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Biomedical subjects

Hiroyuki Shimada

Publications and source records attributed to Hiroyuki Shimada.

At least 55 records · Page 3Linked to original sources
PubMed2004

New intervention program for preventing falls among frail elderly people: the effects of perturbed walking exercise using a bilateral separated treadmill.

OBJECTIVE: To determine the effects of a perturbed walking exercise using a bilateral separated treadmill in physically disabled elderly. DESIGN: Participants of the study were 32 long-term care facility residents and outpatients aged 66-98 yrs. Participants were randomly assigned to a usual exercise group or to a treadmill exercise group. Perturbed gait exercise on a treadmill continued for 6 mos. Number of falls and time to first fall during a 6-mo period, balance and gait functions, and reaction time were evaluated before and after intervention. RESULTS: The treadmill exercise group showed significant improvement in balance and reaction time when compared with the usual exercise group. Number of falls in the treadmill exercise group was 21% lower than that in the usual exercise group. However, this difference was not significant. No significant differences were seen in time to first fall. CONCLUSIONS: Gait training with unexpected perturbation seems to have a beneficial impact on physical function in disabled elderly individuals. The results suggest that this program may be used as an exercise intervention to reduce falls in institutional settings.

Accidental Falls↗
PubMed2004

Position-specific expression of Hox genes along the gastrointestinal tract.

Hox genes play a critical role in morphogenesis of the early embryo along the anteroposterior axis. In mammals, 39 Hox genes with extensive homology are organized into 13 paralogous groups, forming four clusters on four separate chromosomes. The genes within each cluster are arranged in a 3' to 5' direction and expressed in a temporally and spatially coordinated manner along the anteroposterior axis in the vertebrae, limbs and viscera, including the gastrointestinal tract, but little is known about their spatial expression in the adult gastrointestinal tract. We used the quantitative polymerase chain reaction (PCR) intercalater method with SYBR Green to quantify human Hox gene expression in the adult gastrointestinal tract tissue: esophagus, stomach, duodenum, jejunum, ileum, ileocecum, cecum, ascending colon, transverse colon, descending colon and rectum. Hox gene expression was normalized to glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) gene expression. The spatial expression pattern was analyzed by the multivariate method. The expression level of all 39 Hox genes could be measured in a reproducible manner. Genes with higher expression in the foregut-derived segments tended to have lower expression in hindgut-derived segments, whereas those with low expression in the former tended to have higher in the latter. Principal components analysis and permax analysis revealed a position-specific expression pattern of Hox genes along the anteroposterior axis of the adult gastrointestinal tract. The pattern recapitulates the expression pattern in the embryonic gastrointestinal tract. We suggest that Hox genes may play a pivotal role in the position-specific regenerative process of intestinal epithelial cells.

Chromatography, High Pressure Liquid↗
PubMed2004

TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat.

Escherichia coli is a major cause of neonatal bacterial sepsis and meningitis. We recently identified a gene, traJ, which contributes to the ability of E. coli K1 to penetrate the blood-brain barrier in the neonatal rat. Because very little is known regarding the most critical step in disease progression, translocation to the gut and dissemination to the lymphoid tissues after a natural route of infection, we assessed the ability of a traJ mutant to cause systemic disease in the neonatal rat. Our studies determined that the traJ mutant is significantly less virulent than the wild type in the neonatal rat due to a decreased ability to disseminate from the mesenteric lymph nodes to the deeper tissues of the liver and spleen and to the blood during the early stages of systemic disease. Histopathologic studies determined that although significantly less or no mutant bacteria were recovered from the spleen and livers of infected neonatal rats, the inflammatory response was considerably greater than that in wild-type-colonized tissues. In vitro studies revealed that macrophages internalize the traJ mutant less frequently than they do the wild type and by a morphologically distinct process. Furthermore, we determined that tissue macrophages and dendritic cells within the liver and spleen are the major cellular targets of E. coli K1 and that TraJ significantly contributes to the predominantly intracellular nature of E. coli K1 within these professional phagocytes exclusively during the early stages of systemic disease. These data indicate that, contrary to earlier indications, E. coli K1 resides within professional phagocytes, and this is essential for the efficient progression of systemic disease.

