The expression of Foxp3 protein by retroviral vector-mediated gene transfer of Foxp3 in C57BL/6 mice / 대한수의학회지

The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require CD4+CD25+ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both CD4+CD25+ T cell and CD4+Foxp3+ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of CD4+CD25+ T cell and CD4+Foxp3+ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.

Overexpression of Galectin-3 in Macrophages of C57BL/6 mice with Experimental Autoimmune Encephalomyelitis / 대한수의학회지

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and has long been used as an animal model for human multiple sclerosis. Development of EAE requires coordinated expression of a number of genes that are involved in the activation and effector functions of inflammatory cells. Galectin-3 (Gal-3) is a member of the beta-galactoside-binding lectin family and plays an important role in inflammatory responses through its functions on cell activation, cell migration or inhibition of apoptosis. We investigated the functional role of Gal-3 in EAE mice following immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. During the peak stage of EAE, the localization of Gal-3 in inflammatory cells markedly increased in subarachnoid membranes and perivascular regions of CNS. In contrast, Gal-3 was weakly detected in cerebrum and spinal of the recovery stage of EAE. Consistent with this finding, western blot analysis revealed that Gal-3 expression was significantly increased at the peak stage while it was slightly decreased at the recovery stage in the CNS. In addition, the population of CD11b+ macrophage expressing Gal-3 in spleen of EAE mice was markedly increased compared with control mice. In fact, most of activated macrophages isolated from spleen of EAE mice expressed Gal-3. Taken together, our results demonstrate that the over-expression of Gal-3 in activated macrophages may play a key role in promoting inflammatory cells in the CNS during EAE.

Glatiramer acetate inhibits the activation of NFkappaB in the CNS of experimental autoimmune encephalomyelitis / 대한수의학회지

Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B (NFkappaB) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, NFkappaB activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of NFkappaB activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of NFkappaB and phospho-IkappaB proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of NFkappaB and phospho-IkappaB significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of NFkappaB and phophorylation of IkappaB in the CNS. Subsequently, the inhibition of NFkappaB activation and IkappaB phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.

Development and application of stent-based image guided navigation system for oral and maxillofacial surgery / 대한구강악안면방사선학회지

PURPOSE: The purpose of this study was to develop a stent-based image guided surgery system and to apply it to oral and maxillofacial surgeries for anatomically complex sites. MATERIALS AND METHODS: We devised a patient-specific stent for patient-to-image registration and navigation. Threedimensional positions of the reference probe and the tool probe were tracked by an optical camera system and the relative position of the handpiece drill tip to the reference probe was monitored continuously on the monitor of a PC. Using 8 landmarks for measuring accuracy, the spatial discrepancy between CT image coordinate and physical coordinate was calculated for testing the normality. RESULTS: The accuracy over 8 anatomical landmarks showed an overall mean of 0.56+/-0.16 mm. The developed system was applied to a surgery for a vertical alveolar bone augmentation in right mandibular posterior area and possible interior alveolar nerve injury case of an impacted third molar. The developed system provided continuous monitoring of invisible anatomical structures during operation and 3D information for operation sites. The clinical challenge showed sufficient accuracy and availability of anatomically complex operation sites. CONCLUSION: The developed system showed sufficient accuracy and availability in oral and maxillofacial surgeries for anatomically complex sites.

Quantitative analysis of the TMJ movement with a new mandibular movement tracking and simulation system / 대한구강악안면방사선학회지

PURPOSE: The purpose of this study was to develop a system for the measurement and simulation of the TMJ movement and to analyze the mandibular movement quantitatively. MATERIALS AND METHODS: We devised patient-specific splints and a registration body for the TMJ movement tracking. The mandibular movements of the 12 subjects with facial deformity and 3 controls were obtained by using an optical tracking system and the patient-specific splints. The mandibular part was manually segmented from the CT volume data of a patient. Three-dimensional surface models of the maxilla and the mandible were constructed using the segmented data. The continuous movement of the mandible with respect to the maxilla could be simulated by applying the recorded positions sequentially. Trajectories of the selected reference points were calculated during simulation and analyzed. RESULTS: The selected points were the most superior point of bilateral condyle, lower incisor point, and pogonion. There were significant differences (P<0.05) between control group and pre-surgical group in the maximum displacement of left superior condyle, lower incisor, and pogonion in vertical direction. Differences in the maximum lengths of the right and the left condyle were 0.59+/-0.30 mm in pre-surgical group and 2.69+/-2.63 mm in control group, which showed a significant difference (P<0.005). The maximum of differences between lengths of the right and the left calculated during one cycle also showed a significant difference between two groups (P<0.05). CONCLUSION: Significant differences in mandibular movements between the groups implies that facial deformity have an effect on the movement asymmetry of the mandible.

Treatment of Talipes Equinus Deformity Using Free Radial Forearm Flap and Achilles Tendon Lengthening

PURPOSE: Talipes equinus deformity is defined as impossibility of heel weight-bearing and lacking of improvement of toe-tip gait despite sufficient duration of conservative treatment. The incidence of equinus deformity induces post-traumatic extensive soft tissue defect and subsequently increases it. Severe equinus deformities of the foot associated with extensive scarring of the leg and ankle were corrected using achilles Z-lengthening and free-tissue transfer. METHODS: Free radial forearm flap was done in nine cases of eight patients from January 2000 to November 2006. Causes of deformity were post-traumatic contracture (one patient) and post-burn scar contracture (seven patients). Seven patients were male, one patient was female. Mean age was 32.1 (range, 10-57). Flap donors were covered with artificial dermis (Terudermis(R)) and split thickness skin graft (five cases), and medium thickness skin graft only (four cases). RESULTS: The size of flaps varied from 6x12 to 15 x12cm (average, 12x7.8cm). Achilles tendon was lengthened 4.2cm on average. Free radial forearm flap was satisfactory in all cases. All patients could ambulate normally after the surgery. Cases having donor coverage with Terudermis(R) were aesthetically better than those having skin grafts only. CONCLUSION: This study suggested that severe equinus deformities associated with extensive scarring of the leg and ankle can be corrected effectively free radial forearm flap and Achilles tendon lengthening.

