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ID PMID Title PublicationDate abstract
16930096 Health psychology: psychological adjustment to chronic disease. 2007 Chronic diseases carry important psychological and social consequences that demand significant psychological adjustment. The literature is providing increasingly nuanced conceptualizations of adjustment, demonstrating that the experience of chronic disease necessitates adaptation in multiple life domains. Heterogeneity in adjustment is apparent between individuals and across the course of the disease trajectory. Focusing on cancer, cardiovascular disease, and rheumatic diseases, we review longitudinal investigations of distal (socioeconomic variables, culture/ethnicity, and gender-related processes) and proximal (interpersonal relationships, personality attributes, cognitive appraisals, and coping processes) risk and protective factors for adjustment across time. We observe that the past decade has seen a surge in research that is longitudinal in design, involves adequately characterized samples of sufficient size, and includes statistical control for initial values on dependent variables. A progressively convincing characterization of risk and protective factors for favorable adjustment to chronic illness has emerged. We identify critical issues for future research.
18320526 Mycobacterium chelonae keratitis in a patient with Sjögren's syndrome. 2008 Mar PURPOSE: In this report a case of Mycobacterium chelonae keratitis in a patient without any previously described risk factors is described. The only risk factor found was a rheumatoid arthritis related Sjogren''s syndrome. METHODS: Case report. RESULTS: A 60-year-old woman was referred to the hospital with an infectious keratitis of the left eye of 3 months duration, unresponsive to empirical therapy with ofloxacin and tobramycin drops. Her medical history included a longstanding rheumatoid arthritis and a secondary ocular surface syndrome. Upon arrival the left eye showed diffuse corneal edema and centrally several large infiltrates with fluffy edges, surrounded by several smaller satellite infiltrates. The cornea was scraped for culture and grew M chelonae and sensitivity testing showed sensitivity to ciprofloxacin, clofazimine, and clarithromycin. Systemically, ciprofloxacin 750 mg and clarithromycin 500 mg twice daily were prescribed orally. Topical therapy consisted of topical erythromycin 10 mg/mL and ofloxacin 3 mg/mL every 2 hours. Treatment was continued for a total of 10 months during which the infiltrates cleared completely, but the central cornea remained scarred. CONCLUSIONS: M chelonae can be a cause of infectious keratitis in patients without known risk factors for rapidly growing mycobacterium keratitis. Especially in the case of ocular infections that show no response to regular antibacterial treatment, mycobacterial infection should be considered. Good communication between the ophthalmologist and the microbiologist is crucial for a rapid diagnosis.
17196718 Trigger wrist. 2007 Apr Trigger wrist is a relatively rare phenomenon. The pathological entities to which the term trigger wrist is applied are not well defined in the literature. We present three cases of trigger wrist as a result of flexor tendon pathology, review the literature and discuss the use of the term "trigger wrist".
18632808 Biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in patients with 2008 Aug Rheumatoid arthritis (RA) involves the accumulation of monocyte-derived macrophages in the affected synovial tissue. This process of cell migration could be portrayed scintigraphically to monitor noninvasively the effects of therapy on the progress of the disease. For this purpose, labeling of purified autologous monocytes with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) at very high specific radioactivity has recently been developed. The aim of this study was to assess the biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in adult patients with RA. METHODS: In 8 patients with RA, monocytes were isolated from 100 mL of blood and labeled with 99mTc-HMPAO to a yield of 10 Bq/cell. Multiple whole-body scans were performed up to 20 h after reinjection of an average of 200 MBq of 99mTc-HMPAO-labeled monocytes. Urine and blood samples were collected. The fraction of administered activity in 7 source organs was quantified from the attenuation-corrected geometric mean counts in conjugate views. Radiation-absorbed doses were estimated with OLINDA/EXM software. RESULTS: Autologous monocytes labeled with 99mTc-HMPAO at high intracellular yields showed in vivo kinetics comparable with labeled leukocytes, with initial trapping in the lungs followed by distribution into the liver, spleen, and bone marrow. The radiation-absorbed estimates for 99mTc-HMPAO-labeled monocytes were comparable with those for 99mTc-HMPAO-labeled mixed white blood cells, with an effective dose of 0.011 mSv/MBq. CONCLUSION: 99mTc-HMPAO-labeled monocytes have biodistribution and radiation dosimetry similar to those of 99mTc-HMPAO-labeled mixed white blood cells and might therefore be used for in vivo monitoring of immunomodulating therapy in patients with RA.
