260 research outputs found

    The prevalence of axial spondyloarthritis in the UK: a cross-sectional cohort study

    Get PDF
    Background: Accurate prevalence data are important when interpreting diagnostic tests and planning for the health needs of a population, yet no such data exist for axial spondyloarthritis (axSpA) in the UK. In this cross-sectional cohort study we aimed to estimate the prevalence of axSpA in a UK primary care population. Methods: A validated self-completed questionnaire was used to screen primary care patients with low back pain for inflammatory back pain (IBP). Patients with a verifiable pre-existing diagnosis of axSpA were included as positive cases. All other patients meeting the Assessment of SpondyloArthritis international Society (ASAS) IBP criteria were invited to undergo further assessment including MRI scanning, allowing classification according to the European Spondyloarthropathy Study Group (ESSG) and ASAS axSpA criteria, and the modified New York (mNY) criteria for ankylosing spondylitis (AS). Results: Of 978 questionnaires sent to potential participants 505 were returned (response rate 51.6 %). Six subjects had a prior diagnosis of axSpA, 4 of whom met mNY criteria. Thirty eight of 75 subjects meeting ASAS IBP criteria attended review (mean age 53.5 years, 37 % male). The number of subjects satisfying classification criteria was 23 for ESSG, 3 for ASAS (2 clinical, 1 radiological) and 1 for mNY criteria. This equates to a prevalence of 5.3 % (95 % CI 4.0, 6.8) using ESSG, 1.3 % (95 % CI 0.8, 2.3) using ASAS, 0.66 % (95 % CI 0.28, 1.3) using mNY criteria in chronic back pain patients, and 1.2 % (95 % CI 0.9, 1.4) using ESSG, 0.3 % (95 % CI 0.13, 0.48) using ASAS, 0.15 % (95 % CI 0.02, 0.27) using mNY criteria in the general adult primary care population. Conclusions: These are the first prevalence estimates for axSpA in the UK, and will be of importance in planning for the future healthcare needs of this population. Trial registration: Current Controlled Trials ISRCTN7687321

    Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

    Get PDF
    Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

    Expression of pathogenesis related genes in response to salicylic acid, methyl jasmonate and 1-aminocyclopropane-1-carboxylic acid in Malus hupehensis (Pamp.) Rehd

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Many studies have been done to find out the molecular mechanism of systemic acquired resistance (SAR) in plants in the past several decades. Numbers of researches have been carried out in the model plants such as arabidopsis, tobacco, rice and so on, however, with little work done in woody plants especially in fruit trees such as apple. Components of the pathway of SAR seem to be extremely conserved in the variety of species. <it>Malus hupehensis</it>, which is origin in China, is strong resistance with rootstock. In the study, we attempted to make the expression pattern of pathogenesis related (PR) genes which were downstream components of the SAR pathway in response to salicylic acid(SA), methyl jasmonate(MeJA) and 1-aminocyclopropane-1-carboxylic acid(ACC) in <it>Malus hupehensis</it>.</p> <p>Findings</p> <p>In order to analyze the expression pattern, the partial sequence of three PR genes from <it>Malus hupehensis</it>, <it>MhPR1</it>, <it>MhPR5 </it>and <it>MhPR8 </it>was isolated. These three PR genes were induced by SA, MeJA and ACC. However, <it>MhPR1</it>, <it>MhPR5 </it>and <it>MhPR8 </it>performed a distinct pattern of expression in different plant organs. <it>MhPR5 </it>and <it>MhPR8 </it>were basal expression in leaves, stems and roots, and <it>MhPR1 </it>was basal expression only in stems. The expression of <it>MhPR1</it>, <it>MhPR5 </it>and <it>MhPR8 </it>was enhanced during the first 48 h post-induced with SA, MeJA and ACC.</p> <p>Conclusions</p> <p>The results showed that a distinct pattern of expression of PR genes in <it>Malus hupehensis </it>which differed from the previous reports on model plants arabidopsis, tobacco and rice. <it>MhPR1</it>, <it>MhPR5 </it>and <it>MhPR8 </it>were induced by SA, MeJA and ACC, which were regarded as the marker genes in the SAR response in <it>Malus hupehensis</it>. In contrast with herbal plants, there could be specific signal pathway in response to SA, JA and ET for woody plants.</p

    Contextual adaptation of the Personnel Evaluation Standards for assessing faculty evaluation systems in developing countries: the case of Iran

