To evaluate the carcinogenicity of p27 knockout (KO) mice with RNA-guided endonuclease (RGENs)-mediated p27 mutant exon I gene (IΔ), alterations in the carcinogenic phenotypes including tumor spectrum, tumor suppressor proteins, apoptotic proteins and cell cycle regulators were observed in p27 (IΔ) KO mice after treatment with 7,12-Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)(DT) for 5 months. The target region (544~571 nt) in exon I of the p27 gene was successfully disrupted in p27 (IΔ) KO mice using the RGEN-induced non-homologous end joining (NHEJ) technique. After DT exposure for 5 months, a few solid tumors (identified as squamous cell carcinoma) developed on the surface of back skin of DT-treated p27 (IΔ) KO mice. Also, squamous cell hyperplasia with chronic inflammation was detected in the skin dermis of DT-treated p27 (IΔ) KO mice, while the Vehicle+p27 (IΔ) KO mice and WT mice maintained their normal histological skin structure. A significant increase was observed in the expression levels of tumor suppressor protein (p53), apoptotic proteins (Bax, Bcl-2 and Caspase-3) and cell-cycle regulator proteins (Cyclin D1, CDK2 and CDK4) in the skin of DT-treated p27 (IΔ) KO mice, although their enhancement ratio was varied. Taken together, the results of the present study suggest that squamous cell carcinoma and hyperplasia of skin tissue can be successfully developed in new p27 (IΔ) KO mice produced by RGEN-induced NHEJ technique following DT exposure for 5 months.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cell Cycle ; Dermis ; Epithelial Cells* ; Exons ; Hyperplasia* ; Inflammation ; Mice* ; Phenotype ; Skin ; Tumor Suppressor Proteins

OBJECTIVE: Pfirrmann disc degeneration grade is one of morphologic disc degeneration grading system and it was reliable on routine T2-weighted magnetic resonance (MR) images. The purpose of this study was to evaluate the agreement of Pfirrmann disc degeneration grade, and check the alternative technique of disc degeneration grading system. METHODS: Fifteen volunteers (4 medical doctors related to spinal disease, 2 medical doctors not related to spinal disease, 6 nurses in spinal hospital, and 3 para-medicines) were included in this study. Three different digitalized MR images were provided all volunteers, and they checked Pfirrmann disc degeneration grade of each disc levels after careful listening to explanation. Indeed, all volunteers checked the signal intensity of disc degeneration at the points of nucleus pulposus (NP), disc membrane, ligaments, fat, and air to modify the quantitative Pfirrmann disc degeneration grade. RESULTS: Total 225 grade results of Pfirrmann disc degeneration grade and 405 signal intensity results of quantitative Pfirrmann disc degeneration grade were analyzed. Average interobserver agreement was "moderate (mean±standard deviation, 0.575±0.251)" from poor to excellent. Completely agreed levels of Pfirrmann disc degeneration grade were only 4 levels (26.67%), and the disagreement levels were observed in 11 levels; two different grades in 8 levels (53.33%) and three different grades in 3 levels (20%). Quantitative Pfirrmann disc degeneration showed relatively cluster distribution with the interobserver deviations of 0.41-1.56 at the ratio of NP and disc membrane, and it showed relatively good cluster and distribution indicating that the proposed grading system has good discrimination ability. CONCLUSION: Pfirrmann disc degeneration grade showed the limitation of different interobserver results, but this limitation could be overcome by using quantitative techniques of MR signal intensity. Further evaluation is needed to access its advantage and reliabilities.
Discrimination (Psychology) ; Intervertebral Disc Degeneration* ; Ligaments ; Membranes ; Spinal Diseases ; Volunteers