18512710 Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheu 2008 Jun 15 OBJECTIVE: To assess the effects of treatment with rituximab plus methotrexate on patient-reported outcomes in patients with active rheumatoid arthritis (RA) who experienced inadequate response to anti-tumor necrosis factor therapy. METHODS: Patients with active RA were randomly assigned to rituximab (1,000 mg on days 1 and 15) or placebo. The primary end point was the proportion of patients with an American College of Rheumatology 20% response at week 24. Additional goals were to assess treatment effects on pain, fatigue, functional disability, health-related quality of life, and disease activity by comparing mean changes between groups. The analysis was conducted in the intent-to-treat population. The proportion of patients who achieved the minimum clinically important difference on the Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Short Form 36 (SF-36) was determined. RESULTS: Rituximab patients had statistically significantly greater pain relief. The FACIT-F showed significantly greater improvement in rituximab patients than placebo patients from weeks 12 through 24. Mean improvement from baseline in functional disability (measured by the HAQ DI) was significantly greater in rituximab patients from weeks 8 to 24. The mean +/- SD change from baseline for the SF-36 Physical Component Score was 6.64 +/- 8.74 for rituximab patients and 1.48 +/- 7.32 for placebo patients (P < 0.0001). The mean change from baseline for the SF-36 Mental Component Score was 5.32 +/- 12.41 for rituximab patients and 2.25 +/- 12.23 for placebo patients (P = 0.0269). CONCLUSION: Rituximab produced rapid, clinically meaningful, and statistically significant improvements in patient-reported pain, fatigue, functional disability, health-related quality of life, and disease activity. These effects were sustained throughout the study.
17763441 Serious infection following anti-tumor necrosis factor alpha therapy in patients with rheu 2007 Sep OBJECTIVE: In a recent observational study, we found that the risk of serious infection following anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in patients with rheumatoid arthritis (RA) was not importantly increased compared with the background risk in routinely treated RA patients with similar disease severity. Observational data sets are, however, subject to a number of important biases related to selection factors for the timing of starting and stopping therapy. Infection risk is also likely to vary with duration of therapy. This study was undertaken to examine the influences of these biases and of the method of analysis on the risk of infection. METHODS: We compared the risk of serious infection in 8,659 patients treated with anti-TNFalpha with that in 2,170 patients treated with traditional disease-modifying antirheumatic drugs (DMARDs) recruited to the British Society for Rheumatology Biologics Register. We applied a number of statistical models in which we varied the length of the followup period by using different definitions of the date of discontinuation of treatment and different lag periods of risk following drug cessation. RESULTS: When the at-risk period was defined as "receiving treatment", the adjusted incidence rate ratio comparing patients receiving anti-TNFalpha therapy with patients receiving DMARD therapy was 1.22 (95% confidence interval [95% CI] 0.88-1.69). Limiting followup to the first 90 days, however, revealed an adjusted incidence rate ratio of 4.6 (95% CI 1.8-11.9). Rates of infection were increased in the 90 days immediately following drug discontinuation and beyond, explained by selection factors for drug discontinuation. CONCLUSION: These findings show that overall, the way in which UK rheumatologists select patients for starting and discontinuing anti-TNFalpha therapy explains our previous finding of no increase in risk. However, there may be important increases in true risk, notably early in the course of treatment, that would become more evident depending on the definition of at-risk period.
