Biomedical subjects

Shinichi Kikuchi

Publications and source records attributed to Shinichi Kikuchi.

At least 19 recordsLinked to original sources

PubMed2007

Etodolac, a selective cyclooxygenase-2 inhibitor, induces apoptosis by activating caspases in human malignant rhabdoid tumor cells (FRTK-1).

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor presenting in the kidney and soft tissue in childhood. However, effective treatment for MRT has not been established. We investigated the antitumor effect of etodolac, a selective cyclooxygenase-2 inhibitor, on MRT cells in vitro using the MRT cell line FRTK-1. Etodolac induced apoptosis of FRTK-1 cells through activation of caspase-8, -9 and -3. Moreover, several caspase inhibitors completely or partially inhibited etodolac-induced apoptosis. Our data indicated that etodolac had an antitumor effect on MRT cells and holds promise as a novel therapeutic strategy for MRT.

Amino Acid Chloromethyl Ketones↗

PubMed2006

Inferring rules of Escherichia coli translational efficiency using an artificial neural network.

Although the machinery for translation initiation in Escherichia coli is very complicated, the translational efficiency has been reported to be predictable from upstream oligonucleotide sequences. Conventional models have difficulties in their generalization ability and prediction nonlinearity and in their ability to deal with a variety of input attributions. To address these issues, we employed structural learning by artificial neural networks to infer general rules for translational efficiency. The correlation between translational activities measured by biological experiments and those predicted by our method in the test data was significant (r=0.78), and our method uncovered underlying rules of translational activities and sequence patterns from the obtained skeleton structure. The significant rules for predicting translational efficiency were (1) G- and A-rich oligonucleotide sequences, resembling the Shine-Dalgarno sequence, at positions -10 to -7; (2) first base A in the initiation codon; (3) transport/binding or amino acid metabolism gene function; (4) high binding energy between mRNA and 16S rRNA at positions -15 to -5. An additional inferred novel rule was that C at position -1 increases translational efficiency. When our model was applied to the entire genomic sequence of E. coli, translational activities of genes for metabolism and translational were significantly high.

Base Sequence↗

PubMed2006

Acute calcific tendinitis of the thumb in a child: a case report.

Acute calcific tendinitis is rare in hand and digit, especially in children. We describe a rare case of acute calcific tendinitis of the thumb [extensor pollicis longus (EPL) tendon] in a 10-year-old boy. Plain radiographs showed a calcium deposit in the EPL tendon. Conservative therapy completely resolved all symptoms in 1 week. The calcium deposit shown on plain radiographs became smaller and completely disappeared within 6 weeks.

Calcinosis↗

PubMed2006

Parameter estimation for stiff equations of biosystems using radial basis function networks.

BACKGROUND: The modeling of dynamic systems requires estimating kinetic parameters from experimentally measured time-courses. Conventional global optimization methods used for parameter estimation, e.g. genetic algorithms (GA), consume enormous computational time because they require iterative numerical integrations for differential equations. When the target model is stiff, the computational time for reaching a solution increases further. RESULTS: In an attempt to solve this problem, we explored a learning technique that uses radial basis function networks (RBFN) to achieve a parameter estimation for biochemical models. RBFN reduce the number of numerical integrations by replacing derivatives with slopes derived from the distribution of searching points. To introduce a slight search bias, we implemented additional data selection using a GA that searches data-sparse areas at low computational cost. In addition, we adopted logarithmic transformation that smoothes the fitness surface to obtain a solution simply. We conducted numerical experiments to validate our methods and compared the results with those obtained by GA. We found that the calculation time decreased by more than 50% and the convergence rate increased from 60% to 90%. CONCLUSION: In this work, our RBFN technique was effective for parameter optimization of stiff biochemical models.

Algorithms↗

PubMed2006

Discrepancy between disability and the severity of low back pain: demographic, psychologic, and employment-related factors.