OBJECTIVE: Spinal fusion operation is an effective treatment in the spinal pathology, but it could change the physiological distribution of load at the instrumented and adjacent segments. This retrospective study compared the radiological and clinical outcomes of patients undergoing lumbar fusion with semirigid rods versus rigid rods system. METHODS: Using transpedicular fixation and posterior lumbar interbody fusion at the level of L4/L5, 20 patients were treated with semirigid rods (WavefleX, SR group), and 20 patients with rigid rods (titanium, RR group). Clinical and radiological outcomes were evaluated, including visual analog score for lower back pain and leg pain, Prolo functional and economic scores, statues of implanted instruments, fusion rate, and complications during 24-month follow-up. RESULTS: Clinical scores were significantly improved until postoperative 24-month follow-up as compared with preoperative scores in both groups (p<0.05), with similar levels of improvement observed at the same time points postoperatively between the 2 groups. Prolo economic scores were significantly improved in SR group compared to RR until 12 months, but this improvement became similar after 18 months. The overall fusion rate was 94.1% until the 24-month follow-up for both groups. No significant complication was observed in both groups. CONCLUSION: The results of the present study indicate that semirigid rods system with posterior lumbar interbody fusion showed similar clinical and radiological result with rigid rods system until 2 years after instrumentation. The WavefleX rods system, as a semirigid rods with unique characteristics, may be an effective alternative treatment for patients in lumbar fusion.
Follow-Up Studies ; Humans ; Leg ; Low Back Pain ; Pathology ; Retrospective Studies ; Spinal Fusion ; Spine*

OBJECTIVE: To correct apical vertebral rotation for adolescent idiopathic scoliosis (AIS), direct vertebral derotation (DVD) or simple rod rotation (SRR) might be considered. The aim of the present study is to introduce the surgical experiences of AIS by a Korean neurosurgeon and to evaluate the effectiveness of SRR for apical vertebral rotation. METHODS: A total of 9 patients (1 male and 8 females) underwent scoliosis surgery by a neurosurgeon of our hospital. The Lenke classifications of the patients were 1 of 1B, 2 of 1C, 1 of 2A, 1 of 2C, 3 of 5C and 1 of 6C. Surgery was done by manner of simple rod rotation on the concave side and in situ coronal bending. Coronal Cobb's angles, vertebral rotation angles and SRS-22 were measured on a plain standing X-ray and CT before and after surgery. RESULTS: The mean follow up period was 25.7 months (range : 5-52). The mean number of screw positioning level was nine (6-12). The mean age was 16.4 years (range : 13-25) at surgery. The mean Risser grade was 3.7+/-0.9. The apical vertebral rotation measured from the CT scans was 25.8+/-8.5degrees vs. 9.3+/-6.7degrees (p<0.001) and the Coronal Cobb's angle was 53.7+/-10.4degrees vs. 15.4+/-6.5degrees (p<0.001) preoperatively and postoperative, respectively. The SRS-22 improved from 71.9 preoperatively to 90.3 postoperatively. There were no complications related with the operations. CONCLUSION: SRR with pedicle screw instrumentation could be corrected successfully by axial rotation without complications. SRR might serve as a good option to correct AIS deformed curves of AIS.
Adolescent* ; Classification ; Follow-Up Studies ; Humans ; Male ; Neurosurgery ; Scoliosis* ; Tomography, X-Ray Computed

BACKGROUND: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-kappaB. METHODS: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. RESULTS: DPT promoted the activation of CD8+ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-gamma production and induction of cytotoxic T lymphocyte activity. CONCLUSION: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.
Animals ; Dendritic Cells ; Immunotherapy ; Interleukin-12 ; Lymph Nodes ; Lymphocyte Culture Test, Mixed ; Lymphocytes ; Mice ; Phenotype ; Podophyllotoxin ; T-Lymphocytes ; Toll-Like Receptors ; Up-Regulation ; Vaccination ; Vaccines

Authors performed extrapedicular screws fixation in thoracic spines. Because patient had very narrow thoracic pedicles, classical transpedicular screws fixation could not be accomplished. In case of narrow thoracic pedicles, extrapedicular screws fixation would be a good alternative technique. We describe here a method for thoracic extrapedicular screws fixation.
Humans ; Spine

Giant dumbbell neurofibroma is a rare tumor which belongs to large family that is the nerve sheath tumor composed of two main types of tumors that include neurofibroma and schwannoma. Neurofibroma arises from a mesenchymal origin closer to a fibroblast which differs from the schwannoma arising from the progenitor of the schwann cell. I report on one case of giant lumbar dumbbell neurofibroma that occured in the spinal and paraspinal retoperitoneal region which was removed by combined and one-year delayed surgery.
Fibroblasts ; Humans ; Neurilemmoma ; Neurofibroma