16635649 Clinical significance of lifetime mood and panic-agoraphobic spectrum symptoms on quality 2006 May BACKGROUND: Previous studies suggested that rheumatoid arthritis (RA) is associated with depressive and anxiety symptomatology. The well-being and functioning of patients with RA may be significantly influenced by subthreshold psychiatric comorbidity. Health-related quality of life (HRQoL) of patients with RA, compared with the Italian norms and patients with diabetes, was assessed by the influence of lifetime mood and panic-agoraphobic spectrum symptoms and demographic and clinical variables. METHODS: Ninety-two patients were consecutively recruited at the Department of Rheumatology at the University Hospital of Pisa, Italy. All patients met diagnostic criteria of RA according to the American College of Rheumatology. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short-Form Health Survey questionnaire (MOS SF-36). Mood and panic-agoraphobic spectra were assessed by two different structured self-report instruments: the Mood Spectrum (MOODS-SR) and the Panic-Agoraphobic Spectrum (PAS-SR), respectively. RESULTS: Patients with RA were compared, as regards the MOS SF-36 scale scores, with the Italian normative population and patients with diabetes. Compared with the Italian population, patients with RA showed significantly lower MOS SF-36 scale scores, except for role emotional. Moreover, patients with RA scored significantly lower on the role physical, bodily pain, and social functioning scales compared with patients with diabetes and higher on role emotional and mental health. A significant worsening of all MOS SF-36 scale scores was related to higher scores of the depressive domains of MOODS-SR, except for social functioning and bodily pain. A statistically significant negative association was also found between PAS-SR total score and the MOS SF-36 scales physical functioning, vitality, role emotional, and mental health. There were no statistically significant correlations between MOS SF-36 scales and the manic MOODS spectrum. In the multivariate models, the negative correlations between depressive MOODS, role emotional, and mental health were confirmed and the severity of arthritis showed a significant impact on all MOS SF-36 areas with the exception for social functioning; moreover, manic MOODS was associated with better general health. CONCLUSIONS: The present report shows that lifetime depressive spectrum symptoms negatively affects HRQoL of patients with RA and subthreshold mania improves the perception of general health. Diagnosis and appropriate clinical management of depression, including subthreshold symptoms, might enhance HRQoL in these patients.
17207389 Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern v 2006 Nov BACKGROUND: Greater intake of vitamin D has been associated with a lower risk of rheumatoid arthritis (RA) and low serum vitamin D together with higher prevalence of RA seem common among North European people when compared to Southern Europe. OBJECTIVES: To evaluate serum 25-hydroxyvitamin D [25(OH)D] levels in female RA patients from North (Estonia) and South (Italy) Europe and to correlate them with the disease activity score (DAS28) during winter and summer. METHODS: Fifty-four RA Italian patients (IP) and 64 RA Estonian patients (EP) were evaluated for serum 25(OH)D levels in winter and summer time, as well as for DAS28 score. Normal female controls (C) were 35 (IC) and 30 (EC) age-matched subjects, respectively. 25(OH)D concentrations were measured by a competitive radioimmunoassay. Statistical analysis was performed by "r" Pearson correlation, "t" Student with Bonferroni correction and by repeated ANOVA measures (summer and winter) with two factors (country and clinical status). RESULTS: 25(OH)D levels were found significantly higher in IP versus EP (p = 0.0116) both in winter and in summer time. Differences were observed also in controls. The variations (increase) of 25(OH)D levels between winter and summer were found significant (p = 0.0005) in both IP and EP. Differences were observed also in controls. No significant differences were found concerning 25(OH)D levels between RA patients and their controls in either country. Interestingly, a significant negative correlation between 25(OH)D and DAS28, was found in summer only in IP (r =-0.57, p < 0.0001) and in winter in EP (r =-0.40, p < 0.05). CONCLUSION: Significantly lower 25(OH)D serum levels were observed in RA patients from North versus South Europe with a circannual rhythm in winter and summer time. In addition, 25(OH)D values showed a significant correlation (negative) with RA clinical status (DAS28) in both North and South European RA patients, suggesting possible effects of vitamin D among other factors on disease activity.
17223880 Perforating folliculitis associated with tumour necrosis factor-alpha inhibitors administe 2007 Feb Perforating dermatoses are characterized by transepithelial elimination of dermal structures. We report a 61-year-old man with rheumatoid arthritis who developed a perforating folliculitis following the administration of two tumour necrosis factor (TNF)-alpha inhibitors, infliximab and etanercept. To our knowledge, no perforating disorders have been reported associated with these drugs. This report suggests, for the first time, a role for TNF-alpha in the pathogenesis of perforating folliculitis.
