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OBJECTIVEThis study investigated neurological improvements after conservative treatment in patients with complete motor paralysis caused by acute cervical spinal cord injury (SCI) without bone and disc injury.METHODSThis study was retrospective. The authors evaluated neurological outcomes after conservative treatment of 62 patients with complete motor paralysis caused by cervical SCI without bone and disc injury within 72 hours after trauma. The sequential changes in their American Spinal Injury Association Impairment Scale (AIS) grades were reviewed at follow-up 24–72 hours, 1 week, and 1, 3, and 6 months after treatment.RESULTSOf the 31 patients with a baseline AIS grade of A, 2 (6.5%) patients improved to grade B, 5 (16.1%) improved to grade C, and 2 (6.5%) improved to grade D by the 6-month follow-up. The 22 (71.0%) patients who remained at AIS grade A 1 month after injury showed no neurological improvement at the 6-month follow-up. Of the 31 patients with a baseline AIS grade of B, 12 (38.7%) patients showed at least a 1-grade improvement at the 1-month follow-up; 11 (35.5%) patients improved to grade C and 16 (51.6%) patients improved to grade D at the 6-month follow-up.CONCLUSIONSEven in patients with complete motor paralysis caused by cervical SCI without bone and disc injury within 72 hours after trauma, approximately 30% of the patients with an AIS grade of A and 85% of the patients with an AIS grade B improved neurologically after conservative treatment. It is very important to recognize the extent of neurological improvement possible with conservative treatment, even for severe complete motor paralysis.

Study DesignRetrospective review.PurposeTo describe a safe and effective surgical procedure for old distractive flexion (DF) injuries of the subaxial cervical spine.Overview of LiteratureSurgical treatment is required in old cases when a progression of the kyphotic deformity and/or persistent neck pain and/or the appearance of new neurological symptoms are observed. Since surgical treatment is more complicated and dangerous in old cases than in acute distractive-flexion cases, the indications for surgery and the selection of the surgical procedure must be carefully conducted.MethodsTo identify a safe and effective surgical procedure, the procedure selected, reason(s) for its selection, and associated neurological complications were investigated in 13 patients with old cervical DF injuries.ResultsNo neurological complications were observed in nine patients (DF stage 2 or 3) who underwent the anterior-posterior-anterior (A-P-A) method and two patients (DF stage 1) who underwent the posterior method. It was initially planned that two patients (DF stage 2) who underwent the P-A method would be treated using the Posterior method alone; however, anterior discectomy was added to the procedure after the development of a severe spinal cord disorder.ConclusionsThe A-P-A method (anterior discectomy, posterior release and/or partial facetectomy, reduction and instrumentation, anterior bone grafting) is considered to be a suitable surgical procedure for old cervical DF injuries.

