Biomedical subjects
S Kikuchi
Publications and source records attributed to S Kikuchi.
Embarking on rice functional genomics via cDNA microarray: use of 3' UTR probes for specific gene expression analysis.
Explore the source record for details and available documents.
2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats.
STUDY DESIGN: This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs. OBJECTIVE: The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor-alpha at the same molecular weight to study its neuropathologic effect on rat nerve root and dorsal root ganglion preparations in vivo. SUMMARY OF BACKGROUND DATA: Expressed by herniated nucleus pulposus in culture, tumor necrosis factor-alpha causes neuropathologic injury in nerve roots and neuropathic pain states in which mechanical allodynia is seen in response to peripheral stimuli. METHODS: Western blotting was used to identify the molecular weight of the operative tumor necrosis factor-alpha protein form, and measures of optical density were used for semiquantitative determination of concentration. Plastic-embedded nerve roots and dorsal root ganglion were used for neuropathologic evaluation, and von Frey stimulation was used to quantify mechanical allodynia. RESULTS: The 17-kDa form of tumor necrosis factor-alpha is expressed by herniated nucleus pulposus at a concentration of approximately 0.48 ng per herniated rat lumbar disc. Exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots. CONCLUSIONS: The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.
Disclosure of results of gastric-cancer operations in Japan.
Explore the source record for details and available documents.
Aureusidin synthase: a polyphenol oxidase homolog responsible for flower coloration.
Aurones are plant flavonoids that provide yellow color to the flowers of some popular ornamental plants, such as snapdragon and cosmos. In this study, we have identified an enzyme responsible for the synthesis of aurone from chalcones in the yellow snapdragon flower. The enzyme (aureusidin synthase) is a 39-kilodalton, copper-containing glycoprotein catalyzing the hydroxylation and/or oxidative cyclization of the precursor chalcones, 2',4',6',4-tetrahydroxychalcone and 2',4',6',3,4-pentahydroxychalcone. The complementary DNA encoding aureusidin synthase is expressed in the petals of aurone-containing varieties. DNA sequence analysis revealed that aureusidin synthase belongs to the plant polyphenol oxidase family, providing an unequivocal example of the function of the polyphenol oxidase homolog in plants, i.e., flower coloration.
Effect of 1,25-dihydroxyvitamin D(3) on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L-buthionine sulfoximine and 1-methyl-4-phenylpyridine.
A decrease in intracellular glutathione content may be related to the primary event in Parkinson's disease, so increasing the glutathione level may have a therapeutic benefit. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D(3) [1, 25-(OH)(2)D(3)] has been recently reported to enhance the intracellular glutathione concentration in the central nervous system. Exposing rat cultured mesencephalic neurons for 24 hr to a mixture of L-buthionine sulfoximine (BSO) and 1-methyl-4-phenylpyridium ions (MPP(+)) resulted in a relatively selective damage to dopaminergic neurons. This damage has been accompanied by a reduction of intracellular glutathione levels. Low doses, i.e., 1-100 nM, of 1,25-(OH)(2)D(3) protect cultured dopaminergic neurons against this toxicity, although higher concentrations of this active form of vitamin D have been found to enhance the toxic effect. Generation of reactive oxygen species (ROS) by this toxicity has been attenuated in cultures being pretreated with low concentrations of 1,25-(OH)(2)D(3). Because the hormone increases the intracellular glutathione content in cultures, determining how this hormone suppresses ROS generation may involve the enhancement of the antioxidative system. These data suggest that low doses of 1,25-(OH)(2)D(3) are able to protect mesencephalic dopaminergic neurons against BSO/MPP(+)-induced toxicity that causes a depletion in glutathione content.
Estrogen receptor gene polymorphism in Japanese patients with multiple sclerosis.
