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Yu M Tan,
Mikkel Østergaard,
Anthony Doyle,
Nicola Dalbeth,
Maria Lobo,
Quentin Reeves,
Elizabeth Robinson,
William J Taylor,
Peter B Jones,
Karen Pui, Jamie Lee,
Fiona M McQueen
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ABSTRACT: The aim of this study was to investigate the magnetic resonance imaging (MRI) features of bone disease in the arthritis mutilans (AM) form of psoriatic arthritis (PsA).
Twenty-eight patients with erosive PsA were enrolled (median disease duration of 14 years). Using x-rays of both hands and feet, 11 patients were classified as AM and 17 as non-AM (erosive psoriatic arthritis without bone lysis)by two observers. MRI scans (1.5T) of the dominant hand (wrist and fingers scanned separately) were obtained using standard contrast-enhanced T1-weighted and fat-saturated T2-weighted sequences. Scans were scored separately by two readers for bone erosion, oedema and proliferation using a PsA MRI scoring system. X-rays were scored for erosions and joint space narrowing.
On MRI, 1013 bones were scored by both readers. Reliability for scoring erosions and bone oedema was high (intraclass correlation coefficients = 0.80 and 0.77 respectively) but only fair for bone proliferation (intraclass correlation coefficient = 0.42). MRI erosion scores were higher in AM patients (53.0 versus 15.0, p = 0.004) as were bone oedema and proliferation scores (14.7 versus 10.0, p = 0.056 and 3.6 versus 0.7, p = 0.003 respectively). MRI bone oedema scores correlated with MRI erosion scores and X-ray erosion and joint space narrowing scores (r = 0.65, p = 0.0002 for all) but not the disease activity score 28-C reactive protein (DAS28CRP) or pain scores.
In this patient group with PsA, MRI bone oedema, erosion and proliferation were all more severe in the AM-form. Bone oedema scores did not correlate with disease activity measures but were closely associated with X-ray joint damage scores. These results suggest that MRI bone oedema may be a pre-erosive feature and that bone damage may not be coupled with joint inflammation in PsA.
Arthritis research & therapy 02/2009; 11(1):R2. · 4.27 Impact Factor
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Jamie Lee,
Robert Sinkovits,
Dennis Mock,
Eva Rab,
Jennifer Cai,
Peng Yang,
Brian Saunders,
Robert Hsueh,
Sangdun Choi,
Shankar Subramaniam,
Richard Scheuermann
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ABSTRACT: Abstract
Background
Activation of naïve B lymphocytes by extracellular ligands, e.g. antigen, lipopolysaccharide (LPS) and CD40 ligand, induces a combination of common and ligand-specific phenotypic changes through complex signal transduction pathways. For example, although all three of these ligands induce proliferation, only stimulation through the B cell antigen receptor (BCR) induces apoptosis in resting splenic B cells. In order to define the common and unique biological responses to ligand stimulation, we compared the gene expression changes induced in normal primary B cells by a panel of ligands using cDNA microarrays and a statistical approach, CLASSIFI ( Cl uster Assi gnment f or Biological I nference), which identifies significant co-clustering of genes with similar Gene Ontology™ annotation.
Results
CLASSIFI analysis revealed an overrepresentation of genes involved in ion and vesicle transport, including multiple components of the proton pump, in the BCR-specific gene cluster, suggesting that activation of antigen processing and presentation pathways is a major biological response to antigen receptor stimulation. Proton pump components that were not included in the initial microarray data set were also upregulated in response to BCR stimulation in follow up experiments. MHC Class II expression was found to be maintained specifically in response to BCR stimulation. Furthermore, ligand-specific internalization of the BCR, a first step in B cell antigen processing and presentation, was demonstrated.
Conclusion
These observations provide experimental validation of the computational approach implemented in CLASSIFI, demonstrating that CLASSIFI-based gene expression cluster analysis is an effective data mining tool to identify biological processes that correlate with the experimental conditional variables. Furthermore, this analysis has identified at least thirty-eight candidate components of the B cell antigen processing and presentation pathway and sets the stage for future studies focused on a better understanding of the components involved in and unique to B cell antigen processing and presentation.
BMC Bioinformatics. 01/2006;
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Xiaocui Zhu,
Rebecca Hart,
Mi Sook Chang,
Jong-Woo Kim,
Sun Young Lee,
Yun Anna Cao,
Dennis Mock,
Eugene Ke,
Brian Saunders,
Angela Alexander, [......],
Zhen Yan,
Robert Hsueh, Jamie Lee,
Richard H Scheuermann,
David A Fruman,
William Seaman,
Shankar Subramaniam,
Paul Sternweis,
Melvin I Simon,
Sangdun Choi
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ABSTRACT: We examined the major patterns of changes in gene expression in mouse splenic B cells in response to stimulation with 33 single ligands for 0.5, 1, 2, and 4 h. We found that ligands known to directly induce or costimulate proliferation, namely, anti-IgM (anti-Ig), anti-CD40 (CD40L), LPS, and, to a lesser extent, IL-4 and CpG-oligodeoxynucleotide (CpG), induced significant expression changes in a large number of genes. The remaining 28 single ligands produced changes in relatively few genes, even though they elicited measurable elevations in intracellular Ca(2+) and cAMP concentration and/or protein phosphorylation, including cytokines, chemokines, and other ligands that interact with G protein-coupled receptors. A detailed comparison of gene expression responses to anti-Ig, CD40L, LPS, IL-4, and CpG indicates that while many genes had similar temporal patterns of change in expression in response to these ligands, subsets of genes showed unique expression patterns in response to IL-4, anti-Ig, and CD40L.
