Search PubMed⌕ Search

Biomedical subjects

Y Toyama

Publications and source records attributed to Y Toyama.

At least 19 recordsLinked to original sources
PubMed2007

Upregulation of forces and morphogenic asymmetries in dorsal closure during Drosophila development.

Tissue dynamics during dorsal closure, a stage of Drosophila development, provide a model system for cell sheet morphogenesis and wound healing. Dorsal closure is characterized by complex cell sheet movements, driven by multiple tissue specific forces, which are coordinated in space, synchronized in time, and resilient to UV-laser perturbations. The mechanisms responsible for these attributes are not fully understood. We measured spatial, kinematic, and dynamic antero-posterior asymmetries to biophysically characterize both resiliency to laser perturbations and failure of closure in mutant embryos and compared them to natural asymmetries in unperturbed, wild-type closure. We quantified and mathematically modeled two processes that are upregulated to provide resiliency--contractility of the amnioserosa and formation of a seam between advancing epidermal sheets, i.e., zipping. Both processes are spatially removed from the laser-targeted site, indicating they are not a local response to laser-induced wounding and suggesting mechanosensitive and/or chemosensitive mechanisms for upregulation. In mutant embryos, tissue junctions initially fail at the anterior end indicating inhomogeneous mechanical stresses attributable to head involution, another developmental process that occurs concomitant with the end stages of closure. Asymmetries in these mutants are reversed compared to wild-type, and inhomogeneous stresses may cause asymmetries in wild-type closure.

Animals↗
PubMed2006

Epithelioid sarcoma arising on the forearm of a 6-year-old boy: case report and review of the literature.

Epithelioid sarcoma is a rare malignant tumor that occurs mainly in young adults and most frequently involves the distal portion of the upper extremities. The tumor is particularly rare in children and more frequently involves the head and neck; only one case involving the forearm has been reported in a child under 10 years of age, and he was treated with amputation. We report the case of a 6-year-old boy with an epithelioid sarcoma of the forearm whose initial management had been inappropriate. The patient was ultimately treated with limb sparing surgery. Two years later, no local recurrence was evident but pleural metastases were detected.

Forearm↗
PubMed2006

Ischemia-induced disturbance of neuronal network function in the rat spinal cord analyzed by voltage-imaging.

Using a voltage-imaging technique, we analyzed the acute effect of ischemia, hypoxia and hypoglycemia on the neuronal network function of the rat spinal cord. Ischemic, hypoxic, or hypoglycemic stress was loaded to spinal cord slices with an oxygen- and glucose-free, oxygen-free, or glucose-free mock cerebrospinal fluid, respectively. Depolarizing signals in the dorsal horn, induced by dorsal root stimulation, consisted of fast (pre-synaptic) and slow (post-synaptic) components. The slow component was attenuated much more than the fast component under an ischemic condition (P<0.0002). Post-synaptic neuronal activities in lamina III-IV were suppressed earlier than those in lamina I-II. The nerve fiber was relatively resistant to ischemia. As long as the fast component was preserved in the dorsal horn, the suppression of the fast and slow components was reversible. There was a significant difference (P<0.05) in the recovered slow component sizes between the group in which the fast component was suppressed by more than 20% by ischemia and the group in which the suppression was less than 20%. Further prolonged stress irreversibly eliminated most of the slow component, and attenuated the fast component (to 59+/-8%) accompanied by cellular damage in histology. Suppression of neural activity by hypoxic or hypoglycemic stress was less prominent than that by ischemia. Prolonged ischemic stress suddenly and irreversibly eliminated depolarizing signals in the ventral horn accompanied by morphological damage of motoneurons. Immunohistochemical staining was negative for apoptosis. We have, for the first time, analyzed the processes of spinal cord disturbance induced by ischemia, hypoxia and hypoglycemia at the neuronal network level by directly observing the regional neuronal network activities within the spinal cord. We conclude that synaptic transmission in the dorsal horn, especially in deep regions, is vulnerable and first affected by these stresses. Severe ischemic stress induces irreversible dysfunction of neurons accompanied by eventual cell death in both dorsal and ventral horns.