Several prognostic studies looked for an association between the degree of spinal cord injury (SCI), as depicted by primary magnetic resonance imaging (MRI) within 72 hours of injury, and neurologic outcome. It was not clearly demonstrated whether the MRI at any time correlates with neurologic prognosis.The purpose of the present study was to investigate the relationship between acute MRI features and neurologic prognosis, especially walking ability of patients with cervical spinal cord injury (CSCI). Moreover, at any point, MRI was clearly correlated with the patient's prognosis.Retrospective image study.From January 2010 to October 2015, 102 patients with CSCI were treated in our hospital. Patients who were admitted to our hospital within 3 days after injury were included in this study. The diagnosis was 78 patients for CSCI with no or minor bony injury and 24 patients for CSCI with fracture or dislocation. A total of 88 men and 14 women were recruited, and the mean patient age was 62.6 years (range, 16-86 years). Paralysis at the time of admission was graded as A in 32, B in 15, C in 42, and D in 13 patients on the basis of the American Spinal Injury Association (ASIA) impairment scale. Patients with CSCI with fracture or dislocation were treated with fixation surgery and those with CSCI with no or minor bony injury were treated conservatively. Patients were followed up for an average of 168 days (range, 25-496 days).Neurologic evaluation was performed using the ASIA motor score and the modified Frankel grade at the time of admission and discharge.Magnetic resonance imaging was performed for all patients at admission. Using the MRI sagittal images, we measured the vertical diameter of intramedullary high-intensity changed area with T2-weighted images at the injured segment. We studied separately the patients divided into two groups: 0-1 day admission after injury, and 2-3 days admission after injury. We evaluated the relationship between the vertical diameter of T2 high-intensity changed area in MR images and neurologic outcome in these two groups. This study does not contain any conflict of interest.In the group admitted at 0-1 day after injury, there was a relationship between the vertical diameter of T2 high-intensity area in MR image and the ASIA motor score at admission and at discharge, but correlation coefficient was low (0.3766 at admission and 0.4239 at discharge). On the other hand, in the group admitted at 2-3 days after injury, there was a significant relationship between the vertical diameter of T2 high-intensity area in MR image and the ASIA motor score at admission and at discharge, and correlation coefficient was very high (0.6840 at admission and 0.5293 at discharge). In the group admitted at 2-3 days after injury, a total of 17 patients (68%) recovered to walk with or without a cane. Receiver operating characteristic (ROC) curve analysis demonstrated that the optimal vertical diameter of T2 high-intensity area cutoffvalue for patients who were able to walk at discharge was 45.8 mm. If the vertical diameter of T2 high-intensity area cutoff value was 45 mm, there was a significant positive correlation with being able to walk at discharge (p.0001).From our study, 2-3 days after injury, a significant relationship was observed between the vertical diameter of T2 high-intensity area and the neurologic prognosis at discharge. Zero to 1 day after injury, the relationship between the vertical diameter of T2 high-intensity area and the neurologic prognosis at discharge was weak. Neurologic prognosis is more correlated with MRI after 2-3 days after the injury. If the vertical diameter of T2 high-intensity area was45 mm, the patients were able to walk with or without a cane at discharge. T2 high-intensity changed area can reflect the neurologic prognosis in patients with CSCI.

Retrospective chart audits. To investigate the optimal timing at which permanent complete cervical spinal cord injury (CSCI) can be confirmed when evaluating paralysis caused by traumatic CSCI. Department of Orthopedic Surgery, Spinal Injuries Center, Japan. Two-hundred and three patients with CSCI that was classified with an American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A (AIS A) within 72 h of the initial diagnosis of traumatic CSCI were included in the present study. Neurological data from the time of the initial diagnosis to 1 year after the injury were extracted. The number of those with recovery from AIS A and changes of AIS in the recovery were examined. Thirty-five of 203 (17%) patients whose injuries were initially classified with an AIS A showed recovery from AIS A. Thirty-four of 35 (97%) patients showed recovery from AIS A within 8 weeks after injury. If CSCI patients with AIS A have not recovered by 8 weeks, the likelihood that they will recover from AIS A is marginal. However, this conversely means that we must consider the possibility that a patient with a traumatic CSCI classified with an AIS A may still show recovery from AIS A within the first 8 weeks after injury.

Introduction Compressive-flexion type cervical spine fracture is typically accompanied by apparent dislocation of the facet joints, undesirable cervical alignment, and devastating neurological dysfunction, which provides strong rationale for rendering prompt operative treatment. However, the validity of conservative treatment for compressive-flexion cervical spine injury in cases with preserved congruity of the facet joints has yet to be elucidated. The purpose of this study is to evaluate the long-term outcome of cervical alignment following conservative treatment for compressive-flexion cervical spine injury with preserved congruity of the facet joints. Methods A total of 662 patients who experienced spinal cord injury from 2007 to 2017 were included and underwent retrospective review in a single institute. Thirteen patients were identified as receiving conservative therapy following compressive-flexion cervical spine fractures with spinal cord injury. Clinical and radiological results were collected, including vertical fractures of the vertebral column, laminar fractures, progression of local kyphosis, and neurological status. The degree of the local cervical kyphosis was evaluated with two methods: the posterior tangent method and the endplate method. Results All 13 patients were male, and the mean age at the time of injury was 28.4 years. The mean follow-up period was 3 years. Although none of the patients presented neurological deterioration after the injury, the degree of local kyphosis was increased at the time of final follow-up compared to what was observed at the time of injury. Patient age at the time of injury and concurrent vertical fracture of vertebral body could have been influencing factors for the progression of the kyphosis. While laminar fracture affected the kyphosis at the time of injury, it was not a strong influencing factor of the overall progression of local kyphosis. Conclusions The conservative option for the compressive-flexion cervical injury allowed us to treat without exacerbating neurological symptoms as long as the facet joints are preserved. However, in terms of cervical alignment, surgical stabilization may have been desirable for these patients. Notably, the younger patients and the patients with vertical fracture of the cervical vertebral column in this type of injury required closer observation to help prevent the progression of local kyphosis.