STUDY DESIGN: Survey of a random sample of all registered residents of Japan between the ages of 20 and 79 years (n = 2966), focusing on those who had had low back pain (LBP) within the past month (n = 906). OBJECTIVE: To learn more about the characteristics of people in whom the severity of LBP and the disability attributed to that pain are discrepant. SUMMARY OF BACKGROUND DATA: LBP can cause disability, but levels of pain and of disability can be discrepant. Some people with severe pain are only slightly disabled, some with mild pain are very disabled, and others have no such discrepancy. METHODS.: Severity of LBP was measured with a visual analog scale. Disability was measured with the Roland-Morris Disability Questionnaire, which quantifies disability in many daily activities, not necessarily disability related to employment. The respondents also provided demographic information, and completed the SF-36 and questionnaires about perceived stress, employment, and satisfaction with employment. RESULTS: In about 45% of those patients with LBP, the severity of the pain and level of disability attributed to that pain were discrepant. People with a high level of disability despite only mild pain were older, felt more stress, were more depressed, worked more overtime, and were less satisfied with their job content, income, working conditions, and relationships with coworkers. People with little disability despite severe pain were the opposite in all those respects. CONCLUSIONS: A group of patients with LBP can be identified for whom the most appropriate interventions should consider psychosocial factors.

Adult↗

PubMed2006

TNF-alpha and phosphorylation of ERK in DRG and spinal cord: insights into mechanisms of sciatica.

STUDY DESIGN: Characterize extracellular signal-regulated kinase (ERK) and its phosphorylation (pERK) in neural tissues after topical application of tumor necrosis factor-alpha (TNF-alpha) to L5 nerve root. OBJECTIVE: Identify time-course, localization, and expression of pERK. SUMMARY OF BACKGROUND DATA: TNF-alpha has a key role in disc herniation and sciatica as an inflammatory component of the nucleus pulposus. ERK is associated with neuronal signal transduction and nociception. METHODS: We studied tissue from naive rats, vehicle-treated rats, and rats receiving rat recombinant TNF-alpha using Western blots of total and phosphorylated ERK (pERK). We used immunohistochemistry of pERK with neuronal nuclear (NeuN) antibody to identify its cellular distribution. RESULTS: Topical application of TNF-alpha to rat nerve root increased pERK in ipsilateral dorsal root ganglion (DRG) neurons and glia within 5 hours. pERK was not expressed in DRG during the first hour after TNF-alpha application, nor was it seen at anytime in spinal cord dorsal horn. DRG satellite cells had increased pERK 5 hours after TNF-alpha or vehicle treatment. TNF-alpha treatment increased pERK in small- and medium-sized DRG neurons and to a lesser degree in large neurons. CONCLUSIONS: These findings suggest that ERK signaling plays a role in the activation of DRG cells following inflammatory injuries to nerve roots and further documents the importance of inflammation in the pathogenesis of painful spine disorders.

Administration, Topical↗

PubMed2006

Changes of low back pain after vascular reconstruction for abdominal aortic aneurysm and high aortic occlusion: a retrospective study.

BACKGROUND: The purpose of the present study is to clarify the influence of acute and chronic interruption of blood flow from lumbar arteries as well as the influence of vascular reconstruction on low back pain, back muscles, and lumbar discs. METHODS: Subjects were 34 patients with AAA in whom vascular reconstruction was performed. A second group was comprised of 9 patients with HAO. The presence of low back pain before surgery and at follow-up examination was retrospectively examined in the AAA group and the HAO group to investigate postoperative changes. The CSA and degeneration of the multifidus muscle and the lumbar discs on magnetic resonance imaging were assessed in the AAA group and control group. RESULTS: Low back pain, significant atrophy, or degeneration of the multifidus muscle or degeneration of the lumbar disc did not newly develop after surgery in the AAA group. These results indicated that acute interruption of lumbar arteries did not induce the development or deterioration of low back pain and organic changes in the back muscles or lumbar discs. The frequency of low back pain before surgery was significantly higher in the HAO group than that in the AAA group. However, the frequency of low back pain after surgery did not differ significantly between the 2 groups because low back pain in the HAO group was improved after surgery. CONCLUSION: The finding that low back pain was improved by merely performing treatment for the vascular system might provide support for the presence of vascular backache.

Acute Disease↗

PubMed2006

Mid-term and long-term follow-up data after placement of the Graf stabilization system for lumbar degenerative disorders.

