In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p,1026) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177). Evidence for influence of rs6136 on transcription factor binding was also found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA.

Darbo tikslas. Įvertinti kineziologinio teipavimo poveikį pacientų, sergančių reumatoidiniu artritu, rankos funkcijai. Darbo uždaviniai: 1. Nustatyti pacientų rankos funkcijos pokyčius taikant kineziologinį teipavimą kartu su kineziterapija. 2. Nustatyti pacientų rankos funkcijos pokyčius taikant kineziterapiją. 3. Palyginti pacientų rankos funkcijos pokyčius abiejose grupėse. Tyrimo metodai. Goniometrija plaštakos judesių amplitudei vertinti (buvo vertinamas plaštakos lenkimas, tiesimas, stipininis ir alkūninis nukrypimas), dinamometrija plaštakos raumenų griebimo jėgai vertinti, modifikuotas Keitel indeksas rankos funkcinei būklei vertinti, Artrito poveikio vertinimo skalė rankos funkcijai vertinti. Tyrimo dalyviai. Tyrime dalyvavo 22 LSMUL Všį Kauno Klinikų Konsultacinės Poliklinikos, Kauno Dainavos poliklinikos ir Kauno Kalniečių poliklinikos pacientai, sergantys RA. Visos tiriamosios - moterys. Tiriamųjų amžiaus vidurkis - 61,18±1,34m. Vidutinė ligos trukmė – 5,73±0,45m. Visos tiriamosios atsitiktinai buvo suskirstytos į dvi grupes: 1. Tiriamojoje grupėje buvo 10 moterų, kurioms buvo taikomas kineziologinis teipavimas ir kineziterapija. 2. Kontrolinę grupę sudarė 12 moterų. Kontrolinei grupei buvo taikoma tik kineziterapija. Kineziterapijos programa truko 2 mėnesius (t.y. 9 savaites), procedūros atliekamos 3 kartus per savaitę. Ištyrimas buvo atliekamas prieš tyrimą ir tyrimo pabaigoje. Išvados: 1. Taikant kineziologinį teipavimą ir kineziterapiją po tyrimo buvo... [toliau žr. visą tekstą] / The aim of the research. To evaluate the effect of Kinesiology Taping on hand function in patients with Rheumatoid Arthritis. The goals of the research. 1. To estimate the changes of hand function applying Kinesiology Taping and physical therapy. 2. To estimate the changes of hand function applying only physical therapy. 3. To compare the changes of hand function applying Kinesiology Taping and physical therapy, and physical therapy alone. The methods of the research. Wristʼs range of motion was measured by goniometry method, the handgrip strength was assessed using dynamometer. Modyfied Keitel function test and Arthritis Impact Measurement Scale was used to evaluate hand function. The participants of the research. The study involved 22 subjects (100 pct. women) who had Rheumatoid arthritis. Mean age - 61,18±1,34 years. Subjects were randomly divided into two groups: the research group consisted of 10 individuals, Kinesiology Taping was applied to them together with physical therapy, and the control group consisted of 15 individuals, only physical therapy procedures was applied to them. The physical therapy program lasted for 2 months (9 weeks), the procedures was performed three times a week. The evaluation was performed twice: before and after procedures. Conclusions: 1. After the physical therapy program the wristʼs range of motion, handgrip strength and hand function significantly increased when applying Kinesiology Taping and physical therapy (p<0.05). 2. After the... [to full text]

Aim: The overall aim of this thesis was to explore and describe patients’ and healthcare providers’ experiences of the causes, management and interaction in the care of rheumatoid arthritis (RA). Method: The thesis is based on four studies. Studies I and II contain data from an epidemiologic project involving patients who were recently diagnosed with RA. The patients answered an open-ended question about their conception of the cause of their RA (Study I). Qualitative data from 38 patients were analysed using the phenomenographic approach in order to identify variation in conceptions. The results of Study I formed the basis for categorizing the conceptions of 785 patients in the search for patterns of background factors (Study II). Study III aimed to explore how patients experienced their management of RA in everyday life. Data were collected by interviews with 16 patients and analysed according to Grounded Theory (GT). In study IV, the aim was to explore healthcare providers’ experiences of their interaction with patients’ management of RA. Data were collected by interviews with 18 providers representing different professions and analysed using GT. Findings:  Patients’ conceptions of the cause of their RA revealed new aspects from the patient perspective that can complement pathogenetic models. Two descriptive categories emerged: consequences beyond personal control and overloaded circumstances, which included six categories of conceptions (Study I). The most common conceptions of the cause of RA were unexpected effects of events followed by work and family-related stress (Study II). Background factors that influenced the conceptions of the cause were age, sex and educational level. Patient management of RA involved using personal resources together with grasping for support from others in their striving for a good life. When linking these aspects together, four ways of management emerged: mastering, struggling, relying and being resigned (Study III). Healthcare providers’ experiences of their interaction with patients’ management shed light upon the important issue of delivering knowledge and advice. The providers’ attitudes constituted one cornerstone and patients’ responses the other. The providers reported that the interaction led to different outcomes: completed delivery, adjusted delivery and failed delivery. Conclusions: The findings contribute new knowledge from both patients’ and healthcare providers’ perspectives, which could be used to develop a more person-centred approach in rheumatology care. Person-centred care involves taking patients’ beliefs and values into account in addition to creating a trusting relationship between patient and provider. A successful person-centred approach requires an organisation that supports the person-centred framework.

