10 results on '"Maciewicz, Rose A."'
Search Results
2. MEK inhibition drives anti-viral defence in RV but not RSV challenged human airway epithelial cells through AKT/p70S6K/4E-BP1 signalling
- Author
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Baturcam, Engin, Vollmer, Stefan, Schlüter, Holger, Maciewicz, Rose A., Kurian, Nisha, Vaarala, Outi, Ludwig, Stephan, and Cunoosamy, Danen Mootoosamy
- Published
- 2019
- Full Text
- View/download PDF
3. Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGF?1) gene in knee and hip osteoarthritis
- Author
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Muthuri, Stella G., Doherty, Sally, Zhang, Weiya, Maciewicz, Rose A., Muir, Kenneth R., and Doherty, Michael
- Abstract
Introduction: The objective was to investigate potential gene-environment interaction between body mass index (BMI) and each of eight TGF?1 polymorphisms in knee and hip osteoarthritis (OA).Methods: We conducted a case-control study of Caucasian men and women aged 45 to 86 years from Nottingham, United Kingdom (Genetics of OA and Lifestyle (GOAL) study). Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee/hip OA. We used logistic regression to investigate the association of TGF?1 polymorphisms and OA when stratifying by BMI. Knee and hip OA were analyzed separately with adjustment for potential confounders. Additive and multiplicative interactions were examined.Results: 2,048 cases (1,042 knee OA, 1,006 hip OA) and 967 controls were studied. For hip OA, the highest risk was in overweight (BMI ?25 kg/m2) individuals with the variant allele of single-nucleotide polymorphism (SNP)rs1800468 (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.55, 3.15). Evaluation of gene-environment interaction indicated significant synergetic interaction (relative excess risk due to interaction (RERI) = 0.93, synergy index (SI) = 4.33) with an attributable proportion due to interaction (AP) of 42% (AP = 0.42; 95% CI 0.16, 0.68). Multiplicative interaction was also significant (OR for interaction (ORINT) = 2.27, P = 0.015). For knee OA, the highest risk was in overweight individuals with homozygous genotype 11 of SNP rs2278422 (OR = 6.95, P < 0.001). In contrast, the variant allele indicated slightly lower risks (OR = 4.72, P < 0.001), a significant antagonistic interaction (RERI = -2.66, SI = 0.59), AP = -0.56 (95%CI -0.94, -0.17) and a significant multiplicative interaction (ORINT = 0.47, P = 0.013).Conclusion: TGF?1 gene polymorphisms interact with being overweight to influence the risk of large joint OA.
- Published
- 2013
4. Beer and wine consumption and risk of knee or hip osteoarthritis: a case control study.
- Author
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Muthuri, Stella G., Weiya Zhang, Maciewicz, Rose A., Muir, Kenneth, and Doherty, Michael
- Published
- 2015
- Full Text
- View/download PDF
5. The association between ANKH promoter polymorphism and chondrocalcinosis is independent of age and osteoarthritis: results of a case-control study.
- Author
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Abhishek, Abhishek, Doherty, Sally, Maciewicz, Rose, Muir, Kenneth, Zhang, Weiya, Doherty, Michael, and Valdes, Anna M.
- Published
- 2014
- Full Text
- View/download PDF
6. Chondrocalcinosis is common in the absence of knee involvement.
- Author
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Abhishek, Abhishek, Doherty, Sally, Maciewicz, Rose, Muir, Kenneth, Weiya Zhang, and Doherty, Michael