OBJECT: The Graf pedicle screw and ligament device is designed to provide flexible stabilization to prevent abnormal spinal movement. The purpose of this study was to investigate radiographic and clinical outcomes during a minimal 5-year follow-up period. METHODS: Between 1991 and 1997, 43 consecutive patients (whose mean age was 61 years) with lumbar degenerative disease underwent decompression and stabilization in which the Graf system was placed. Data were available for 31 patients who attended follow up for the minimal 5-year period. In a retrospective review, the authors assessed measurements on radiographs, clinical results (using Japanese Orthopaedic Association [JOA] Scale scores), and low-back pain (using a visual analog scale [VAS] score), preoperatively and postoperatively at 1, 3, 5, and/or 10 years. Radiographic measurements included sagittal and frontal range of motion (ROM), regional lordosis, and posterior disc height as well as the extent of degenerative spondylolisthesis. Final follow-up JOA and VAS scores were significantly better than preoperative scores. Sagittal and frontal ROM was significantly reduced at 1 and 5 years, respectively, compared with preoperative values, and a gradual reduction persisted throughout the follow-up period. Compared with its preoperative status, the disc height ratio (adjacent segments to the operated level) was reduced 5 years after surgery. A significant inhibition of the vertebral slippage was detected only in the flexion position. CONCLUSIONS: Analysis of these data indicated that the Graf system eventually leads to successful fusion, suggesting the presence of stability in all three dimensions. The use of the Graf system should continue to be evaluated as an alternative device in the treatment of lumbar degenerative disease.

Adult↗

PubMed2006

Establishment and characterization of a new cell line, FRTK-1, derived from human malignant rhabdoid tumor of the kidney, with overexpression of epidermal growth factor receptor and cyclooxygenase-2.

A new human malignant rhabdoid tumor (MRT) cell line (designated FRTK-1) was established from MRT of the kidney of an 18-month-old boy. The cell line is maintained for over 24 months with more than 100 passages. FRTK-1 cells in vitro showed 2 different growth patterns, adherent and non-adherent patterns. The FRTK-1 cells showed the same morphological and immunophenotypical characteristics as primary tumor cells of kidney. Cytogenetic and molecular analyses revealed a non-sense mutation in the hSNF5/INI1 gene and loss of expression of hSNF5/INI1 gene product protein. Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) were expressed in the FRTK-1 cells. Until now, there has been no report of MRT cell lines with expression of COX-2. Therefore, FRTK-1 cell line might be useful for investigating biological behavior and developing new molecular targeting antitumor drugs for MRT with expression of EGFR or COX-2.

Adolescent↗

PubMed2005

The histologic effects of pulsed and continuous radiofrequency lesions at 42 degrees C to rat dorsal root ganglion and sciatic nerve.

STUDY DESIGN: Experimental histologic study of the effects of radiofrequency (RF) or convective heating of the rat dorsal root ganglion or sciatic nerve to 42 degrees C. OBJECTIVE: To determine whether treatment causes neuropathologic changes in an effort to explore the mechanisms and safety of pulsed RF pain therapy. SUMMARY OF BACKGROUND DATA: Clinical data suggest that low temperature pulsed RF energy delivered to the DRG is a safe and effective form of therapy for low back pain. However, the mechanism by which this treatment modifies pain is unclear. METHODS: A total of 118 Sprague-Dawley rats were divided into five groups for different RF and thermal treatments. All treatments increased tissue temperature to 42 degrees C. Treatments of the DRG included pulsed RF, continuous RF, and conductive heat. The generator output was increased until 42 degrees C was obtained in the tissue and was then maintained for 120 seconds. As a positive control, some rat sciatic nerves were treated with continuous RF lesions at 80 degrees C. Animals were killed for histologic study at 2, 7, or 21 days after treatment. Tissue was fixed in gluteraldehyde and embedded in plastic resin for detailed light microscopic neuropathologic evaluation. RESULTS: The methods used to heat the tissue to 42 degrees C caused no significant difference in pathology. However, subclinical changes included endoneurial edema caused by alterations in the function of the blood-nerve barrier, fibroblast activation, and collagen deposition. Tissue returned to normal conditions by 7 days in nerve and 21 days in the DRG. These minor structural changes observed at the light microscopic level in normal animals do not exclude the possibility that there would be nonstructural changes in gene expression or cytokine upregulation in injured tissue. Lesions at 80 degrees C caused consistent thermal injury characterized by Wallerian degeneration of nerve fibers. CONCLUSIONS: The data support the hypothesis that pulsed RF treatment does not rely on thermal injury of neurologic tissue to achieve its effect.

