Martijn Gerritsen, J.A. van Tunen, Leo D. Roorda, Wilfred F. Peter, Willem F. Lems, R.E. Voorneman, John Cheung, G.J. Tijhuis, J.M. Dekker, and Wouter H Bos
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medicine.medical_specialty ,Rheumatology ,business.industry ,Physical therapy ,medicine ,Biomedical Engineering ,Severe pain ,Exercise therapy ,Orthopedics and Sports Medicine ,Osteoarthritis ,medicine.disease ,business - Published
- 2015
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22. Anti-inflammatory therapy after selective laser trabeculoplasty: a randomized, double-masked, placebo-controlled clinical trial
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Delan, Jinapriya, Mark, D'Souza, Hussein, Hollands, Sherif R, El-Defrawy, Isabella, Irrcher, Donald, Smallman, James P, Farmer, John, Cheung, Todd, Urton, Andrew, Day, Xiaoquin, Sun, and Robert J, Campbell
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Aged, 80 and over ,Male ,Analysis of Variance ,Prednisolone ,Anti-Inflammatory Agents ,Trabeculectomy ,Middle Aged ,Exfoliation Syndrome ,Ketorolac Tromethamine ,Cross-Sectional Studies ,Double-Blind Method ,Trabecular Meshwork ,Humans ,Female ,Ocular Hypertension ,Laser Therapy ,Treatment Failure ,Glaucoma, Open-Angle ,Intraocular Pressure ,Aged - Abstract
To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes.Randomized, double-masked, placebo-controlled trial.Patients with primary open-angle or pseudo-exfoliation glaucoma.Patients undergoing SLT were randomized to receive placebo (artificial tears), prednisolone acetate 1%, or ketorolac tromethamine 0.5% eye drops 4 times per day for 5 days commencing immediately after SLT.Change in intraocular pressure (IOP) from baseline to the 1-month post-SLT visit.Mean change in IOP at the 1-month primary outcome time point, as well as all other time points, was not significantly different among groups (P = 0.99). Likewise, a repeated-measures, mixed-effects model did not find significant differences in IOP outcome at the 1-month time point (P = 0.95). The IOP was reduced in all groups at the 1-month post-SLT time point and all other time points, and no significant differences were found between groups using separate unadjusted cross-sectional analyses of variance (P0.15 for analyses at all time points). Treatment failure rates were not different among groups (P = 0.75), and at 1 year after SLT, the percentage of patients maintaining a 20% IOP reduction ranged from 18% to 22% in the 3 study groups.Anti-inflammatory therapy after SLT does not seem to substantially influence the IOP-lowering effect of SLT. In this study of patients with low baseline IOP, SLT showed limited efficacy in achieving a sustained reduction in IOP.
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- 2013
23. Cylindrical shell subject to local loads applied on an arbitrarily shaped area
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Lin Seng Ong, S.T. John Cheung, and A.S. Tooth
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Applied Mathematics ,Mechanical Engineering ,Multiple integral ,Mathematical analysis ,Shell (structure) ,Condensed Matter Physics ,Numerical integration ,symbols.namesake ,Fourier transform ,Mechanics of Materials ,Modeling and Simulation ,Discrete Fourier series ,symbols ,Gaussian quadrature ,General Materials Science ,Series expansion ,Fourier series ,Mathematics - Abstract
The problem of a cylindrical shell subject to local loads over an arbitrary shaped base is being analysed. Governing equations for the cylindrical shell are solved by the double Fourier series expansion technique, yielding solutions for stresses and displacements in terms of Fourier load coefficients. The load coefficients are double integral functions, which have variable integral limits when the load has a non-rectangular base profile. To evaluate the load coefficients, two methods are studied. In the first method, the discrete Fourier approximation technique is employed. In the second method, the double integral expression is converted into a boundary line integral by means of Green's Theorem. For a boundary with no analytical expression, it can be approximated by a series of line segments and integration is carried out along each line segment. The numerical integration is accomplished by the Clenshaw-Curtis quadrature rule. The boundary integral method is simpler and easier to implement in the computer than the discrete Fourier approximation method.
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- 1996
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24. Utility of Array Comparative Genomic Hybridization in Cytogenetic Analysis
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K-John Cheung, Rashmi R. Singh, and Douglas E. Horsman
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medicine.medical_specialty ,Breakpoint ,Ring chromosome ,Cytogenetics ,medicine ,Chromosomal translocation ,Karyotype ,Computational biology ,Biology ,Genome ,Virtual karyotype ,Comparative genomic hybridization - Abstract
Conventional comparative genomic hybridization (CGH), high-resolution oligonucleotide, and BAC array CGH have modernized the field of cytogenetics to enable access to unbalanced genomic aberrations such as whole or partial chromosomal gains and losses. The basic principle of array CGH involves hybridizing differentially labeled proband/test (e.g., tumor) and normal reference DNA on an array of oligonucleotide or BAC clones instead of normal metaphases as in conventional CGH. The sub-megabase resolution tiling BAC arrays are extremely useful for the analysis of acquired aberrations in cancer genomes. Array CGH can be extremely useful to identify the chromosomal makeup of marker and ring chromosomes, to define/delineate the precise location/bands involved in structural aberrations and the accurate localization of translocation breakpoints in both simple and complex karyotypes either alone or in combination with standard karyotype analysis.