The Journal of Immunology 01/2005; 173(12):7141-9. · 5.79 Impact Factor
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ABSTRACT: Over the last 20 years, pension coverage has shifted from defined benefit plans, where benefits are based on years of service and final salary and generally paid as an annuity, to 401(k) plans, where individual and employer contributions and earnings on those contributions are awarded as a lump sum at retirement. Although the majority of workers lucky enough to have a pension will rely on a 401(k) plan, these plans are coming up short. The main reason is that 401(k) plans shift all the risks and decision-making from the employer to the individual, and individuals make mistakes all along the way. One of the most serious mistakes occurs when young people cash out small pension accounts upon changing jobs. The regulation issued today from the U.S. Department of Labor with regard to provisions in the 2001 Economic Growth and Tax Relief Reconciliation Act should help solve the “cash out” problem.
10/2004;
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ABSTRACT: Abstract
Background
Immature B lymphocytes and certain B cell lymphomas undergo apoptotic cell death following activation of the B cell antigen receptor (BCR) signal transduction pathway. Several biochemical changes occur in response to BCR engagement, including activation of the Syk tyrosine kinase. Although Syk activation appears to be necessary for some downstream biochemical and cellular responses, the signaling events that precede Syk activation remain ill defined. In addition, the requirements for complete activation of the Syk-dependent signaling step remain to be elucidated.
Results
A mutant form of Syk carrying a combination of a K395A substitution in the kinase domain and substitutions of three phenylalanines (3F) for the three C-terminal tyrosines was expressed in a murine B cell lymphoma cell line, BCL<sub>1</sub>.3B3 to interfere with normal Syk regulation as a means to examine the Syk activation step in BCR signaling. Introduction of this kinase-inactive mutant led to the constitutive activation of the endogenous wildtype Syk enzyme in the absence of receptor engagement through a 'dominant-positive' effect. Under these conditions, Syk kinase activation occurred in the absence of phosphorylation on Syk tyrosine residues. Although Syk appears to be required for BCR-induced apoptosis in several systems, no increase in spontaneous cell death was observed in these cells. Surprisingly, although the endogenous Syk kinase was enzymatically active, no enhancement in the phosphorylation of cytoplasmic proteins, including phospholipase Cγ2 (PLCγ2), a direct Syk target, was observed.
Conclusion
These data indicate that activation of Syk kinase enzymatic activity is insufficient for Syk-dependent signal transduction. This observation suggests that other events are required for efficient signaling. We speculate that localization of the active enzyme to a receptor complex specifically assembled for signal transduction may be the missing event.
BMC Immunology. 01/2002;
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ABSTRACT: 56 p. transcript of an interview with Eliza Kneller conducted by Jamie Lee on July 21, 1982. Taken from the Provincial Museum and Archives of Alberta, tape number IH-OT.006, transcript disc 111. Consists of an interview where she tells of a frightening trip through the woods as a child. Other no
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ABSTRACT: 46 p. transcript of an interview with Eliza Kneller conducted by Jamie Lee on July 23, 1982. Tape number IH-OT.006A, transcript disc 112. Consists of an interview with Eliza Kneller where she describes the smallpox epidemic following World War I. She gives a description of basket making, an account of life in a Catholic school in Chicago and an account of New Year's celebrations amongst children. Other no
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ABSTRACT: 33 p. transcript of an interview with Eliza Kneller conducted by Jamie Lee on July 23, 1982. Taken from the Provincial Museum and Archives of Alberta, tape number IH-OT.006B, transcript disc 112. Consists of an interview where she gives a brief account of Indian medicine; she mentions accounts she has heard of the War of 1812; and mentions certain superstitions. Other no
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ABSTRACT: 42 p. transcript of an interview with Eliza Kneller conducted by Jamie Lee on July 28, 1982. Taken from the Provincial Museum and Archives of Alberta, tape number IH-OT.006C, transcript disc 111. Consists of an interview with Eliza Kneller where she discusses her life in the United States. She tells of a premonition of the death of her son. Other no
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ABSTRACT: 19 p. transcript of an interview with Carl Lewis conducted by Jamie Lee on July 5, 1982. Taken from the Provincial Museum and Archives of Alberta, tape number IH-OT.007, transcript disc 104. Consists of an interview with Carl Lewis where he discusses his trips throughout North and South American visiting various Indian tribes. He also discusses the role of the rifle in the conquest of North America. He gives a general account of the course of historical events in Canada. Other no
