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1.  Radiographic Assessment of Effect of Congenital Monosegment Synostosis of Lower Cervical Spine between C2-C6 on Adjacent Mobile Segments 
Asian Spine Journal  2014;8(5):615-623.
Study Design
A prospective radiographic study of cervical spine with congenital monosegment fusion.
To evaluate the effect of cervical synostosis on adjacent segments and the vertebral morphology.
Overview of Literature
There are numerous clinical studies of adjacent segment disease (ASD) after monosegment surgical fusion. However, there was no report on ASD in the cervical spine with congenital monosegment synostosis.
Radiograms of 52 patients, aged 5 to 90 years, with congenital monosegment synostosis (CMS) between C2 and C6, who complained of neck/shoulder discomfort or pain were studied. 51 were normally aligned and one was kyphotically aligned.
Spondylosis was not found in the patients below 35 years of age. Only 12 out of 24 patients with normally aligned C2-3 synostosis had spondylosis in 19 more caudal segments, and only one at C3-4. A patient with kyphotic C2-3 had spondylolysis at C3-4. In 8 patients with C3-4 synostosis, spondylosis was found in only 9 caudal segments (4 at C4-5, 4 at C5-6, and 1 at C6-7). The caudate C4-5 disc was the most liable to degenerate in comparison with other caudate segments. Caudal corporal flaring and inwaisting of the synostotic vertebra were the features that were the most evident. In 2 of 9 C4-5 and 7 out of 10 C5-6 synostosis patients, spondylosis was found at the two adjacent cephalad and caudate segments, respectively. Only corporal inwaisting without flaring was found. In all cases, spondylosis was confined to the adjacent segments. More advanced spondylosis was found in the immediate caudal segment than the cephalad one.
It is concluded that spondylosis at the mobile segments in a synostotic spine is thought to be a fusion-related pathology rather than solely age-related disc degeneration. Those data suggested that CMS definitely precipitated the disc degeneration in the adjacent segments.
PMCID: PMC4206811  PMID: 25346814
Synostosis; Cervical; Congenital; Alignment; Adjacent segment disease
2.  Asteropsins B–D, sponge-derived knottins with potential utility as a novel scaffold for oral peptide drugs 
Biochimica et biophysica acta  2013;1840(3):977-984.
Known linear knottins are unsuitable as scaffolds for oral peptide drug due to their gastrointestinal instability. Herein, a new subclass of knottin peptides from Porifera is structurally described and characterized regarding their potential for oral peptide drug development.
Asteropsins B–D (ASPB, ASPC, and ASPD) were isolated from the marine sponge Asteropus sp. The tertiary structures of ASPB and ASPC were determined by solution NMR spectroscopy and that of ASPD by homology modeling.
The isolated asteropsins B–D, together with the previously reported asteropsin A (ASPA), compose a new subclass of knottins that share a highly conserved structural framework and remarkable stability against the enzymes in gastrointestinal tract (chymotrypsin, elastase, pepsin, and trypsin) and human plasma.
Asteropsins can be considered as promising peptide scaffolds for oral bioavailability.
General significance
The structural details of asteropsins provide essential information for the engineering of orally bioavailable peptides.
PMCID: PMC4139099  PMID: 24225326
Knottin; Marine sponge; Asteropus sp; NMR; Solution structure; Oral peptide drug delivery
3.  Effect of Correction of the Contractured Flexed Osteoarthritic Knee on the Sagittal Alignment by Total Replacement 
Asian Spine Journal  2013;7(3):204-211.
Study Design
A prospective analysis of an adaptive change of the spinopelvic alignment after total knee arthroplasty.
To evaluate the effect of correction of the contractured knee in flexion on the spinopelvic alignment by total knee arthroplasty.
Overview of Literature
Flexion contracture of the knee joint may affect the body posture and precipitate the symptoms in the lumbar spine, which is known as the 'knee-spine syndrome'.
Fifteen patients who could be followed at least over 12 months were used in this study. Neutral whole spine lateral standing radiograms taken at certain intervals were analyzed. The subjects were divided into two groups (group A, the patients who obtained over 10° correction; group B, the others). The sacral slope, the pelvic tilt and the pelvic incidence were measured preoperatively and at 12 months and thereafter postoperatively in all the patients. Also, the thoracic kyphosis, lumbar lordosis, and lumbosacral angle were measured, including the spinal sagittal balance, S1 overhang and spino-sacral angle.
