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1.
Lupus ; 24(8): 816-21, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25542903

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) patients have seriously impaired quality of life (QoL). In addition to activity and damage indices used in the past, tools to evaluate QoL in SLE have been developed in recent years. In this study, we test the validity of the Turkish version of the Lupus-QoL (LupusQoL-TR) score, and investigate its association with clinical findings and activity indices. METHODS: A total of 132 patients diagnosed with SLE according to ACR 1997 criteria were included. The clinical and demographic features, and biochemical data were retrieved from hospital records. SLE Disease Activity Index (SLEDAI) and damage score (SLICC-ACR) were determined at the time of administration of Lupus-QoL questionnaire. The Lupus-QoL includes 34 questions divided into eight domains. We reevaluated the LupusQoL-TR and pretested its understandability. SLE patients were concomitantly administered the LupusQoL-TR and generic SF-36. Internal consistency, test-retest reliability, convergent and discriminant validity were calculated. RESULTS: The mean age of our SLE patients was 37.9 ± 12.8 years. Internal consistency reliability ranged from 0.88 to 0.93, and test-retest reliability from 0.84 to 0.94. LupusQoL-related domains in SF-36 were correlated (from 0.66 to 0.74). Most LupusQoL-TR domains, except planning, were able to discriminate between active and inactive SLE groups. Scores in all domains of the LupusQoL-TR were found to be discriminative for patients with and without damage according to SLICC-ACR score. CONCLUSION: The LupusQoL-TR was found to be a valid patient-reported outcome measure method when evaluating QoL in Turkish SLE patients.


Subject(s)
Lupus Erythematosus, Systemic/complications , Quality of Life , Severity of Illness Index , Adult , Female , Humans , Male , Middle Aged , Outcome and Process Assessment, Health Care , Reproducibility of Results , Surveys and Questionnaires , Turkey
2.
Ann Rheum Dis ; 68(8): 1352-9, 2009 Aug.
Article in English | MEDLINE | ID: mdl-18647856

ABSTRACT

OBJECTIVES: To investigate whether human bone marrow-derived mesenchymal stem cells (BM-MSCs) and articular chondrocytes (ACs) affect the in vitro proliferation of T lymphocytes and peripheral blood mononuclear cells (PBMCs) driven by the homeostatic interleukin (IL)2, IL7 and IL15 cytokines binding to the common cytokine receptor gamma-chain (gamma(c)) in the absence of T cell receptor (TCR) triggering. METHODS: PBMCs, total T cells and T cell subsets (CD4+ and CD8+) were stimulated with IL2, IL7 or IL15 and exposed to cultured BM-MSCs and ACs at varying cell:cell ratio either in contact or in transwell conditions. Lymphocyte proliferation was measured by (3)H-thymidine uptake or by flow cytometry of carboxyfluorescein succinimidyl ester (CFSE)-labelled lymphocytes. RESULTS: MSCs and ACs enhanced and inhibited lymphocyte proliferation depending on the extent of lymphocyte baseline proliferation and on the MSC/AC to lymphocyte ratio. Enhancement was significant on poorly proliferating lymphocytes and mostly at lower MSC/AC to lymphocyte ratio. Suppression occurred only on actively proliferating lymphocytes and at high MSC/AC to lymphocyte ratio. Neither enhancement nor inhibition required cell-cell contact. CONCLUSIONS: There is a dichotomous effect of MSCs/ACs on lymphocytes proliferating in response to the homeostatic IL2, IL7 and IL15 cytokines likely to be encountered in homeostatic and autoimmune inflammatory conditions. The effect is determined by baseline lymphocyte proliferation, cell:cell ratio and is dependent on soluble factor(s). This should be taken into account when planning cellular therapy for autoimmune disease (AD) using stromal-derived cells such as MSCs.


Subject(s)
Chondrocytes/immunology , Interleukins/immunology , Mesenchymal Stem Cells/immunology , T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cartilage, Articular/immunology , Cell Communication/immunology , Cell Proliferation , Cells, Cultured , Humans , Immune Tolerance , Lymphocyte Activation/immunology , T-Lymphocytes/physiology
3.
Br J Cancer ; 96(7): 1072-82, 2007 Apr 10.
Article in English | MEDLINE | ID: mdl-17342088

ABSTRACT

Cancer cells' growth in three-dimensional (3D) architectures promotes resistance to drugs, cytokines, or irradiation. We investigated effects of 3D culture as compared to monolayers (2D) on melanoma cells' recognition by tumour-associated antigen (TAA)-specific HLA-A(*)0201-restricted cytotoxic T-lymphocytes (CTL). Culture of HBL, D10 (both HLA-A(*)0201+, TAA+) and NA8 (HLA-A(*)0201+, TAA-) melanoma cells on polyHEMA-coated plates, resulted in generation of 3D multicellular tumour spheroids (MCTS). Interferon-gamma (IFN-gamma) production by HLA-A(*)0201-restricted Melan-A/MART-1(27-35) or gp 100(280-288)-specific CTL clones served as immunorecognition marker. Co-culture with melanoma MCTS, resulted in defective TAA recognition by CTL as compared to 2D as witnessed by decreased IFN-gamma production and decreased Fas Ligand, perforin and granzyme B gene expression. A multiplicity of mechanisms were potentially involved. First, MCTS per se limit CTL capacity of recognising HLA class I restricted antigens by reducing exposed cell surfaces. Second, expression of melanoma differentiation antigens is downregulated in MCTS. Third, expression of HLA class I molecules can be downregulated in melanoma MCTS, possibly due to decreased interferon-regulating factor-1 gene expression. Fourth, lactic acid production is increased in MCTS, as compared to 2D. These data suggest that melanoma cells growing in 3D, even in the absence of immune selection, feature characteristics capable of dramatically inhibiting TAA recognition by specific CTL.


Subject(s)
Antigens, Neoplasm/immunology , Melanoma/immunology , Spheroids, Cellular/immunology , T-Lymphocytes, Cytotoxic/immunology , Cell Culture Techniques , Fas Ligand Protein/genetics , Fas Ligand Protein/metabolism , Granzymes/genetics , Granzymes/metabolism , HLA-A1 Antigen/immunology , HLA-A2 Antigen/immunology , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Humans , MART-1 Antigen , Melanoma/secondary , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Neoplasm Proteins/immunology , Perforin , Pore Forming Cytotoxic Proteins/genetics , Pore Forming Cytotoxic Proteins/metabolism , Spheroids, Cellular/metabolism , Spheroids, Cellular/pathology , T-Lymphocytes, Cytotoxic/metabolism , Tumor Cells, Cultured
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