Biomedical subjects

Tomohisa Sekimoto

Publications and source records attributed to Tomohisa Sekimoto.

7 recordsLinked to original sources

PubMed2005

Evaluation of circulatory compromise in the leg in lumbar spinal canal stenosis.

To evaluate whether hemoglobin oxygen saturation and hemoglobin concentration of the leg are useful indicators for circulatory compromise in patients with lumbar spinal canal stenosis, we investigated the changes in the indices during level gait using reflectance spectrophotometry. Thirty-three patients with lumbar spinal stenosis were studied. Preoperatively, the hemoglobin oxygen saturation was greater in the 33 patients than in the control subjects. The indices increased in the control subjects more than those in the patients. Postoperatively, the increases in hemoglobin oxygen saturation were greater in the patients with lumbar spinal canal stenosis than before decompression and the hemoglobin concentration tended to approximate that in the control subjects. The results suggest these indices might be useful for monitoring disease severity in patients with lumber spinal canal stenosis. In addition to stenotic ischemia in the spinal canal, it is thought that the neurogenic intermittent claudication is secondarily caused by circulatory failure in the lower extremities attributable to the autonomic nervous dysfunction.

Aged↗

PubMed2005

Characterization of an exchangeable gene trap using pU-17 carrying a stop codon-beta geo cassette.

We have developed a new exchangeable gene trap vector, pU-17, carrying the intron-lox71-splicing acceptor (SA)-beta geo-loxP-pA-lox2272-pSP73-lox511. The SA contains three stop codons in-frame with the ATG of beta galactosidase/neomycin-resistance fusion gene (beta geo) that can function in promoter trapping. We found that the trap vector was highly selective for integrations in the introns adjacent to the exon containing the start codon. Furthermore, by using the Cre-mutant lox system, we successfully replaced the beta geo gene with the enhanced green fluorescent protein (EGFP) gene, established mouse lines with the replaced clones, removed the selection marker gene by mating with Flp-deleter mice, and confirmed that the replaced EGFP gene was expressed in the same pattern as the beta geo gene. Thus, using this pU-17 trap vector, we can initially carry out random mutagenesis, and then convert it to a gain-of-function mutation by replacing the beta geo gene with any gene of interest to be expressed under the control of the trapped promoter through Cre-mediated recombination.

Animals↗

PubMed2003

Evaluation of human beta-enolase as a serum marker for exercise-induced muscle damage.

OBJECTIVE: To evaluate whether the serum beta-enolase level is a useful indicator of exercise-induced muscle damage in athletes. DESIGN: Blood samples were taken from 49 adult amateur marathon runners before and immediately after a marathon race, and the serum levels of beta-enolase and creatine phosphokinase were measured. SETTING: The Aoshima Taiheiyo Marathon 2000, Miyazaki, Japan, on a cloudy day in December with an ambient temperature of 18 degrees C. SUBJECTS: Forty-nine adult amateur marathon runners (42 men and 7 women) who regularly participated in runs. INTERVENTION: The intervention was a marathon run. MAIN OUTCOME MEASURES: Serum beta-enolase was measured using a sensitive sandwich enzyme-linked immunosorbent assay. Serum creatine phosphokinase was measured using a standard procedure. RESULTS: The mean beta-enolase concentration was 9.45 +/- 3.11 ng/mL before the race. It increased to 22.11 +/- 8.80 ng/mL after the race, representing a proportional increase of 1.57 +/- 1.46. The serum concentration of beta-enolase after the race was significantly higher than that before the race (P < 0.0001). Moreover, the serum beta-enolase level increased as much as the creatine phosphokinase level after the race, and strongly correlated with creatine phosphokinase (r = 0.828, P < 0.0001). The proportional increase of beta-enolase also correlated with that of creatine phosphokinase (r = 0.441, P < 0.005). CONCLUSIONS: Our data suggest that the absolute values of the serum beta-enolase are more appropriate to relate to muscle damage.

Adult↗

PubMed2002

Targeted disruption of the Tab1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis.

The transforming growth factor-beta (TGF-beta) superfamily consists of a group of secreted signaling molecules that perform important roles in the regulation of cell growth and differentiation. TGF-beta activated kinase-1 binding protein-1 (TAB1) was identified as a molecule that activates TGF-beta activated kinase-1 (TAK1). Recent studies have revealed that the TAB1-TAK1 interaction plays an important role in signal transduction in vitro, but little is known about the role of these molecules in vivo. To investigate the role of TAB1 during development, we cloned the murine Tab1 gene and disrupted it by homologous recombination. Homozygous Tab1 mutant mice died, exhibiting a bloated appearance with extensive edema and hemorrhage at the late stages of gestation. By histological examinations, it was revealed that mutant embryos exhibited cardiovascular and lung dysmorphogenesis. Tab1 mutant embryonic fibroblast cells displayed drastically reduced TAK1 kinase activities and decreased sensitivity to TGF-beta stimulation. These results indicate a possibility that TAB1 plays an important role in mammalian embryogenesis and is required for TAK1 activation in TGF-beta signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Naso-maxillary deformity due to frontonasal expression of human transthyretin gene in transgenic mice.