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- 2011
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25. Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis
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Joseph M. Connors, Marco A. Marra, Ryan D. Morin, Tesa M. Severson, Douglas E. Horsman, Jessica E. Paul, Joslynn G. Affleck, Sohrab P. Shah, Randy D. Gascoyne, Hong Qian, Wan L. Lam, K-John Cheung, Thomas Relander, Christian Steidl, Susana Ben-Neriah, Nathalie A. Johnson, Kerry J. Savage, Jacqueline E. Schein, Adele Telenius, Richard D. Moore, and Carolyn J. Brown
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Oncology ,Male ,Cancer Research ,Candidate gene ,medicine.medical_specialty ,Pathology ,Chromosomes, Artificial, Bacterial ,Follicular lymphoma ,medicine.disease_cause ,Disease-Free Survival ,Loss of heterozygosity ,Antibodies, Monoclonal, Murine-Derived ,International Prognostic Index ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Genetic Predisposition to Disease ,Lymphoma, Follicular ,Exome sequencing ,In Situ Hybridization, Fluorescence ,Mutation ,Comparative Genomic Hybridization ,business.industry ,Cancer ,DNA Methylation ,Middle Aged ,medicine.disease ,Prognosis ,Lymphoma ,Chromosomes, Human, Pair 1 ,Multivariate Analysis ,CpG Islands ,Female ,Chromosome Deletion ,business ,Rituximab ,Receptors, Tumor Necrosis Factor, Member 14 - Abstract
Clinical correlative studies have linked 1p36 deletions with worse prognosis in follicular lymphoma (FL). In this study, we sought to identify the critical gene(s) in this region that is responsible for conferring inferior prognosis. BAC array technology applied to 141 FL specimens detected a minimum region of deletion (MRD) of ∼97 kb within 1p36.32 in 20% of these cases. Frequent single-nucleotide polymorphism–detected copy-neutral loss of heterozygosity was also found in this region. Analysis of promoter CpGs in the MRD did not reveal differential patterns of DNA methylation in samples that differed in 1p36 status. Exon sequencing of MRD genes identified somatic alterations in the TNFRSF14 gene in 3 of 11 selected cases with matching normal DNA. An expanded cohort consisting of 251 specimens identified 46 cases (18.3%) with nonsynonymous mutations affecting TNFRSF14. Overall survival (OS) and disease-specific survival (DSS) were associated with the presence of TNFRSF14 mutation in patients whose overall treatment included rituximab. We further showed that inferior OS and DSS were most pronounced in patients whose lymphomas contained both TNFRSF14 mutations and 1p36 deletions after adjustment for the International Prognostic Index [hazard ratios of 3.65 (95% confidence interval, 1.35–9.878, P = 0.011) and 3.19 (95% confidence interval, 1.06–9.57, P = 0.039), respectively]. Our findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes. Cancer Res; 70(22); 9166–74. ©2010 AACR.
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- 2010
26. Hypotheses of Cancer Weakening and Origin
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CHAN, John Cheung Yuen, primary
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- 2015
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27. No Superiority of Cemented Metal-on-Metal vs Metal-on-Polyethylene THA at 5-Year Follow-up
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Wierd P. Zijlstra, John Cheung, Maurits S. Sietsma, Jos J. A. M. van Raay, and Robert Deutman
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musculoskeletal diseases ,medicine.medical_specialty ,5 year follow up ,medicine.medical_treatment ,Prosthesis ,law.invention ,Primary outcome ,Randomized controlled trial ,law ,medicine ,Humans ,Orthopedics and Sports Medicine ,Arthroplasty, Replacement, Knee ,Aged ,business.industry ,Clinical performance ,Surgery ,Radiography ,Treatment Outcome ,Metals ,Polyethylene ,Orthopedic surgery ,Metal on polyethylene ,Hip Joint ,Hip Prosthesis ,Joint Diseases ,business ,Follow-Up Studies ,Total hip arthroplasty - Abstract
A randomized controlled trial was performed to compare the cemented Stanmore metal-on-metal (Biomet, Warsaw, Indiana) total hip arthroplasty (THA; 102 hips) to the cemented Stanmore metal-on-polyethylene (Biomet) THA (98 hips). The primary outcome was clinical performance. Radiological performance, serum cobalt analysis, and prosthetic survival were secondary outcome measures. At a mean follow-up of 5.6 years, 5 patients were lost to follow-up, 18 died, and 4 were revised (3 metal-on- metal, 1 metal-on-polyethylene). Harris Hip Scores improved from 48 to 90 in the metal-on-metal patients (P.001) and from 46 to 87 in the metal-on-polyethylene patients (P.001). Oxford Hip Scores changed from 40 to 19 in the metal-on-metal group (P.001) and from 40 to 18 in the metal-on-polyethylene group (P.001). For both Harris and Oxford Hip Scores, there was no significant difference between the 2 groups. Five-year survival with revision for any reason was 97% (95% CI 93%-100%) in the metal-on-metal group and 99% (95% CI 97%-100%) in the metal-on-polyethylene group. All revisions were indicated for aseptic loosening (metal-on-metal: 3 cup revisions; metal-on-polyethylene: 1 total revision). At 5-year follow-up, cemented metal-on-metal THA showed no clinical superiority over metal-on-polyethylene THA.
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- 2009
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28. The significance of TP53 in lymphoid malignancies: mutation prevalence, regulation, prognostic impact and potential as a therapeutic target
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Douglas E. Horsman, K-John Cheung, and Randy D. Gascoyne
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medicine.medical_specialty ,endocrine system diseases ,Tumor suppressor gene ,Lymphoma ,medicine.medical_treatment ,medicine.disease_cause ,Targeted therapy ,law.invention ,stomatognathic system ,law ,Internal medicine ,Medicine ,Humans ,neoplasms ,Regulation of gene expression ,Mutation ,Hematology ,business.industry ,Cancer ,medicine.disease ,Genes, p53 ,Prognosis ,Gene Expression Regulation, Neoplastic ,Immunology ,Cancer research ,Suppressor ,Tumor Suppressor Protein p53 ,business - Abstract
The tumour suppressor TP53 (previously termed p53) mediates a pathway that is considered to be one of the most important mechanisms in the maintenance of genomic stability. The function of TP53 can be abrogated by genomic deletion, mutation, or deregulation of upstream and downstream participants in the TP53 pathway. While aberrations of TP53 are widely prevalent in non-haematological malignancies (over 60%), they are present in much lower frequency in haematological malignancies (
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- 2009
29. Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances
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Adele Telenius, Joseph M. Connors, Abdulwahab J. Al-Tourah, Thomas Relander, Douglas E. Horsman, Randy D. Gascoyne, Nathalie A. Johnson, Raymond T. Ng, Wan L. Lam, Sohrab P. Shah, K-John Cheung, Betty Lai, Kevin Murphy, and Christian Steidl
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Male ,Biopsy ,Immunology ,Follicular lymphoma ,Gene Dosage ,Computational biology ,Biology ,Biochemistry ,Gene dosage ,International Prognostic Index ,Predictive Value of Tests ,Risk Factors ,medicine ,Humans ,Lymphoma, Follicular ,Survival analysis ,Genetics ,Comparative Genomic Hybridization ,Models, Genetic ,Proportional hazards model ,Gene Expression Profiling ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,Markov Chains ,Lymphoma ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,Female ,Algorithms ,Comparative genomic hybridization - Abstract
The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using an analytical approach that defined regions of copy number change as intersections between visual annotations and a Hidden Markov model–based algorithm, we identified 71 regional alterations that were recurrent in at least 10% of cases. These ranged in size from approximately 200 kb to 44 Mb, affecting chromosomes 1, 5, 6, 7, 8, 10, 12, 17, 18, 19, and 22. We also demonstrated by cluster analysis that 46.2% of the 106 cases could be sub-grouped based on the presence of +1q, +6p/6q−, +7, or +18. Survival analysis showed that 21 of the 71 regions correlated significantly with inferior overall survival (OS). Of these 21 regions, 16 were independent predictors of OS using a multivariate Cox model that included the international prognostic index (IPI) score. Two of these 16 regions (1p36.22-p36.33 and 6q21-q24.3) were also predictors of transformation risk and independent of IPI. These prognostic features may be useful to identify high-risk patients as candidates for risk-adapted therapies.