Estrogen has been reported to have immunosuppressive functions, and to inhibit the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Since estrogen shows its biological effects via estrogen receptors (ER), we investigate the possible role of ER genes (ERG) in the pathogenesis of MS. PvuII and XbaI polymorphisms in ERG were detected by PCR-RFLP from the DNA of 79 conventional MS patients and 73 healthy controls. The [P] allele in the profiles in PvuII was significantly more prevalent in MS patients than in the controls (P<0.0005). In the study of XbaI polymorphism, the onset age of MS patients with the Xx genotype was earlier than that of the xx genotype group (mean age+/-S.D.; 22.60+/-8.04, and 27.49+/-9.14, respectively) (P<0.05) by ANOVA followed by Fisher's PLSD. Although the Xx genotype group tended to earlier onset age than the XX genotype group (29.60+/-11.10), this difference did not reach. On the basis of these results, PvuII polymorphism might be associated with susceptibility to MS, and XbaI polymorphism with onset age of MS. ERG polymorphism should be further studied in other populations to improve strategies for treatment of MS.
Macrophage migration inhibitory factor in the cerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro-Behçet's disease.
Macrophage migration inhibitory factor (MIF) is becoming increasingly recognized as an important regulator of immune and inflammatory responses. It is released by activated T lymphocytes and macrophages and up-regulates the proinflammatory activity of these cells. MIF is required for antigen- and mitogen-driven T cell activation, and stimulates macrophages to release cytokines and nitric oxide. On the basis of the recent suggestion that pharmacological modulation of MIF production and neutralization of its activity may have important implications for treatment of a variety of autoimmune or inflammatory conditions, we determined the level of MIF in the cerebrospinal fluid (CSF) of patients with conventional-form multiple sclerosis (C-MS) and optic-spinal form multiple sclerosis (OpS-MS), and neuro-Behçet's disease (NBD). As control, the CSF of patients with non-inflammatory neurological diseases (NIND) was used. The concentration of MIF in CSF samples was significantly elevated in relapsed cases of C-MS (4.13+/-1.07 ng/ml) (mean+/-S.D.) compared with control samples (2.38+/-0.60 ng/ml) (P<0.0001), whereas MIF in the CSF of C-MS patients in remission was not elevated (2.65+/-0.67 ng/ml). The concentration of MIF in the CSF of OpS-MS patients in relapse (5.53+/-1.74 ng/ml) was higher than that of patients with C-MS in relapse (P<0.05). In NBD patients, the concentration of MIF in CSF was significantly elevated (7.47+/-5.61 ng/ml) compared with control samples (P<0.01) and correlated well with cell count in these samples (r=0.910, P<0.005). These results suggest that MIF may play a pivotal role in immune-mediated diseases of the central nervous system, and that MIF may be useful in the study of differences between C-MS and OpS-MS.
Cloning and characterization of the promoter of murine cytohesin-1 gene.
Mouse cytohesin-1 (CTH-1) is a guanine nucleotide exchange factor, specific for ADP ribosylation factors. The CTH-1 gene promoter was characterized by deletion mapping and mutational analysis. The region between -101 and -38 relative to the transcription start site showed the essential promoter activity when transfected into both NIH3T3 and COS7 cells. The nucleotides of the core promoter region contain three tandem GC boxes, which can offer potential binding sites for the ubiquitous transcription factor Sp-1 family. Mutational analysis revealed that these tandem GC boxes are indispensable for activation of the gene transcription.
Mandibulofacial dysostosis: CT evaluation of the temporal bones for surgical risk assessment in patients of bilateral aural atresia.