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- 2012
- Full Text
- View/download PDF
7. Self-reported adult footwear and the risks of lower limb osteoarthritis: the GOAL case control study.
- Author
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McWilliams, Daniel F, Muthuri, Stella, Muir, Kenneth R, Maciewicz, Rose A, Zhang, Weiya, and Doherty, Michael
- Abstract
Background: Biomechanical factors may play a role in osteoarthritis (OA) development and progression. Previous biomechanical studies have indicated that types of footwear may modulate forces across the knee joint, and high heeled womens' shoes in particular are hypothesised to be detrimental to lower limb joint health. This analysis of data from a case control study investigated persistent users of different adult footwear for risks of knee and hip OA. Our underlying hypotheses were that high heeled, narrow heeled, and hard soled shoe types were putative risk factors for lower limb OA.Methods: Data on footwear were initially obtained from participants during the Genetics of Osteoarthritis and Lifestyle (GOAL) hospital-based, case control study using standardised interview-delivered questionnaires. An additional questionnaire was later sent to GOAL study participants to verify findings and to further investigate specific shoe use per decade of life. Persistent users of footwear types (high or narrow heel; sole thickness or hardness) were identified from early adulthood. Participants were grouped into single sex knee OA, hip OA or control groups. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were calculated.Results: Univariate analysis of persistent users of women's high heeled and narrow heeled shoes during early adulthood showed negative associations with knee OA and hip OA. After logistic regression, persistent narrow heel users were associated with less risk of OA (knee OA aOR 0.59, 95% CI 0.35 - 1.00 and hip aOR: 0.50, 95% CI 0.30 - 0.85), and other analyses were not statistically significant. Further analysis suggested that women with hip OA may have stopped wearing high and narrow heeled footwear to attenuate hip pain in early adulthood. Consistent associations between shoe soles and OA were not found.Conclusions: In general, persistent users of high and narrow heeled shoes during early adulthood had a negative association with knee or hip OA. This does not necessarily imply a causal relationship, as changing footwear during early adulthood to modulate index joint pain may provide a possible explanation. Despite the findings of previous biomechanical studies of high heels, we did not find a positive association between women's shoes and lower limb osteoarthritis. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
8. Evidence of changes to skeletal muscle contractile properties during the initiation of disease in the ageing guinea pig model of osteoarthritis.
- Author
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Tonge DP, Bardsley RG, Parr T, Maciewicz RA, and Jones SW
- Abstract
Background: Osteoarthritis (OA) is the most common joint disorder in the world and represents the leading cause of pain and disability in the elderly population. Advancing age remains the single greatest risk factor for OA. Several studies have characterised disease development in the guinea pig ageing model of OA in terms of its joint histopathology and inflammatory cytokine profile. However, the quadriceps muscle has yet to be studied in relation to age-related disease onset or early disease progression. Therefore, we examined whether the initiation of OA in the Dunkin Hartley guinea pig is associated with changes in the quadriceps skeletal muscle. Male Dunkin Hartley guinea pigs (N = 24) were group housed with free access to standard guinea pig chow and water. At 2, 3, 5 and 7 months of age, six animals were selected based on their proximity to the median weight of the cohort. OA severity was graded at each time point by the assessment of toluidine blue stained step coronal sections of the total knee joint. Serum CTX II was measured as a potential biomarker of OA severity. Myosin Heavy Chain (MHC) isoforms were determined by a validated real-time PCR assay. Oxidative and glycolytic potential was determined in quadriceps homogenates via the measurement of ICDH and LDH activity., Results: Initiation of OA in the DH strain guinea pig occurred between 2 and 3 months of age and progressed until 7 months when the final analyses were conducted. Serum CTX II significantly decreased during this early period of OA initiation and levels were unrelated to the histopathological severity of knee OA at any of the time points assessed. MHC mRNA measurements revealed a significant elevation in MHC IIX mRNA (associated with fast-twitch skeletal muscle fibres) coincident with the initiation of OA at 3 months of age, with preliminary findings suggestive of a positive correlation to OA severity at this time point., Conclusions: These preliminary findings suggest that disease initiation in the ageing guinea pig model of OA is not associated with overt quadriceps muscle atrophy but instead is coincident with altered expression of mRNAs associated with quadriceps skeletal muscle contractile properties (specifically fast-twitch MHC IIX).
- Published
- 2013
- Full Text
- View/download PDF
9. Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis.