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- 2008
30. AB0857 Standardized Optimization of Analgesics in Patients with Knee Osteoarthritis and Severe Pain – a Feasibility Study
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Martijn Gerritsen, Wilfred F. Peter, M. van der Leeden, Wouter H Bos, J.A. van Tunen, Leo D. Roorda, J. Dekker, M. van der Esch, R.E. Voorneman, John Cheung, G.J. Tijhuis, and W.F. Lems
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business.industry ,Immunology ,Analgesic ,Osteoarthritis ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Acetaminophen ,Knee pain ,Rheumatology ,Opioid ,Anesthesia ,medicine ,Immunology and Allergy ,medicine.symptom ,Medical prescription ,Adverse effect ,business ,Cancer pain ,medicine.drug - Abstract
Background Prescription of analgesics is complex in patients with knee OA and severe pain. We developed a protocol for the standardized prescription of analgesics based on the World Health Organization analgesic ladder (1) and the Beating osteoARTritis (BART) strategy for stepped care in hip and knee OA (2). Objectives The aim of this study was to evaluate the feasibility and outcome of the analgesic protocol. Methods Forty-nine patients with knee OA and severe knee pain (NRS≥7; range 0-10) were included. Analgesics were prescribed following an incremental protocol (Figure 1) for a period of six weeks. Pain intensity was evaluated every two weeks. When there was insufficient pain reduction (NRS-pain>5), a consultation at the rheumatologist was planned to offer an analgesic of the next step. Analgesics of the next step were added to analgesics of the previous step(s). Analgesic use was recorded. Knee pain (NRS-pain) and activity limitations (WOMAC-PF) were measured. Data were collected at baseline and after six weeks. Subsequently, patients started with exercise therapy. Results At baseline 84% of the patients used analgesics. Of all patients, 77% used acetaminophen, 36% used NSAIDs and 16% used weak opioids. At baseline, analgesics were used irregularly and at an suboptimal dose. Analgesic use after six weeks is described in Figure 1. The maximal daily dosage was used in 93% of the patients that used acetaminophen, in 66% of the patients that used NSAIDs, and in 44% of the patients that used weak opioids. Combinations of analgesics were common. No serious adverse events occurred. In 39% of the patients NRS-pain was ≤5 after six weeks. Despite NRS-pain>5, a further step in the analgesic protocol was not accepted by the patient (n=14) or not prescribed by the rheumatologist (n=13), the latter mostly due to contra-indications or side effects. Statistically significant and clinically relevant mean improvements from baseline were 19% (p Conclusions After six weeks, patients used analgesics regularly and often at a preferential dose. Prescription of analgesics following an incremental protocol reduces pain and activity limitations in patients with knee OA and severe pain. References World Health Organization. Cancer pain relief: with a guide to opioid availability. Available at: http://whqlibdoc.who.int/publications/9241544821.pdf (accessed 14 January 2014). Smink AJ, et al. Clin Rheumatol 2011;30:1623-9. Disclosure of Interest None declared
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- 2015
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31. THU0627-HPR Exercise Therapy in Patients with Knee Osteoarthritis and Severe Pain is Enabled by Optimization of Analgesics – a Feasibility Study
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M. van der Esch, J.A. van Tunen, Martijn Gerritsen, Wilfred F. Peter, Leo D. Roorda, Wouter H Bos, G.J. Tijhuis, R.E. Voorneman, M. van der Leeden, John Cheung, W.F. Lems, and J. Dekker
- Subjects
medicine.medical_specialty ,Activities of daily living ,business.industry ,Immunology ,Analgesic ,Osteoarthritis ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Acetaminophen ,law.invention ,Knee pain ,Rheumatology ,Randomized controlled trial ,law ,medicine ,Physical therapy ,Immunology and Allergy ,Severe pain ,In patient ,medicine.symptom ,business ,medicine.drug - Abstract
Background Severe pain in patients with knee OA hampers the ability to exercise. A protocol for the optimization of analgesics in combination with exercise therapy was developed. The purpose of this protocol is to reduce pain and thereby allowing the patient to participate in exercise therapy. Objectives The objective of the present study was to evaluate the feasibility and outcome of the protocol. Methods Forty-nine patients with knee OA and severe knee pain (NRS-pain≥7, range 0-10) were included in this study. Analgesics were prescribed following an incremental protocol. The incremental steps were (1) acetaminophen, (2) NSAIDs, (3) weak opioids and (4) intra-articular steroid injections. After six weeks of analgesic use a supervised exercise therapy program for 12 weeks was added, consisting of muscle strengthening exercises and training of daily activities. Knee pain was assessed with NRS-pain and activity limitations were assessed with WOMAC-PF. Data were collected at baseline, after six weeks, and after 18 weeks. Results In intention-to-treat analyses statistically significant improvements in pain and activity limitations were found after six weeks of analgesic use and after the complete intervention. Mean improvements from baseline were 30% (p Conclusions The combined intervention of analgesics and exercise therapy allows most patients with knee osteoarthritis and severe pain to participate in exercise therapy, leading to reduction of pain and activity limitations. These promising results need to be confirmed in a randomized controlled trial. Disclosure of Interest None declared
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- 2015
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32. From DNA Photolesions to Mutations, Skin Cancer and Cell Death
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Nathalie Bastien, Cecilia Becerril, Vyacheslav A Bespalov, Serge Boiteux, Ihor P Boszko, Douglas E Brash, Jean Cadet, Colleen Caney, K-John Cheung Jr, Antonio Conconi, Raphael M Culerrier, Jocelyn David, R Jeremy H Davies, Julie Desnoyers, Thierry Douki, Elliot Drobetsky, Jean-Claude Ehrhart, Deirdre Fahy, Murray A Francis, Fabien P Gosselet, Pal Grof, Dong-Hyun Lee, Caroline Leger, Gang Li, Geraldine Mathonnet, Bruce C McKay, Leon H F Mullenders, Dennis H Oh, Daniel Perdiz, Gerd P Pfeifer, Photini Pitsikas, Jean-Pierre Pouget, Andrew J Rainbow, Dindial Ramotar, Jean-Luc Ravanat, Anne Reynaud-Angelin, Patrick Rochette, Alain Sarasin, Girish M Shah Shah, Michael J Smerdon, Jennifer Spronck, Sharon M Starrs, Clarke S Stevenson, John-Stephen Taylor, and Momchil D Vodenicharov
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Programmed cell death ,chemistry.chemical_compound ,Chemistry ,medicine ,Cancer research ,Skin cancer ,medicine.disease ,DNA - Abstract
As modern day society takes an increasing interest in outdoor activities, its exposure to sunlight has never been greater. As a consequence, countries throughout the world are experiencing a dramatic increase in the incidences of skin carcinomas and melanomas. From DNA photolesions to mutations, skin cancer and cell death provides an authoritative source of information for photobiologists interested in the series of genetic events that occur in the skin, and eventually lead to cancer. With contributions from eminent scientists in the field, this book includes the latest information on DNA photolesions and repair, as well as the key mechanisms of solar UV in skin cancer initiation and development. Significant information relating to UV-induced photolesions and mechanisms of skin tumour occurrence is also included. By providing the basic phenomena underlying the science and an overview of the biological events that take place when cells are exposed to solar UV radiation, From DNA photolesions to mutations, skin cancer and cell death is suitable to all researchers interested in the process of photocarcinogenesis.