Prospective cohort study. To elucidate serial changes in dysphagia and elucidate the critical period for dysphagia following acute traumatic cervical spinal cord injury (CSCI). Spinal Injuries Center, Fukuoka, Japan. We prospectively examined individuals with acute traumatic CSCI admitted within 2 weeks after injury. Severity of dysphagia was evaluated using both the dysphagia severity scale (DSS) and functional oral intake scale (FOIS) at 2 weeks, 1 month, 2 months, and 3 months after injury. Condition of oral intake before injury was assessed by history taking. American Spinal Injury Association (ASIA) impairment scale grade and motor scores were also assessed at the same timepoints, and the correlation between dysphagia and paresis was analyzed. Sixty-five individuals with CSCI were assessed consecutively for 3 months after injury. Swallowing function, evaluated using both the DSS and FOIS, was significantly decreased at 2 weeks after injury, but significantly improved thereafter. Significant correlations between severity of dysphagia (DSS and FOIS scores) and motor scores were found at 2 weeks after injury (rs = 0.66 and 0.61; p

Study design Retrospective review. Objective To evaluate the influence of static compression factors and dynamic factors based on the various degrees of traumatic force on the cervical spinal cord injury (SCI) in patients with ossification of the posterior longitudinal ligament. Summary of background data Spinal cord disorder occurs as a result of various factors, including static factors and traumatic force. Discussions about the severity of paralysis resulting from SCI must therefore focus on dynamic factors based on the traumatic force as well as on static compression factors. However, the past reports did not describe the influence of traumatic force in detail. Methods Fifty patients presenting with cervical SCI associated with ossification of the posterior longitudinal ligament were included in this study. The American Spinal Injury Association motor score 3 days after injury, the degree of the traumatic force, and the spinal cord compression rate were investigated, and the relationships among these factors were investigated. Results Paralysis at the time of injury was not determined by static factors alone or by traumatic force alone. The severity of paralysis at the time of injury was determined on the basis of a combination of both the static factors and the degree of traumatic force. Conclusion Both the degree of spinal cord compression and the degree of traumatic force were found to be important factors associated with the severity of cervical SCI in patients with ossification of the posterior longitudinal ligament. Level of evidence 4.

Study design A retrospective imaging and clinical study. Objective To evaluate the extraneural soft-tissue damage and its clinical relevance in patients with traumatic cervical spinal cord injury (SCI) without major bone injury. Summary of background data To date, various kinds of cervical discoligamentous injuries have been demonstrated on magnetic resonance images in patients with SCI without bony injury. However, it has not been clear whether these magnetic resonance imaging abnormalities are actually related to spinal segmental instability and the patients' neurological status. Methods Eighty-eight adult patients with acute traumatic cervical SCI without major bone injury were examined by flexion-extension lateral radiographs and magnetic resonance images within 2 days after trauma. We excluded patients with flexion recoil injury; therefore, most of the patients included were considered to have sustained a hyperextension injury. Instability of the injured cervical segment was defined when there was more than 3.5-mm posterior translation and/or more than a 11° difference in the intervertebral angle between the site of interest and adjacent segments. The neurological status was evaluated according to the American Spinal Injury Association motor score. Results On magnetic resonance images, the damage to the anterior longitudinal ligament and intervertebral disc were apparent in 44 and 37 patients, respectively. Various degrees of prevertebral fluid collection (prevertebral hyperintensity) were demonstrated in 76 patients. These magnetic resonance imaging abnormalities were significantly associated with initial cervical segmental instability as judged by flexion-extension radiographs. Interestingly, the American Spinal Injury Association motor score had a significant association with either magnetic resonance imaging abnormalities or segmental instability but not with the cervical canal diameter. Conclusion A considerable proportion of the patients with traumatic cervical SCI without major bone injury were shown to have various types of soft-tissue damage associated with cervical segmental instability at the early stages of the injury. The severity of paralysis greatly depended on these discoligamentous injuries.