OBJECTIVE: Spontaneous intracerebral hemorrhage (sICH) is a leading cause of morbidity and mortality, especially in Asian countries. Nevertheless, few reports of sICH in young people have been published. This study investigates the clinical features of sICH in young people. METHODS: Between February 1999 and December 2007, we retrospectively reviewed the medical records of patients aged 45 years diagnosed with sICH at our institute. We analyzed the causes, locations, risk factors, and final outcomes of sICH in these patients. RESULTS: Twenty-one patients (14.5%) were younger than 25 years, while 27 patients (18.6%) were 25~34 years old. Ninety-seven patients (66.9%) were between the ages of 35~45. The most common cause of sICH was hypertension (57.9%). The most common location of sICH was in the lobar region (35.2%). Vascular anomaly was the main cause in both the <25 age group (76.2%) and the 25~34 age group (70.4%). The diagnostic rate of angiography was 75% for the under 25 age group and 80% in the 25~34 age group. CONCLUSIONS: Hypertension is the most common cause of sICH in people between 35 and 45, and vascular anomaly is the main cause in people under 35 years of age. Thus, angiography should be mandatory for people under 35 with sICH, and for people with lobar hemorrhage. For young people, early diagnosis of hypertension and strict blood pressure control is recommended.
Aged ; Angiography ; Asian Continental Ancestry Group ; Blood Pressure ; Cerebral Hemorrhage ; Early Diagnosis ; Hemorrhage ; Humans ; Hypertension ; Medical Records ; Retrospective Studies ; Risk Factors

Atlantoaxial facet joint osteoarthritis is rare, often undiagnosed because it may be misdiagnosed as occipital neuralgia, or degenerative cervical spondylosis. Unilateral occipitocervical pain aggravated by head rotation is a specific symptom. Conservative treatment is usually effective. But when the patient complains of intractable neck pain localized to occipitocervical junction and unresponsive to medical therapy, surgical treatment should be considered. Though a few reports of surgically treated atlantoaxial osteoarthritis has been published, surgical outcome is favorable. A case of a surgically treated atlantoaxial osteoarthritis is presented with a review of the literatures.
Head ; Humans ; Neck Pain ; Neuralgia ; Osteoarthritis* ; Spondylosis ; Zygapophyseal Joint

OBJECTIVE: Juvenile rheumatoid arthritis (JRA) is classified as polyarticular, oligoarticular, and systemic onset type by clinical symptoms presented during first six months. This study was performed to investigate the clinical features and course of systemic onset JRA. METHODS: We performed a retrospective study for patients who were diagnosed as JRA between March 2000 and March 2006 according to the JRA criteria of the International League of Association for Rheumatology (ILAR). RESULTS: Of the 216 JRA patients, 33 patients (11 male/ 22 female) were systemic onset type. Because of insufficient data, 6 patients were excluded. Chief complaints at the time of diagnosis were fever (81.5%) and arthralgia (77.7%). During the disease course, all patients manifested fever and arthritis, rash (59.2%) and splenomegaly (22.2%) also occurred. Most patients had symmetric (81.5%) arthritis, and involved more than five joints (59.3%) including knee and wrist. Anemia, leukocytosis, and thrombocytosis were common laboratory abnormalities. Almost all patients had elevated level of C-reactive protein and erythrocyte sediment rate. Some patients had positive results about immunologic marker such as rheumatoid factor (3.8%), antinuclear antibody (57.7%), and antiperinuclear factor (9.5%). Therapeutic regimens included glucocorticoids (88.9%), nonsteroidal anti-inflammatory drugs (81.5%), methotrexate (81.5%), and hydroxychloroquine (55.6%). Biologic agents were applied in 5 patients, and 3 showed improvement of disease activity. Combination therapy was introduced in 18.5% of patients, and 63% of patients still required medications. CONCLUSION: In Korea, systemic onset JRA patients had variable clinical manifestations and chronic course of disease, which often extended into adulthood.
Anemia ; Antibodies, Antinuclear ; Arthralgia ; Arthritis ; Arthritis, Juvenile* ; Biological Factors ; Biomarkers ; C-Reactive Protein ; Diagnosis ; Erythrocytes ; Exanthema ; Fever ; Glucocorticoids ; Humans ; Hydroxychloroquine ; Joints ; Knee ; Korea ; Leukocytosis ; Methotrexate ; Retrospective Studies ; Rheumatoid Factor ; Rheumatology ; Splenomegaly ; Thrombocytosis ; Wrist