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- 2005
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33. Semi-automatic landmark detection in digital X-ray images of the spine
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Olivier, Gerard, Pierre, Lelong, Milena, Planells-Rodriguez, Sherif, Makram-Ebeid, Bert, Verdonck, Marcel, Breeuwer, Rutger, Nijlunsing, John, Cheung, and Albert, Veldhuizen
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Radiographic Image Enhancement ,Scoliosis ,Humans ,Spine - Abstract
Quantitative diagnosis of 3D scoliotic deformities depends on a number of dedicated measurements. Existing methods rely on the manual determination of a series of anatomical landmarks in X-ray images. We have developed an automatic method to alleviate the burden of this tedious task. Our method looks for a compromise between local image information and global prior constraints and finds the most probable points using dynamic programming optimization. Remaining errors can be quickly corrected by effective user interaction. The first results are promising.
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- 2004
34. 3D reconstruction and analysis of the vertebral body line
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Pierre, Lelong, Olivier, Gerard, Sherif, Makram-Ebeid, Bert, Verdonck, Marcel, Breeuwer, Rutger, Nijlunsing, John, Cheung, and Albert, Veldhuizen
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Image Processing, Computer-Assisted ,Humans ,Spinal Diseases ,Spine - Abstract
Quantitative analysis of 3D spinal deformities includes measurements related to individual vertebrae and measurements related to the overall shape of the spine. For the latter aspect, we propose to build a 3D model of the line that connects all vertebrae centres. We present two methods that allow reconstructing this vertebral body line in a quick and easy way. Various new descriptors of the spinal shape can be automatically computed. A study is under way to assess their clinical relevance and reliability.
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- 2004
35. The relation between electromyography and growth velocity of the spine in the evaluation of curve progression in idiopathic scoliosis
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Jim R. van Horn, John Cheung, Natasha M. Maurits, Albert G. Veldhuizen, J.C. Cool, Wim J. Sluiter, and J.P. Halbertsma
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Male ,medicine.medical_specialty ,Adolescent ,Radiography ,Scoliosis ,Electromyography ,Sensitivity and Specificity ,Central nervous system disease ,Predictive Value of Tests ,medicine ,Deformity ,Humans ,Orthopedics and Sports Medicine ,Prospective Studies ,Child ,Muscle, Skeletal ,Cobb angle ,medicine.diagnostic_test ,business.industry ,Nomogram ,medicine.disease ,Spine ,Surgery ,Predictive value of tests ,Disease Progression ,Female ,Neurology (clinical) ,medicine.symptom ,Nuclear medicine ,business - Abstract
Study Design. A prospective study in which patients with idiopathic scoliosis were examined longitudinally by radiographic and electromyographic measurements according to a protocol. Objectives. To measure the growth velocity of the spine and the electromyographic ratio of the paraspinal muscles to determine their relation to progression of the scoliotic curve. Summary of Background Data. Several factors have been reported to be involved in the progression of idiopathic scoliosis. Possible factors may be growth disturbances and muscular abnormality. Methods. Thirty patients with idiopathic scoliosis were examined over periods of 4 to 5 months. The periods were scored for progression, defined as an increase in Cobb angle of >10degrees. Spinal growth velocity was measured as the length difference of the scoliotic spine between two consecutive radiographs. The electromyographic activity on both sides of the spine expressed as an electromyographic ratio was measured during relaxed upright standing using bipolar surface electrodes. Predictability of progression was evaluated with regression analysis and receiver operating characteristic analysis. Results. There was an independent association between both spinal growth velocity and electromyographic ratio and progression of the scoliotic curve. An equal sensitivity and specificity of spinal growth velocity for progression of 79.1% was observed at a growth velocity cutoff point of 11 mm/year. Similarly, a cutoff point of 1.25 for the electromyographic ratio could be determined with a predictive value for progression of 68.9%. In the presented nomogram, a spinal growth velocity >15 mm/year combined with an electromyographic ratio >2 gave an 89% probability of progression of the scoliotic deformity. Growth velocities Conclusions. The combined measurement of spinal growth velocity and electromyographic ratio has significant predictive potential and may be valuable in the evaluation and treatment of idiopathic scoliosis.
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- 2004
36. Salicylate induces an antibiotic efflux pump in Burkholderia cepacia complex genomovar III (B. cenocepacia)
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Bindu M. Nair, K-John Cheung, Adam Griffith, and Jane L. Burns
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Reverse Transcriptase Polymerase Chain Reaction ,Burkholderia cepacia complex ,Gene Expression Profiling ,Infant ,General Medicine ,Sequence Analysis, DNA ,Salicylates ,Trimethoprim ,Article ,Chloramphenicol ,Ciprofloxacin ,Multigene Family ,Drug Resistance, Bacterial ,Humans ,Bacterial Outer Membrane Proteins - Abstract
An antibiotic efflux gene cluster that confers resistance to chloramphenicol, trimethoprim, and ciprofloxacin has been identified in Burkholderia cenocepacia (genomovar III), an important cystic fibrosis pathogen. Five open reading frames have been identified in the cluster. There is apparently a single transcriptional unit, with llpE encoding a lipase-like protein, ceoA encoding a putative periplasmic linker protein, ceoB encoding a putative cytoplasmic membrane protein, and opcM encoding a previously described outer membrane protein. A putative LysR-type transcriptional regulatory gene, ceoR, is divergently transcribed upstream of the structural gene cluster. Experiments using radiolabeled chloramphenicol and salicylate demonstrated active efflux of both compounds in the presence of the gene cluster. Salicylate is an important siderophore produced by B. cepacia complex isolates, and both extrinsic salicylate and iron starvation appear to upregulate ceoR promoter activity, as does chloramphenicol. These results suggest that salicylate is a natural substrate for the efflux pump in B. cenocepacia and imply that the environment of low iron concentration in the cystic fibrosis lung can induce efflux-mediated resistance, even in the absence of antibiotic selective pressure.