The average correction of the contractured knee in flexion were 13.8° in group A and 2.7° in group B. The median of changes of the sacral slope were 4.2° in group A and -0.4° in group B. These results revealed that there was a significant increase of the sacral slope for group A (p=0.001). However, there were no significant differences between the other parameters.
The sacral slope appears to be affected by the change of the flexion contracture after total knee arthroplasty.
PMCID: PMC3779772  PMID: 24066216
Sagittal; Alignment; Spine; Pelvis; Total knee arthroplasty
4.  Identification of Chromosomal HP0892-HP0893 Toxin-Antitoxin Proteins in Helicobacter pylori and Structural Elucidation of Their Protein-Protein Interaction* 
The Journal of Biological Chemistry  2013;288(8):6004-6013.
Background: HP0892 of H. pylori shares high structural similarity with other toxin-antitoxin (TA) system toxins.
Results: RNase activity and cell toxicity of HP0892 is inhibited by HP0893 via strong protein-protein interaction.
Conclusion: HP0892-HP0893 pair is a TA system with a protein-protein interaction mode similar to other TA pairs.
Significance: It is highly probable that HP0892-HP0893 TA pair is involved in H. pylori virulence.
Bacterial chromosomal toxin-antitoxin (TA) systems have been proposed not only to play an important role in the stress response, but also to be associated with antibiotic resistance. Here, we identified the chromosomal HP0892-HP0893 TA proteins in the gastric pathogen, Helicobacter pylori, and structurally characterized their protein-protein interaction. Previously, HP0892 protein was suggested to be a putative TA toxin based on its structural similarity to other RelE family TA toxins. In this study, we demonstrated that HP0892 binds to HP0893 strongly with a stoichiometry of 1:1, and HP0892-HP0893 interaction occurs mainly between the N-terminal secondary structure elements of HP0892 and the C-terminal region of HP0893. HP0892 cleaved mRNA in vitro, preferentially at the 5′ end of A or G, and the RNase activity of HP0892 was inhibited by HP0893. In addition, heterologous expression of HP0892 in Escherichia coli cells led to cell growth arrest, and the cell toxicity of HP0892 was neutralized by co-expression with HP0893. From these results and a structural comparison with other TA toxins, it is concluded that HP0892 is a toxin with intrinsic RNase activity and HP0893 is an antitoxin against HP0892 from a TA system of H. pylori. It has been known that hp0893 gene and another TA antitoxin gene, hp0895, of H. pylori, are both genomic open reading frames that correspond to genes that are potentially expressed in response to interactions with the human gastric mucosa. Therefore, it is highly probable that TA systems of H. pylori are involved in virulence of H. pylori.
PMCID: PMC3581365  PMID: 23297406
Helicobacter pylori; Nuclear Magnetic Resonance; Protein Structure; Protein-Protein Interactions; Ribonuclease; HP0892; HP0893; YafQ; Toxin-Antitoxin System; Virulence
5.  Spinal tuberculosis in children: Retrospective analysis of 124 patients 
Indian Journal of Orthopaedics  2012;46(2):150-158.
There is a paucity of report on spinal tuberculosis in children. We report a retrospective analysis of 124 children with TB spine treated over 30 years.
Materials and Methods:
We retrospectively reviewed 124 children; of cervical (n=36), cervicothoracic (n=4), thoracic (n=53), and lumbar and lumbosacral tuberculosis (n=31) with no skip or multifocal lesions treated between 1971-2004. The age ranged from 2 to 15 years of age with 28 children less than 5 years of age, 58 were between 6 and 10 years, and 38 were over 10 years, 18 had paraplegia of various degrees. Ninety-one children were treated conservatively, while 33 children were subjected to surgery for focal debridement (n=23), posterior interspinous wiring and cementation (n=4), and posterior instrumentation with rods and segmental wiring (n=14). Triple chemotherapy (isoniazid, streptomycin, and PAS) was given for 18 months (3HSPa, 15Hpa) between 1971 and 1975, and triple or quadruple chemotherapy (isoniazid, rifampicin, ethambutol, or pyrazinamide) after 1976 to 2004 for 12 months (12RHZ or 12 RHZE). Some of the children in the current series belonged to the British MRC conservative study patients. The average duration of followup was 5 years and 8 months (range 1.6-20 years).