We present the results of detailed CT investigation of nine patients with mandibulofacial dysostosis (MFD). We also graded the severity of microtia according to Marx's classification system. The results revealed a positive correlation between the severity of microtia and the severity of deformity of the external auditory canal, and attic formation. In 13 ears, the stapes was not adequately visualized to allow any comment on its form. The angle of the first genu of the facial nerve ranged from 55.0 to 123.6 degrees (mean +/-S.D.; 99.5 +/-18.5 degrees ), indicating that this angle is more obtuse in MFD patients than in normal subjects. The eustachian tube and tympanic sinus were present in all the ears examined. None of the patients had mastoid pneumatization. In four ears, the lateral semicircular canal was dysplastic. Eleven ears of six patients scored less than 5 in the grading system developed by Jahrsdoerfer for assessment of the suitability for atresia surgery. These findings indicate that most patients with mandibulofacial dysostosis are poor surgical candidates.
Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles.
We have previously reported that the association between Bsm I polymorphism, one of the vitamin D receptor genes (VDRG) polymorphism, and multiple sclerosis (MS). In this report, we investigated the further possible role or relevance of VDRG in the pathogenesis of MS. Apa I polymorphism was detected by PCR-RFLP from the DNA of 77 conventional MS patients and 95 healthy controls. The study of the Bsm I and Apa I haplotypes was carried out by employing previously reported Bsm I data. The AA genotype and the [A] allele in the profiles were significantly more prevalent in MS patients than in controls (P=0.0070 and P=0.0321, respectively). In the [A] allele-positive MS patients, the positive rate of DPB1*0501 in HLA was significantly higher than that of the [A] allele-positive controls and that of the [A] allele-negative MS patients even when the corrected P value (P(corr)) was applied (P(corr)=0.0220 and P(corr)=0.0077, respectively). The frequency of DRB1*1501 was higher in the [A] allele-positive patients than in the [A] allele-positive controls and the [A] allele-negative patients (P(uncorr)=0.0431 and P(uncorr)=0.0089, respectively), but the P values did not reach statistical significance after P corrections. The rate of Bsm I and Apa I haplotypes was much higher in bA/bA-positive MS patients than in the controls (P=0.0003), and in the bA positive MS patients, the positive rate of DPB1*0501 was higher than that of the bA-positive controls and that of the bA-negative MS patients (P(corr)=0.0308 and P(corr)=0.0033, respectively). These results indicate that VDRG polymorphism may be associated with susceptibility to MS, and HLA alleles may correlate with risk for MS together with VDRG.
Deep brain stimulation of subthalamic area for severe proximal tremor.
Proximal tremors are often refractory to nucleus ventrointermedius thalami thalamotomy. Subthalamotomy has been suggested to be effective for treatment of tremor, although this procedure is associated with considerable adverse effects, and has rarely been considered a suitable treatment modality. The authors demonstrate the efficacy and safety of subthalamic deep brain stimulation in two patients, one with a severe, refractory proximal essential tremor and one with tremor with dystonia.
Application of nucleus pulposus to the nerve root simultaneously reduces blood flow in dorsal root ganglion and corresponding hindpaw in the rat.
STUDY DESIGN: An experimental study to clarify the effects of nucleus pulposus on blood flow in the dorsal root ganglion and hindpaws. OBJECTIVES: To investigate the effects of application of nucleus pulposus to nerve root on blood flow in the dorsal root ganglion and the corresponding hindpaw. SUMMARY OF BACKGROUND DATA: It has been reported experimentally that application of nucleus pulposus into the epidural space induces morphologic and functional changes in the nerve roots and induces compartment syndrome in the dorsal root ganglia. However, it has not been clarified which of these changes induces symptoms in the lower limbs. METHODS: Sixteen adult, female Sprague-Dawley rats had the left L5 nerve root and associated dorsal root ganglions exposed. Autologous nucleus pulposus was applied to the L5 nerve root, just proximal to the dorsal root ganglion (NP group). For control, the same volume of muscle tissue was applied similarly to the neural tissue (control group). Blood flow in the dorsal root ganglion, corresponding hindpaw, and the contralateral hindpaw was continuously monitored by two-channel laser Doppler flowmeter for 3 hours. After measurement of blood flow, the nerve root and dorsal root ganglion were processed for histology and evaluated by light microscope. RESULTS: Blood flow in the NP group was reduced, not only in the dorsal root ganglion, but also in the corresponding hindpaw. These reductions were statistically significant compared with the control group (P < 0.01). Edema was the principal pathologic finding seen consistently in the nerve roots and in many of the associated dorsal root ganglia from nucleus pulposus-treated animals. CONCLUSION: Application of nucleus pulposus to nerve root decreased blood flow in the dorsal root ganglion and corresponding hindpaw. These basic pathophysiologic changes are associated with compression injuries caused by herniated discs and are accepted neuropathologic mechanisms of injury associated with painful neuropathies. These acute observations in the dorsal root ganglion and the hindpaw may be important initial factors in the pathogenesis of radicular leg pain (sciatica) due to disc herniation.