Animals↗
PubMed2006

Surgical outcomes of spinal cord astrocytomas.

STUDY DESIGN: Retrospective case series. OBJECTIVES: To analyze prognostic factors for patients with spinal cord astrocytomas. SETTING: Department of Orthopaedic Surgery, Keio University, Japan. METHODS: Seven patients received total excisions (group T), eight underwent partial excisions (group P), and 15 had excisional biopsies (group B). Impacts of the tumor histological grade, the level of the tumor, the types of surgical interventions, and the use of adjuvant radiotherapies on the survival and functional outcomes of 30 patients (18 in low-grade and 12 high-grade malignancy tumors) were analyzed. RESULTS: The survival rate of the low-grade malignancy group was significantly higher than that of the high-grade group. The survival rate of the patients with thoracic astrocytomas was significantly higher than those with cervical astrocytomas. In both the low- and high-grade groups, the survival rates in groups P/T were significantly higher than those in group B. In the low-grade group, five patients, whose preoperative functional statuses were classified as 'fair' or better, remained 'fair' or better after surgery. In the high-grade group, the postoperative functional statuses were classified as 'no change' or 'aggravated' in all except two patients. No significant difference in the survival rates was detected between patients with and without adjuvant radiotherapy. CONCLUSIONS: The tumor grade and the extent of tumor resection were significant prognostic factors for survival rate. In low-grade malignancy group, good motor function was retained when surgeries were performed before substantial neurological deterioration. The efficacy of postoperative radiotherapy has yet to be determined and needs further study.

Adolescent↗
PubMed2006

Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction.

The aim of this study was to clarify vascular endothelial growth factor (VEGF) expression and angiogenesis in the patellar tendon (PT) autograft in the early phase after anterior cruciate ligament (ACL) reconstruction using a rabbit model. The right knees of 30 Japanese white rabbits underwent ACL reconstruction using the medial third of the PT complex. We evaluated the grafted tendon at 1, 2, 3, 4, and 8 weeks after ACL reconstruction by immunohistology for proliferating cell nuclear antigen, VEGF, and CD31, which is a marker for vascular endothelial cells. At week 1 , few cells were observed at the midsubstance of the grafted tendon. A number of proliferating cells were observed at the surface area of the PT graft 2 weeks after graft transplantation, while no vessel formation was observed in the graft at the same time. VEGF was highly expressed 2-3 weeks postoperatively. Vessel formation in the PT graft increased with time from 3 to 8 weeks after ACL reconstruction. The rates of proliferating cells and VEGF-expressing cells decreased with time from 3 to 8 weeks. This study has suggested that VEGF is involved in the graft remodeling process particularly at the early phase after ACL reconstruction.

Animals↗
PubMed2006

Association between PADI4 and rheumatoid arthritis: a meta-analysis.

OBJECTIVE: Polymorphisms and haplotypes of the peptidylarginine deiminase type 4 gene (PADI4) have been reported to be associated with rheumatoid arthritis (RA) in a Japanese population. However, subsequent replication studies showed conflicting results. The aim of this study was to determine whether meta-analysis would prove the existence of the association. METHODS: PubMed was searched using the term 'PADI4' for articles from the publication of the first study to December 2005. Replication studies that tested the association between PADI4 and RA were reviewed for meta-analysis. The Breslow-Day test for homogeneity across the studies was calculated. The Mantel-Haenszel procedure was used to pool odds ratios (OR) with 95% confidence intervals (CI) to evaluate the association. RESULTS: Six replication studies, one from Japan and five from Europe and North America, fulfilled the selection criteria for inclusion in the meta-analysis. Homogeneity was confirmed across the replication studies. The common OR was 1.14 (95% CI = 1.07-1.21) for allelic distribution. The association was confirmed when only five replication studies in the European descent populations were combined (P = 0.0096, common OR = 1.10). CONCLUSIONS: Our meta-analysis showed a positive association between PADI4 and RA not only in the Japanese population but also in populations of European descent.