- Author
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Muthuri SG, Doherty S, Zhang W, Maciewicz RA, Muir KR, and Doherty M
- Subjects
- Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Predisposition to Disease genetics, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Body Mass Index, Gene-Environment Interaction, Osteoarthritis, Hip genetics, Osteoarthritis, Knee genetics, Transforming Growth Factor beta1 genetics
- Abstract
Introduction: The objective was to investigate potential gene-environment interaction between body mass index (BMI) and each of eight TGFβ1 polymorphisms in knee and hip osteoarthritis (OA)., Methods: We conducted a case-control study of Caucasian men and women aged 45 to 86 years from Nottingham, United Kingdom (Genetics of OA and Lifestyle (GOAL) study). Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee/hip OA. We used logistic regression to investigate the association of TGFβ1 polymorphisms and OA when stratifying by BMI. Knee and hip OA were analyzed separately with adjustment for potential confounders. Additive and multiplicative interactions were examined., Results: 2,048 cases (1,042 knee OA, 1,006 hip OA) and 967 controls were studied. For hip OA, the highest risk was in overweight (BMI ≥ 25 kg/m2) individuals with the variant allele of single-nucleotide polymorphism (SNP) rs1800468 (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.55, 3.15). Evaluation of gene-environment interaction indicated significant synergetic interaction (relative excess risk due to interaction (RERI) = 0.93, synergy index (SI) = 4.33) with an attributable proportion due to interaction (AP) of 42% (AP = 0.42; 95% CI 0.16, 0.68). Multiplicative interaction was also significant (OR for interaction (ORINT) = 2.27, P = 0.015). For knee OA, the highest risk was in overweight individuals with homozygous genotype 11 of SNP rs2278422 (OR = 6.95, P <0.001). In contrast, the variant allele indicated slightly lower risks (OR = 4.72, P <0.001), a significant antagonistic interaction (RERI = -2.66, SI = 0.59), AP = -0.56 (95%CI -0.94, -0.17) and a significant multiplicative interaction (ORINT = 0.47, P = 0.013)., Conclusion: TGFβ1 gene polymorphisms interact with being overweight to influence the risk of large joint OA.
- Published
- 2013
- Full Text
- View/download PDF
10. Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized.
- Author
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Hunter DJ, Gerstenfeld L, Bishop G, Davis AD, Mason ZD, Einhorn TA, Maciewicz RA, Newham P, Foster M, Jackson S, and Morgan EF
- Subjects
- Aged, Aged, 80 and over, Bone Density, Female, Humans, Middle Aged, Postmenopause, Sclerosis, Bone Marrow Diseases pathology, Bone and Bones pathology, Calcification, Physiologic, Osteoarthritis, Knee pathology
- Abstract
Introduction: Although the presence of bone marrow lesions (BMLs) on magnetic resonance images is strongly associated with osteoarthritis progression and pain, the underlying pathology is not well established. The aim of the present study was to evaluate the architecture of subchondral bone in regions with and without BMLs from the same individual using bone histomorphometry., Methods: Postmenopausal female subjects (n = 6, age 48 to 90 years) with predominantly medial compartment osteoarthritis and on a waiting list for total knee replacement were recruited. To identify the location of the BMLs, subjects had a magnetic resonance imaging scan performed on their study knee prior to total knee replacement using a GE 1.5 T scanner with a dedicated extremity coil. An axial map of the tibial plateau was made, delineating the precise location of the BML. After surgical removal of the tibial plateau, the BML was localized using the axial map from the magnetic resonance image and the lesion excised along with a comparably sized bone specimen adjacent to the BML and from the contralateral compartment without a BML. Cores were imaged via microcomputed tomography, and the bone volume fraction and tissue mineral density were calculated for each core. In addition, the thickness of the subchondral plate was measured, and the following quantitative metrics of trabecular structure were calculated for the subchondral trabecular bone in each core: trabecular number, thickness, and spacing, structure model index, connectivity density, and degree of anisotropy. We computed the mean and standard deviation for each parameter, and the unaffected bone from the medial tibial plateau and the bone from the lateral tibial plateau were compared with the affected BML region in the medial tibial plateau., Results: Cores from the lesion area displayed increased bone volume fraction but reduced tissue mineral density. The samples from the subchondral trabecular lesion area exhibited increased trabecular thickness and were also markedly more plate-like than the bone in the other three locations, as evidenced by the lower value of the structural model index. Other differences in structure that were noted were increased trabecular spacing and a trend towards decreased trabecular number in the cores from the medial location as compared with the contralateral location., Conclusions: Our preliminary data localize specific changes in bone mineralization, remodeling and defects within BMLs features that are adjacent to the subchondral plate. These BMLs appear to be sclerotic compared with unaffected regions from the same individual based on the increased bone volume fraction and increased trabecular thickness. The mineral density in these lesions, however, is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition.
- Published
- 2009
- Full Text
- View/download PDF
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