16829989 [Usefulness of anti-cyclic citrullinate peptide antibody determination in synovial fluid a 2006 Apr OBJECTIVE: To assess the role of anti-cyclic citrullinated peptide (CCP) antibody detection in synovial fluid (SF) of RA patients compared to OA patients. METHODS: We evaluated in 25 RA subjects and 14 OA patients, presenting a knee-joint effusion, the main clinical and laboratory parameters including the number of painful and/or swollen joints, Ritchie index, morning stiffness, ESR, CRP and analysis of SF obtained by therapeutic arthrocentesis. IgG anti-CCP (ELISA), rheumatoid factor (RF) and total IgG (nephelometry method) were measured in SF and paired serum samples. RESULTS: We found anti-CCP antibodies and RF in 64% (16/25) and 60% (15/25) of RA sera, respectively; 72% (18/25) of RA patients were positive for anti-CCP antibodies or RF. We found a higher SF/serum ratio for anti-CCP (p<0.004) compared to that for total IgG. The calculation of anti-CCP concentration as IgG anti-CCP (units)/total IgG (g L-1) revealed higher values in SF than in serum (p<0.046) in RA patients. Among these, correlation analysis showed that anti-CCP/total IgG values in SF correlated with the relative concentration of serum anti-CCP/total IgG (rs=0.842; p<0.00001) and serum anti-CCP antibody levels (rs=0.799; p<0.0001). We did not find any correlation between SF anti-CCP levels and the main characteristics of SF as well as the clinical or laboratory parameters. CONCLUSION: Our study give evidence for a preferential production of anti-CCP antibodies at RA joint level, confirming the pathogenetic role of these autoantibodies. Moreover, SF determination of anti-CCP, corrected for the total amount of the corresponding immunoglobulin, may be helpful as diagnostic tool in selected cases.
17875550 The MHC2TA -168A/G polymorphism and risk for rheumatoid arthritis: a meta-analysis of 6861 2008 Jul BACKGROUND: An association between major histocompatibility complex (MHC) genes, particularly those within the class II HLA region, and rheumatoid arthritis (RA) is well established, and accounts for an estimated 30% of the genetic component in RA. The MHC class II transactivator gene (MHC2TA) on chromosome 16p13 has recently emerged as the most important transcription factor regulating genes required for class II MHC-restricted antigen presentation. Previous studies of a promoter region polymorphism (-168A/G, rs3087456) in the MHC2TA gene and RA have yielded conflicting results. OBJECTIVE: To assess the association of the MHC2TA -168A/G polymorphism (rs3087456) and risk for RA by meta-analysis. METHODS: Meta-analysis was performed for 6861 patients with RA and 9270 controls from 10 case-control studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each study. Summary ORs and 95% CIs were calculated for random effects models. RESULTS: No effect was observed for the G risk allele (OR 1.02, 95% CI 0.93 to 1.12, p = 0.70) or the GG risk genotype (OR 1.14, 95% CI 0.95 to 1.36, p = 0.16). CONCLUSIONS: Our results indicate that the MHC2TA -168A/G polymorphism (rs3087456) is not associated with RA yet underscore the importance of including shared epitope allele carrier status, secondary phenotypes and more complete characterisation of MHC2TA variation in future studies.
17611977 Hypersensitivity pneumonitis associated with leflunomide therapy. 2007 Sep Disease progression in rheumatoid arthritis is controlled with disease modifying drugs, many of which have toxic side effects. Pulmonary side effects are common and this has resulted in the development of newer medications with less pulmonary toxicity. We observed that even these newer drugs can be associated with potentially very serious pulmonary toxicity, with hypersensitivity pneumonitis developing after the initiation of leflunomide therapy. We urge caution in the use of leflunomide in patients with pulmonary side effects from other drugs or who have underlying pulmonary disease.
16838043 Selective recruitment of CXCR3+ and CCR5+ CCR4+ T cells into synovial tissue in patients w 2006 Jun The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.
17720720 Co-activation of synovial fibroblasts by laminin-111 and transforming growth factor-beta i 2008 Apr We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-beta induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix proteases (TIMPs). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative reverse transcription-polymerase chain reaction. Production of MMPs was monitored by a multiplexed immunoarray. Signal transduction pathways were studied by immunoblotting. Attachment of synovial fibroblasts to LM-111 in the presence of transforming growth factor-beta induced significant increases in MMP-3 mRNA (12.35-fold, p < 0.001) and protein (mean 62 ng/ml, sixfold, p < 0.008) and in expression of MMP-10 mRNA (11.68-fold, p < 0.05) and protein (54 ng/ml, 20-fold, p > or = 0.02). All other TIMPs and MMPs investigated failed to show this LM-111-facilitated transforming growth factor-beta response. No phosphorylation of nuclear factor-kappaB was observed. We conclude that co-stimulation of synovial fibroblasts by LM-111 together with transforming growth factor-beta suffices to induce significant expression of MMP-3 and MMP-10 by synovial fibroblasts and that this induction is independent of nuclear factor-kappaB phosphorylation.