Arthritis, Rheumatoid↗
PubMed2005

Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage from patients with rheumatoid arthritis.

OBJECTIVES: To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells. METHODS: Human articular cartilage specimens were obtained from joints from RA and osteoarthritis (OA) patients and normal joints (controls). Transcript levels of MCP-4 in cartilage were determined by real-time polymerase chain reaction. Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast-like synoviocytes (FLS) were treated with various concentrations of recombinant MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay. RESULTS: The gene expression of MCP-4 was significantly higher in cartilage from RA patients than in that from OA patients (P = 0.00902) and in normal cartilage (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients (mean 94.7 +/- 37.6 pg/ml) was significantly higher than in serum from OA patients (mean 49.2 +/- 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 +/- 23.9 pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid from RA patients (mean 247.2 +/- 161.2 pg/ml) was also significantly higher than in that from OA patients (mean 29.6 +/- 50.5 pg/ml, P = 0.000019). Moreover, MCP-4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner. CONCLUSIONS: MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and activates the proliferation of rheumatoid synovial cells, thereby leading to joint destruction in RA.

Arthritis, Rheumatoid↗
PubMed2005

Transplantation of embryonic spinal cord-derived neurospheres support growth of supraspinal projections and functional recovery after spinal cord injury in the neonatal rat.

Great interest exists in using cell replacement strategies to repair the damaged central nervous system. Previous studies have shown that grafting rat fetal spinal cord into neonate or adult animals after spinal cord injury leads to improved anatomic growth/plasticity and functional recovery. It is clear that fetal tissue transplants serve as a scaffold for host axon growth. In addition, embryonic Day 14 (E14) spinal cord tissue transplants are also a rich source of neural-restricted and glial-restricted progenitors. To evaluate the potential of E14 spinal cord progenitor cells, we used in vitro-expanded neurospheres derived from embryonic rat spinal cord and showed that these cells grafted into lesioned neonatal rat spinal cord can survive, migrate, and differentiate into neurons and oligodendrocytes, but rarely into astrocytes. Synapses and partially myelinated axons were detected within the transplant lesion area. Transplanted progenitor cells resulted in increased plasticity or regeneration of corticospinal and brainstem-spinal fibers as determined by anterograde and retrograde labeling. Furthermore, transplantation of these cells promoted functional recovery of locomotion and reflex responses. These data demonstrate that progenitor cells when transplanted into neonates can function in a similar capacity as transplants of solid fetal spinal cord tissue.

Animals↗
PubMed2005

Establishment of graded spinal cord injury model in a nonhuman primate: the common marmoset.

Most previous studies on spinal cord injury (SCI) have used rodent models. Direct extrapolation of the results obtained in rodents to clinical cases is difficult, however, because of neurofunctional and anatomic differences between rodents and primates. In the present study, the development of histopathologic changes and functional deficits were assessed quantitatively after mild, moderate, and severe spinal cord contusive injuries in common marmosets. Contusive SCI was induced by dropping one of three different weights (15, 17, or 20 g) at the C5 level from a height of 50 mm. Serial magnetic resonance images showed significant differences in the intramedullary T1 low signal and T2 high signal areas among the three groups. Quantitative histologic analyses revealed that the number of motor neurons, the myelinated areas, and the amounts of corticospinal tract fibers decreased significantly as the injury increased in severity. Motor functions were evaluated using the following tests: original behavioral scoring scale, measurements of spontaneous motor activity, bar grip test, and cage-climbing test. Significant differences in all test results were observed among the three groups. Spontaneous motor activities at 10 weeks after injury were closely correlated with the residual myelinated area at the lesion epicenter. The establishment of a reliable nonhuman primate model for SCI with objective functional evaluation methods should become an essential tool for future SCI treatment studies. Quantitative behavioral and histopathologic analyses enabled three distinct grades of injury severity (15-g, 17-g, and 20-g groups) to be characterized with heavier weights producing more serious injuries, and relatively constant behavioral and histopathologic outcomes.