BACKGROUND: Retinoic acid, a metabolic product of retinol, is essential for craniofacial morphogenesis. Transthyretin (TTR) is a plasma protein delivering retinol to tissues. We produced several transgenic mouse lines using the human mutant TTR (hTTRMet30) gene to establish a mouse model of familial amyloidotic polyneuropathy. One of the lines showed an autosomal dominant inheritance of naso-maxillary deformity termed Nax. RESULTS: The Nax malformation was characterized by a hypoplastic developmental defect of the frontonasal region. Homozygous mice with higher transgene expressions showed more severe phenotypes, but a subline, in which the copy number and expression of the transgene was reduced, showed a normal phenotype, indicating that the hTTRMet30 expression caused the malformation. Nax mice began to express the hTTRMet30 gene in the nasal placode from embryonic day 10.5 (E10.5), which was 2 days earlier than in the other transgenic lines with a normal phenotype. Excessive cell death was observed in the nasal placode of the E10.5 Nax embryos. In addition, the forced expression of hTTRMet30 in the nasal placode of transgenic mice resulted in similar phenotypes. CONCLUSION: The expression of the hTTRMet30 gene in the nasal placode at E10.5 induced apoptotic cell death, leading to hypoplastic deformity in the frontonasal region.

Animals↗

PubMed2002

Region-specific gastrointestinal Hox code during murine embryonal gut development.

Hox genes encode transcription factors, and they are involved in the specification of each body part along the anteroposterior (AP) body axis during embryogenesis. To clarify AP pattern formation of the digestive tract, the expression patterns of Hox genes belonging to paralogous groups 4 and 5, and parts of groups 6 and 7, were systematically examined by whole-mount and section in situ hybridization. The Hox gene expression pattern of paralogous groups 4-9 in the developing gut at 12.5 days post-coitum was fully examined. All HoxA and HoxB genes in paralogous groups 4-8 were expressed in the stomach, in contrast to the HoxC and HoxD genes. In the midgut region, all Hox cluster genes showed colinear expression within each cluster, yielding the Hox code; the more 3' located genes were expressed more rostrally and the 5' group genes more caudally. The colinear expression of HoxA and HoxB cluster genes started from the duodenum, that of HoxC cluster genes started from the jejunum, and HoxD cluster genes were expressed in the caudal part of the midgut, ileum and cecum. In the hindgut region, HoxD cluster genes and Abd-B family genes were expressed. Thus, a different Hox code seems to exist in each subdomain of developing gut (foregut, midgut and hindgut). The visceral mesoderm restricted expression also suggested that the Hox code primarily functions in mesenchymal specification, and then leads to the regional differentiation of gut subdomains as the result of epithelial-mesenchymal interactions.

Animals↗

PubMed2002

Effect of direct angiogenesis inhibition in rheumatoid arthritis using a soluble vascular endothelial growth factor receptor 1 chimeric protein.

OBJECTIVE: We evaluated the effect of direct angiogenesis inhibition in synovium of patients with rheumatoid arthritis (RA), using a soluble vascular endothelial growth factor receptor 1 (VEGFR1) chimeric protein. METHODS: Dispased cells from active RA synovial tissues were cocultured on OP9 stromal cells. Control synovial tissues were obtained from patients with injury of the anterior cruciate ligament. Chimeric protein (30 microg/ml) of the extracellular domain of VEGFR1 fused to the Fc portion of human IgG1 (VEGFR1-Fc) was added to culture medium. After 10 days, the cells were stained with anti-CD31 antibody and anti-Tie-2 antibody. RESULTS: Endothelial cells from patients with active RA had high angiogenic growth capacity compared with controls. Proliferation of these endothelial cells was strongly suppressed by VEGFR1-Fc. Quantitative analysis revealed that VEGFR1-Fc inhibited angiogenesis in a dose dependent manner. CONCLUSION: VEGFR1-Fc is able to suppress angiogenesis in rheumatoid synovium, suggesting that direct inhibition of angiogenesis activity could serve as a novel therapeutic strategy to prevent progressive synovial hyperplasia and inflammatory reactions in active RA.

Angiogenesis Inhibitors↗