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Biomedical subjects

S Kawaguchi

Publications and source records attributed to S Kawaguchi.

At least 19 recordsLinked to original sources
PubMed2001

Crystal structure of the CENP-B protein-DNA complex: the DNA-binding domains of CENP-B induce kinks in the CENP-B box DNA.

The human centromere protein B (CENP-B), one of the centromere components, specifically binds a 17 bp sequence (the CENP-B box), which appears in every other alpha-satellite repeat. In the present study, the crystal structure of the complex of the DNA-binding region (129 residues) of CENP-B and the CENP-B box DNA has been determined at 2.5 A resolution. The DNA-binding region forms two helix-turn-helix domains, which are bound to adjacent major grooves of the DNA. The DNA is kinked at the two recognition helix contact sites, and the DNA region between the kinks is straight. Among the major groove protein-bound DNAs, this 'kink-straight-kink' bend contrasts with ordinary 'round bends' (gradual bending between two protein contact sites). The larger kink (43 degrees ) is induced by a novel mechanism, 'phosphate bridging by an arginine-rich helix': the recognition helix with an arginine cluster is inserted perpendicularly into the major groove and bridges the groove through direct interactions with the phosphate groups. The overall bending angle is 59 degrees, which may be important for the centromere-specific chromatin structure.

Amino Acid Sequence↗
PubMed2001

Prediction of progression of spinal deformity in Duchenne muscular dystrophy: a preliminary report.

STUDY DESIGN: Discriminatory power was statistically estimated for multiple combinations of risk indicators for the progression of spinal deformity in Duchenne muscular dystrophy (DMD). OBJECTIVE: To differentiate DMD cases in which spinal deformity will rapidly and severely progress from those with lesser progression of spinal deformity. SUMMARY OF BACKGROUND DATA: Early surgical intervention using instrumentation has recently been advocated for DMD patients to prevent the progression of spinal deformity. However, early determination of cases needing surgical intervention is difficult because of variations in the severity of the clinical courses of DMD patients. METHODS: Charts and spinal radiographs of 12 DMD patients were reviewed retrospectively. Patterns of progression in spinal deformity were classified into three types according to Oda's classification. Discriminant analysis was conducted to categorize the patients into either a severe progression group (type-1 and type-2 patients) or a less severe progression group (type-3 patients and patients without spinal deformity) on the basis of four predictors: 1) vital capacity at the age of 10 years, 2) the age at which ambulation ceased, 3) curve pattern of spinal scoliosis, and 4) Cobb angles of spinal scoliosis at the age of 10 years. RESULTS: Eleven of the twelve DMD patients showed spinal deformity. Three were classified as type 1, six were classified as type 2, and two were classified as type 3. The remaining patient showed no spinal deformity. Multiple discriminant analysis correctly predicted the severity of the clinical course of 91.7% of the DMD patients. Vital capacity at age 10 was found to be the strongest predictor among the variables. CONCLUSIONS: Through multiple discriminant analysis, the clinical course of spinal deformity in DMD patients was correctly predicted in 92% of subjects. This method would be useful to determine early which DMD cases need surgical intervention for treatment of spinal deformity.

Child↗
PubMed2001

Immunophenotypic analysis of the inflammatory infiltrates in herniated intervertebral discs.

STUDY DESIGN: The herniated portion of the lumbar disc was analyzed immunohistochemically for inflammatory infiltrates to determine their immunophenotype. OBJECTIVE: To investigate the pathomechanism behind spontaneous regression of herniated discs. SUMMARY OF BACKGROUND DATA: Spontaneous regression of herniated intervertebral discs has been increasingly reported. The inflammatory response of the host has been suggested as a factor in this phenomenon. However, whether the inflammation is induced from direct chemical irritation of the nucleus pulposus material or whether it is secondary to an autoimmune response to the nucleus pulposus remains controversial. METHODS: The herniated portion of the disc was collected from 38 patients who underwent surgery for lumbar disc herniation. Thin cryostat sections were made, and the extent to which inflammatory cells had infiltrated the disc specimen was defined. Then the immunophenotype of cellular infiltrates in the herniated disc specimens was assessed by immunostaining using a series of antibodies for lymphocyte, monocyte, macrophage, and dendritic cell markers. RESULTS: The inflammatory infiltrates in 14 of the 38 herniated discs were subjected to immunohistochemical analysis. None of them expressed the immunophenotypic markers of the lymphocyte (CD20, CD45RO, CD4, CD8, TCRgammadelta), mature monocyte (CD33), or dendritic cell (CD1a, CD80, CD86, S100). Abundant infiltration of CD68-positive cells that lacked CD33 but had a variable amount of CD11b, CD11c, and CD40 likely represents a process of differentiation from monocytes to macrophages. CONCLUSIONS: These findings are consistent with an immunophenotype of inflammatory responses to tissue injury or chemical irritation rather than antigen-specific immune responses. Therefore, understanding the mechanism of tissue repair is fundamentally important in the management of patients with disc herniations.