The fully human monoclonal antibody KMTR2 acts as a strong direct agonist for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), which is capable of inducing apoptotic cell death without cross-linking. To investigate the mechanism of direct agonistic activity induced by KMTR2, the crystal structure of the extracellular region of TRAIL-R2 and a Fab fragment derived from KMTR2 (KMTR2-Fab) was determined to 2.1 Å resolution. Two KMTR2-Fabs assembled with the complementarity-determining region 2 of the light chain via two-fold crystallographic symmetry, suggesting that the KMTR2-Fab assembly tended to enhance TRAIL-R2 oligomerization. A single mutation at Asn53 to Arg located at the two-fold interface in the KMTR2 resulted in a loss of its apoptotic activity, although it retained its antigen-binding activity. These results indicate that the strong agonistic activity, such as apoptotic signaling and tumor regression, induced by KMTR2 is attributed to TRAIL-R2 superoligomerization induced by the interdimerization of KMTR2.

A retrospective radiographic study with a minimum 2-year follow-up.To evaluate the relationships between the cervical articular facets' morphology and the incidence of traumatic cervical spinal cord injury (CSCI) without major fracture or dislocation.Spinal Injuries Center, Japan.This study included 113 patients with traumatic CSCI without major fracture or dislocation. Eighty-four healthy volunteers without neurological deficits or cervical cord pathology on magnetic resonance imaging (MRI) were defined as control subjects. We used a plain sagittal radiograph to measure the facet sagittal angles (FSA) at four cervical segments in all the CSCI patients and controls. We defined the FSA as the angle between the inferior margin of the superior cervical spinal body and the inferior articular process of the superior vertebra.Most frequent incidence of CSCI was seen at C3-4 segment (54%). With respect to CSCI at C3-4 segment, 55.7% of the subjects showed smallest FSA at C3-4 segment.Most of the traumatic CSCI at C3-4 segment showed raised cervical articular facets at C3-4 segment. On the basis of our results, we hypothesized that the raised cervical articular facets might have an important role in the etiology of traumatic CSCI. The cervical spinal cord at the C3-4 segment might receive the highest load during acute hyperextension of the cervical spine because of the C3-4 articular facets' morphology.

Metabolic flux analysis using (13)C enrichment data of intracellular free amino acids (FAAs) can improve the time resolution of flux estimation compared to analysis of proteinogenic amino acid data owing to the faster turnover times of FAAs. The nature of the (13)C enrichment dynamics of FAAs remains obscure, however, especially with regard to its dependence on culture conditions, even though an understanding of dynamic behavior is important for precise metabolic flux estimation. In this study, we analyzed the (13)C enrichment dynamics of free and proteinogenic amino acids in a series of continuous culture experiments with Escherichia coli. The results indicated that the effect of protein degradation on the (13)C enrichment of FAAs was negligible under cellular growth conditions. Furthermore, they showed that the time scale necessary for (13)C enrichment dynamics of FAAs to reach a steady state depends on culture conditions such as oxygen uptake rate, which was likely due to different pool sizes of intracellular metabolites. The results demonstrate the importance of analyzing (13)C enrichment dynamics for the precise estimation of metabolic fluxes using FAA data.

STUDY DESIGN A retrospective, consecutive case series. OBJECTIVE To determine the risk factors that have a significant correlation with the severity of neurologic impairment in thoracolumbar and lumbar burst fractures. SUMMARY OF BACKGROUND DATA The correlation between spinal canal stenosis due to bony fragments and the severity of neurologic deficits in thoracolumbar and lumbar burst fractures remains controversial. Moreover, there have so far been no reports in the literature in which the risk factors (spinal canal stenosis and the disruption of posterior ligamentous complex) causing a severe neurologic deficit were analyzed using a multiple logistic regression model. METHODS A review of the clinical data (neurologic impairments on admission and a finding of posterior ligamentous complex disruption at the time of operation), axial computed tomography, and plain lateral radiography of 216 patients in thoracolumbar (T11-L1) and lumbar (L2-L5) burst fractures was performed. The factors related to neurologic impairments were analyzed using a multiple logistic regression model. RESULTS In all cases, both the spinal canal stenosis (P < 0.01) and disruption of posterior ligamentous complex (P < 0.01) were significant risk factors. Interestingly, these two risk factors varied according to the injury levels: at thoracic level, the spinal canal stenosis (P < 0.01); at the first lumbar spine, the disruption of the posterior ligamentous complex (P < 0.01); and at the lumbar spine below L2, both of the spinal canal stenosis (P < 0.01) and the disruption of posterior ligamentous complex (P < 0.05) were significant risk factors, respectively. CONCLUSION In the patients with thoracolumbar and lumbar burst fractures, the significance of the two important risk factors related to clinical results, namely, the stenosis ratio of spinal canal and the disruption of posterior ligamentous complex, were found to vary depending on the level of injury.

