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Biomedical subjects

Yuichi Tamura

Publications and source records attributed to Yuichi Tamura.

7 recordsLinked to original sources

A fused gene of nucleoprotein (NP) and herpes simplex virus genes (VP22) induces highly protective immunity against different subtypes of influenza virus.

We evaluated the immunogenicity and protective activity of plasmid DNA vaccines encoding the influenza virus NP gene (pNP) alone or in combination with the herpes simplex virus type 1 protein 22 gene (pVP22). Optimal immune responses were observed in BALB/c mice immunized with the combination of pVP22 plus pNP, as assessed by enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICCS). These mice also showed maximal resistance following challenge with the A/PR/8/34 (H1N1) and A/Udron/72 (H3N2) strains of influenza virus. The susceptibility of immunized mice to virus infection was significantly increased following depletion of either CD4+ or CD8+ T cells. These results indicate that a plasmid DNA vaccine encoding pVP22 plus NP induces a high level of cross-protective immunity against influenza virus subtypes.

Animals↗

The F(ab)'2 fragment of an Abeta-specific monoclonal antibody reduces Abeta deposits in the brain.

This work examines whether administering the F(ab' )2 fragment of an IgG1 monoclonal antibody (mAb) targeting the N-terminal 1-13 amino acids of the beta-amyloid peptide (Abeta mAb) reduces amyloid deposition in Alzheimer's disease (AD). The F(ab')2 fragment was injected intraperitoneally or intracranially into Tg2576 mice, a murine model of human AD. Both routes of administration significantly reduced Abeta plaque formation in the brain, as determined immunohistochemically and by monitoring levels of Abeta1-40 and Abeta1-42 peptide. Use of the F(ab')2 fragment significantly reduced phagocytic infiltration in the CNS when compared to intact mAb. Since IgG1 Abs do not fix complement, these findings suggest that effective in vivo clearance of amyloid deposits can be achieved without stimulation of FcR-reactive phagocytes or activation of the complement cascade.

Alzheimer Disease↗

Surface-based registration accuracy of CT-based image-guided spine surgery.

Registration is a critical and important process in maintaining the accuracy of CT-based image-guided surgery. The aim of this study was to evaluate the effects of the area of intraoperative data sampling and number of sampling points on the accuracy of surface-based registration in a CT-based spinal-navigation system, using an optical three-dimensional localizer. A cadaveric dry-bone phantom of the lumbar spine was used. To evaluate registration accuracy, three alumina ceramic balls were attached to the anterior and lateral aspects of the vertebral body. CT images of the phantom were obtained (1-mm slice thickness, at1-mm intervals) using a helical CT scanner. Twenty surface points were digitized from five zones defined on the basis of anatomical classification on the posterior aspects of the target vertebra. A total of 20 sets of sampling data were obtained. Evaluation of registration accuracy accounted for positional and rotational errors. Of the five zones, the area that was the largest and easiest to expose surgically and to digitize surface points was the lamina. The lamina was defined as standard zone. On this zone, the effect of the number of sampling points on the positional and rotational accuracy of registration was evaluated. And the effects of the additional area selected for intraoperative data sampling on the registration accuracy were evaluated. Using 20 surface points on the posterior side of the lamina, positional error was 0.96 mm +/- 0.24 mm root-mean-square (RMS) and rotational error was 0.91 degrees +/- 0.38 degrees RMS. The use of 20 surface points on the lamina usually allows surgeons to carry out sufficiently accurate registration to conduct computer-aided spine surgery. In the case of severe spondylosis, however, it might be difficult to digitize the surface points from the lamina, due to a hypertrophic facet joint or the deformity of the lamina and noisy sampling data. In such cases, registration accuracy can be improved by combining use of the 20 surface points on the lamina with surface points on other zones, such as on the both sides of the spinous process.

Analysis of Variance↗

Polygene DNA vaccine induces a high level of protective effect against HIV-vaccinia virus challenge in mice.

Single HIV-1 subtype DNA vaccine is unlikely to provide reactive protection across a wide range of HIV strains since the HIV virus changes the antigenic sites, particularly, in env gene. To overcome these issues, we constructed a multivalent poly-epitope DNA vaccine. A polygenic DNA vaccine encoding 20 antigenic epitopes from the HIV-1 Env, Gag, and Pol proteins of several clades was constructed using humanized and optimized codons and it was named here hDNA vaccine. In mice, this hDNA vaccine stimulated the following strong (1) antigen-specific serum antibody (Ab) responses, (2) delayed-type hypersensitivity, (3) the activation of IFN-gamma secretion cells targeting gp120 and synthetic antigenic peptides, in addition (4) a significant level of several peptide specific cytotoxic T lymphocytes (CTL) responses. Challenged with modified vaccinia viruses vPE16 and vP1206 expressing HIV-1 env and gag.pol genes, respectively, demonstrated the viral titers in the ovary of the mice vaccinated with hDNA significantly less compared to the unvaccinated mice. Thus, the use of polygene DNA vaccine appears to induce a high level of HIV-specific immune responses and is very effective against challenge with recombinant HIV-vaccinia viruses.