Animals↗
PubMed2004

[A randomized controlled trial of a treadmill training with the perturbation to improve the balance performance in the community dwelling elderly subjects].

We had developed a gait perturbation system based on a treadmill composed of two separate walking belts. The servomotors in this treadmill are controlled by a personal computer. A falling perturbation can be generated by the sudden and random deceleration of the walking belts. The purpose of this study was to determine, in a cohort of community dwelling elderly subjects, whether our treadmill training with the perturbation would improve balance performance. The 29 participants aged over 65 years were randomly assigned to receive either perturbed treadmill training or ordinary treadmill training. The single leg standing time with the eyes opened and closed, the functional reach test (FR), the timed up and go test (TUG), the 10 m maximum gait speed and the latency of the bilateral tibialis anterior muscle (LTA) were measured at the pre training period and after the 4-week training period. These indexes were measured again one month after the training period. There were no significant differences between the perturbed training subjects and the ordinary training subjects in these indexes in the pre-training period. Following training period, the perturbed training subjects were improved in FR (mean +/- SD: pre 30.3 +/- 5.0 cm, post 33.5 +/- 5.0 cm, p<.01). TUG (mean +/- SD; pre 5.13 +/- .68 sec, post 4.86 +/- .53 sec, p<.05) and LTA (the perturbed side, mean +/- SD; pre 134 +/- 30 msec, post 116 +/- 22 msec, p<.01, the non-perturbed side, mean SD:pre 132 +/- 35 msec, post 114 +/- 27 msec, p <.05). On the other hand, the ordinary training subjects were improved only in TUG (mean +/- SD; pre 4.93 +/- . 52 sec, post 4.60 +/- .39 sec. p<.01). Additionally, the improvements of the LTA on the perturbed training subjects were retained one month after the training period (the perturbed side, mean +/- SD: pre 134 +/- 30 msec, after 1-month 117 +/- 19 msec, p<.01, the non-perturbed side, mean +/- SD: pre 132 +/- 35 msec, after 1-month 115 +/- 24 msec, p<.05). The improvements of LTA may represent the improvements of the ability of the stepping reaction which is one of the important factors to avoid the falling. Our treadmill training with perturbation improves the balance performance and may decrease the risk of falling in the community dwelling elderly subjects.

Accidental Falls↗
PubMed2004

[Effects of introducing a risk manager for prevention of falls in a long-term care facility].

The purpose of this study was to identify the effects of an effort to prevent accidental falls by supervising residents with a high risk of falling in a long-term care facility. Sixty-four subjects with physical disabilities or cognitive impairment who were receiving residential care participated in this study. The fall-risk manager kept the residents under observation through recreational activities or conversation. The intervention was carried out for 50 days, three times per week (Tuesday, Thursday, and Saturday), eight hours per day. There was no significant difference in the total number of falls between the intervention days and non-intervention days (Monday, Wednesday, and Friday). However, introducing the fall-risk manager into the long-term care facility resulted in a slight improvement in cognitive function in the residents. Although this study did not show a significant beneficial effect for fall prevention, potential effects of fall-risk reduction were noted by the intervention method through introducing a fall-risk manager in a long-term care facility.

Accidental Falls↗
PubMed2004

[Activity of the central nervous system and calcium].

The calcium influx plays an important role of the neuronal signal transduction of the central nervous system. There are several pathways of the calcium influx, such as voltage dependent calcium channel and receptor associated calcium channel. It has been demonstrated that these channels are associated with not only neurons but also glial cells. These channels are also indicated to be related to the neuronal plasticity of the hippocampus and cerebellum. Recently, the transcription factor CREB are also reported as the new mechanism of memory in hippocampus.

Calcium Channels↗
PubMed2003

Revision of the International Neuroblastoma Pathology Classification: confirmation of favorable and unfavorable prognostic subsets in ganglioneuroblastoma, nodular.