All children attained healed status and showed neural recovery (n=18). The patients attained healed status at 18 months in the first series and at 12 months in the second series after chemotherapy. Spontaneous intercorporal fusion occurred only in 10 (8.06%) of 124 children. Sagittal curve during growth showed three different patterns: Unchanged, decreased, and increased curves. The residual kyphosis was unavoidable in cases with growth plate damage. Kyphosis increased in cases with wedged monovertebra and fused wedged block vertebra, though it was different at different level.
The vertebral reformation and curve correction were possible only through the growth plates. The posterior instrumented stabilization alone could correct and/or prevent progress of the kyphosis. However, for active tuberculosis, posterior instrumented stabilization combined with anterior radical surgery should be reserved only for the advanced tuberculosis with instability, rapid progress of kyphosis, and/or unacceptable pre-existing kyphosis, though there is a new trend of prophylactic posterior instrumentation even for the early tuberculosis.
PMCID: PMC3308655  PMID: 22448052
Tuberculosis; spine; children; kyphosis; instrumented stabilization
6.  Activity Optimization of an Undecapeptide Analogue Derived from a Frog-Skin Antimicrobial Peptide 
Molecules and Cells  2011;31(1):49-54.
While natural antimicrobial peptides are potential therapeutic agents, their physicochemical properties and bioactivity generally need to be enhanced for clinical and commercial development. We have previously developed a cationic, amphipathic α-helical, 11-residue peptide (named herein GA-W2: FLGWLFKWASK-NH2) with potent antimicrobial and hemolytic activity, which was derived from a 24-residue, natural antimicrobial peptide isolated from frog skin. Here, we attempted to optimize peptide bioactivity by a rational approach to sequence modification. Seven analogues were generated from GA-W2, and their activities were compared with that of a 12-residue peptide, omiganan, which is being developed for clinical and commercial applications. Most of the modifications reported here improved antimicrobial activity. Among them, the GA-K4AL (FAKWAFKWLKK-NH2) peptide displayed the most potent antimicrobial activity with negligible hemolytic activity, superior to that of omiganan. The therapeutic index of GAK4AL was improved more than 53- and more than 31-fold against Gram-negative and Gram-positive bacteria, respectively, compared to that of the starting peptide, GAW2. Given its relatively shorter length and simpler amino acid composition, our sequence-optimized GA-K4AL peptide may thus be a potentially useful antimicrobial peptide agent.
PMCID: PMC3906872  PMID: 21110126
activity optimization; amphipathic helix; antimicrobial activity; antimicrobial peptide; hemolytic activity; sequence modification
7.  Structural and biochemical characterization of HP0315 from Helicobacter pylori as a VapD protein with an endoribonuclease activity 
Nucleic Acids Research  2012;40(9):4216-4228.
VapD-like virulence-associated proteins have been found in many organisms, but little is known about this protein family including the 3D structure of these proteins. Recently, a relationship between the Cas2 family of ribonucleases associated with the CRISPR system of microbial immunity and VapD was suggested. Here, we show for the first time the structure of a member of the VapD family and present a relationship of VapD with Cas2 family and toxin–antitoxin (TA) systems. The crystal structure of HP0315 from Helicobacter pylori was solved at a resolution of 2.8 Å. The structure of HP0315, which has a modified ferredoxin-like fold, is very similar to that of the Cas2 family. Like Cas2 proteins, HP0315 shows endoribonuclease activity. HP0315-cleaved mRNA, mainly before A and G nucleotides preferentially, which means that HP0315 has purine-specific endoribonuclease activity. Mutagenesis studies of HP0315 revealed that D7, L13, S43 and D76 residues are important for RNase activity, in contrast, to the Cas2 family. HP0315 is arranged as an operon with HP0316, which was found to be an antitoxin-related protein. However, HP0315 is not a component of the TA system. Thus, HP0315 may be an evolutionary intermediate which does not belong to either the Cas2 family or TA system.