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- 2003
37. The tumour suppressor p33ING1 does not regulate migration and angiogenesis in melanoma cells
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Gang Li and K-John Cheung
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Vascular Endothelial Growth Factor A ,Cancer Research ,Skin Neoplasms ,Tumor suppressor gene ,Angiogenesis ,Blotting, Western ,Cell Cycle Proteins ,Endothelial Growth Factors ,Biology ,Cell Movement ,medicine ,Tumor Cells, Cultured ,Humans ,Genes, Tumor Suppressor ,Melanoma ,Extracellular Matrix Proteins ,Lymphokines ,Wound Healing ,Vascular Endothelial Growth Factor Receptor-1 ,Neovascularization, Pathologic ,Vascular Endothelial Growth Factors ,Tumor Suppressor Proteins ,Lymphokine ,Intracellular Signaling Peptides and Proteins ,Nuclear Proteins ,Proteins ,Cell migration ,Transfection ,Cell cycle ,medicine.disease ,Vascular Endothelial Growth Factor Receptor-2 ,DNA-Binding Proteins ,Vascular endothelial growth factor A ,Oncology ,Matrix Metalloproteinase 9 ,Cancer research ,Intercellular Signaling Peptides and Proteins ,Matrix Metalloproteinase 2 ,Matrix Metalloproteinase 1 ,Inhibitor of Growth Protein 1 - Abstract
The tumour suppressor ING1 shares many biological functions with p53, such as cell cycle arrest, DNA repair, apoptosis, and chemosensitivity. Since p53 inhibits invasion and angiogenesis of melanoma cells, we sought to investigate if p33ING1 (one of ING1 isoforms) is also involved in these biological processes. We first overexpressed p33ING1 in melanoma cells and assessed the protein levels in MMP-1, MMP-2, and MMP-9. Results from Western blot analysis showed no significant difference in these matrix metalloproteinase levels between cells transfected with vector, p33ING1, and antisense p33ING1. Wound healing assay was performed to examine if p33ING1 plays a role in migration and invasion. Results showed that there was no difference between vector, p33ING1, and antisense p33ING1 groups in melanoma cell migration across the wound. Western blot analysis also indicated that there is no difference in the levels of proteins which are directly involved in angiogenesis, such as VEGF, Flt-1, and Flk-1, between cells transfected with vector, p33ING1, and antisense p33ING1. Furthermore, functional studies indicated that cultured medium derived from p33ING1-transfected melanoma cells did not stimulate the growth of HUVEC cells, compared to controls, providing support to the lack of functional role of p33ING1 in angiogenesis. In conclusion, we demonstrate in vitro that p33ING1, unlike p53, does not play a role in angiogenesis and migration in melanoma cells.
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- 2002
38. A new orthotic device in the non-operative treatment of idiopathic scoliosis
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Gert Nijenbanning, GJ Bulthuis, Albert G. Veldhuizen, and John Cheung
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musculoskeletal diseases ,Pelvic tilt ,Male ,medicine.medical_specialty ,Biomedical Engineering ,Biophysics ,Scoliosis ,Milwaukee brace ,Models, Biological ,orthosis ,medicine ,Humans ,DEFORMITIES ,Orthodontics ,BOSTON ,Braces ,Cobb angle ,business.industry ,Equipment Design ,equipment and supplies ,musculoskeletal system ,medicine.disease ,Sagittal plane ,Orthotic device ,Brace ,MILWAUKEE BRACE ,Surgery ,spine biomechanics ,Radiography ,medicine.anatomical_structure ,Treatment Outcome ,Torque ,Coronal plane ,Female ,Stress, Mechanical ,business ,SPINE ,Follow-Up Studies - Abstract
A transverse force system, consisting of an anterior progression force counteracted by a posterior force and torque, acts on the vertebrae of a scoliotic spine. The aim of the newly introduced TriaC brace is to reverse this transverse force pattern by externally applied and constantly present orthotic forces. In the frontal plane the force system in the TriaC brace is in accordance with the force system of the conventional braces. However, in the sagittal plane the force system acts only in the thoracic region. As a result, there is no pelvic tilt, and it provides flexibility without affecting the correction forces during body motion. In the current preliminary study it is demonstrated that the brace prevents further progression of the Cobb angle and axial rotation in idiopathic scoliosis. The new brace has the added advantage of comfort for the wearer, and it offers a better cosmetic appearance, as well as, potentially, a better compliance. (C) 2002 IPEM. Published by Elsevier Science Ltd. All rights reserved.
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- 2002
39. The p53 stabilizing compound CP-31398 induces apoptosis by activating the intrinsic Bax/mitochondrial/caspase-9 pathway
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Gang Li, K-John Cheung, Yvonne Luu, and Jason A. Bush
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Programmed cell death ,DNA repair ,Caspase 3 ,Antineoplastic Agents ,Apoptosis ,Cytochrome c Group ,Mitochondrial apoptosis-induced channel ,Membrane Potentials ,Bcl-2-associated X protein ,Neoplasms ,Proto-Oncogene Proteins ,Tumor Cells, Cultured ,Humans ,Caspase ,bcl-2-Associated X Protein ,Caspase-9 ,biology ,Carcinoma ,Cell Biology ,Molecular biology ,Caspase 9 ,Cell biology ,Mitochondria ,Cell Transformation, Neoplastic ,Eukaryotic Cells ,Pyrimidines ,Proto-Oncogene Proteins c-bcl-2 ,Caspases ,Colonic Neoplasms ,biology.protein ,Tumor Suppressor Protein p53 ,Cell Division - Abstract
p53 is considered the guardian of the genome and has a number of biological functions, including cell cycle arrest, DNA repair, and apoptosis. In a recent study by Foster and colleagues, the pharmacological compound CP-31398 was found to stabilize wild-type p53 to enhance its transcriptional activity and inhibit tumor growth in mice. We hypothesize that CP-31398 induces apoptosis by stabilizing the p53 protein and activating the mitochondrial-mediated pathway. Using the wild-type p53 HCT116+/+ and the p53-deficient HCT116-/- colon carcinoma cell lines, we demonstrate here that CP-31398 induces apoptosis in a dose-, time-, and p53-dependent manner. CP-31398 dramatically elevated p53 and p21(Waf1) protein levels in HCT116+/+, while a smaller p53-independent p21(Waf1) induction by CP-31398 in HCT116-/- cells was also observed. Moreover, we also found that CP-31398 increased Bax expression, altered mitochondrial membrane potential causing the release of cytochrome c, and induced the cleavage of caspases-9 and -3. Taken together, our results indicate that CP-31398 induces p53-dependent apoptosis by activating the Bax/mitochondrial/caspase-9 pathway. Elucidating the mechanism by which CP-31398 induces cell death may establish it as an anticancer agent.
