Kyu Yeol Lee

Comparison of Pyogenic Spondylitis and Tuberculous Spondylitis

Pyogenic spondylitis and tuberculous spondylitis are common causes of spinal infection. It is difficult to differentiate tuberculous spondylitis and pyogenic spondylitis clinically and radiologically. Recently magnetic resonance imaging has been reported to be beneficial for early diagnosis and differential diagnosis of the spondylitis, and is being used extensively for diagnosis. However, the diagnosis must be considered in combination with corresponding changes in clinical manifestations, radiological findings, blood and tissue cultures and histopathological findings. Conservative treatments, including antimicrobial medications, are started initially. Surgical treatments, which include anterior or posterior approach, single-stage or two-stage surgery, with or without instrumentation, may be performed as indicated.

Interferon gamma induced by resveratrol analog, HS-1793, reverses the properties of tumor associated macrophages

Macrophages are capable of both inhibiting and promoting the growth and spread of cancers, depending on their activation state. Tumor-associated macrophages (TAM) are a kind of alternatively activated M2 macrophage, which may contribute to tumor progression. Following our previous study to evaluate the anti-tumor effect of a synthetic resveratrol analog HS-1793, the current study demonstrated that HS-1793 treatment significantly increased IFN-γ secreting cells in splenocytes and decreased CD206+ macrophage infiltration compared to CD68+ cells in the tumor site with a higher expression of IFN-γ. As these results suggested that IFN-γ increased locally at the tumor sites could modulate the status of TAM, we designed an in vitro model to study macrophage morphology and functions in relation to the tumor microenvironment. Human monocytic cell line THP-1 cells stimulated with phorbol-12-myristate-13-acetate (PMA) differentiated to macrophages with M2-like phenotypes. TAM-like properties of CD206(high), CD204(high), IL-10(high), TGF-β(high), IL-6(low), IL-12(low), VEGF(high), and MMP-9(high) and promotion of tumor cell invasion were more pronounced in M-2-polarized THP-1 macrophages generated by differentiating THP-1 cells with PMA and subsequently polarizing them with Th2 cytokines (IL-4/IL-13). Upon IFN-γ exposure, THP-1-derived TAM changed their phenotypes to the M-1-like morphology and intracellular granular pattern with an expression of an increased level of proinflammatory and immunostimulatory cytokines and a reduced level of immunosuppressive and tumor progressive mediators. These results explain the underlying mechanism of the anti-tumor activity of HS-1793. The elevated level of IFN-γ production after HS-1793 treatment evoked reprogramming of M-2 phenotype TAM, which efficiently countered the immunosuppressive and tumor progressive influences of TAM.

Cell type-specific Stat3 activation by gp130-related cytokines in the peripheral nerves

Nerve injury-induced activation of signal transducer and activator of transcription 3 (STAT3) in sensory neurons and Schwann cells has been implicated in peripheral nerve regeneration. In this study, we investigated the role of gp130-related cytokines including interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF) in STAT3 activation in dorsal root ganglion neurons, Schwann cells, and endoneurial fibroblasts. We found that IL-6, but not CNTF or LIF, activated STAT3 in Schwann cells. However, CNTF and LIF, but not IL-6, activated STAT3 in dorsal root ganglion neurons. Furthermore, LIF was the primary activator of STAT3 in endoneurial fibroblasts. These findings indicate that gp130 cytokines may have cell type-specific roles in peripheral nerve regeneration.

Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells

Osteosarcoma (OS) is the most common primary malignant bone cancer in children and adolescents. Although paclitaxel (PCX) has been considered one of the most important cancer chemotherapeutic drugs, the current protocols for OS treatment do not incorporate this agent. Therefore, the purpose of this study was to evaluate the induction of cell death in OS cells after exposure to PCX, to identify the cell death mechanism(s) activated by PCX and to investigate whether autophagy is associated with PCX-induced apoptosis. The results of the present study confirmed that exposure to low PCX concentrations can induce apoptotic cell death in Saos-2 cells; furthermore, caspase-3 activation, PARP degradation and XIAP downregulation were observed in combination with PCX-induced apoptosis. The potential involvement of mitochondrial events (intrinsic apoptotic pathway) in PCX-induced apoptosis in OS cells was verified by the alteration (depolarization) of mitochondrial membrane potential. In addition, pretreatment with 3-methyladenine (3-MA), a specific inhibitor of autophagy, significantly increased PCX-induced apoptotic cell death in Saos-2 cells. The augmentation of PCX-induced apoptosis by 3-MA was accompanied by increase in the cytochrome c release from the mitochondria, caspase-3 activity and XIAP downregulation, which suggests that inhibiting autophagy further stimulates the PCX-induced mitochondrion-related (intrinsic) apoptotic pathway by provoking caspase-3 activation. Thus, autophagy observed during PCX-induced apoptosis in Saos-2 OS cells represents the role of cytoprotection in cellular homeostatic processes. In conclusion, the results of this study revealed that PCX exposure effectively induces OS cell death by apoptosis associated with the mitochondrial-mediated caspase-dependent pathway. PCX can increase autophagic activity and suppressing autophagy enhances PCX-induced apoptosis in OS cells. Therefore, it is suggested that combination treatment involving low-dose PCX therapy and autophagy inhibitor therapy could be an effective and potent strategy for improved chemotherapy for OS in the near future.