Prospective study of surgical treatment of degenerative spondylolisthesis: comparison between decompression alone and decompression with graf system stabilization.
STUDY DESIGN: A prospective study of patients with degenerative spondylolisthesis who underwent decompression of the spine, with and without stabilization using the Graf system. OBJECTIVES: To assess the clinical result of decompression alone and decompression using the Graf system. SUMMARY OF BACKGROUND DATA: The clinical outcome of lumbar stabilization for degenerative spondylolisthesis remains uncertain. There is no prospective study of differences in clinical outcome between patients who undergo decompression alone and those who undergo decompression and stabilization using the Graf system. METHODS: Eighty-eight patients with degenerative spondylolisthesis were included in this study. All patients reported leg symptoms. Decompression alone (Group D) was performed in 42 patients during a 5-year period from 1988 through 1992. Decompression and stabilization with the Graf system (Group G) was performed in 46 patients during a 4-year period from 1993 through 1996. There was no statistical difference regarding sex, the age at operation, compensable cases, and preoperative duration between two groups. The two groups were evaluated at follow-up examinations 1 and 3 years after surgery. The clinical results were evaluated for all patients by means of a 4-grade scale, visual analog scale, recurrence of leg symptoms, and persistent low back pain. The radiographic and clinical findings were examined by an independent investigator. RESULTS: The results according to the 4-grade scale deteriorated with time in both groups. There was no statistical difference between the two groups in the 4-grade scale, visual analog scale, or recurrence of leg symptoms at each follow-up time. Persistent low back pain in Group G was significantly lower than that in Group D at both the 1- and 3-year follow-ups. CONCLUSIONS: Although lumbar Graf stabilization had no effect in preventing the recurrence of leg symptoms, there was a significant effect on reduction of low back pain at the 1- and 3-year follow-ups.
Selective vulnerability of spinal motor neurons to reactive dicarbonyl compounds, intermediate products of glycation, in vitro: implication of inefficient glutathione system in spinal motor neurons.
We investigated the effects of two reactive dicarbonyl compounds, methylglyoxal (MG) and 3-deoxyglucosone (3-DG), on cultured spinal cord neurons. Incubation of cortical and spinal neurons with MG and 3-DG for 24 h induced neuronal death in a dose-dependent manner. Spinal motor neurons were more vulnerable than spinal non-motor neurons and cortical neurons. Treatments with glutathione (GSH)-augmenting agents showed protective effects against MG and 3-DG neurotoxicity. Motor neurons were better protected than non-motor neurons. Cotreatment, but not pretreatment, of aminoguanidine (AG), a known inhibitor of advanced glycation end-products (AGEs) from crosslinking, showed a protective effect on spinal neurons with no difference in protective rates between motor and non-motor spinal neurons. Treatments with GSH depleting agents enhanced the neurotoxicity of MG and 3-DG on spinal neurons. Motor neurons were more vulnerable than non-motor neurons with GSH-depleting treatments prior to MG and 3-DG exposures. These data demonstrate that spinal motor neurons are more vulnerable to dicarbonyl compounds, and this selectivity might be related to the relatively inefficient GSH system in spinal motor neurons.