Corynebacterium glutamicum was genetically engineered to produce L-alanine from sugar under oxygen deprivation. The genes associated with production of organic acids in C. glutamicum were inactivated and the alanine dehydrogenase gene (alaD) from Lysinibacillus sphaericus was overexpressed to direct carbon flux from organic acids to alanine. Although the alaD-expressing strain produced alanine from glucose under oxygen deprivation, its productivity was relatively low due to retarded glucose consumption. Homologous overexpression of the gapA gene encoding glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in the alaD-expressing strain stimulated glucose consumption and consequently improved alanine productivity. In contrast gapA overexpression did not affect glucose consumption under aerobic conditions, indicating that oxygen deprivation engendered inefficient regeneration of NAD+ resulting in impaired GAPDH activity and reduced glucose consumption in the alanine-producing strains. Inactivation of the alanine racemase gene allowed production of L-alanine with optical purity greater than 99.5%. The resulting strain produced 98 g l(-1) of L-alanine after 32 h in mineral salts medium. Our results show promise for amino acid production under oxygen deprivation.

歩行障害により発症した脊髄くも膜嚢腫の1例を経験したので報告する．症例は59歳，女性．2ヶ月前より痙性歩行，下肢脱力，歩行障害が出現したため当センター入院となる．58歳時に小脳橋角部くも膜嚢腫手術の既往があった．著明な痙性歩行．Th12以下で痛覚，触覚は低下し，両第1足趾の位置覚は消失．両下肢腱反射は亢進．左下肢筋力に低下を認めた．CTMでは左Th8/9，9/10レベルでの脊髄の圧迫が著明であった．この症例に対しTh8-10椎弓切除術，嚢腫摘出術，経くも膜下腔的嚢腫壁開放術，くも膜下腔―くも膜下腔bypass術を施行した．術後は筋力，下肢の位置覚共に回復し，独歩可能となった．くも膜嚢腫の発生には何らかの先天性素因の関与が示唆された．

When human antibody genes were expressed in the methylotrophic yeast Ogataea minuta, the secreted antibody became partially degraded. To suppress the degradation, a vacuolar protease-deficient strain was constructed and its antibody production was evaluated. Although antibody productivity was improved in the vacuolar protease-deficient strain, the secreted antibody still became partially degraded. Peptide sequencing revealed that the cleavage occurred in the CH1 region of the heavy chain, implying that the cleavage was caused by an aspartic protease, Yps1p. To inhibit this cleavage, Yps1p-deficient strains were constructed and their antibody production was evaluated. As a result, the partial degradation of the antibody was suppressed in the O. minuta multiple-protease-deficient strains.

Study design Retrospective case series. Purpose To clarify the influence of cervical spinal canal stenosis (CSCS) on neurological functional recovery after traumatic cervical spinal cord injury (CSCI) without major fracture or dislocation. Overview of literature The biomechanical etiology of traumatic CSCI remains under discussion and its relationship with CSCS is one of the most controversial issues in the clinical management of traumatic CSCI. Methods To obtain a relatively uniform background, patients non-surgically treated for an acute C3-4 level CSCI without major fracture or dislocation were selected. We analyzed 58 subjects with traumatic CSCI using T2-weighted mid-sagittal magnetic resonance imaging. The sagittal diameter of the cerebrospinal fluid (CSF) column, degree of canal stenosis, and neurologic outcomes in motor function, including improvement rate, were assessed. Results There were no significant relationships between sagittal diameter of the CSF column at the C3-4 segment and their American Spinal Injury Association motor scores at both admission and discharge. Moreover, no significant relationships were observed between the sagittal diameter of the CSF column at the C3-4 segment and their neurological recovery during the following period. Conclusions No relationships between pre-existing CSCS and neurological outcomes were evident after traumatic CSCI. These results suggest that decompression surgery might not be recommended for traumatic CSCI without major fracture or dislocation despite pre-existing CSCS.