Animals↗
PubMed2005

Transplantation of human neural stem cells for spinal cord injury in primates.

Recent studies have shown that delayed transplantation of neural stem/progenitor cells (NSPCs) into the injured spinal cord can promote functional recovery in adult rats. Preclinical studies using nonhuman primates, however, are necessary before NSPCs can be used in clinical trials to treat human patients with spinal cord injury (SCI). Cervical contusion SCIs were induced in 10 adult common marmosets using a stereotaxic device. Nine days after injury, in vitro-expanded human NSPCs were transplanted into the spinal cord of five randomly selected animals, and the other sham-operated control animals received culture medium alone. Motor functions were evaluated through measurements of bar grip power and spontaneous motor activity, and temporal changes in the intramedullary signals were monitored by magnetic resonance imaging. Eight weeks after transplantation, all animals were sacrificed. Histologic analysis revealed that the grafted human NSPCs survived and differentiated into neurons, astrocytes, and oligodendrocytes, and that the cavities were smaller than those in sham-operated control animals. The bar grip power and the spontaneous motor activity of the transplanted animals were significantly higher than those of sham-operated control animals. These findings show that NSPC transplantation was effective for SCI in primates and suggest that human NSPC transplantation could be a feasible treatment for human SCI.

Animals↗
PubMed2005

Enhancement of energetic electrons and protons by cone guiding of laser light.

Energetic electrons and protons are observed when a target consisting of a reentrant cone with a disk at the tip is irradiated by a petawatt (PW) laser at an intensity of approximately 10(19) W cm(-2). The angular distribution of the electrons and protons, dependent on the open angle of the reentrant cone, is found to differ from that in the case when a target with planar geometry is used. Two jet beams are observed, in directions parallel to the cone axis and normal to the cone-shaped wall. The number and cutoff energies of the generated protons are also related to the open angle of the cone. The efficiency of the generation of energetic electrons from the cone target is 2-3 times higher than that from a simple plane target. These results indicate a guiding of the PW laser beam in the cone geometry.

Journal Article↗
PubMed2005

Bilateral multiple malignant transformation of Ollier's disease.

We treated a 26-year-old man with a 19-year history of Ollier's disease. Secondary chondrosarcomas developed metachronously at four separate locations: both femora, left proximal tibia and fibular head. All four lesions were surgically excised, and each specimen was histologically identified as grade 1 or 2 chondrosarcoma. Clinical follow-up for 20 years beginning at the time of first tumor surgery has shown no evidence of local recurrence or metastasis. This is the first report of multiple bilateral metachronous malignant transformation of multiple chondromatoses in a patient with Ollier's disease.

Adult↗
PubMed2005

Endoscopic resection of cystic lesions in the lumbar spinal canal: a report of two cases.

We report excellent outcomes in two patients with cystic lesions in the lumbar spinal canal who underwent resection using the METRx micro-endoscopic discectomy (MED) system. Pathological examinations revealed the diagnoses of a synovial cyst and a discal cyst, respectively. Both of them were allowed to walk the next day after surgery with complete pain relief. Micro-endoscopic surgery provides excellent visualization of the spinal canal and allows minimally invasive removal of the pathological lesions. This technique can be an effective alternative to conventional open surgery for cystic lesions in the lumbar spine.

Adult↗
PubMed2004

Plasma devices to guide and collimate a high density of MeV electrons.