BACKGROUND: Ganglioneuroblastoma, nodular (GNBn) comprises one of the categories of peripheral neuroblastic tumors. All tumors in this category, according to the original International Neuroblastoma Pathology Classification, are classified into an unfavorable histology group. Subsequently, it has been reported that GNBn can be divided into two prognostic subsets, a favorable subset (FS) and an unfavorable subset (US). METHODS: Histology slides from 70 patients who were enrolled in Children's Cancer Group studies 3881 and 3891 and who had a diagnosis of GNBn were reviewed jointly by the members of International Neuroblastoma Pathology Committee (INPC): 1) to confirm the diagnosis of GNBn, 2) to identify the FS and US by applying the same age-linked criteria that were used to distinguish the favorable histology group and unfavorable histology group in conventional neuroblastoma tumors from the neuroblastomatous component of GNBn tumors, and 3) to verify the significant prognostic difference between these two subsets. The patients had been used in a previous study, and survival data for the patients were updated since the time of their last report. RESULTS: The review clarified and illustrated morphologic characteristics of classical GNBn and it variants. The diagnosis of GNBn was confirmed in 67 of 70 patients. There were 22 patients with GNBn in the FS and 45 patients with GNBn in the US. The estimated survival differences between the FS and US patients with GNBn were statistically significant (8-year event free survival rate: 86.1% vs. 32.2%; P = 0.0003; overall survival rate: 90.5% vs. 33.2%; P = 0.0003). CONCLUSIONS: This study confirmed the recently defined prognostic subsets of GNBn. The INPC proposes to modify the International Neuroblastoma Pathology Classification by distinguishing the FS and the US among patients with GNBn tumors.

Child↗
PubMed2003

Lytic bone lesions in human neuroblastoma xenograft involve osteoclast recruitment and are inhibited by bisphosphonate.

Neuroblastoma is the second most common solid tumor in childhood and frequently metastasizes to the bone marrow and the bone matrix. The mechanism involved in bone metastasis and destruction in neuroblastoma is poorly understood. Using a model of bone invasion in immunodeficient mice, we demonstrated that neuroblastoma cells recruited osteoclasts to generate osteolytic lesions and invade the bone matrix. In further support of a contributory role for osteoclasts in neuroblastoma bone invasion, we demonstrated that treatment with the bisphosphonate compound, ibandronate, significantly delayed the progression of osteolytic lesions. The data suggest that bisphosphonates may be clinically effective in the treatment of bone metastases in neuroblastoma.

Adrenal Glands↗
PubMed2003

Anaplastic large cell lymphoma in Japanese children: retrospective analysis of 34 patients diagnosed at the National Research Institute for Child Health and Development.

This report presents a retrospective study of 34 Japanese children diagnosed at a single laboratory as having anaplastic large cell lymphoma (ALCL). Most of the pathological features of the Japanese ALCL children observed, such as anaplastic lymphoma kinase protein expression, in addition to most of the clinical characteristics and the outcomes of the patients, are very similar to those reported by European groups. To our knowledge, this is the first report describing the details of the clinicopathological features of Japanese ALCL patients. A further International study, including Japanese patients, might contribute to the establishment of an optimal treatment for paediatric ALCL.

Adolescent↗
PubMed2003

Pediatric tumor cells express erythropoietin and a functional erythropoietin receptor that promotes angiogenesis and tumor cell survival.