AIDS Vaccines↗

[The advanced technology of three-dimensional medical imaging in spine, bone and joints].

The advanced technology of three-dimensional (3-D) medical imaging allows us to understand the patient specific anatomy in detail. Especially, in orthopedic surgery, treated spinal diseases or the disorders of bone and joints, the 3-D computed tomography(CT), such as multi-slice CT and helical CT is a useful tool for clinical diagnosis and surgical treatment. Since 1995, by the use of these 3-D CT image data, computer navigation system and surgical robot were developed and applied to a spinal instrumentation surgery and an artificial joint replacement. Now surgeons can perform the precise and safe surgical procedure by the computer guidance on the base of 3-D medical imaging.

Arthrography↗

Mechanical stress-induced apoptosis of endplate chondrocytes in organ-cultured mouse intervertebral discs: an ex vivo study.

STUDY DESIGN: Various amounts of static mechanical load were applied to mouse intervertebral discs in organ cultures. The apoptosis then was examined using nick end labeling. Two mitogen-activated protein kinase (MAPK) inhibitors were added to the medium. OBJECTIVES: To establish an experimental model for detecting factors regulating chondrocyte apoptosis induced by mechanical stress, and to determine the role of MAPK and p38 in the stress-induced apoptotic pathway of endplate chondrocytes. SUMMARY OF BACKGROUND DATA: The cause of degenerative change in the cartilaginous endplate (CEP) remains unclear. The authors' previous findings using a mouse model suggested that apoptosis in the cartilaginous endplate may play a role in intervertebral disc degeneration, and that mechanical stress may induce apoptosis. If apoptosis of endplate chondrocytes is involved in the cascade of intervertebral disc degeneration, then how apoptosis is induced by mechanical stress should be important in preventing disc degeneration. However, the mechanism of apoptosis induced by mechanical stress remains unclear. METHODS: Mouse coccygeal discs were harvested and organ cultured. Various static compression loads (0, 0.2, 0.4, 0.8, and 1.0 MPa) were applied on intervertebral discs placed in culture bottles for 24 hours. Paraffin-embedded sections of the harvested discs were stained using Safranin-O and the nick end labeling procedure. The apoptotic cells were counted in the cartilaginous endplate and junctional anulus fibrosus of each intervertebral disc. In addition, U0126 (MAPK inhibitor) and SB202190 (p38 inhibitor) were added to the culture medium to determine their regulatory roles in the apoptosis of endplate chondrocytes induced by mechanical load. RESULTS: Histologically, loaded discs became bulged, and the disc space became narrow. Apoptosis was absent in discs without load, but was particularly noticeable in loaded discs (load weight, 1.0 MPa). The number of apoptotic cells increased depending on the weight of the load. The two MAPK inhibitors significantly increased the number of apoptotic cells. CONCLUSIONS: Chondrocyte apoptosis was induced using a static mechanical load especially in the cartilaginous endplate in an organ culture. Apoptosis occurred similarly to previous findings using an in vivo model. This culture system thus reflected the apoptosis demonstrated in vivo. Because biologically active reagents such as MAPK inhibitors can be simply added to culture media, this system may be a useful method for detecting factors that influence apoptosis induced by mechanical stress. Both MAPK inhibitors increased the occurrence of apoptosis. This suggests that these two MAPKs can counteract the apoptotic pathway induced by mechanical stress.

Animals↗

Accuracy evaluation of a shape-based registration method for a computer navigation system for total knee arthroplasty.

This study evaluated the effect of computed tomography (CT) slice thickness, reconstruction pitch, intraoperative data sampling area, and data sampling volume on the accuracy of registration and determined a clinically acceptable trade-off between accuracy and surgical invasiveness. One cadaveric femur and one cadaveric tibia were used. Computed tomography of the femur and tibia were obtained using a helical scanner. Three sets of slice thickness and slice pitch were chosen for data acquisition, and two additional sets of reconstructed data were made. Bone contours were extracted by removing surrounding substrate. Surface models of bones were made from the resulting data. Registration of surface models to real objects was performed by measuring the position of various surface points on various areas of each object using an OPTOTRAK pen-probe (Northern Digital Inc, Ontario, Canada). The following trade-off is proposed as clinically optimal: perform CT with 3-mm slice thickness and 1-mm reconstruction pitch, and sample a periarticular area of 30 sampling points. The accuracy of registration in terms of position and angle was 0.8 mm and 0.6 degrees of bias with 0.2 mm and 0.3 degrees of root-mean-square in the femur, and 0.5 mm and 0.4 degrees of bias with 0.2 mm and 0.3 degrees of root-mean-square in the tibia.

Arthroplasty, Replacement, Knee↗