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ABSTRACT: 39 p. transcript of an interview with Hettie Sylvester conducted by Jamie Lee on July 29, 1982. Tape number IH-OT.012, transcript disc 109. Consists of an interview where she gives a general account of her working life, difficulties encountered with the Children's Aid Society and its role in the disruption of the nuclear family. Other no
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ABSTRACT: 25 p. transcript of an interview with Marie Taylor conducted by Jamie Lee on July 9, 1982. Taken from the Provincial Museum and Archives of Alberta, tape number IH-OT.014, transcript disc 109. Consists of an interview where she gives a very brief description of life during the Depression. Other no
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ABSTRACT: The objective of this study was to determine effects of supplementing coastal bermudagrass (Cynodon dactylon; CBG) hay with Strophostyles helvula (98 g kg-1 crude protein (CP), 476 g kg-1 neutral detergent fiber (NDF)), S. leiosperma (117 g kg-1 CP, 497 g kg-1 NDF), or cottonseed meal (506 g kg-1 CP, 352 g kg-1 NDF; CSM) upon intake of CBG hay (127 g kg-1 CP, 691 g kg-1 NDF) and apparent digestibility of dietary organic matter (OM), NDF, and true digestibility of CP. Six Boer-Spanish goats (46.22 ł 3.99 Kg) were fed CBG plus S. helvula, S. leiosperma, or CSM at 0.34 and 0.68% of BW in a 6x6 Latin square with 3x2 factorial arrangement of treatments. The CBG was fed ad libitum, and the legumes/CSM were fed in two equal daily feedings during a 7-d adjustment period and 7-d collection period in metabolism crates. Feces were collected every 24-h, and CBG, legumes/CSM, and fecal samples were analyzed for OM, NDF, and CP. There were no supplement type-amount interactions (P> 0.05). Supplement type did not affect OM digestibility (P = 0.21), but OM digestibility increased 6.4% (P = 0.05) at the 0.68% versus 0.34% level of supplementation with the legumes or CSM. Supplementation with CSM and S. leiosperma improved NDF digestibility 7% versus supplementation with S. helvula (P = 0.02); and as supplement amount increased NDF digestibility by 5.5% (P = 0.02). The diet supplemented with CSM had the greatest CP digestibility, and S. helvula CP was 6% less digestible than S. leiosperma (P = 0.02). As supplement amount increased, CP digestibility increased 7% (P = 0.01). Intake of DM, OM, and NDF of CBG was unaffected (P = 0.56) by supplementation with CSM, S. helvula, and S. leiosperma, but total diet NDF intake of diets supplemented with CSM and S. helvula was 10.5% less than diet supplemented with S. leiosperma (P = 0.01). Considering digestibility and intake, CSM and S. leiosperma were the best supplements fed in this experiment. Strophostyles leiosperma is recommended as use for diet supplementation for goats when CBG hay basal diet is fed. "Major Subject: Agronomy." Title from author supplied metadata (automated record created on Oct. 15, 2004.). Vita. Abstract. Thesis (M.S.)--Texas A & M University, 2004. Includes bibliographical references. Text (Thesis). Mode of access: World Wide Web. System requirements: World Wide Web access and Adobe Acrobat Reader.
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ABSTRACT: Interferons-α and -β (IFN-α and β) are cytokines that are widely known to induce potent anti-viral activity. However, it has become increasingly apparent that IFN-α and -β exert a variety of other biological effects, including anti-tumour and immunomodulatory activities, and are increasingly used clinically to treat a range of malignancies, myelodysplasias and autoimmune diseases, e.g. IFN-β for multiple sclerosis. The most widely used bioassays for the IFNs are based on their anti-viral activity, but these do not predict the biological activity of the IFNs in anti-tumour and immunomodulatory therapies. Thus, we have developed anti-cytokine-based bioassays that may be more reflective of such activity and which have several advantages over existing anti-viral bioassays. The anti-cytokine bioassay is based on the ability of IFN-α, -β and -ω to inhibit granulocyte-macrophage-colony-stimulating factor (GM-CSF) induced proliferation of the erythroleukaemic cell line TF-1. This assay can take only 24 h, is sensitive to 200 fg (0.04 IU) IFN-α or -β and 100 fg (0.02 IU) IFN-ω and is able to detect down to these levels in serum or plasma samples. The usefulness of anti-cytokine bioassays for IFN-α, -β and -ω is not restricted to the GM-CSF/TF-1 cell format and other alternatives are available, such as erythropoietin (EPO)/TF-1 cells and EPO/UT-7-EPO cells. These assays can be made specific for each of the IFNs by including neutralising antibodies in the bioassay.
Journal of Immunological Methods.
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Jamie Lee,
Josef Spidlen,
Jennifer Cai,
Jeff Furlong,
Maura Gasparetto,
Elizabeth M. Goralczyk,
Kirstin Jansen,
Tobias Kollmann,
Megan Kong,
Robert Leif,
Shannon K. McWeeney,
Thomas D. Moloshok