Molecular Genetic Analyses of Charcot-Marie-Tooth Disease Type 1A in Korean

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant inherited demyelinating peripheral neuropathy characterized by progressive distal muscular atrophy and marked slowing of nerve conduction velocities. A 1.5 Mb DNA duplication within chromosome 17p11.2-p12 has been reported. This disease appears to be caused by an altered copy number of the PMP-22 gene within the critical region. METHODS: DNA analysis was carried out for 158 persons from 40 unrelated families. PCR was done by D17S122 and D17S261. The DNA of the patients was ana-lyzed to detect three alleles for the presence of duplication. RESULTS: CMT1A duplication was found in 7 families (64%) of the patients with CMT1 by D17S122, but not by D17S261. CONCLUSIONS: We have found seven families of Charcot-Marie-Tooth disease type 1A with chromosome 17p11.2-p12 duplication by D17S122. We recommend the screening test by D17S122 for the detection of CMT1A in Korean because genetic analysis done by D17S261 was not informative.

Molecular Genetic Analyses of Charcot-Marie-Tooth Disease Type 1A in Korean

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant inherited demyelinating peripheral neuropathy characterized by progressive distal muscular atrophy and marked slowing of nerve conduction velocities. A 1.5 Mb DNA duplication within chromosome 17p11.2-p12 has been reported. This disease appears to be caused by an altered copy number of the PMP-22 gene within the critical region. METHODS: DNA analysis was carried out for 158 persons from 40 unrelated families. PCR was done by D17S122 and D17S261. The DNA of the patients was ana-lyzed to detect three alleles for the presence of duplication. RESULTS: CMT1A duplication was found in 7 families (64%) of the patients with CMT1 by D17S122, but not by D17S261. CONCLUSIONS: We have found seven families of Charcot-Marie-Tooth disease type 1A with chromosome 17p11.2-p12 duplication by D17S122. We recommend the screening test by D17S122 for the detection of CMT1A in Korean because genetic analysis done by D17S261 was not informative.

Findings of repetitive nerve stimulation test in myasthenia gravis: A case-control study

Authors had perforrned repetitive nerve stimulation tests on orbicularis oculi, flexor carpi ulnaris, and abductor digiti quinti muscles in 21 myasthenic patients and 40 normal controls using conventional Oh's rnethod and analysed statistically in detail. The results were as follows: 1) There were no significant statistical differences in CMAP and postexercise potentiation between normal controls and myastheic patients, but there were statistically significant decremental responses in both low-and high-rate of stimulation in myasthenic patients, with characteristic posttetanic potentiation and posttetanic exhaustion. 2) There were no statistical differences among Desmedt's, Stalberg's, and Oh's methods in determining the decremental ratio in low-rate of stimulation. 3) The proximal muscles showed more prominent decremental responses than distal muscles in myasthenic patients, and in three myasthenic patients, (14.3%) there were no statistically significant decremental responses in all tested muscles in spite of postivie edrophonium responses. 4) The gerleralized type myasthenic patients showed more prominent decremental responses than oclular type myasthenic patients. 5) Among the myasthenic patients, the oclular type myasthenic patients showed no statistically significant decremental response in both low-and high-rate of stimulation performed on flexor carpi ulnaris and abductor digiti quinti muscles.

Two Cases of Diabetic Thoracic Radiculopathy

Diabetic thoracic radiculopathy is not uncommon, but unfamiliar disease entity complicated by long standing diabetes mellitus. It is characterized by typical distressing sensory disturbances and lancinating pains on abdomen and flanks along the thoracic dermatomes in long-standing diabetic patients, which subsides spontaneously. Diagnosis is made by clinical findings and electrodiagnostic technics and other conditions that can affect thoracic spinal root level should be rulled out. With reviewing some literatures, we present two cases which showed the characteristic features of this disorder.

A Case of Tuberculous Brain Abscess

Tuberculous brain abscess, an unusual complication of tuberculosis, has been rarely reported worldwide.It should be differentiated from tuberculomas of the brain and pyogenic brain abscess, but on the basis of clinical, laboratory, and roentgenographic information the differential diagnosis is difficult and only pathological plus bacteriological evidence can suffice it. We report a case of tuberculous brain abscess developed during antituberculous therapy in 20-year-old girl who had been suffered from pulmonary tuberculosis and tuberculous meningitis.

A Case of Overlap Myasthenic Syndrome

Myasthenia gravis (MG) differs from the Lambert-Eaton syndrome (LES) clinically, electrophysiologically, and therapeutically. However. There had been a few reports documenting the coexistence of MG and LES in the same patient, which is termed as "overlap myasthenic syndrome". We had studied a patient who had showed all the clinical characteristics of MG including positive response to pyridostigmin. Unlike the usual response in MG, there had been an abnormal incremental responses at post-exercise and high rate stimulation with abnormal decremental responses at low-rate stimulation in repetitive nerve stimulation test, which satisfies the diagnostic criteria of both MG as LES.