Animals↗

PubMed2005

Nerve growth factor content in dorsal root ganglion as related to changes in pain behavior in a rat model of experimental lumbar disc herniation.

STUDY DESIGN: The time courses of nerve growth factor content and pain-related behavior were examined using experimental disc herniation models. OBJECTIVES: To investigate a relationship between nerve growth factor level and pain behavior. SUMMARY OF BACKGROUND DATA: An induction of nerve growth factor in the periphery is regarded as a major contributor of inflammatory hyperalgesia and neuropathic pain. However, it has not been clarified quantitatively whether disc herniation induces changes in nerve growth factor levels in the dorsal root ganglion in relation to pain-related behavior. METHODS: A total of 140 rats were used in this study. The animals had their left L4 nerve roots and associated dorsal root ganglion exposed and were equally divided into 4 groups: L4-L5 disc puncture, displacement of L4 nerve roots/dorsal root ganglion, the combination of disc puncture and displacement, and sham exposure. The content of nerve growth factor in the affected dorsal root ganglion was assessed by enzyme-linked immunosorbent assay as well as pain behavior during a postoperative 21-day period. RESULTS: Disc puncture resulted in nerve growth factor induction at postoperative day 3, but not apparent behavioral changes. Mechanical displacement induced nerve growth factor at postoperative day 1 and mechanical allodynia at postoperative day 3, respectively (P < 0.05). In the combination model, there were more pronounced changes in nerve growth factor induction and both mechanical and thermal threshold during 7 days after surgery (P < 0.05). CONCLUSIONS: These data suggest the possibilities that elevated nerve growth factor level is partly involved in pain behavior and further the combined model mimicking the clinical situation, which causes the marked neuronal responses, is helpful to advance the understanding of the mechanisms underlying sciatica due to lumbar disc herniation.

Animals↗

PubMed2005

Large-scale prediction of cationic metabolite identity and migration time in capillary electrophoresis mass spectrometry using artificial neural networks.

We developed a computational technique to assist in the large-scale identification of charged metabolites. The electrophoretic mobility of metabolites in capillary electrophoresis-mass spectrometry (CE-MS) was predicted from their structure, using an ensemble of artificial neural networks (ANNs). Comparison between relative migration times of 241 various cations measured by CE-MS and predicted by a trained ANN ensemble produced a correlation coefficient of 0.931. When we used our technique to characterize all metabolites listed in the KEGG ligand database, the correct compounds among the top three candidates were predicted in 78.0% of cases. We suggest that this approach can be used for the prediction of the migration time of any cation and that it represents a powerful method for the identification of uncharacterized CE-MS peaks in metabolome analysis.

Cations↗

PubMed2005

Effect of acute nerve root compression on endoneurial fluid pressure and blood flow in rat dorsal root ganglia.

The objective of the current study was to test the hypothesis that crush injury to nerve root increases endoneurial fluid pressure (EFP) and decreases blood flow in the associated dorsal root ganglion (DRG). A total of 21 adult, female Sprague-Dawley rats had their left L5 nerve root and DRG exposed. The L5 nerve root was clamped for 2 s with a vascular suture clip just proximal to the DRG (compression group). Sham-operated animals without compression were used for control (control group). EFP was recorded with a servo-null micropipette system using a glass micropipette with tip diameter of 4 mum before and after 3 h of treatment. After the final measurement of EFP, DRG was excised and processed for histology. Blood flow in the DRG was continuously monitored by laser Doppler flow meter for 3 h. Three hours after treatment, EFP was 4.7+/-2.7 cm H(2)O in the compression group and 2.2+/-1.2 cm H(2)O in the control group (P<0.05). Edema was the principal pathologic findings seen consistently in the DRG from animals in the compression group. Blood flow in the compression group was reduced 10 min after compression. This reduction was statistically significant compared with that of the control (P<0.01). An acute compression to the nerve root increased endoneurial edema, increased EFP in the associated DRG, and reduced DRG blood flow. This combination of increased EFP and decreased blood flow in the DRG may result in neuronal ischemia and sensory dysfunction. These acute pathophysiologic changes may thus have a role in the pathogenesis of low back pain and sciatica due to disc herniation and spinal canal stenosis.