Erythropoietin was traditionally considered an erythroid-restricted cytokine, but recent evidence indicates a broader role for it in nonhematopoietic tissues, specifically in neural development. Pediatric solid tumors are mostly developmental in origin, and more than 50% of the solid tumors are neural in origin. We found erythropoietin receptor and erythropoietin expression in common pediatric tumor cells: neuroblastomas, Ewing's sarcoma family of tumors, pediatric brain tumors (medulloblastoma, astrocytoma, and ependymoma), Wilms tumors, rhabdomyosarcomas, and hepatoblastomas (n = 24), and in cell lines derived from some of these tumors (n = 25). Expression of erythropoietin in tumor cell lines was hypoxia-inducible. Addition of exogenous erythropoietin to tumor cell lines expressing erythropoietin receptor increased nuclear DNA binding activity of nuclear factor kappa B and increased the expression of the antiapoptotic genes bcl-1, bcl-xL, and mcl-1. Additionally, exogenous erythropoietin increased production and secretion of angiogenic growth factors, vascular endothelial growth factor, or placenta growth factor from the tumor cell lines, which promoted endothelial cell proliferation and chemotaxis. Erythropoietin receptor expression that promotes tumor cell survival and releases angiogenic growth factors in pediatric tumors has not been previously described. Therefore, a careful evaluation of the impact of erythropoietin is warranted in vivo, in xenograft models of pediatric tumors, followed by evaluation in pediatric patients with cancer.

Cell Hypoxia↗
PubMed2003

Relationship with dynamic balance function during standing and walking.

OBJECTIVE: To investigate the relationship between dynamic balance functions in young adults and elderly adults while standing and walking. DESIGN: In standing balance tests, the Sensory Organization Test (SOT) of six combinations of three visual and two support-surface conditions was used to measure standing balance, and the Motor Coordination Test (MCT) was used to provoke automatic postural reactions through a series of sudden translations of support surface. The gait test measured maximum anterior acceleration (MAA) and maximum posterior acceleration (MPA) of the trunk during perturbed walking using a bilaterally separated treadmill, and calculated latency until MAA and latency until MPA. RESULTS: The elderly adults showed more significant functional decline than young adults in SOT1, SOT4, SOT6, medium intensity MCT, large intensity MCT, and MPA. In the correlation analysis of the outcome from the standing examinations, close correlations among SOT4, SOT5, and SOT6 conditions were observed in both groups of young adults and elderly adults. In the MCT, there was very close correlation between varied translation intensity in two groups. On the other hand, the only weak correlation between SOT and MCT findings was between SOT4 and large intensity MCT in elderly adults (r = -0.471, P = 0.049). In the gait test, although correlation was not significant in young adults, the significant correlations between MAA and latency until MAA (r = 0.705, P = 0.001) and latency until MAA and latency until MPA (r = 0.497, P = 0.036) were recognized in elderly adults. In the balance function findings of the standing examinations and the gait examinations, there was significant correlation between medium intensity MCT and latency until MAA (r = -0.552, P = 0.018) in young adults, and SOT6 and latency until MPA (r = -0.473, P = 0.047) in elderly adults. However, no relationship was observed in most of other factors. CONCLUSIONS: Most falls experienced by elderly people are caused by tripping or slipping during walking. The fact that walking balance function did not correlate with standing balance function indicates that multifaceted evaluation is important to comprehend dynamic balance function while standing and walking.

Acceleration↗
PubMed2003

Citrobacter koseri brain abscess in the neonatal rat: survival and replication within human and rat macrophages.

A unique feature of Citrobacter koseri is the extremely high propensity to initiate brain abscesses during neonatal meningitis. Previous clinical reports and studies on infant rats have documented many Citrobacter-filled macrophages within the ventricles and brain abscesses. It has been hypothesized that intracellular survival and replication within macrophages may be a mechanism by which C. koseri subverts the host response and elicits chronic infection, resulting in brain abscess formation. In this study, we showed that C. koseri causes meningitis and brain abscesses in the neonatal rat model, and we utilized histology and magnetic resonance imaging technology to visualize brain abscess formation. Histology and electron microscopy (EM) revealed that macrophages (and not fibroblasts, astrocytes, oligodendrocytes, or neurons) were the primary target for long-term C. koseri infection. To better understand C. koseri pathogenesis, we have characterized the interactions of C. koseri with human macrophages. We found that C. koseri survives and replicates within macrophages in vitro and that uptake of C. koseri increases in the presence of human pooled serum in a dose-dependent manner. EM studies lend support to the hypothesis that C. koseri uses morphologically different methods of uptake to enter macrophages. FcgammaRI blocking experiments show that this receptor primarily facilitates the entry of opsonized C. koseri into macrophages. Further, confocal fluorescence microscopy demonstrates that C. koseri survives phagolysosomal fusion and that more than 90% of intracellular C. koseri organisms are colocalized within phagolysosomes. The ability of C. koseri to survive phagolysosome fusion and replicate within macrophages may contribute to the establishment of chronic central nervous system infection including brain abscesses.