Adult↗
PubMed2001

Traumatic paraplegia in snowboarders.

STUDY DESIGN: Patients with traumatic paraplegia resulting from snowboarding accidents were reviewed. OBJECTIVE: To understand the clinical features and mechanisms of paraplegic snowboarding injuries. SUMMARY OF BACKGROUND DATA: The recent explosion in the popularity of snowboarding has resulted in dramatically increased numbers of snowboarding injuries. However, little information is available as to the types and mechanisms of snowboard-related spinal injuries and their neurologic involvement. METHODS: The subjects of this study were six male patients, with an average age of 23.7 years, referred to the authors' institution for neurologic deficits associated with spinal injuries between January 1996 and March 1999. The clinical features of these patients were reviewed with respect to the mechanism of the injury, fracture pattern, neurologic status, treatment, and clinical outcome. The mean follow-up period was 23.7 months. RESULTS: The six snowboarders with traumatic paraplegia constituted a very homogenous group with the following features: They were all young men between the ages of 23 and 25 years. All the injuries had occurred at the vertebral junctions. The primary mechanism of the fractures was a backward fall from an intentional jump. The fracture patterns were of the flexion-distraction type. These homologous features suggest that this snowboarding group is at high risk for severe spinal injury. CONCLUSION: The high risk of traumatic paraplegia for a group within the snowboarding population requires the development and provision of injury prevention strategies specific to this group.

Adult↗
PubMed2001

The crystal structure of the ttCsaA protein: an export-related chaperone from Thermus thermophilus.

The CsaA protein was first characterized in Bacillus subtilis as a molecular chaperone with export-related activities. Here we report the 2.0 Angstrom-resolution crystal structure of the Thermus thermophilus CsaA protein, designated ttCsaA. Atomic structure and experiments in solution revealed a homodimer as the functional unit. The structure of the ttCsaA monomer is reminiscent of the well known oligonucleotide-binding fold, with the addition of extensions at the N- and C-termini that form an extensive dimer interface. The two identical, large, hydrophobic cavities on the protein surface are likely to constitute the substrate binding sites. The CsaA proteins share essential sequence similarity with the tRNA-binding protein Trbp111. Structure-based sequence analysis suggests a close structural resemblance between these proteins, which may extend to the architecture of the binding sites at the atomic level. These results raise the intriguing possibility that CsaA proteins possess a second, tRNA-binding activity in addition to their export-related function.

Amino Acid Sequence↗
PubMed2001

Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry.

The EMAPII (endothelial monocyte-activating polypeptide II) domain is a tRNA-binding domain associated with several aminoacyl-tRNA synthetases, which becomes an independent domain with inflammatory cytokine activity upon apoptotic cleavage from the p43 component of the multisynthetase complex. It comprises a domain that is highly homologous to bacterial tRNA-binding proteins (Trbp), followed by an extra domain without homology to known proteins. Trbps, which may represent ancient tRNA chaperones, form dimers and bind one tRNA per dimer. In contrast, EMAPII domains are monomers. Here we report the crystal structure at 1.14 Angstroms of human EMAPII. The structure reveals that the Trbp-like domain, which forms an oligonucleotide-binding (OB) fold, is related by degenerate 2-fold symmetry to the extra-domain. The pseudo-axis coincides with the dyad axis of bacterial TtCsaA, a Trbp whose structure was solved recently. The interdomain interface in EMAPII mimics the intersubunit interface in TtCsaA, and may thus generate a novel OB-fold-based tRNA-binding site. The low sequence homology between the extra domain of EMAPII and either its own OB fold or that of Trbps suggests that dimer mimicry originated from convergent evolution rather than gene duplication.

Amino Acid Sequence↗
PubMed2001

Regeneration and recovery of the hearing function of the central auditory pathway by transplants of embryonic brain tissue in adult rats.