16583427 Extent of occupational hand use among persons with rheumatoid arthritis. 2006 Apr 15 OBJECTIVE: Occupational hand use is increasing due to increased computer use and could place persons with rheumatoid arthritis (RA) at risk for work disability. Although hand involvement in RA is typical, there is little information about occupational hand use in relation to RA. Study objectives were to describe the extent of occupational hand use by persons with RA; the types of jobs that require extensive hand use; the relationship between occupational hand use and joint pain; and the extent of occupational hand use among persons with shorter versus longer disease duration. METHODS: Cross-sectional survey data from 2,761 employed participants with RA from a US national cohort were used. Extent of occupational hand use was measured by the hand-use item from a job physical demand scale used in prior RA studies. Analyses included descriptive statistics and chi-square tests. RESULTS: The mean age was 50.6 years, 78.5% were women, 91.8% were white, and 68.8% had more than a high school education. Eighty-three percent of participants reported extensive occupational hand use. Large portions of participants in all types of jobs reported extensive hand use, 92% with administrative support jobs and 69% with operator/laborer jobs. Participants with extensive occupational hand use were more likely to have hand joint pain than those with moderate hand use (66% versus 58%; P = 0.004). Extensive hand use did not vary by disease duration (83% and 84% in participants with < or =15 and >15 years' duration, respectively). CONCLUSION: Extensive occupational hand use was ubiquitous among employed persons with RA and was associated with greater hand pain.
17153599 Cytotoxicity of taurine metabolites depends on the cell type. 2006 We report that the effect of Tau-Cl on the cell fate strongly depends on the cellular context. In leukemic Jurkat cells Tau-Cl (> 200 microM) triggers mitochondrial, p53-independent apoptosis and amplifies PCD induced by anti-Fas treatment. In contrast, Tau-Cl affects RA FLS in a dose-dependent manner. At the noncytotoxic (200-400 microM) concentrations it induces: (i) p53-dependent growth arrest (Kontny et al., 2005), and (ii) Bax translocation and caspase 9 activity. Although the last events are characteristic for apoptotic state, there is not execution of RA FLS apoptosis, probably due to simultaneous inhibition of caspase 3 activity and prevention of PARP degradation. The last two events suggest an excessive ATP deprivation in Tau-Cl-treated RA FLS. At sufficiently high concentrations (> or = 500 microM) Tau-Cl causes therefore necrosis of these cells. Altogether our results suggest that Tau-Cl is able to eliminate the cells with both functional (RA FLS) and mutated (Jurkat) p53 tumor suppressor. This observation is clinically relevant because Tau-Cl is used in many animal inflammatory models and its sodium salt (used in this study) has been introduced to human therapy (Gottardi and Nagl, 2002; Teuchner et al., 2005).
17195138 Histopathology of pulmonary fibrotic disorders. 2006 Dec Interstitial lung diseases encompass a broad spectrum of disorders that vary greatly in their clinical presentation, natural history, pathology, pathogenesis, prognosis, and treatment. Their correct classification requires integration of clinical, radiological, and pathological findings. Although these disorders may be well defined, interpretation of lung biopsy findings is often difficult, with surprisingly significant interobserver variability. This article reviews the histopathology of the major interstitial lung diseases, including the idiopathic interstitial pneumonias and pulmonary fibrotic disorders associated with collagen vascular diseases and smoking. In addition, the differential diagnosis of each of these disorders is discussed.