Animals↗
PubMed2003

Entry and intracellular replication of Escherichia coli K1 in macrophages require expression of outer membrane protein A.

Interactions between Escherichia coli K1, which causes meningitis in neonates, and macrophages have not been explored well. In this study we found that E. coli K1 was able to enter, survive, and replicate intracellularly in both murine and human macrophage cell lines, as well as in monocytes and macrophages of newborn rats. In addition, we demonstrated that OmpA (+) E. coli also enters and replicates in human peripheral blood monocytes in vitro. Outer membrane protein A (OmpA) expression on E. coli contributes to binding to macrophages, phagocytosis, and survival within macrophages. Opsonization with either complement proteins or antibody is not required for uptake and survival of the bacteria within the macrophages. Transmission electron microscopy and immunocytochemistry studies with the infected macrophages indicated that OmpA(+) E. coli multiplies enormously in a single phagosome and bursts the cell. Internalization of OmpA(+) E. coli by RAW 264.7 cells occurred by both actin- and microtubule-dependent processes, which are independent of RGD-mediated integrin receptors. Internalization and intracellular survival within phagocytic cells thus may play an important role in the development of bacteremia, which is crucial for E. coli crossing of the blood-brain barrier.

Animals↗
PubMed2003

[Surgical removal of choroidal neovascularization in angioid streaks].

PURPOSE: All the studies so far on surgical removal of choroidal neovascularization (CNV) in angioid streaks(AS) were conducted on a small number of cases. Therefore, a definitive evaluation of the surgical method was not available. The present study aimed to evaluate this surgical modality. SUBJECTS AND METHOD: We performed surgical removal of foveal CNV accompanied by AS. Eighteen eyes of seventeen patients were available for follow-up of over 12 months. Surgical indications included foveal CNV, fluorescence leakage from the CNV in late-phase fluorescein angiography, and visual acuity of 0.3 or lower. RESULTS: The best visual acuity was improved in 44% and unchanged in 44%. The final visual acuity was improved in 33% and unchanged in 39%. 22% had a preoperative visual acuity of 0.2 or above; and 44% and 17% achieved best and final visual acuity, respectively, of 0.2 or above. Since all cases developed atrophy of the choriocapillaris in the fovea, none of the cases were capable of fixation within atrophy. The fixation point was localized outside atrophy in 56% and fixation was poor in 44%. The diameter of postoperative atrophy of choriocapillaris was significantly greater (p < 0.05) than the preoperative CNV diameter. CNV recurred in 8 eyes(44%), 88% of which occurred within one year. CONCLUSION: Surgical removal of CNV in AS is an effective method to maintain preoperative visual acuity.

Aged↗
PubMed2003

[Surgical removal of juxtafoveal and extrafoveal choroidal neovascularization in age-related macular degeneration].

PURPOSE: In the treatment of age-related macular degeneration (AMD), the effect on the fovea of photocoagulation of juxtafoveal choroidal neovascularization(CNV) and extrafoveal CNV near the fovea has been of concern, and so usefulness of surgical excision of CNV was evaluated. SUBJECTS AND METHODS: Fifteen eyes with AMD that underwent removal of juxtafoveal CNV and extrafoveal CNV near the fovea and had been followed for over one year were included in this study. Eligibility criteria were preoperative visual acuity of 0.3 or less and evidence of CNV activity by fundus angiography. RESULTS: Visual acuity of 0.4 or more was obtained in 60% of the eyes with best visual acuity and 47% with final visual acuity. The mean best visual acuity was 0.51 in cases with Gass type 2, 0.51 in type 1 + 2 CNV, and 0.21 in type 1 CNV. Good post-operative visual acuity was obtained in type 2 and 1 + 2 cases with type 2 CNV at the foveal side accompanied by preoperative foveal retinal sensitivity of 25 dB or more. There was little improvement of visual acuity in type 1 CNV because the retinal pigmented epithelium defect occurred at the fovea. CONCLUSION: For juxtafoveal CNV and extrafoveal CNV near the fovea in AMD, type 2 and 1 + 2 cases with type 2 CNV at the foveal side are thought to be candidates for surgery. Especially, relatively good postoperative visual acuity was obtained in cases with preoperative foveal retinal sensitivity of 25 dB or above. Active surgical removal is thought to be indicated for these cases.