PMCID: PMC3351183  PMID: 22241770
8.  Surgical management of severe rigid tuberculous kyphosis of dorsolumbar spine 
International Orthopaedics  2010;35(1):75-81.
To assess the effectiveness of deformity correction and safety of the two major corrective spinal surgical procedures, 35 patients, aged 14–47 years, were placed into two groups according to procedures performed. Sixteen patients (group A) had four-stage procedures including initial halo-pelvic distraction after anterior release and a subsequent three procedural steps plus brace. Nineteen patients (group B) had one-set two-stage procedures: wire segmental stabilisation in eight cases and rod/hook and/or pedicle screw stabilisation in 11 cases. Average preoperative kyphosis in group A was 88° and postoperative at zero, three, six, and 18 months were 29˚, 33˚, 35˚ and 35˚, respectively, while those of group B were 86˚ preoperative and postoperative 27˚, 31˚, 33˚, and 33˚, respectively. Neural complication developed in five cases: one in group A and four in group B. It was concluded that the one-set two-stage procedure is more efficient, time-saving, and cost-effective, though it is highly challenging with relatively high rates of neural complication.
PMCID: PMC3014483  PMID: 20349356
9.  Chronic Osteomyelitis of the Lumbar Transverse Process 
Clinics in Orthopedic Surgery  2011;3(3):254-257.
Pyogenic spondylitis involving only the posterior element of a vertebra is rare. To the best of our knowledge, there have been no reports of osteomyelitis of the transverse process. We report here on a 45-year-old male with a one month history of swelling associated with lower back pain. The magnetic resonance imaging showed a paraspinal soft tissue mass, and computed tomography revealed a fine osteolytic lesion in the right transverse process of the 5th lumbar spine, and this was all consistent with chronic osteomyelitis. A mixed staphylococcal infection was identified. Open drainage, resection of the transverse process and intravenous injection of anti-staphylococcal antibiotics resolved the back pain and reduced the erythrocyte sedimentation rate to normal. Pyogenic osteomyelitis of the transverse process is extremely rare, which can cause a misdiagnosis or a delayed diagnosis. Careful consideration of this disease is needed when evaluating patients who complain of back pain.
PMCID: PMC3162208  PMID: 21909475
Osteomyelitis; Transverse process; Lumbar spine
11.  Identification of H-Ras-Specific Motif for the Activation of Invasive Signaling Program in Human Breast Epithelial Cells12 
Neoplasia (New York, N.Y.)  2011;13(2):98-107.
Increased expression and/or activation of H-Ras are often associated with tumor aggressiveness in breast cancer. Previously, we showed that H-Ras, but not N-Ras, induces MCF10A human breast epithelial cell invasion and migration, whereas both H-Ras and N-Ras induce cell proliferation and phenotypic transformation. In an attempt to determine the sequence requirement directing the divergent phenotype induced by H-Ras and N-Ras with a focus on the induction of human breast cell invasion, we investigated the structural and functional relationships between H-Ras and N-Ras using domain-swap and site-directed mutagenesis approaches. Here, we report that the hypervariable region (HVR), consisting of amino acids 166 to 189 in H-Ras, determines the invasive/migratory signaling program as shown by the exchange of invasive phenotype by swapping HVR sequences between H-Ras and N-Ras. We also demonstrate that the H-Ras-specific additional palmitoylation site at Cys184 is not responsible for the signaling events that distinguish between H-Ras and N-Ras. Importantly, this work identifies the C-terminal HVR, especially the flexible linker domain with two consecutive proline residues Pro173 and Pro174, as a critical domain that contributes to activation of H-Ras and its invasive potential in human breast epithelial cells. The present study sheds light on the structural basis for the Ras isoform-specific invasive program of breast epithelial cells, providing information for the development of agents that specifically target invasion-related H-Ras pathways in human cancer.
PMCID: PMC3033589  PMID: 21403836
12.  Spinal deformity 
Indian Journal of Orthopaedics  2010;44(2):123-126.
