Persistent infection of Chlamydia in reactive arthritis.
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Arthritis, Reactive↗
Biomedical subjects
M Rihl
Publications and source records attributed to M Rihl.
Involvement of neurotrophins and their receptors in spondyloarthritis synovitis: relation to inflammation and response to treatment.
OBJECTIVE: To investigate whether expression of the four members of the neurotrophin (NT) family and their four corresponding receptors is related to synovial inflammation in patients with spondyloarthritis (SpA). MATERIAL AND METHODS: Synovial fluid (SF) and serum NTs and their receptors were measured by ELISA. Immunohistochemistry was used for synovial tissue biopsy specimens from patients with SpA, rheumatoid arthritis, and osteoarthritis (OA). In SpA synovium, immunoreactivity of the receptors trkA and NGFRp75 was also assessed before and after 12 weeks of treatment with the monoclonal anti-tumour necrosis factor alpha antibody, infliximab. RESULTS: mRNA transcripts of all NTs and receptors were expressed in the inflamed synovium. At the protein level, brain derived neurotrophic factor and NT-3 were significantly higher in the SF of patients with SpA than in those with OA. In contrast, ELISA of serum samples showed that the highest member in SpA was NT-4. Immunohistochemistry demonstrated that the NT receptors trkA and NGFRp75 were highly expressed in the inflamed synovium of patients with SpA, correlating with vascularity and lymphoid aggregates, respectively. Additionally, immunoreactivity of both receptors was significantly decreased after infliximab treatment. CONCLUSIONS: NTs and their receptors are expressed in inflamed peripheral joints of patients with SpA. Their expression is not constitutive but related to inflammation and they may be involved in the local disease processes.
Adult↗
[Arthropathy of hereditary hemochromatosis].
Hereditary hemochromatosis (HH) is the most common autosomal recessive disorder in populations of caucasian origin with a prevalence of 1 : 200-400 for homozygous patients. Currently, 4 types of HH are distinguished. The classical and most common form is type 1 hemochromatosis which is characterized by HFE gene mutations on chromosome 6. The disease results from an excessive iron absorption leading to multiple manifestations such as hepatomegaly, diabetes mellitus, cardiomyopathy, infertility, and hepatic fibrosis/cirrhosis if untreated. A distinct clinical feature of hemochromatosis is represented by involvement of the joints (arthropathy of hemochromatosis) which occurs frequently and often before iron overload is present. Severity of arthropathy usually does not correlate with the extent of iron overload. In contrast to most other manifestations, it is not improved by iron depletion but can be treated symptomatically. This review outlines clinical aspects as well as pathogenesis, diagnosis and therapy of the disease.
Arthritis↗
Technical validation of cDNA based microarray as screening technique to identify candidate genes in synovial tissue biopsy specimens from patients with spondyloarthropathy.
OBJECTIVES: To validate the use of cDNA based microarray on synovial biopsies by analysing the experimental variability due to amplification of RNA, reproducibility of the assay, heterogeneity of the tissue, and statistical analysis. METHODS: Total RNA was extracted from three spondyloarthropathy (SpA) and three osteoarthritis (OA) synovial tissue biopsy specimens and from the peripheral blood mononuclear cells (PBMC) of four healthy donors. Exponential RNA amplification by SMART-PCR was compared with linear amplification. Reproducibility was tested by comparing different microarray systems and by performing duplicate experiments. Sample heterogeneity was assessed by comparing overall gene expression profiles, histopathology, and analysis of genes expressed in the synovium and normal PBMC. Statistical analysis using t test and Bonferroni adjustment was verified by permutation of class labels. RESULTS: Gene expression was concordant in 12/14 (86%) cytokine/chemokine genes between both microarrays and different RNA amplification systems. When one microarray system was used, expressed genes were 78-95% concordant in duplicate experiments. Gene expression profiles had a higher degree of similarity between SpA synovium than between PBMC or OA synovium despite clear histopathological differences between synovial samples. Comparison of SpA synovium with OA synovium and with PBMC yielded 11 and 18 expressed transcripts, respectively; six were shared in both comparisons. Permutations of SpA and OA samples yielded only one expressed gene in 19 comparisons. CONCLUSIONS: These data provide evidence that microarrays can be used for analysis of synovial tissue biopsies with high reproducibility and low variability of the generated gene expression profiles.
Adult↗
Alpha beta but not gamma delta T cell clones in synovial fluids of patients with reactive arthritis show active transcription of tumour necrosis factor alpha and interferon gamma.