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- 2002
40. The tumour suppressor p33ING1 does not enhance camptothecin-induced cell death in melanoma cells
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K-John, Cheung and Gang, Li
- Subjects
Cell Death ,Tumor Suppressor Proteins ,Intracellular Signaling Peptides and Proteins ,Nuclear Proteins ,Proteins ,Cell Cycle Proteins ,Antineoplastic Agents, Phytogenic ,DNA-Binding Proteins ,Tumor Cells, Cultured ,Humans ,Camptothecin ,Genes, Tumor Suppressor ,Tumor Suppressor Protein p53 ,Melanoma ,Inhibitor of Growth Protein 1 - Abstract
The tumour suppressor ING1 shares many biological functions with p53, such as cell cycle arrest, DNA repair, apoptosis, and chemosensitivity. Previous findings indicate that the isoform p24ING1 is capable of enhancing chemosensitivity in human fibroblasts. To investigate if the p33ING1 isoform is also involved in chemosensitivity, we overexpressed p33ING1 in melanoma cells and assessed for cell death after treatment with camptothecin. Results from the sulforhodamine B cell survival assay and flow cytometry analysis show no significant difference among cells transfected with vector, p33ING1, and antisense p33ING1. Furthermore, co-transfection of the p33ING1 and p53 constructs had no effect on the frequency of cell death, indicating that there is no synergistic effect between the two tumour suppressors in camptothecin-induced cell death in melanoma cells. This is in contrast to previously observed collaboration between p33ING1 and p53 in DNA repair and apoptosis. Taken together, we demonstrate that p33ING1 does not enhance camptothecin-induced cell death in melanoma cells.
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- 2002
41. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53
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Gang Li, Jason A. Bush, and K-John Cheung
- Subjects
Programmed cell death ,Curcumin ,Skin Neoplasms ,Cell Survival ,Antineoplastic Agents ,Apoptosis ,X-Linked Inhibitor of Apoptosis Protein ,Caspase 8 ,chemistry.chemical_compound ,Tumor Cells, Cultured ,Humans ,FADD ,fas Receptor ,Enzyme Inhibitors ,Melanoma ,Receptor Aggregation ,Enzyme Precursors ,biology ,Dose-Response Relationship, Drug ,NF-kappa B ,Proteins ,Cell Biology ,Fas receptor ,Caspase 9 ,Cell biology ,XIAP ,chemistry ,Caspases ,biology.protein ,Cancer research ,Tumor Suppressor Protein p53 - Abstract
In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.
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- 2001
42. The reliability of quantitative analysis on digital images of the scoliotic spine
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Rutger Nijlunsing, Jim R. van Horn, Bert Verdonck, D. J. Wever, Albert G. Veldhuizen, Jean P. Klein, John Cheung, and J.C. Cool
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Radiography ,Kyphosis ,VERTEBRAL ROTATION ,Scoliosis ,Standard deviation ,Digital image ,medicine ,Humans ,Orthopedics and Sports Medicine ,Diagnosis, Computer-Assisted ,Arthrography ,Child ,Reliability (statistics) ,Orthodontics ,Observer Variation ,ADOLESCENT IDIOPATHIC SCOLIOSIS ,Cobb angle ,business.industry ,computer digital images ,Reproducibility of Results ,Repeatability ,medicine.disease ,intraobserver repeatability ,Spine ,Surgery ,radiographs ,GROWTH ,Female ,business - Abstract
Although analysis of scoliotic deformity is still studied extensively by means of conventional roentgenograms, computer-assisted digital analysis may allow a faster, more accurate and more complete evaluation of the scoliotic spine. In this study, a new computer-assisted measurement method was evaluated. This method uses digital reconstruction images for quantitative analysis of the scoliotic spine. The aim of the current study was to determine the reliability of the computer-assisted measuring method, which was done by establishing coefficients of repeatability for a variety of measurements. Measurements were carried out by five observers on 30 frontal and 10 lateral scoliotic digital reconstruction images. Each image was measured on three separate occasions by placing anatomical vertebral landmarks and drawing lines with a computer pointing device. The computer then calculated a number of geometrical shape parameters from scale calibration, landmarks and lines. The intra- and interobserver results were subjected to an analysis of variance to assess the level of agreement, and the means and standard deviations were calculated. The coefficient of repeatability (CR) was taken to be equal to two standard deviations. The mean intraobserver CR was found to be 3.1degrees for the Cobb angle on the frontal digital image and 3.3degrees for the kyphosis Cobb angle on the lateral overview. The mean difference in the intraobserver CR of the Cobb angle between measurements made by placing landmarks and those made by drawing lines was not statistically significant (P>0.05). The mean intraobserver CR for the other parameters can be summarized as follows: for lateral deviation it was 0.8 mm, for axial rotation 4.0degrees and for length of the spine 3.3 mm. The interobserver bias was negligible. It can be concluded that the reliability of our new method for quantifying geometrical variables on digital reconstruction images is better than measurements on conventional roentgenograms in previously published reports. The presented method is therefore considered to be more accurate for research of spinal deformities and more adequate for clinical management of scoliosis.
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- 2001
43. LabShare: Towards a National Approach to Laboratory Sharing
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Dr Colin Kestell, Dr Steven Grainger, Prof John Cheung, Lowe, D., Murray, S., Weber, L., de la Villefromoy, M., Johnston, A., Lindsay, Euan, Nageswaran, W., Nafalski, A., Dr Colin Kestell, Dr Steven Grainger, Prof John Cheung, Lowe, D., Murray, S., Weber, L., de la Villefromoy, M., Johnston, A., Lindsay, Euan, Nageswaran, W., and Nafalski, A.