Tumor associated macrophages provide the survival resistance of tumor cells to hypoxic microenvironmental condition through IL-6 receptor-mediated signals.

Hypoxia and infiltration of tumor-associated macrophages (TAM) are intrinsic features of the tumor microenvironment. Tumor cells that remain viable in hypoxic conditions often possess an increased survival potential and tend to grow aggressively. TAM also respond to a variety of signals in the hypoxic tumor microenvironment and express a more M2-like phenotype. In this study, the established mouse tumor tissues showed a dense infiltration of CD206+ macrophages at the junctions between the normoxic and hypoxic regions and an increased IL-6 receptor (IL-6R) expression of tumor cells in the areas of CD206+ TAM accumulation, which indicates a role of M2 phenotype TAM in survival adaptation of tumor cells preparing for an impending hypoxic injury before changes in oxygen availability. Cocultured mouse FM3A or human MCF-7 tumor cells with tumor infiltrating macrophages isolated from mouse tumor tissues and M2-polarized macrophages generated from human THP-1 cells, respectively, showed significantly decreased rate of cell death in cultures exposed to hypoxia. The acquisition of survival resistance was attributed to increased IL-6 production by M2 TAM and increased expression of IL-6R in tumor cells in the coculture system. MCF-7 cells cocultured with M2 TAM showed activated JAK1/STAT3 and Raf/MEK/JNK pathways contributing to tyrosine and serine phophorylation of STAT3, respectively. However, only tyrosine phosphorylated STAT3 was detected in the nucleus, which induced upregulation of Bcl-2 and downregulation of Bax and Bak. Finally, knockdown of IL-6R by small interfering RNA significantly counteracted coculture-induced signals and completely abolished the survival resistance to hypoxic injury. Thus, we present evidence for the role of M2 phenotype TAM in IL-6 receptor-mediated signals, particularly tyrosine phosphorylation of STAT3, responsible for the prosurvival adaptation of tumor cells to hypoxia.

Interleukin-6 induces proinflammatory signaling in Schwann cells: a high-throughput analysis.

Interleukin-6 plays an important role in peripheral nerve regeneration. We recently reported that IL-6 targets Schwann cells in the peripheral nerve for its function. In this study, we analyzed genes whose expression is regulated by IL-6 in a cell line derived from Schwann cells, the peripheral glia, using the Illumina gene microarray. At measurements 3 and 12h after IL-6 treatment, 35 genes were found to be upregulated by IL-6. Most upregulated genes were proinflammatory genes that are known to be induced in inflammatory conditions. Interestingly, the expression of immunoproteasome subunits was upregulated by IL-6 in Schwann cells. Treatment with forskolin, an agent that mimics axonal signaling, suppressed the expression of IL-6-inducible genes. Finally, we found for the first time that sciatic nerve injury induced immunoproteasome expression in vivo. These findings indicate that IL-6 is involved in peripheral nerve regeneration by regulating proinflammatory signaling in Schwann cells.

Treatment outcome of cervical tear drop fracture.