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Faculty evaluations can identify needs to be addressed in effective development programs. Generic evaluation models exist, but these require adaptation to a particular context of interest. We report on one approach to such adaptation in the context of medical education in Iran, which is integrated into the delivery and management of healthcare services nationwide.</p> <p>Methods</p> <p>Using a triangulation design, interviews with senior faculty leaders were conducted to identify relevant areas for faculty evaluation. We then adapted the published checklist of the Personnel Evaluation Standards to fit the Iranian medical universities' context by considering faculty members' diverse roles. Then the adapted instrument was administered to faculty at twelve medical schools in Iran.</p> <p>Results</p> <p>The interviews revealed poor linkages between existing forms of development and evaluation, imbalance between the faculty work components and evaluated areas, inappropriate feedback and use of information in decision making. The principles of Personnel Evaluation Standards addressed almost all of these concerns and were used to assess the existing faculty evaluation system and also adapted to evaluate the core faculty roles. The survey response rate was 74%. Responses showed that the four principles in all faculty members' roles were met <it>occasionally </it>to <it>frequently</it>. Evaluation of teaching and research had the highest mean scores, while clinical and healthcare services, institutional administration, and self-development had the lowest mean scores. There were statistically significant differences between small medium and large medical schools (p < 0.000).</p> <p>Conclusion</p> <p>The adapted Personnel Evaluation Standards appears to be valid and applicable for monitoring and continuous improvement of a faculty evaluation system in the context of medical universities in Iran. The approach developed here provides a more balanced assessment of multiple faculty roles, including educational, clinical and healthcare services. In order to address identified deficiencies, the evaluation system should recognize, document, and uniformly reward those activities that are vital to the academic mission. Inclusion of personal developmental concerns in the evaluation discussion is essential for evaluation systems.</p

    EGFR and HER2 expression in primary cervical cancers and corresponding lymph node metastases: Implications for targeted radiotherapy

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Proteins overexpressed on the surface of tumor cells can be selectively targeted. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are among the most often targeted proteins. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target for imaging in nuclear medicine and for various forms of therapy. So far, the expression of EGFR and HER2 has only been determined in primary cervical cancers, and we have not found published data regarding the receptor status in corresponding metastatic lesions. The goal of this study was to evaluate whether any of these receptors are suitable as target for clinical diagnosis and therapy.</p> <p>Methods</p> <p>Expression of EGFR and HER2 was investigated immunohistochemically in both lymph node metastases and corresponding primary cervical cancers (n = 53). HER2 and EGFR expression was scored using HercepTest criteria (0, 1+, 2+ or 3+).</p> <p>Results</p> <p>EGFR overexpression (2+ or 3+) was found in 64% (35/53) of the primary cervical tumors and 60% (32/53) of the corresponding lymph node metastases. There was a good concordance between the primary tumors and the paired metastases regarding EGFR expression. Only four patients who had 2+ or 3+ in the primary tumors changed to 0 or 1+ in lymph node metastases, and another two cases changed the other way around. None of the primary tumors or the lymph node metastases expressed HER2 protein.</p> <p>Conclusion</p> <p>The EGFR expression seems to be common and stable during cervical cancer metastasis, which is encouraging for testing of EGFR targeted radiotherapy. HER2 appears to be of poor interest as a potential target in the treatment of cervical cancer.</p

    A comparative study between mixed-type tumours from human salivary and canine mammary glands

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours.</p> <p>Methods</p> <p>Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin.</p> <p>Results</p> <p>After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions.</p> <p>Conclusion</p> <p>There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations.</p

    Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).</p> <p>Methods</p> <p>Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.</p> <p>Results</p> <p>We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.</p> <p>Conclusions</p> <p>Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.</p

    Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Low serum paraoxonase (PON) activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE). Our prior studies have shown that the <it>PON1</it>/rs662 (p.Gln192Arg), <it>PON1</it>/rs854560 (p.Leu55Met), <it>PON3</it>/rs17884563 and <it>PON3</it>/rs740264 SNPs (single nucleotide polymorphisms) significantly affect serum PON activity. Since <it>PON1, PON2 </it>and <it>PON3 </it>share high degree of structural and functional properties, in this study, we examined the role of <it>PON2 </it>genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample.</p> <p>Methods</p> <p><it>PON2 </it>SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen <it>PON2 </it>SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP) or TaqMan allelic discrimination methods.</p> <p>Results</p> <p>Our pair-wise linkage disequilibrium (LD) analysis, using an <it>r</it><sup><it>2 </it></sup>cutoff of 0.7, identified 14 <it>PON2 </it>tagSNPs that captured all 19 <it>PON2 </it>variants in our sample, 12 of which were not in high LD with known <it>PON1 </it>and <it>PON3 </it>SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five <it>PON2 </it>SNPs [rs6954345 (p.Ser311Cys), rs13306702, rs987539, rs11982486, and rs4729189; <it>P </it>= 0.005 to 2.1 × 10<sup>-6</sup>] that were significantly associated with PON activity. We found no association of <it>PON2 </it>SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183) and immunologic disorder (rs11981433) in SLE patients (<it>P </it>= 0.013 to 0.042).</p> <p>Conclusions</p> <p>Our data indicate that <it>PON2 </it>genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.</p

    Longer First Introns Are a General Property of Eukaryotic Gene Structure

    Get PDF
    While many properties of eukaryotic gene structure are well characterized, differences in the form and function of introns that occur at different positions within a transcript are less well understood. In particular, the dynamics of intron length variation with respect to intron position has received relatively little attention. This study analyzes all available data on intron lengths in GenBank and finds a significant trend of increased length in first introns throughout a wide range of species. This trend was found to be even stronger when using high-confidence gene annotation data for three model organisms (Arabidopsis thaliana, Caenorhabditis elegans, and Drosophila melanogaster) which show that the first intron in the 5′ UTR is - on average - significantly longer than all downstream introns within a gene. A partial explanation for increased first intron length in A. thaliana is suggested by the increased frequency of certain motifs that are present in first introns. The phenomenon of longer first introns can potentially be used to improve gene prediction software and also to detect errors in existing gene annotations
    corecore