- Abstract
Conventional undergraduate engineering laboratories are valuable in terms of their contributions to students learning but are costly to develop and maintain and have extremely low utilisation rates. These issues can be addressed through cross-institutional sharing of laboratories; however this is limited by the overarching requirement that students are located in a centrally located laboratory. In this paper we describe the nature of the challenges and the potential benefits that can be achieved if a solution can be found. A possible solution is the use of remote laboratories that can be accessed across the internet with a suitable model for laboratory sharing that promotes both institutional and individual engagement. We describe the characteristics that such a model should have.
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- 2009
44. An Investigation into Increasing the Extent of Energy Efficiency Knowledge and Skills in Engineering Education
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Colin Kestell, Steven Grainger, John Cheung, Desha, C., Hargroves, Charlie, Colin Kestell, Steven Grainger, John Cheung, Desha, C., and Hargroves, Charlie
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- 2009
45. Effect of protein kinase inhibitors on IL-8/NAP-1 release from human umbilical vein endothelial cells
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John R. White and Lee John Cheung-Lun
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Umbilical Veins ,Indoles ,medicine.drug_class ,Lactams, Macrocyclic ,Immunology ,Carbazoles ,Biology ,Toxicology ,Umbilical vein ,chemistry.chemical_compound ,Alkaloids ,medicine ,Benzoquinones ,Staurosporine ,Humans ,Pharmacology (medical) ,Pyrroles ,Protein kinase A ,Protein Kinase Inhibitors ,Cells, Cultured ,Pharmacology ,Kinase ,Tumor Necrosis Factor-alpha ,Interleukin-8 ,Quinones ,Protein kinase inhibitor ,Geldanamycin ,KT5720 ,Molecular biology ,Recombinant Proteins ,Biochemistry ,chemistry ,Rifabutin ,Tetradecanoylphorbol Acetate ,Human umbilical vein endothelial cell ,Endothelium, Vascular ,medicine.drug ,Interleukin-1 - Abstract
Several protein kinase inhibitors (PKIs) were investigated for their effects on IL-1 beta, TNF alpha and PMA-induced IL-8 production from human umbilical vein endothelial cells (HUVEC). IL-1 beta (ED50 0.07 ng/ml), TNF alpha (ED50 100 ng/ml) and PMA (ED50 20 ng/ml) induced IL-8 production that could be detected as early as 2 h following stimulation. Staurosporine, a potent but non-specific inhibitor of protein kinases, inhibited PMA-induced (IC50 2 nM) but not IL-1 beta or TNF alpha (IC50200 nM) induced IL-8 production. Neither the cAMP-dependent PKI, KT5720, nor the tyrosine PKIs, genistein, tyrphostin (1-100 microM) or lavendustin A (0.0001-1 microM), inhibited IL-8 production elicited by IL-1 beta. However, the macrolide protein kinase inhibitor geldanamycin (IC50 = 30 nM), but not the closely related analog herbimycin A (5-500 nM), inhibited IL-8 production by 60%. Northern blot analysis of IL-8 mRNA revealed that staurosporine suppressed mRNA increase following stimulation by PMA but not by IL-1. It is proposed that a novel protein kinase susceptible to geldanamycin inhibition may be involved in IL-1-mediated signal transduction.
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- 1993
46. TNFRSF14 Is Mutated in a Subset of Follicular Lymphoma and Correlated with Inferior Prognosis
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Jacqueline E. Schein, Marco A. Marra, Richard D. Moore, Tesa M. Severson, Susanna Ben-Neriah, Betty Lai, Adele Telenius, Nathalie A. Johnson, Jessica E. Paul, Joseph M. Connors, Christian Steidl, Kerry J. Savage, K-John Cheung, Randy D. Gascoyne, Sohrab P. Shah, Thomas Relander, Ryan Morin, Wan L. Lam, Carolyn J. Brown, Hong Qian, Douglas E. Horsman, and Joslynn G. Affleck
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Mutation ,Immunology ,Follicular lymphoma ,Promoter ,Cell Biology ,Hematology ,Biology ,medicine.disease_cause ,medicine.disease ,Biochemistry ,Candidate Tumor Suppressor Gene ,Molecular biology ,Loss of heterozygosity ,CpG site ,medicine ,Gene ,Comparative genomic hybridization - Abstract
Abstract 1919 Poster Board I-942 The secondary genetic events associated with follicular lymphoma (FL) development are obscure as to the identification of critical driver genes. Clinical correlative studies have implicated chromosome band 1p36 deletions and linked them to a propensity for transformation and poor outcome. This region also showed a high frequency of copy-neutral loss of heterozygosity as demonstrated by SNP array analysis. In this study, we applied BAC array comparative genomic hybridization (array CGH) to 141 FL specimens and detected deletion of 1p36 in 20% of the cases with a minimum region of deletion (MRD) of ∼100 kb within the band 1p36.32. The majority of cases displayed heterozygous deletion, while two cases showed homozygous deletion. The MRD encompassed five genes: HES5, LOC115110, TNFRSF14, C1orf93 and MMEL1. Methylation status of CpG in the promoter region of genes in the MRD revealed no difference among samples differing in 1p36 status. However, exonic sequencing of the MRD genes identified somatic base mutations only in the TNFRSF14 gene in four of five selected cases with 1p36 deletion. Lower expression of TNFRSF14 was also found in 1p36 deleted cases. Validation of TNFRSF14 mutations was undertaken in an expanded cohort of 251 FL patients which showed that 45 cases (18%) displayed a total of 50 mutations and that inferior prognosis was significantly associated with TNFRSF14 mutation status. We propose that TNFRSF14, a gene previously implicated in growth inhibition and Fas-induced apoptosis, is a candidate tumor suppressor gene in FL. Disclosures: No relevant conflicts of interest to declare.