Aged↗
PubMed2002

Detecting functional asymmetries through the dipole moment of magnetoencephalography.

To assess the accuracy of magnetoencephalography (MEG) as a tool for quantitative detection of neuronal activity, the dipole moment was estimated at N20m of somatosensory evoked fields (SEFs) produced by median nerve stimulation. Neurologically stable patients were examined twice within 2 weeks. Since the estimated moment values of the two examinations should be essentially the same, we assessed the margin of error for our measurement system. The results showed that a change of more than 5.2 nAm is statistically significant (p=0.05; n=91). The patients were classified as without or with functional asymmetries by measuring the conventional cerebral blood flow (CBF) with single photon emission CT (SPECT), and the dipole moment difference between hemispheres was measured. Hemispheric moment differences were statistically larger for the group with CBF laterality, indicating consistency between conventional CBF results and the moment measurements as a group. Moreover, MEG was able to detect more functional asymmetries than CBF study. The dipole moment provided a reliable quantitative index of cortical response to somatosensory stimulus, and the moment measurement thus holds promise as a clinical tool for direct quantification of cortical response.

Adult↗
PubMed2002

Antidisialoganglioside/granulocyte macrophage-colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcgammaRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis.

Polymorphonuclear leukocytes (PMNs) mediate antibody-dependent cellular cytotoxicity (ADCC), which is increased by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to determine whether PMN ADCC also would be increased by the addition of an antibody/GM-CSF fusion protein and whether this would be associated with the up-regulation and activation of Mac-1 (CD11b/CD18) and with azurophil granule exocytosis. ADCC against LA-N-1 human neuroblastoma cells was evaluated with 4-hour calcein acetoxymethyl ester (calcein-AM) microcytotoxicity assay, electron microscopy, and multi-parameter flow cytometry. With the calcein-AM assay, LA-N-1 cell survival was 10%, 55%, and 75% when PMN ADCC was mediated by the antidisialoganglioside (anti-GD2) immunocytokine hu14.18/GM-CSF, by monoclonal antibody (mAb) hu14.18 mixed with GM-CSF, and by hu14.18 alone. Function-blocking mAbs demonstrated that FcgammaRII and FcgammaRIII were required for ADCC with hu14.18 alone or mixed with GM-CSF, but that only FcgammaRII was required for ADCC with hu14.18/GM-CSF. ADCC mediated by hu14.18 and hu14.18/GM-CSF was Mac-1 dependent. Electron microscopy demonstrated the greatest PMN adhesion, spreading, and lysis of targets with hu14.18/GM-CSF. Monoclonal antibodies blocking Mac-1 function allowed the tethering of PMN to targets with hu14.18/GM-CSF but prevented adhesion, spreading, and cytolysis. Flow cytometry showed that hu14.18 with or without GM-CSF and hu14.18/GM-CSF all mediated Mac-1-dependent PMN-target cell conjugate formation but that GM-CSF was required for the highest expression and activation of Mac-1, as evidenced by the mAb24-defined beta(2)-integrin activation epitope. Hu14.18/GM-CSF induced the highest sustained azurophil granule exocytosis, almost exclusively in PMNs with activated Mac-1. Thus, hu14.18/GM-CSF facilitates PMN ADCC against neuroblastoma cells associated with FcgammaRII and Mac-1-dependent enhanced adhesion and degranulation.

Antibodies↗