Acute Disease↗

PubMed2004

Reverse engineering of biochemical equations from time-course data by means of genetic programming.

Increased research aimed at simulating biological systems requires sophisticated parameter estimation methods. All current approaches, including genetic algorithms, need pre-existing equations to be functional. A generalized approach to predict not only parameters but also biochemical equations from only observable time-course information must be developed and a computational method to generate arbitrary equations without knowledge of biochemical reaction mechanisms must be developed. We present a technique to predict an equation using genetic programming. Our technique can search topology and numerical parameters of mathematical expression simultaneously. To improve the search ability of numeric constants, we added numeric mutation to the conventional procedure. As case studies, we predicted two equations of enzyme-catalyzed reactions regarding adenylate kinase and phosphofructokinase. Our numerical experimental results showed that our approach could obtain correct topology and parameters that were close to the originals. The mean errors between given and simulation-predicted time-courses were 1.6 x 10(-5)% and 2.0 x 10(-3)%, respectively. Our equation prediction approach can be applied to identify metabolic reactions from observable time-courses.

Algorithms↗

PubMed2004

Inflammatory cytokines released from the facet joint tissue in degenerative lumbar spinal disorders.

STUDY DESIGN: A prospective study of surgical cases of degenerative lumbar spinal disorders demonstrated inflammatory cytokines in the facet joint tissue. OBJECTIVE: To quantify various inflammatory cytokines released from the facet joint tissue in surgical cases of degenerative lumbar spinal disorders. SUMMARY OF BACKGROUND DATA: In degenerative lumbar spinal disorders, pain is often caused by osteoarthritis of a facet joint. There are inflammatory mediators such as prostaglandins and leukotrienes in facet joint tissue in lumbar spinal degeneration. However, no reports have studied if there are also inflammatory cytokines in the facet joint, which generated arthropathic changes in degenerative lumbar spinal disorder and if pain is caused by chemical factors associated with inflammation such as inflammatory cytokines. METHODS: Forty patients with degenerative lumbar disorders who had undergone operative treatment were included in this study. Fifty-five joint cartilages and 67 synovia were harvested from the lumbar facet joints in responsible intervertebral levels of patients. There were 24 male and 16 female subjects with average ages of 50 and 67 years, respectively, in 11 cases of lumbar disc herniation and 29 cases of lumbar spinal canal stenosis. Using ELISA and CLEIA methods, joint cartilage and synovial tissues were harvested during surgery from the facet joint at the responsible upper levels to measure IL-1beta, TNF-alpha, and IL-6 in individual tissues. RESULTS: IL-1beta was detected in joint cartilage and synovium in both groups and its positive reaction rate was higher in LSCS than in LDH. There was no difference in IL-1beta concentration in cartilage tissue between the two groups. There was TNF-alpha in the synovium of LSCS. IL-6 was high in joint cartilage and synovium in both groups. The concentration was significantly higher in LSCS than in LDH. CONCLUSIONS: There are inflammatory cytokines in facet joint tissue at high levels in degenerative lumbar spinal disorders. Inflammatory cytokines have a higher concentration rate in lumbar spinal canal stenosis than in lumbar disc herniation. This finding suggests that inflammatory cytokines in degenerated facet joints may have some relation to the cause of pain in degenerative lumbar disorders.

Aged↗

PubMed2004

Infliximab attenuates immunoreactivity of brain-derived neurotrophic factor in a rat model of herniated nucleus pulposus.