OBJECTIVE: To compare the cytokine expression profile of three CD8+, three CD4+, and three gammadelta+ T cell clones all derived from the synovial fluids of three patients with reactive arthritis (ReA). METHODS: Complementary DNA based microarrays containing the specific sequence of 56 cytokine transcripts were used for screening. Selected genes were confirmed by reverse transcriptase-polymerase chain reaction assay. RESULTS: Microarray showed that transcripts encoding for interferon gamma and tumour necrosis factor alpha were expressed by all CD8+ and CD4+ T cell clones. However, gammadelta+ T cells predominantly expressed transforming growth factor beta2 and granulocyte monocyte-colony stimulating factor. CONCLUSION: T lymphocyte clones from the joint of patients with ReA exhibit differential cytokine expression profiles. CD8+ and CD4+ T cells demonstrate a Th1 mediated profile, whereas gammadelta+ T cells show a more heterogeneous and less proinflammatory Th3 driven pattern.
Adult↗
A 588-gene microarray analysis of the peripheral blood mononuclear cells of spondyloarthropathy patients.
OBJECTIVES: To identify genes which are more highly expressed in the peripheral blood mononuclear cells (PBMC) of patients with spondyloarthropathy (SpA), rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in comparison to normal subjects. METHODS: A 588-gene microarray was used as a screening tool to select a panel of such genes from PBMC of these subjects and of normal subjects. Results were then validated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The following genes were more highly expressed in arthritis patients than in normal subjects: macrophage differentiation marker MNDA (myeloid nuclear differentiation antigen), MRP8 and MRP14 (migratory inhibitory factor-related proteins); signalling molecules JAK3 (janus kinase 3) and MAP kinase p38 (mitogen-activated protein kinase); receptors TNFR2/p75, C-C-chemokine receptor type 1 (CCR1), C-X-C-chemokine receptor type 4 (CXCR4) and integrin beta1; and the cytokines/chemokines interleukin (IL) 1beta and IL-8. Expression of CXCR4 was unexpectedly high among all arthritis subjects. Using RT-PCR, ELISA and immunohistology, expression of stromal cell-derived factor 1 (SDF-1) was demonstrated in arthritis joints. CONCLUSIONS: The CXCR4/SDF-1 is a potential pro-inflammatory axis for RA, PsA and SpA.
Adolescent↗
Prediction of creatinine clearance from serum creatinine in patients with rheumatoid arthritis: comparison of six formulae and one nomogram.
The estimation of glomerular filtration rate is important for the medical treatment of patients with rheumatoid arthritis (RA). However, the determination of endogenous creatinine clearance (Clcr) from a 24-h urine collection is an unreliable and time-consuming procedure. We therefore tested the accuracy of six equations and one nomogram for the prediction of Clcr from serum creatinine (Scr) in 38 patients with RA and 20 controls. A positive correlation was found for all methods in the controls (r = 0.83-0.94) and RA patients (r = 0.51-0.69). The methods did not overestimate Clcr in RA. In the RA group the simple formula published by Cockcroft [Clcr = ((140 - age) x body weight)/(72 x Scr), x 0.85 for females] showed the best correlation with the measured Clcr. In RA the Cockroft formula can reliably be used to predict Clcr from Scr.
Adult↗
Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis.
Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.
Adipose Tissue↗
Myocardial fibrosis in polymyositis.
Myocardial involvement in polymyositis is commonly suspected in noninvasive studies, but symptomatic cardiac disease is rare. We describe a 27-year-old woman with a 6 year history of severe polymyositis and persistent elevation of creatine phosphokinase-MB isoenzyme who suddenly developed congestive heart failure and bradycardia-tachycardia syndrome. Autopsy revealed severe myocardial fibrosis without inflammatory cell infiltrates concomitant to active polymyositis of the skeletal muscles despite intensive longterm immunosuppressive therapy.
Adult↗
Angiotensin-converting enzyme inhibition by enalapril: a novel approach to reduce ischemia/reperfusion damage after experimental liver transplantation.