Human autoimmune diseases are hallmarked by inappropriate loss-of-tolerance and self-attacking response of the immune system. Studies included in this thesis are focusing on the implication and functional impact of genetic factors in three autoimmune diseases rheumatoid arthritis (RA), asthma, and systemic lupus erythematosus (SLE). Using genetic association studies, we found in study I and II that sequence variants of the interferon regulatory factor 5 (IRF5) gene were associated with RA and asthma, and the associations were more pronounced in certain disease subtypes. Distinct association patterns or risk alleles of the IRF5 gene variants were revealed in different diseases, indicating that IRF5 contributes to disease manifestations in a dose-dependent manner. In study III, we found that seven out of eight genetic risk loci for SLE, which were originally identified in East Asian populations, also conferred disease risk with the same risk alleles and comparable magnitudes of effect sizes in Caucasians. Remarkable differences in risk allele frequencies were observed for all associated loci across ethnicities, which seems to be the major source of genetic heterogeneity for SLE. In study IV we explored an exhaustive spectrum of sequence variants in the genes inhibitor of kappa light polypeptide gene enhancer in B-cells kinase epsilon (IKBKE) and interferon induced with helicase C domain 1 (IFIH1) by gene resequencing, and identified nine variants in IKBKE and three variants in IFIH1 as genetic risk factors for SLE. One of the associated variants may influence splicing of IKBKE mRNA. In study V we provided genome-wide transcriptional regulatory profiles for IRF5 and signal transducer and activator of transcription 4 (STAT4) using chromatin immunoprecipitation-sequencing (ChIP-seq). The target genes of IRF5 and STAT4 were found to play active roles in pathways related with inflammatory response, and their expression patterns were characteristic for SLE patients. We also identified potential cooperative transcription factors for IRF5 and STAT4, and disease-associated sequence variants which may affect the regulatory function of IRF5 and STAT4. In conclusion, this thesis illuminates the contribution of several genetic risk factors to susceptibility of human autoimmune diseases, which facilitates our understanding of the genetic basis of their pathogenesis.

Bibliography: leaves 172-185. / xii, 185 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the induction of heat shock protein (HSP) by some of the anti-inflammatory agents and antirheumatic agents used in the management of rheumatoid arthritis. Presents HSP induction in peripheral white blood cells cultured in vitro. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1995?

Copy of author's previously published article. / Bibliography: leaves 189-219. / ix, 219, [69] leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Explores pathways by which therapeutic agents may affect the inflammatory reaction in rheumatoid arthritis and confirms and expands observation on anti-rheumatic agents that are capable of regulating the activity as well as the expression and production of a variety of inflammatory mediators related to tissue destruction in the inflamed joint. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1997

Rheumatoid arthritis is a chronic inflammatory autoimmune disease. Measurement of the level of serum markers (sRAGE, S100A9, S100A8 and S100A12) and genetic testing for the presence of the PTPN22 genetic polymorphism could help elucidate the underlying cause of inflammation and complications in RA, such as atherosclerosis. Therefore, serum levels of sRAGE, S100A9, S100A8 and S100A12 were measured by ELISA in patients with established RA (n=138). The associations between the serum levels of these molecules; and inflammatory markers and RA complications were analysed by multiple linear regression modelling. Established RA patients (n=192) were investigated for the PTPN22 C1858T genetic polymorphism by PCR-RFLP. Multiple logistic regression modelling was used to examine the association between PTPN22 C1858T genetic polymorphism and inflammatory markers and RA complications. In RA patients, we found that serum levels of S100A9 were associated with the body mass index (BMI); and the presence of S100A8 and S100A12. The serum levels of S100A8 in RA patients were associated with the presence of anti-citrullinated peptide antibodies, rheumatoid factor and S100A9. The serum levels of S100A12 in RA patients were associated with the presence of anti-citrullinated peptide antibodies and S100A9; and a history of diabetes. Inflammatory markers and RA complications were not associated with the PTPN22 genetic polymorphism in established RA patients; serum level of triglyceride was the only variable associated with PTPN22 C1858T in multiple logistic regression analysis. Taken together, these data suggest that serum levels of sRAGE, S100A9 and S100A12 protein may be useful correlates of inflammation and autoantibody production in RA patients. Further studies are recommended to determine whether these markers predict clinical outcomes when measured at the onset of RA.

Tez (Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı, 2001. / Bibliyografya var.

Thesis (Ph. D.)--University of Adelaide, Dept. of Pathology, 1986. / Includes bibliographical references (leaves 211-260).

Thesis (Ph.D.)--McMaster University (Canada), 1994. / Source: Dissertation Abstracts International, Volume: 56-01, Section: B, page: 0252. Adviser: C. J. L. Lock.