OBJECT Axial neck pain after C3–6 laminoplasty has been reported to be significantly lesser than that after C3–7 laminoplasty because of the preservation of the C-7 spinous process and the attachment of nuchal muscles such as the trapezius and rhomboideus minor, which are connected to the scapula. The C-6 spinous process is the second longest spinous process after that of C-7, and it serves as an attachment point for these muscles. The effect of preserving the C-6 spinous process and its muscular attachment, in addition to preservation of the C-7 spinous process, on the prevention of axial neck pain is not well understood. The purpose of the current study was to clarify whether preservation of the paraspinal muscles of the C-6 spinous process reduces postoperative axial neck pain compared to that after using nonpreservation techniques. METHODS The authors studied 60 patients who underwent C3–6 double-door laminoplasty for the treatment of cervical spondylotic myelopathy or cervical ossification of the posterior longitudinal ligament; the minimum follow-up period was 1 year. Twenty-five patients underwent a C-6 paraspinal muscle preservation technique, and 35 underwent a C-6 nonpreservation technique. A visual analog scale (VAS) and VAS grading (Grades I–IV) were used to assess axial neck pain 1–3 months after surgery and at the final follow-up examination. Axial neck pain was classified as being 1 of 5 types, and its location was divided into 5 areas. The potential correlation between the C-6/C-7 spinous process length ratio and axial neck pain was examined. RESULTS The mean VAS scores (± SD) for axial neck pain were comparable between the C6-preservation group and the C6-nonpreservation group in both the early and late postoperative stages (4.1 ± 3.1 vs 4.0 ± 3.2 and 3.8 ± 2.9 vs 3.6 ± 3.0, respectively). The distribution of VAS grades was comparable in the 2 groups in both postoperative stages. Stiffness was the most prevalent complaint in both groups (64.0% and 54.5%, respectively), and the suprascapular region was the most common site in both groups (60.0% and 57.1%, respectively). The types and locations of axial neck pain were also similar between the groups. The C-6/C-7 spinous process length ratios were similar in the groups, and they did not correlate with axial neck pain. The reductions of range of motion and changes in sagittal alignment after surgery were also similar. CONCLUSIONS The C-6 paraspinal muscle preservation technique was not superior to the C6-nonpreservation technique for preventing postoperative axial neck pain.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically induces apoptosis in tumor cells but may be toxic to human hepatocytes. Although hepatocytes are susceptible to apoptotic signals mediated by TRAIL-receptor 2 (TRAIL-R2), we previously reported that some anti-TRAIL-R2 monoclonal antibodies (mAbs) produce little hepatocyte toxicity. Those mAbs neutralized the cytotoxic activity of TRAIL by inhibiting receptor–ligand binding. The hepatocyte-toxic mAbs did not compete with TRAIL for binding to TRAIL-R2, and potentiated ligand activity in both cancer cells and hepatocytes. A neutralizing antibody to TRAIL inhibited hepatocyte death by anti-TRAIL-R2 mAbs, suggesting that the toxicity may reflect their ability to potentiate membrane-bound TRAIL on hepatocytes.

Sixty-three patients with delayed neurologic deficit due to post-traumatic osteoporotic burst fractutes underwent various kinds of operative methods. Anterior decompression and fusion was performed on eleven patients, posterior decompression and fusion on twenty-five patients, posterior fusion on six patients, posterior spinal shortening on five patients, and vertebroplasty on sixteen patients. Neurologic deficit recovered in all groups but posterior decompression and fusion provided the best results statistically. Posterior spinal shortening improved the correction rate of kyphosis, which did not differ significantly in other groups. Postoperative back pain was less in all patients even though kyphosis remained. Posterior fusion and vertebroplasty provided less blood loss and shorter operative time than other groups. We recommend posterior fusion with vertebroplasty in the absence of posterior compression of the spinal cord. Anterior decompression / fusion or posterior spinal shortening is recommended over surgery for this disease.