STUDY DESIGN: The effect of infliximab, a chimeric monoclonal antibody to TNF-alpha, on induction of brain-derived neurotrophic factor (BDNF) was examined using an experimental herniated nucleus pulposus (NP) model. OBJECTIVES: To investigate whether treatment of infliximab could attenuate an induction of BDNF, which functions as a modulator of pain, following NP application to the nerve root. SUMMARY OF BACKGROUND DATA: Evidence from basic scientific studies proposes that TNF-alpha is involved in the development of NP-induced nerve injuries. However, the therapeutic mechanisms of infliximab against pain have not been elucidated experimentally. METHODS: Twenty rats were used in this study. In the test groups, the animals underwent application of NP to the L4 nerve roots and received a single systemic (intraperitoneal) injection of infliximab at the time of surgery (Infli-0 group, n = 5) or at 1 day after operation (Infli-1 group, n = 5). As a control treatment, sterile water was administered intraperitoneally to 5 rats with NP application (NP group) and to 5 sham-operated rats (sham group). On day 3 after surgery, the L4 dorsal root ganglion (DRG) and L4 spinal segment were harvested and assessed regarding BDNF immunoreactivity. RESULTS.: Application of NP induced a marked increase of BDNF immunoreactivity in number in the DRG neurons and within the superficial layer in the dorsal horn compared with the sham group (P < 0.01). Infliximab treatment in the Infli-0 and Infli-1 groups reduced the BDNF induction in both DRG and spinal cord (P < 0.05). CONCLUSION: These findings indicate that infliximab attenuates the elevated BDNF levels induced by NP. The present study therefore further indicates the importance of TNF-alpha in sciatica due to disc herniation and the possible therapeutic use of a TNF-alpha inhibitor for this condition.

Administration, Topical↗

PubMed2004

Arthroscopic thermal shrinkage for hypermobile lateral meniscus.

BACKGROUND: The posterior segment of the lateral meniscus is relatively mobile as compared with that of the medial meniscus; that is because of its characteristic anatomy. Abnormal mobility of the lateral meniscus with no obvious rupture can be an unusual cause of knee pain and locking during deep knee flexion. PURPOSE: To evaluate results for a small series of patients with hypermobile lateral meniscus, treated with thermal shrinkage of the supporting ligaments. STUDY DESIGN: Series of case reports. METHOD: Five patients with hypermobile lateral meniscus were identified out of 625 patients who underwent meniscus surgery over a 20-month period. Thermal energy was applied to the peripheral zone of the lateral meniscus until abnormal translation was reduced. The patients were followed up an average of 21 months after the surgery. RESULTS: In 4 patients, no recurrence of locking was encountered in the postoperative period. In 1 patient, locking was experienced again 3 months after surgery and meniscal repair was performed. CONCLUSIONS: Thermal shrinkage can be considered an appropriate treatment in place of subtotal meniscectomy or meniscal repair for hypermobility of the lateral meniscus.

Adolescent↗

PubMed2004

Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain.

STUDY DESIGN: An analysis of pathologic changes after different degrees of cauda equina compression. OBJECTIVES: To explore the association between the degree of the cauda equina compression and the extent of pathologic change, expression of tumor necrosis factor (TNF-alpha), and neuropathic pain. To compare with distal nerve compression injury. SUMMARY OF BACKGROUND DATA: Compression of the cauda equina reduces blood flow in compressed nerve roots and causes TNF-alpha expression and neuropathological change. In peripheral nerve, expression of TNF-alpha in Schwann cells is associated with primary demyelination without pain while TNF-alpha expression by macrophages is associated with axonal (Wallerian) degeneration and pain. METHODS: Two square-shaped pieces of silicon were placed into the fourth and sixth epidural space in rats. Various sized silicon was used in each group (mild, moderate, and strong compression groups), while no silicon was used in the sham-operated group. Mechanical allodynia was determined by the von Frey test. Comparisons of the number of TNF-alpha- and apoptosis-positive cells were made using immunohistochemistry. RESULTS: There was no significant mechanical allodynia observed in any group. Some nerve roots showed demyelination following mild cauda equina compression. Axonal degeneration was observed in the moderate and strong cauda equina compression groups. TNF-alpha-immunoreactive cells were increased in all compression groups. Apoptosis of dorsal root ganglion cells was less than apoptosis in the spinal cord. CONCLUSION: Mild cauda equina compression induces TNF-alpha expression and demyelination. Moderate and strong cauda equina compression induces TNF-alpha expression and degeneration associated with macrophage invasion. Neither demyelination nor degeneration in the cauda equina induced mechanical allodynia. Nerve lesions proximal to the dorsal root ganglion do not produce significant mechanical allodynia. Dorsal root ganglion apoptosis may be important for pain.

Animals↗