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- 2009
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47. Genetic Alterations Detected by High-Resolution Array Comparative Genomic Hybridization in Microdissected HRS Cells Correlate with Treatment Outcome in Classical Hodgkin Lymphoma
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Lorena Barclay, Christian Steidl, Sohrab P. Shah, Adele Telenius, Douglas E. Horsman, Randy D. Gascoyne, Joseph M. Connors, and K-John Cheung
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Whole Genome Amplification ,Pathology ,medicine.medical_specialty ,Tiling array ,Immunology ,Cancer ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,genomic DNA ,Reed–Sternberg cell ,medicine ,Cancer research ,Gene ,Laser capture microdissection ,Comparative genomic hybridization - Abstract
INTRODUCTION: Clinical decision making in Hodgkin lymphoma (HL) is primarily based on clinical variables in part because the scarcity of the malignant Hodgkin Reed Sternberg cells (HRS cells) hampers their molecular characterization. However, more recently investigation using laser capture microdissection has allowed a more detailed analysis of these cells. The objective of this study was to detect genomic alterations in HRS cells and correlate these changes with treatment outcome. PATIENTS AND METHODS: We studied 53 patients with classical HL who were primarily treated at the BC Cancer Agency in Vancouver between 1984 and 2006. All received at least 4 cycles of polychemotherapy and stage-dependent radiotherapy if indicated. The cohort included 43 pretreatment samples and 10 biopsies taken at relapse. Treatment failure was defined as disease progression or relapse at any time (n=23), treatment success as absence of progression (n=30). Whole genome amplification (GenomePlex, Sigma) of pools from 500–1000 individually picked, microdissected HRS cells (Molecular Machines & Industries Cellcut with Nikon Eclipse TE2000-S microscope) was performed. 200 ng of amplified DNA was hybridized to 32k submegabase resolution BAC tiling arrays (SMRT) against sex-matched control-DNA. Scoring of array CGH data was performed by computational analysis using CNA-HMMer v0.1 (available at http://www.cs.ubc.ca/~sshah/acgh/) based on a Hidden Markov Model (HMM). Clustering of the 53 cases was performed using the K-medoids algorithm. Areas of amplification bias and known copy number polymorphisms were excluded. RESULTS: On average whole genome amplification generated 500-fold amplification of genomic DNA. The most frequent copy number alterations (>20% of cases) included gains of 2p14–24.3, 9p12–24.3, 12p11.21–13.33, 16p11.2–13.3, 17p11.2–13.3, 17q11.1–25.1, 19p12–13.3, 19q12–13.43, 20q11.21–13.32, 21q22.11–22.2 and losses of 1p36.31–36.33, 6q11.1–27, 7q22.1–36.3, 8p23.1–23.3, 11q22.3–25, 13q33.3–34 and Xq11.2–28. We also identified several small changes ( DISCUSSION: The combination of laser microdissection with subsequent WGA and high resolution array CGH provides a robust and sensitive platform for detecting chromosomal imbalances in microdissected HRS cells. We identified at high-resolution new and recurrent changes defining chromosomal regions that potentially harbor oncogenes and tumor suppressor genes crucial to the pathogenesis of HL. Furthermore, we found copy number alterations that are significantly associated with disease progression which, therefore, could serve as predictive factors for treatment outcome.
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- 2008
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48. High Frequency of 1p36.32 Deletion or Loss of Heterozygosity in Follicular Lymphoma (FL)
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Agnes Baross, Thomas Relander, Douglas E. Horsman, Nathalie A. Johnson, Randy D. Gascoyne, Hong Qian, Joseph M. Connors, Adele Telenius, Jacquie Schein, Betty Lai, K.-John Cheung, Christian Steidl, and Marco A. Marra
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Genetics ,Candidate gene ,Immunology ,Follicular lymphoma ,Chromosomal translocation ,Karyotype ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Molecular biology ,Uniparental disomy ,Loss of heterozygosity ,medicine ,Comparative genomic hybridization ,SNP array - Abstract
Background: The initial genetic event in ∼85% of follicular lymphomas (FL), the most common B-cell lymphoma in North America, is the t(14;18)(q32;q21) resulting in over-expression of the anti-apoptotic protein Bcl-2. The secondary events associated with disease progression are not well understood. Alterations affecting the p arm of chromosome 1 are evident by standard karyotype analysis in ∼20% of FL. We have further examined the relationship between 1p deletion and FL using high resolution genomic analyses. Methods: The prevalence of 1p alterations was investigated in 139 cases of indolent and transformed FL using whole genome tiling path BAC array Comparative Genomic Hybridization (array CGH). Array-based single nucleotide polymorphism analysis was performed on a subset of cases using Affymetrix 500K SNP arrays. Results: Array CGH identified a minimum region of deletion spanning ∼0.5MB within 1p36.32 in 51 cases (37%). In 38 cases (27%) this loss was exhibited in the transformed sample but not the pre-transformation sample. The majority of cases displayed heterozygous deletion, while two cases showed homozygous deletion. The mechanisms of loss included simple deletions, unbalanced translocations with various partner chromosomes and eleven cases with an unbalanced t(1;1)(p36;q12). The Affymetrix 500 SNP array analyses showed copy neutral loss of heterozygosity or acquired uniparental disomy (aUPD) in three of ten cases that were negative for loss by aCGH. Contained within the 1p36.32 minimally deleted region are only a few candidate genes including tumor necrosis factor receptor superfamily 14 (TNFRS14), which has been implicated in growth inhibition of HT-29 human colon adenocarcinoma cells and induction of Fas-mediated apoptosis in non-Hodgkin’s lymphoma. Conclusions: Our data indicate that loss of heterozygosity at 1p36.32 through deletion or aUPD constitutes the most common secondary cytogenetic event in FL. LOH at 1p36 may represent an important step in the progression of indolent to transformed FL. Further studies have been initiated to investigate other possible gene inactivation events such as methylation and mutation.
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- 2007
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49. Cylindrical shell subject to local loads applied on an arbitrarily shaped area
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Ong, L.S., primary, John Cheung, S.T., additional, and Tooth, A.S., additional
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- 1996
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50. Tyrosine hydroxylase expression and Cdk5 kinase activity in ataxic cerebellum.
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K-John Cheung, Jesusa Rosales, and Ki-Young Lee
- Abstract
Abstract Ataxia has been associated with abnormalities in neuronal differentiation and migration, which are regulated by Cyclin-dependent kinase 5 (Cdk5). The cerebellum of mice lacking Cdk5 or its activator, p35, resembles those of ataxic reeler and scrambler mice, suggesting that Cdk5 may contribute to ataxic pathology. As with other ataxic mice, the pogo/pogo mouse shows aberrant cerebellar tyrosine hydroxylase (TH) expression. Since Cdk5 phosphorylates and upregulates TH expression, we sought to analyze (i) Cdk5 activity in the pogo cerebellum, which exhibits abnormal TH expression, and (ii) TH expression in the cerebellum of p35−/− and p39−/− mice, which display reduced Cdk5 activity. Interestingly, we found that increased TH expression in the pogo cerebellum coincided with reduced Cdk5 activity. However, reduced Cdk5 activity in both p35−/− and p39−/− cerebellum did not correspond to defects in TH expression. Together, these suggest that abnormal TH expression in the cerebellum might be regulated by mechanisms other than Cdk5 activity. [ABSTRACT FROM AUTHOR]
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- 2008
- Full Text
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