Monoclonal antibodies have already established a secure position as a very promising strategy for anti-tumor therapeutics. High specificity and high affinity are attractive characteristics of antibodies which make them suitable for clinical applications. Advances in genetic engineering have enabled to generate recombinant antibodies which circumvent the problems of using murine antibodies in human therapy. Immunological effects, specific delivery of antibody conjugated-toxins to target cancer cells, and direct effects through receptor engagement by antibodies have been exploited as mechanisms which generate anti-tumor activity.Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and can induce apoptosis in a wide variety of human cancer cell lines via its interactions with TRAIL receptor 1 (TRAIL-R1) and TRAIL receptor 2 (TRAIL-R2), but does not affect most normal human cells. From the clinical viewpoint, the use of a recombinant soluble form of TRAIL and agonistic antibodies specific for TRAIL-R1 and TRAIL-R2 as anti-tumor agents have been investigated. These promising therapeutic agents are now undergoing clinical investigations.In this review, we summarize the characteristics of recently developed anti-tumor therapeutic antibodies and discuss the current status of therapeutic approaches targeting TRAIL receptors, both by application of TRAIL and by treatment with agonistic monoclonal antibodies. Both these strategies show great promise as therapeutic agents for treatment of cancer patients.

Condensation of nitrobenzaldehydes 3 and alpha-[o-(p-methoxybenzylthio)benzoyl] sulfoxide 4 gave alpha-sulfinyl enones 5. Treatment of 5 with formic acid caused cyclization followed by debenzylation to afford 3-(methylsulfinyl)thioflavanones 6. Double-bond formation with elimination of methanesulfenic acid was performed by refluxing 6 in benzene, and, finally, the nitro group of 2-phenyl-4H-1-benzothiopyran-4-one (thioflavones) 7 was reduced with tin in tetrafluoroboric acid. Various 2'-aminothioflavones 8 thus prepared were evaluated for their inhibitory effects on the ERK-MAP kinase pathway. In a cell-based assay, 2-(2'-amino-3'-methoxyphenyl)-4H-1-benzothiopyran-4-one (8b) showed a more potent inhibitory effect than the corresponding oxygen compound (PD98059, 1) on the Raf-induced activation of the ERK-MAP kinase pathway as well as cell proliferation. Furthermore, compound 8b selectively and potently inhibited the proliferation of tumor cells in which the ERK-MAP kinase pathway is constitutively activated.

Japan Highway Public Corporation (JH) has been developing advanced road operation system. The system was named P-MAC (Protection system of Maintenance vehicle Against Collisions) that prevents maintenance vehicles working at low speed on expressways from rear-end collision. The P-MAC uses vehicle detection sensors and an on board VMS (Variable Message Sign) for warning. The pilot model have been established through some pre-studies and field experiments.

Intramedullary cavernous haemangioma is very rare, and often diagnosed before intramedullary bleeding. We experienced six cases (five female, two male) from 1980 to 2001 in our hospital. Their ages ranged from 24 to 60 years. Lesions were located from the lower cervical to middle thoracic medulla. Magnetic resonance imaging (MRI) showed T2: low indicating intramedullary bleeding in most cases. We used the Frankel scale for neurological assessments. Five at of the six cases underwent laminectomy and microscopic tumor extirpation. Two operated cases suffered complicated posterior cord disturbance. However, five cases except one preoperative Frankel A nainfained Frankel D at the end of follow-up (from one month to seven yers, eight months). The changes in hemoglobin lead to MRI findings: T1; isointensity/T2; hypointensity at acute bleeding, T1; hyperintensity/T2; hyperintensity at subacufe bleeding, and T1; hypointensity/T2; hypointensity at over one month after bleeding. The most important findings of cavernous haemangioma are not enhanced at Gd-DTPA, and there are no abnormal findings by angiography. We recommend patients with symptoms to undergo operation as early as possible when diagnosed as cavernous haemangioma.