The present study is the first report of successful regeneration and recovery of hearing function of the central auditory pathway after transection in the adult rat. The ventral cochlear tract in the brain stem to pons was transected on one side in adult rats. Tissue from embryos (E14 to E16) was used to cover the lesion site. In 30% of the rats examined, the axons regrew beyond the transected site and regenerated into the denervated side and terminated at the normal targets. The hearing function of rats was elucidated by recording the auditory brain stem response (ABR). Rats with successful regeneration showed nearly normal ABR. In rats receiving simple transection without covering embryonic tissue, there was no regeneration and hearing function did not recover. Thus, the present findings contradict the widely held view that the adult mammalian central auditory system cannot be restored following damage.

Animals↗
PubMed2001

Grafting of choroid plexus ependymal cells promotes the growth of regenerating axons in the dorsal funiculus of rat spinal cord: a preliminary report.

Nerve regeneration in the central nervous system has been studied by grafting various tissues and cells. In the present study, we demonstrated that choroid plexus ependymal cells can promote nerve regeneration when grafted into spinal cord lesions. The choroid plexus was excised from the fourth ventricle of adult rats (Wistar), minced into small fragments, and grafted into the dorsal funiculus at the C2 level in adult rat spinal cord from the same strain. Electron microscopy and fluorescence histochemistry showed that ependymal cells of the grafted choroid plexus intimately interacted with growing axons, serving to support the massive growth of regenerating axons. CGRP-positive fibers closely interacted with grafted ependymal cells. HRP injection at the sciatic nerve showed that numerous HRP-labeled regenerating fibers from the fasciculus gracilis extended into the graft 7 days after grafting. This regenerating axons from the fasciculus gracilis was maintained for at least 10 months, with some axons elongating rostrally into the dorsal funiculus. Evoked potentials of long duration were recorded at a level ca. 5 mm rostral to the lesion in the rats 8 to 10 months after grafting. These findings indicate that choroid plexus ependymal cells have the ability to facilitate axonal growth in vivo, suggesting that they may be a promising candidate as graft for the promotion of nerve regeneration in the spinal cord.

Animals↗
PubMed2001

Horse-related injuries in a thoroughbred stabling area in Japan.

To investigate the demographic details and patterns of injuries related to horse handling, we reviewed 637 horse-related injuries in 581 stable- or stud-workers in a representative area of thoroughbred stabling in Japan. We found that (1) injuries occurred most frequently in a group of a relatively young workers, with a seasonal variation; (2) the principal mechanism of injury was kicks, which accounted for 39.2% of all injuries, including 11 serious and one lethal visceral injuries; (3) the upper half of the body was more frequently involved than the lower half; and (4) the peripheral bones (hand and foot) and the ribs accounted for more than half of 148 fractures. These findings are distinct from those in horse-riding injuries reported in the literature and emphasize the importance in developing preventive strategies specifically for workers in horse stables.

Accidents, Occupational↗
PubMed2001

Insufficiency fracture of the spine: a prospective analysis based on radiographic and scintigraphic diagnosis.

To investigate the clinical characteristics of insufficiency fracture of the spine, patients aged 65 years or older, who had been hospitalized for acute low back pain without either an acute traumatic event or a previous history of malignant disease, were examined by plain radiographs and technetium-99m methylene disphosphonate bone scanning. Fifteen patients were diagnosed as having a vertebral insufficiency fracture on the basis of: (a) radiographic oseteopenia of the vertebra; (b) positive bone scan images; and (c) no episode of newly identified malignant disease in a subsequent 1 year follow up. These patients were analysed with respect to age, gender, bone mineral density, the number and distribution of the affected vertebrae, the extent of vertebral deformity, and consistency between radiographic and bone scan findings. Vertebral insufficiency fractures exhibited: (a) strict female predominance; (b) concave deformity of the affected vertebra; (c) a wide range of the vertebral height ratios and fracture distribution; and (d) low consistency between the vertebral deformity assessed by the lateral radiograph and positive activity on bone scanning. These findings represent a unique clinical feature of vertebral insufficiency fracture, and also emphasize the difficulty of radiographic diagnosis, as well as the importance of a comprehensive diagnostic approach.

Aged↗
PubMed2001

Mechanical properties of artificial tracheas composed of a mesh cylinder and a spiral stent.

Much work has been done on the materials used for mesh-type artificial tracheas, but a precise mechanical evaluation of these structures has not yet been performed. In the present study, we determined the mechanical properties of typical mesh-type artificial tracheas and compared them with those of native trachea. Four types of artificial trachea were made and used for the mechanical tests. The basic frame of all the specimens was composed of a mesh cylinder and a spiral stent. The specimen whose mesh was sealed with collagen sponge showed almost the same behavior in the force-strain curve under compression, suggesting that collagen sealing has little effect on mechanical properties. Agreement between measured and estimated mechanical properties was good, especially in the low strain region, suggesting that artificial tracheas can be designed in terms of mechanical properties by mainly considering the basic frame structure.

