No abstract

IL-22 is one of several cytokines with limited homology to IL-10. However, the biological activities of IL-22 are mostly unknown. The purpose of this study was to evaluate the effect of IL-22 on rat experimental autoimmune myocarditis (EAM) and elucidate an aspect of the biological activities of IL-22. Rats were immunized on day 0; IL-22-Ig-treated rats were injected with pCAGGS-IL-22-Ig and control rats with pCAGGS-Ig using hydrodynamics-based gene delivery on day 1 or day 6. IL-22-Ig gene therapy administered on day 1 or day 6 after immunization was effective in controlling EAM as monitored by the heart weight to body weight ratio, and the myocarditis area in rats was sacrificed on day 17. Examination of the expression of IL-22-related genes in purified cells from EAM hearts suggested that IL-22-Ig acting target cells were noncardiomyocytic (NC) noninflammatory cells such as fibroblasts, smooth muscle cells, and endothelial cells. Therefore, we examined the effect of rIL-22 or serum containing IL-22-Ig on the expression of immune-relevant genes in IL-1-stimulated NC cells cultured from EAM hearts. Results showed that the expression of immunologic molecules (PGE synthase, cyclooxygenase-2, MIP-2, MCP-1, IL-6, and cytokine-induced neutrophil chemoattractant-2) in IL-1-stimulated NC cells was significantly decreased by rIL-22 or serum containing IL-22-Ig. EAM was suppressed by hydrodynamics-based delivery of plasmid DNA encoding IL-22-Ig, and the reason for this effectiveness may be that IL-22 suppressed gene expression of PG synthases, IL-6, and chemokines in activated NC noninflammatory cells.

Object The posterior ligamentous complex (PLC) in the thoracic and lumbar spine is one of the region's important stabilizers. The precise diagnosis of PLC injury is required to evaluate the instability of the injured spine; however, the accuracy of magnetic resonance (MR) imaging for diagnosing PLC injury has remained unclear. In this study, the authors compared preoperative MR imaging findings with direct intraoperative observation of PLC injury, clarifying the former's diagnostic accuracy regarding detection of PLC injury associated with the thoracic and lumbar fractures. Methods Data obtained in 35 patients who sustained thoracic or lumbar injuries were reviewed. There were 17 burst fractures, six flexion—distraction injuries, and 12 fracture dislocations. Each patient underwent MR imaging examination within 3 weeks of injury. Three radiologists independently evaluated sagittal MR images in a blinded fashion. The PLC-related information was retrospectively collected from each operative record. The diagnostic accuracy of MR imaging was analyzed by comparing imaging-documented intraoperative findings. The PLC injuries were detected in 23 patients (65.7%) by direct observation during posterior spinal procedures. The diagnostic accuracy of MR imaging in detecting injury of the supraspinous ligament (SSL) and interspinous ligament (ISL) was 90.5 and 94.3%, respectively. The specificity of T1-weighted MR imaging alone for depicting the SSL was significantly greater than T2-weighted imaging alone (p < 0.05). The overall mean κ coefficient for MR imaging findings of PLC injury was 0.803, which indicated excellent interobserver reliability; that for ISL (0.915) was significantly greater than that for SSL (0.69) (p < 0.05). Conclusions This study clarified a high diagnostic accuracy and interobserver reliability of MR imaging for PLC injury. The precise diagnosis of PLC injury is essential to determine the mechanical instability of the injured thoracic and lumbar spine, especially in differentiating unstable (three-column) burst fractures from the relatively stable (two-column) type. The authors conclude that MR imaging is a powerful diagnostic tool to evaluate PLC injury associated with thoracic and lumbar fractures.

Genetic responses that characterize experimental autoimmune myocarditis (EAM) have not yet been determined. To investigate gene expression in the myocardium of EAM, absolute copy numbers of 44 mRNA species [calcium-handling proteins, contractile proteins, natriuretic peptides (NPs), cytokines, chemokines, growth factors, renin-angiotensin-aldosterone (RAA) system, endothelins (ETs) and extracellular matrix] in synthesized cDNA from a fixed quantity of total heart RNA were assessed using real-time reverse-transcriptase PCR at days 0, 14, 21 and 28 after immunization. alpha-Cardiac myosin showed a 26.3-fold decrease and beta-cardiac myosin a 3.75-fold increase at day 14. Atrial NP and brain NP increased 47.7- and 6.35-fold at days 21 and 14 respectively. Angiotensin II type 1 receptor, angiotensin-converting enzyme and ET1 increased 22.3-fold at day 21, 6.30-fold at day 21 and 16.8-fold at day 14 respectively. Aldosterone receptor decreased 2.15-fold at day 14, but aldosterone synthetase was detected only at days 14 and 21. Interleukin (IL)-2, IL-10, interferon-gamma and monocyte chemo-attractant protein-1 increased 9.08-fold at day 14, 398-fold at day 21, 43.1-fold at day 14 and 142-fold at day 14 respectively. Collagen type 3, collagen type 1 and fibronectin increased 34.6-, 1.74- and 44.4-fold respectively at day 21. Interestingly, osteopontin showed a 4540-fold increase and it was the highest mRNA of all at day 14. An isoform of cardiac myosin and NP are dramatically changed in EAM. RAA system and ET expressions are changed differently during the EAM time course. Cytokine, chemokine and extracellular matrix greatly increase and, in particular, large numbers of osteopontin mRNA are expressed in early EAM.

We report brain MRI findings in four patients with typical Kearns-Sayre syndrome (KSS) and correlate them with clinical manifestations. MRI was interpreted as normal in two patients; cerebral and cerebellar atrophy was seen in the other two. On T2-weighted spin-echo images, two patients had high-signal lesions bilaterally in subcortical white matter, thalamus and brain stem. In one patient, the white matter lesion extended into the deep cerebral white matter and the cerebellum was also affected. The other also had bilateral high-signal lesions in the globus pallidus. There was little correlation between neurological deficits and MRI findings. A review of the literature revealed that 10 of the 13 patients with typical KSS previously studied had bilateral subcortical white-matter lesions on T2-weighted images; at least 7 also had high-signal lesions in the brain stem, globus pallidus, thalamus or cerebellum. Although MRI may be normal or show atrophy, the characteristic finding in KSS is a combination of the high-signal foci in subcortical cerebral white matter and in the brain stem, globus pallidus or thalamus.