17127201 Infection and musculoskeletal conditions: Viral causes of arthritis. 2006 Dec Several viruses cause postinfectious arthritis. The disease is a typical manifestation of arthritogenic alphaviruses, rubella virus and human parvovirus B19. In addition, arthritis is not uncommon after infection by HIV, cytomegalovirus, hepatitis B virus, hepatitis C virus, or Epstein-Barr virus (EBV). Also prolonged arthritis may result from viral infections, particularly with alphaviruses and human parvovirus B19. Viruses such as EBV and B19 may have significant roles in initiating chronic arthropathies, which in some cases may be indistinguishable from rheumatoid arthritis.
17893997 Regulation of cytokine-induced HIF-1alpha expression in rheumatoid synovial fibroblasts. 2007 Jun The transcription factor hypoxia-inducible factor (HIF)-1 plays a central physiological role in oxygen and energy homeostasis, and is activated during hypoxia by stabilization of the subunit HIF-1alpha. Activation can also occur by proinflammatory cytokines during inflammation. Hypoxia, as well as proinflammatory cytokines, plays an important role in the synovia in rheumatoid arthritis (RA) patients. Expression of HIF-1alpha has been demonstrated in RA synovial lining layer. The aim of the study was to investigate the regulation of the intracellular signal transduction pathways, involved in the expression of HIF-1alpha, and in the expression of genes regulated by HIF-1alpha in rheumatoid synovial fibroblasts (RSF). RSF were cultured under proinflammatory conditions (IL-1beta and TNF-alpha stimulation) and under chemical hypoxia (CoCl2 treatment). Expression of HIF-1alpha was analyzed in nuclear extracts by Western blotting. The effect of inhibitors of the PI3K and the ERK pathway on HIF-1alpha protein expression was measured. mRNA expression of HIF-1alpha, COX-2, vascular endothelial growth factor (VEGF), and stromal cell-derived factor (SDF)-1 was determined by real-time RT-PCR, and protein production of VEGF and SDF-1 by ELISA. Treatment of the synovial fibroblasts with 150 mM CoCl2 as well as stimulation with 10 ng/mL IL-1beta or TNF-alpha resulted in strong protein expression of HIF-1alpha, measured with Western blotting. Pretreatment with the MEK1/2 inhibitor PD98059 as well as the PI3K inhibitor LY294002 resulted in inhibition of the cytokine-induced HIF-1alpha expression. Furthermore, it was shown that cytokine-induced mRNA expression of HIF-1alpha was inhibited by the PI3K inhibitor. We found that cytokine stimulation induced VEGF mRNA and protein production, but no significant effect of kinase inhibition was found on VEGF production in cytokine-stimulated RSF. Both the ERK pathway and the PI3K pathway are involved in the cytokine-induced HIF-1alpha expression in RSF and in the expression of proangiogenic factors.
18927458 Platelet C4d is associated with acute ischemic stroke and stroke severity. 2008 Dec BACKGROUND AND PURPOSE: Platelets bearing complement C4d were recently reported to be 99% specific for a diagnosis of systemic lupus erythematosus (SLE) and associated with neuropsychiatric lupus. We compared the prevalence of platelet C4d and investigated the clinical associations of platelet C4d in patients with acute ischemic stroke. METHODS: We recruited 80 patients hospitalized for acute ischemic stroke. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIH-SS). Infarct volume was determined by MRI. Platelet C4d was measured by flow cytometry. RESULTS: Mean age was 57.9 years (range: 24.6 to 86.8 years), 58% were male, and 91% were white. Eight patients (10%) with acute ischemic stroke were platelet C4d-positive, which was significantly higher in prevalence compared to healthy controls (0%, P<0.0001) and non-SLE patients with immune/inflammatory disease (2%, P=0.004). The median NIH-SS score and infarct volume for acute stroke patients were 6 (interquartile range [IQR]: 2 to 13) and 3.4 cc (IQR: 1.1 to 16.6), respectively. Platelet C4d-positive patients were more likely to have a severe stroke compared to those with negative platelet C4d (NIH-SS median: 17.5 versus 5, P=0.003). Positive platelet C4d was independently associated with stroke severity (P=0.03) after controlling for age, anticardiolipin antibody (aCL) status, and total anterior circulation of stroke involvement, and also with infarct volume (P=0.005) after controlling for age, aCL status, and old stroke by MRI. CONCLUSIONS: Platelet C4d is associated with severe acute ischemic stroke. Platelet C4d may be a biomarker as well as pathogenic clue that links cerebrovascular inflammation and thrombosis.