Study Design This is a retrospective study. Purpose We wanted to evaluate the clinical results of surgical and conservative treatment for cervical tear drop fracture. Overview of Literature The tear drop fracture of the lower cervical spine is generally associated with a high incidence of neurological deficits and surgery is needed to treat this injury. Tear drop fracture of C2 is usually a stable fracture that is amendable to conservative treatment. Methods We reviewed the outcomes of 25 patients. Cervical tear drop fracture was classified as the extension and flexion types according to the mechanism of injury. The neurologic symptoms were evaluated by the Frankel classification system, and the loss of lordosis and disc height, and the duration of bony union were analyzed. Results Twenty one patients had the flexion type injury and 4 patients had the extension type injury. All the patients with the flexion type were treated by anterior decompression and plate stabilization. All the patients with the extension type were treated conservatively. Ten patients with the flexion type had neurologic deficits. The nerve root injuries recovered fully and the incomplete injuries had an average 1.5 grade recovery. Radiologically, the extension type fracture showed bony union at an average of 12.8 weeks. For the patients with the flexion type fracture, the loss of lordosis was 2.6° and the loss of disc height was 2.1 mm. The period of bony union in 20 cases was 13.0 weeks. Conclusions Anterior plate stabilization was an effective treatment for the flexion type tear drop fracture. Conservative treatment is thought to be one of the good clinical methods for treating the extension type tear drop fracture.

Complications and outcomes of surgery for degenerative lumbar deformity in elderly patients

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Orthopedic Research and Reviews 2014:6 11–15 Orthopedic Research and Reviews Dovepress

The Relationship between Superior Disc-Endplate Complex Injury and Correction Loss in Young Adult Patients with Thoracolumbar Stable Burst Fracture

Background To determine the relationship between superior disc-endplate complex injury and correction loss after surgery in a group of young adult patients with a stable thoracolumbar burst fracture. Methods The study group was comprised of young adult patients who had undergone short-segment posterior fixation and bone grafting under the diagnosis of a stable thoracolumbar burst fracture from March 2008 to February 2014. Follow-up was available for more than 1 year. Before surgery, magnetic resonance imaging was performed to determine injury to the anterior longitudinal ligament, posterior longitudinal ligament, and superior and inferior intervertebral discs and endplates. Correction loss was evaluated by the Cobb angle, intervertebral disc height, upper intervertebral disc angle, vertebral wedge angle, and vertebral body height. Results No significant relation was noted between correction loss and an injury to the anterior longitudinal ligament, posterior longitudinal ligament, inferior intervertebral disc/endplate, and fracture site, whereas an injury to the superior endplate alone and superior disc-endplate complex showed a significant association. Specifically, a superior intervertebral disc-endplate complex injury showed statistically significant relation to postoperative changes in Cobb angle (p = 0.026) and vertebral wedge angle (p = 0.047). Conclusions A superior intervertebral disc-endplate complex injury may have an influence on the prognosis after short-segment fixation in young adult patients with a stable thoracolumbar burst fracture.

Clinical Usefulness of Long-term Application of Fentanyl Matrix in Chronic Non-Cancer Pain: Improvement of Pain and Physical and Emotional Functions

Background Opioids are recently recommended for those who do not gain adequate pain relief from the use of acetaminophen or nonsteroidal anti-inflammatory drugs. Medical opioids are administered in various routes, and transdermal opioid products that can make up for the weaknesses of the oral or intravenous products have been developed. This study is to evaluate the clinical usefulness of fentanyl matrix in terms of the long-term improvement in pain and physical and mental functions. Methods This was a multicenter, open, prospective, observational study that was conducted in 54 institutions in Korea. Patients with non-cancerous chronic pain completed questionnaires, and investigators also completed questionnaires. A total of 1,355 subjects participated in this study, and 639 subjects completed the study. Subjects received transdermal fentanyl matrix (12 µg/hr, 25 µg/hr, or 50 µg/hr depending on the patients response and demand). Subjects visited at 29 ± 7 days, 85 ± 14 days, and 169 ± 14 days after administration, respectively, to receive drug titration and fill out the questionnaires. The results were analyzed using the intention-to-treat (ITT) analysis, full analysis set (FAS), and per-protocol (PP) analysis. The FAS analysis included only 451 participants; the PP analysis, 160 participants; and the ITT analysis, 1,355 participants. Results The intensity of pain measured by the Numeric Rating Scale decreased from 7.07 ± 1.78 to 4.93 ± 2.42. The physical assessment score and mental assessment score of the Short-Form Health Survey 12 improved from 28.94 ± 7.23 to 35.90 ± 10.25 and from 35.80 ± 11.76 to 42.52 ± 10.58, respectively. These differences were significant, and all the other indicators also showed improvement. Adverse events with an incidence of ≥ 1% were nausea, dizziness, vomiting, and pruritus. Conclusions The long-term administration of fentanyl matrix in patients with non-cancerous pain can reduce the intensity of pain and significantly improves activities of daily living and physical and mental capabilities.