The development of ultra-intense lasers has facilitated new studies in laboratory astrophysics and high-density nuclear science, including laser fusion. Such research relies on the efficient generation of enormous numbers of high-energy charged particles. For example, laser-matter interactions at petawatt (10(15) W) power levels can create pulses of MeV electrons with current densities as large as 10(12) A cm(-2). However, the divergence of these particle beams usually reduces the current density to a few times 10(6) A cm(-2) at distances of the order of centimetres from the source. The invention of devices that can direct such intense, pulsed energetic beams will revolutionize their applications. Here we report high-conductivity devices consisting of transient plasmas that increase the energy density of MeV electrons generated in laser-matter interactions by more than one order of magnitude. A plasma fibre created on a hollow-cone target guides and collimates electrons in a manner akin to the control of light by an optical fibre and collimator. Such plasma devices hold promise for applications using high energy-density particles and should trigger growth in charged particle optics.

Journal Article↗
PubMed2004

Ion acceleration from the shock front induced by hole boring in ultraintense laser-plasma interactions.

Ion-acceleration processes have been studied in ultraintense laser plasma interactions for normal incidence irradiation of solid deuterated targets via neutron spectroscopy. The experimental neutron spectra strongly suggest that the ions are preferentially accelerated radially, rather than into the bulk of the material from three-dimensional Monte Carlo fitting of the neutron spectra. Although the laser system has a 10(-7) contrast ratio, a two-dimensional magnetic hydrodynamics simulation shows that the laser pedestal generates a 10 mum scale length in the coronal plasma with a 3 mum scale-length plasma near the critical density. Two-dimensional particle-in-cell simulations, incorporating this realistic density profile, indicate that the acceleration of the ions is caused by a collisionless shock formation. This has implications for modeling energy transport in solid density plasmas as well as cone-focused fast ignition using the next generation PW lasers currently under construction.

Journal Article↗
PubMed2004

Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury.

Endogenous neural stem/progenitor cells (NSPCs) have recently been shown to differentiate exclusively into astrocytes, the cells that are involved in glial scar formation after spinal cord injury (SCI). The microenvironment of the spinal cord, especially the inflammatory cytokines that dramatically increase in the acute phase at the injury site, is considered to be an important cause of inhibitory mechanism of neuronal differentiation following SCI. Interleukin-6 (IL-6), which has been demonstrated to induce NSPCs to undergo astrocytic differentiation selectively through the JAK/STAT pathway in vitro, has also been demonstrated to play a critical role as a proinflammatory cytokine and to be associated with secondary tissue damage in SCI. In this study, we assessed the efficacy of rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) in the treatment of acute SCI in mice. Immediately after contusive SCI with a modified NYU impactor, mice were intraperitoneally injected with a single dose of MR16-1 (100 microg/g body weight), the lesions were assessed histologically, and the functional recovery was evaluated. MR16-1 not only suppressed the astrocytic diffentiation-promoting effect of IL-6 signaling in vitro but inhibited the development of astrogliosis after SCI in vivo. MR16-1 also decreased the number of invading inflammatory cells and the severity of connective tissue scar formation. In addition, we observed significant functional recovery in the mice treated with MR16-1 compared with control mice. These findings suggest that neutralization of IL-6 signaling in the acute phase of SCI represents an attractive option for the treatment of SCI.

Analysis of Variance↗
PubMed2004

Effect of low frequency ultrasonic stimulation on the secretion of siboflavin produced by Ecemothecium Ashbyii.

The structure of the cell membrane of Ecemothecium ashbyii is considered to be one of the main obstacles in the improvement of riboflavin productivity, which impedes the release of riboflavin from the cell into the fermentation broth. The results of the present study show that stimulation on growth and riboflavin biosynthesis phase, the content of riboflavin was most obviously enhanced, as compared with the control and the total riboflavin quantity released by ultrasonic treatment. The optimal stimulation time was from 104 to 112 h and ultrasonic should be loaded every 1.5 h.

Culture Media↗