Intraspinal cysts are rarely observed in patients. They are distinguished from neoplasm using magnetic resonance imaging (MRI) or computed tomography (CT) because they rarely cause bony erosive changes. We treated three cases of intraspinal cysts causing bony erosion. Patients ranged from fifty-five to seventy-one years, and symptoms and signs resembled disc herniation. Signal-intensity patterns and pathological finding of these lesions were variable. They were adjacent to degenerated facet joints. Treatment involved surgical excision of the cysts. Many lumbar intraspinal cysts may be associated with significantly degenerated facet joints. Bleeding into or around the cysts may invade the vertebral body.

A retrospective imaging and clinical study.To evaluate the relationship between magnetic resonance imaging (MRI) features and neurological prognosis in patients with traumatic cervical spinal cord injury (CSCI) without major bone injury.A total of 72 patients with CSCI without major bone injury were treated conservatively in our hospital. MRI was performed for all patients at admission and 1 month following injury. We measured the antero-posterior and cranio-caudal diameter of intramedullary intensity changed area with T1-weighted images at the injured segment. Neurological evaluations were performed using the American Spinal Injury Association (ASIA) motor score and the modified Frankel grade at the time of admission and discharge.There was a significant relationship between the antero-posterior diameter ratio of the T1-weighted low-intensity area on MRI at the subacute stage and the ASIA motor score. The optimal threshold of the T1-weighted low-intensity diameter ratio for predicting the patient's ability to walk with or without assistance at discharge was determined to be 46%. Moreover, 96.8% of the patients with50% T1-weighted low-intensity area recovered to walk with or without a cane at discharge.The T1-low intensity area may be an important predictive factor for the neurological recovery of CSCI without major bone injury.

Local Sagittal Alignment after Indirect Reduction and 2-Level Short-Segment Pedicle Screw Fixation of Thoracolumbar Burst Fractures The treatment of thoracolumbar burst fractures with short-segment pedicle screw fixation alone has been associated with progressive loss of correction and instrumentation failure. However, some burst fractures can be treated successfully by this technique without correction loss or implant failure.

The treatment of alkynylselenonium salt and various thiophenol derivatives with a catalytic amount of triethylamine gave beta-arylthioalkenylselenonium salts in good yields. The alkenylselenonium salts thus prepared reacted with nucleophiles such as acetylides, thiolates, and alkoxides to produce (Z)-beta-arylthio-alpha-functionalized ethenes in high yields. The vinylselenonium salts bearing a hydroxy group on a beta-side chain caused intramolecular cyclization upon treatment with sodium hydride to produce medium-membered heterocyclic compounds containing sulfur and oxygen atoms. The reactions giving (Z)-beta-arylthio-alpha-functionalized ethenes would proceed via the formation of selenurane intermediates followed by the ligand coupling reaction.

The treatment of alkynylselenonium salts and thiophenol derivatives with a catalytic amount of triethylamine afforded β-arylthiovinylselenonium salts in good yields. The reactions of the vinylselenonium salts with nucleophiles produced (Z)-β-arylthio-α-functionalized ethenes in high yields. In addition, the vinylselenonium salts bearing a hydroxy group, 2d-f, 2h, underwent intramolecular cyclization upon treatment with sodium hydride to produce medium-membered heterocyclic compounds containing S and O atoms.

In mammalian cells, the p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to a variety of environmental stresses and inflammatory stimuli. However, the role of p38 MAPK signaling in unchallenged conditions remains largely unknown. We have isolated mutations in a Drosophila p38 MAPKK gene homolog, licorne (lic), and show that during oogenesis, lic is required in the germ line for correct asymmetric development of the egg. In lic mutant egg chambers, oskar mRNA posterior localization is not properly maintained, resulting in anteroposterior patterning defects in the embryo. Furthermore, lic loss-of-function in the germ line leads to reduced EGF receptor activity in dorsal follicle cells and ventralization of the egg shell. Both these defects are associated with a diminution of gurken protein levels in the oocyte. Our phenotypic data argue for a role of lic in a post-transcriptional regulation of the grk gene. Furthermore, they show that in addition to the well-characterized Ras/Raf/ERK MAPK pathway acting in the follicle cells, another related signaling cascade, the p38 MAPK pathway, is required in the germ line for correct axes determination. These results provide the first genetic demonstration of an essential function for a p38 pathway during development.