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Biomedical subjects

S Kawaguchi

Publications and source records attributed to S Kawaguchi.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2001

Endovascular stent grafting for the treatment of blunt thoracic aortic injury.

OBJECTIVE: Recent advances of endovascular stent-grafting (ESG) provide a new therapeutic option with minimum surgical damage for blunt aortic injury (BAI) during its acute phase. To clarify the effectiveness of ESG for BAI, a prospective clinical study at a university hospital was conducted. METHODS: All patients with blunt thoracic injury underwent thoracic contrast-enhanced computed tomographic (CT) scan. Six patients age 48.8 +/- 19.8 years, with Injury Severity Scores of 35.8 +/- 8.1, and with BAI were treated according to our protocol. The stent-graft covered by woven Dacron was placed at the injury site. Endoleakage was then checked by aortography and CT scan was again performed once a day on days 7 through 14. RESULTS: All patients had injury of the aortic isthmus. ESG placement was performed within 8 hours after injury except in one (48 hours). The operating time was 159.5 +/- 21.1 minutes and bleeding volume was 105 +/- 26.6 mL. No endoleakage was found. Repeat CT scan revealed disappearance of hematoma. All patients except one had an event-free clinical course. One patient died because of rupture of the ascending aorta on day 6; however, autopsy revealed evidence of the healing process at the injury site sealed by ESG. CONCLUSION: An ESG is a valid therapeutic option with minimal surgical invasion for patients with acute-phase aortic injury.

Adult↗
PubMed2001

Effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis.

OBJECTIVE: We evaluated the effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis by use of data obtained from ophthalmic artery color Doppler flow imaging. METHODS: We examined 11 patients with ocular ischemic syndrome due to internal carotid artery stenosis (>70% stenosis) who were being treated by carotid endarterectomy. Ophthalmic artery color Doppler flow imaging indicated ophthalmic artery flow direction and peak systolic flow velocity and was performed before and at 1 week, 1 month, and 3 months after surgery. RESULTS: We assessed the ophthalmic arteries of 11 patients via color Doppler flow imaging. Before undergoing carotid endarterectomy, five patients showed reversed ophthalmic artery flow. In the other six patients who experienced antegrade ophthalmic artery flow, the average peak systolic flow velocity was 0.09 +/- 0.05 m/s (mean +/- standard deviation). Preoperative reversed flow resolved in each patient 1 week after undergoing surgery. All patients showed antegrade ophthalmic artery flow. The average peak systolic flow velocity in the patients who had preoperative antegrade flow rose significantly, to 0.21 +/- 0.14 m/s (P < 0.05). There was no significant change as compared with findings at 1 week after surgery. During the follow-up period (mean, 32.4 mo), no patients complained of recurrent visual symptoms. At the end of the study period, visual acuity had improved in five patients and had not worsened in the other six patients. CONCLUSION: Carotid endarterectomy was effective for improving or preventing the progress of chronic ocular ischemia caused by internal carotid artery stenosis.

Angiography↗
PubMed2001

A new peritoneal dissemination model established from the human pancreatic cancer cell line.

We established a new cell line, HPC-3P4a, with high peritoneal disseminated potential in nude mice. HPC-3P4a was derived from a human pancreatic carcinoma cell line (HPC-3) that had low capacity for peritoneal dissemination. HPC-3P4a developed peritoneal dissemination in 10 of 11 (90.9%) cases, whereas parental HPC-3 developed peritoneal dissemination in one of six (16.7%) cases. The metastatic foci in the peritoneum showed essentially the same histologic appearance of parental involvement. The tumorigenicity, motility, and adhesive activity of HPC-3P4a to the extracellular matrix were stronger than were those of the HPC-3. In FACS analysis, HPC-3P4a significantly increased the expression of alpha6 and alpha(v)beta5 integrins, while it decreased alpha2 integrin, hCD44H, and hCD44v 10, as compared with HPC-3. The VEGF production of HPC-3P4a was significantly lower than that of HPC-3. Analysis of gene macroarrays showed a variety of cytokines, interleukin, and other immunomodulatory, and their receptors were up-regulated and down-regulated on an mRNA level in HPC-3P4a cells, compared with HPC-3 cells. Intrasplenic injection of HPC-3P4a produced no liver metastasis. We named our original highly liver metastatic cell line HPC-3H4 (previously reported). This HPC-3H4 cell was established by repeated intrasplenic injection from parental cell HPC-3; thus, it developed high liver metastasis. Moreover, HPC-3H4 developed peritoneal dissemination by intra-abdominal injection. In contrast, HPC-3P4a did not develop liver metastasis by intrasplenic injection. These findings are very interesting and might suggest that the process of hematogenous metastasis differed from that of peritoneal dissemination. Thus, this cell line may be useful for investigating the mechanism of peritoneal dissemination in human pancreatic cancer.

Adenocarcinoma↗
PubMed2001

Endotracheal/endobronchial metastases : clinicopathologic study with special reference to developmental modes.

BACKGROUND: Endotracheal/endobronchial metastases (EEMs) from nonpulmonary neoplasms are rare. However, their definition and developmental modes have not yet been fully elucidated. METHODS: EEMs were defined as documented nonpulmonary neoplasms metastatic to the subsegmental or more proximal central bronchus, in a bronchoscopically visible range. The clinical and pathologic features of 16 cases were reviewed, with special emphasis on the developmental modes based on five criteria: location in the tracheobronchial tree, number of lesions, laterality of lesions, depth of lesions, and relationship with the associated bronchus. RESULTS: The developmental modes were proposed on the basis of the above five criteria as follows: type I, direct metastasis to the bronchus; type II, bronchial invasion by a parenchymal lesion; type III, bronchial invasion by mediastinal or hilar lymph node metastasis; and type IV, peripheral lesions extended along the proximal bronchus. Primary tumors included colorectal in six patients, breast in three patients, uterus in two patients, osteosarcoma of the bone in two patients, and maxillary, larynx, and parotid carcinoma in one patient each, respectively. The mean recurrence interval was 65.3 months. The developmental modes were as follows: type I, five patients; type II, one patient; type III, four patients; and type IV, nine patients. Three patients underwent surgical resection. One patient has remained well for 5 years after operation. Median and mean survival times were 9 months and 15.5 months, respectively. CONCLUSION: The mean recurrence interval was long at 65.3 months, but the mean survival time was short at 15.5 months. Type I accounted for only 5 of 16 patients. Type II was found in only one patient. It is thought that this type is a rare form. Type IV affected nine patients. Treatment plans must be individualized, because in some cases, long-term survival can be expected.

Bone Neoplasms↗