Animals↗
PubMed2001

Spatiotemporal distribution of GAP-43 in the developing rat spinal cord: a histological and quantitative immunofluorescence study.

In the rat spinal cord we studied developmental changes in spatiotemporal expression of the growth-associated protein GAP-43, which is known to play an important role in neural development, axonal regeneration, and modulation of synaptic function. GAP-43 was expressed predominantly in the white matter at embryonic day 13 to postnatal day 7, evenly in the white and gray matter at the 2nd to the 3rd postnatal week, and predominantly in the gray matter after the 5th postnatal week. The shifting of predominance was quantitatively assessed. On the basis of histological findings and quantitative assessment of GAP-43 immunoreactivity, it appears likely that the development proceeds from the phase of mostly axonal elongation during the embryonic period and the 1st postnatal week, via the phase of axonal elongation and formation of end arbors and synaptic organization during the 2nd to the 4th postnatal week, to the phase of final maturation of synaptic organization. GAP-43 was continuously expressed through adulthood in neuropil of the gray matter, the pyramidal tract, and the dorsal portion of the lateral funiculus that was identified as serotonergic by confocal laser scanning microscopic studies. The continuous expression may imply perpetual remodeling in these structures even in adulthood.

Animals↗
PubMed2001

Effect of sonication on nitroxide-controlled free radical polymerization of styrene.

Effect of sonication on the autopolymerization of styrene in the presence of 2,2,6,6-tetramethylpiperidinyl-1-oxy as the mediating radical was investigated at 110-135 degrees C. The thermal polymerization under sonication proceeded in the manner of a "living" radical polymerization to afford well-defined polystyrene. The sonication was found to decrease the induction period and increase the polymerization rate.

Journal Article↗
PubMed2001

Survival of neural stem cells in the cochlea.

Adult rat hippocampus-derived neural stem cells (NSCs) have been reported to have been successfully grafted in several brain regions. To evaluate the possibility of treatment of sensorineural hearing loss using NSCs, survival of NSCs in the cochlea was estimated. NSCs were grafted into newborn rat cochleas. Within 2-4 weeks of grafting to the cochlea, some NSCs survived in the cochlear cavity. Some of them had adopted the morphologies and positions of hair cells. This suggests that NSCs can adapt to the environment of the cochlea and gives hope for treatment of the damaged cochlea and sensorineural hearing loss.

Animals↗
PubMed2001

Reversible hypophosphatemia during moderate hypothermia therapy for brain-injured patients.

OBJECTIVE: Because plasma potassium, which may similarly change as plasma phosphate (P), decreases during moderate hypothermia, plasma P, a requisite electrolyte for the cell function, may alter during therapeutic moderate hypothermia for brain-injured patients. In 22 such patients who underwent moderate hypothermia or were treated with normothermia, plasma concentrations of P and other chemicals were examined. DESIGN: A prospective study. SETTING: The intensive care unit of a medical university hospital. PATIENTS AND INTERVENTIONS: In 15 consecutive patients with brain injury who underwent moderate hypothermia and 7 serial patients treated with normothermia, plasma concentrations of P, potassium, glucose, blood gas tension and pH, daily urine volume, and water balance were examined. Inequality in the numbers of patients of the two groups was the result of patient exclusion because of multiple trauma, aluminum hydroxide administrations, hyperventilation, preexisting diabetes mellitus, or administration of insulin. Daily blood sampling was done around 8 am. Inclusion criteria included a Glasgow Coma Scale score assessment < or = 8 at admission to the emergency room and evidence of injury on computerized tomography scanning of the brain. MEASUREMENT AND MAIN RESULTS: Hypothermia decreased plasma P levels as compared with those of normothermia within 4 days after the injury (this period was similar to the duration of the hypothermic phase in the hypothermia group). Such reduction related to changes in blood glucose levels, but not to any in the urine volume, or water balance. The P decrease occurred during the hypothermic phase, but subsequently there was a recovery of P after the rewarming phase. The changes in plasma potassium levels were similar to those in plasma P concentrations during the course. Such changes were accompanied by a recovery of decreased heart rate that occurred during the hypothermic phase. CONCLUSION: The results suggest that moderate hypothermia of 32-33 degrees C decreases plasma P levels. Further studies are required to examine whether P repletion may overcome certain hemodynamic derangements during moderate hypothermia in brain-injured patients.

Adolescent↗