Angiotensin-converting enzyme (ACE) inhibitors have proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. Whether this favorable effect can be related to other models of ischemia and reperfusion has not yet been investigated. Therefore, we studied in a model of syngeneic liver transplantation in the rat the effect of recipient enalapril treatment on postischemic liver injury. Untreated animals served as the control group. Treatment with enalapril was started 5 minutes before reperfusion by intravenous infusion of enalapril at a dosage of 5 mg/kg/h. By means of in vivo microscopy, the sinusoidal perfusion rate and leukocyte adherence in sinusoids and postsinusoidal venules were analyzed during 45 to 60 minutes of reperfusion. Liver function was monitored by measuring bile output over a period of 60 minutes. Analysis of coagulation factors (prothrombin time, factor V, fibrinogen) and liver enzymes (alanine transaminase [ALT], aspartate transaminase [AST]) served for the evaluation of organ dysfunction and damage secondary to ischemia/reperfusion injury. The sinusoidal perfusion rate was significantly improved by enalapril treatment (94.7% [1.0] vs. 75.3% [3.8]; mean [SEM]; P = .005). In addition, leukocyte-sticking in both liver sinusoids and postsinusoidal venules was remarkably reduced in enalapril-treated animals as compared with controls (stickers/lobule: 21.0 [3.3] vs. 59.2 [2.1]; P = .0004; stickers/mm2 venular surface: 20.5 [4.7] vs. 110.3 [18.1]; P = .0004). Moreover, bile output was increased (1.13 [0.35] vs. 0.43 [0.18] g bile/60 min x 100 g liver; P = .06). Values for PT (22.5% [2.1] vs. 9.7% [1.8]; P = .005), factor V 99.4% [9.5] vs. 49.5% [8.5]; P = .007), and fibrinogen (64.1% [7.7] vs. 12.8% [3.2]; P = .001) were significantly improved, paralleled by a remarkable reduction in serum ALT (1,428 U/L [190] vs. 2,315 [248]; P = .02). Our data show for the first time that ACE inhibition in the liver recipient by enalapril attenuates hepatic ischemia/reperfusion damage after experimental liver transplantation. Our results may offer a novel approach to reduce ischemia/reperfusion injury in clinical liver transplantation.
Angiotensin-Converting Enzyme Inhibitors↗
Conditioning of liver grafts by donor bolus pretreatment with epoprostenol.
Despite improved preservation methods, graft dysfunction after liver transplantation continues to contribute considerably to postoperative morbidity and mortality. In clinical and experimental studies prostaglandin (PG)I2 analogs proved effective in the treatment of liver damage of different origin. Using in vivo fluorescence microscopy in a rat liver transplantation model, we studied the effect of donor bolus pretreatment with the PGI2 analog epoprostenol on hepatic graft revascularization. After epoprostenol bolus pretreatment (group 1: liver transplantation/PGI2), perfusion of liver sinusoids after reperfusion was significantly improved as compared with untreated donor livers (group 2: liver transplantation (95.2+/-0.6% vs. 75.3+/-3.8%, mean +/- SEM; P=0.001) and epoprostenol was found almost in the range of that in normal nontransplanted livers (99.4+/-0.2%). In addition, leukocyte adherence in liver lobules (21.0+/-3.5 vs. 115+/-11.5 n/lobule; P=0.001) and postsinusoidal venules (23.0+/-3.8 vs. 113+/-11.3 n/mm2 endothelial surface; P=0.002) was significantly reduced in the pretreated grafts. Bile production in the recipient was significantly increased by epoprostenol pretreatment of the donor (1.88+/-0.4 vs. 0.63+/-0.13 g/100 g liver*1 hr; P=0.015), indicating restored liver function. These results suggest that the prostacyclin analog epoprostenol is effective in preconditioning the graft prior to transplantation, i.e., improving preservation and increasing graft resistance to ischemia/reperfusion injury. Thus, favorable effects on early graft function after clinical liver transplantation may be achieved by introducing epoprostenol pretreatment into the harvesting procedure.
Animals↗
Impact of enalapril on microvascular perfusion and leukocyte adherence in a model of rat liver transplantation assessed by in vivo microscopy.
ACE inhibitors have been proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. In an attempt to investigate this effect in a model of syngeneic liver transplantation in the rat, we compared a control group with an ACE inhibitor treatment group, in which enalapril was given i.v. before and during reperfusion. By means of in vivo microscopy, sinusoidal perfusion rate, permanent leukocyte sticking in sinusoids and postsinusoidal venules, and leukocyte rolling in postsinusoidal venules were assessed. Liver function was evaluated by measuring bile output. The sinusoidal perfusion rate was significantly improved by enalapril treatment. Leukocyte sticking in both sinusoids and postsinusoidal venules was found to be remarkably reduced in enalapril-treated animals; the fraction of rolling leukocytes remained unchanged. Bile output was increased in enalapril-treated animals. These results demonstrated, in a model of rat liver transplantation, that ACE inhibition by enalapril is effective in reducing hepatic ischemia/reperfusion damage as assessed by the leukocyte-endothelium interaction using in vivo microscopy and postreperfusion bile production.
Angiotensin-Converting Enzyme Inhibitors↗
Pulmonary rejection diagnosis after lung and heart-lung transplantation.
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Azathioprine↗