PMCID: PMC2856386  PMID: 20418998
13.  Low Grade Fibromyxoid Sarcoma in Thigh 
Clinics in Orthopedic Surgery  2009;1(4):240-243.
A low grade fibromyxoid sarcoma is a rare soft tissue tumor that has a tendency to develop in the deep soft tissue of young adults and the potential for local recurrence or distant metastasis. There have been several case reports and sporadic reports in the literature. However, only 1 case has been reported in Korea but without a follow-up result. We describe a 54-year-old female patient with a low-grade fibromyxoid sarcoma of the thigh that had been growing slowly for 34 years. A marginal resection of this tumor was performed. Currently, the patient is doing well without evidence of local recurrence or distant metastasis at 5 years after surgery.
PMCID: PMC2784966  PMID: 19956483
Low grade fibromyxoid sarcoma; Thigh
14.  Multiple Pyogenic Spondylodiscitis with Bilateral Psoas Abscesses Accompanying Osteomyelitis of Lateral Malleolus - A Case Report - 
Asian Spine Journal  2008;2(2):102-105.
A psoas abscess is a potentially life-threatening infection. Multiple pyogenic spondylodiscitis with bilateral psoas abscesses accompanying an osteomyelitis of the lateral malleolus is an extremely rare event. We present our experience with needle aspiration for the treatment of osteomyelitis of the lateral malleolus and CT-guided percutaneous catheter drainage for a psoas abscess in an elderly patient. Both infections were completely resolved without recurrence. A psoas abscess should be included in the differential diagnosis of a patient with low back pain during musculoskeletal infection. Percutaneous needle aspiration or CT-guided percutaneous catheter drainage is an effective method for treating certain musculoskeletal infections.
PMCID: PMC2852090  PMID: 20404964
Spondylodiscitis with psoas abscess; Osteomyelitis of lateral malleolus; CT-guided percutaneous drainage
15.  Lumbar Pyogenic Spondylodiscitis and Bilateral Psoas Abscesses Extending to the Gluteal Muscles and Intrapelvic Area Treated with CT-guided Percutaneous Drainage - A Case Report - 
Asian Spine Journal  2008;2(1):51-54.
Bilateral psoas abscesses extending to the gluteal muscle and intrapelvic area are uncommon. We present our experience with computed tomography (CT)-guided percutaneous catheter drainage for the treatment of multiple aggressive abscesses in a diabetic patient. The abscesses completely resolved after the procedures. Psoas abscess should be considered in the differential diagnosis of older diabetic patients with fever, flank or back pain, and flexion contracture of the hip joint. CT scanning is a useful method in diagnosing abscesses, and CT-guided percutaneous catheter drainage is an effective treatment method in selected patients.
PMCID: PMC2857484  PMID: 20411143
Psoas abscess extending into the gluteal muscle and intrapelvic area; Diabetic patient; CT-guided percutaneous drainage
16.  Spinal Epidural Abscess with Pyogenic Arthritis of Facet Joint Treated with Antibiotic-Bone Cement Beads - A Case Report - 
Asian Spine Journal  2007;1(1):61-64.
Most epidural abscesses are a secondary lesion of pyogenic spondylodiscitis. An epidural abscess associated with pyogenic arthritis of the facet joint is quite rare. To the best of our knowledge, there is no report of the use of antibiotic-cement beads in the surgical treatment of an epidural abscess. This paper reports a 63-year-old male who sustained a 1-week history of radiating pain to both lower extremities combined with lower back pain. MRI revealed space-occupying lesions, which were located in both sides of the anterior epidural space of L4, and CT scans showed irregular widening and bony erosion of the facet joints of L4-5. A staphylococcal infection was identified after a posterior decompression and an open drainage. Antibiotic- bone cement beads were used as a local controller of the infection and as a spacer or an indicator for the second operation. An intravenous injection of anti-staphylococcal antibiotics resolved the back pain and radicular pain and normalized the laboratory findings. We point out not only the association of an epidural abscess with facet joint infection, but also the possible indication of antibiotic-bone cement beads in the treatment of epidural abscesses.
PMCID: PMC2857502  PMID: 20411156
Epidural abscess; Facet joint infection; Lumbar spine; Antibiotic-bone cement bead

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