Sensory innervation of the lumbar dura mater passing through the sympathetic trunk in rats.
STUDY DESIGN: Sensory innervation of the lumbar dura mater passing through the sympathetic trunk was investigated by neuronal tracing and immunohistochemical methods. OBJECTIVE: To assess an anatomic basis indicating that sympathetic block in the higher lumbar region is effective for patients with low back pain. SUMMARY OF BACKGROUND DATA: Low back pain is elicited by disorder or mechanical stimulation of the lumbar dura mater. Clinically, the authors often have observed patients in whom root block at the responsible level or sympathetic block at the higher level could relieve low back pain. Therefore, there may be two different sensory routes, the segmental innervation at the same level and nonsegmental fibers from higher dorsal root ganglia. METHODS: The tracers were injected into the sympathetic trunk between L3 and L4 of rats. The lumbar dorsal root ganglia and dura mater were examined, and labeled cells were measured in size and the distribution. To establish the sensory property, the materials were processed in immunohistochemistry for calcitonin gene-related peptide. RESULTS: Many small- to medium-sized neurons were retrogradely labeled L1 and L2 dorsal root ganglia after injection into the sympathetic trunk. The anterogradely labeled fibers were found in the dura mater at L4 and L5. Some of the labeled neurons and fibers were immunoreactive for calcitonin gene-related peptide. CONCLUSION: Sensory fibers from the upper lumbar ganglia innervated the lower lumbar dura mater directly. These sensory nerves may mediate low back pain and possibly interact with sympathetic nerves.
Up-regulation of type II adenylyl cyclase mRNA in kindling model of epilepsy in rats.
The expression level of type II adenylyl cyclase mRNA (ACII) was analyzed by northern blotting in amygdaloid kindled rats. Remarkable increases in ACII mRNA were observed in the bilateral cerebral cortex and hippocampus at 24 h after the last generalized seizure. The elevated expression level in the hippocampus persisted for 4 weeks on the stimulated side. There were no changes in expression level in single-stimulated and partially-kindled states. These results suggest that the involvement of ACII might have an effect on the mechanisms of seizure generalization and the maintenance of persistent epileptogenesis rather than on the acquisition process.
Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer.
HYPOTHESIS: Reoperation benefits patients with locoregional, persistent, or recurrent medullary thyroid cancer (MTC). Currently available localizing studies have limited utility for detecting all foci of residual MTC. DESIGN: A retrospective study with a mean follow-up time of 7.5 years (median, 13 years; range, 2.2-29 years). SETTING: A tertiary referral medical center. PATIENTS: Thirty-three patients who underwent 46 reoperations for locoregional residual MTC. RESULTS: Sixty-four percent of residual MTC was located in the lateral cervical nodes, 22% in the central cervical nodes or thyroid bed, and 14% in the anterior mediastinum (197 of 1128 nodes resected were positive for MTC). After reoperation, basal calcitonin levels were undetectable in 2 patients, reduced by greater than 50% in 10 patients, and either increased or were not reduced by greater than 50% in the remaining patients. On reoperation, one patient had a thoracic duct injury that required reexploration and ligation. Patients who had a greater than 50% decrease in calcitonin levels after reoperation were less likely to develop distant metastases compared with patients who did not have a greater than 50% decrease (P<.05). The sensitivities of magnetic resonance imaging (n = 31), computed tomographic scan (n = 16), ultrasound (n = 9), and dimercaptosuccinic acid scan (n = 3) were 91%, 86%, 88%, and 100%, respectively. CONCLUSIONS: Although reoperation in patients with residual MTC rarely results in biochemical cure, cervical reexploration is safe and in selected patients may limit MTC progression. Lateral cervical node dissection could be beneficial at the time of initial surgical treatment because of the high frequency of residual MTC in the lateral cervical nodes. Noninvasive imaging studies were helpful but far from perfect for guiding the reexploration for locoregional residual MTC.