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Satoshi Kawaguchi

Publications and source records attributed to Satoshi Kawaguchi.

44 records · Page 3Linked to original sources

Adenovirus-mediated in vivo B7-1 gene transfer induces anti-tumor immunity against pre-established primary tumor and pulmonary metastasis of rat osteosarcoma.

We have previously reported that an osteosarcoma vaccine generated by ex vivo transfection of B7-1 cDNA induces protective as well as curative immunity against B7-1-negative parental osteosarcoma. Because establishment of human osteosarcoma cell lines, which is a prerequisite for ex vivo gene transfer, is rarely successful, we, in the present study, investigated the therapeutic efficacy of adenovirus-mediated in vivo B7-1 gene transfer to pre-established primary tumor as well as pulmonary metastasis of osteosarcoma. Adenovirus-mediated rat B7-1 gene transfer induced (a) expression of B7-1 molecules in osteosarcoma cells by both in vitro and in vivo infection procedures, (b) curative immunity against pre-established primary osteosarcoma and, subsequently, hosts gained protection against additional challenge of parental B7-1-negative osteosarcoma cells, (c) systemic immunity against pre-established pulmonary metastasis, and (d) activation of regional lymph node CD4(+) T cells, expansion of dendritic cells and natural killer cells and the secretion of interferon-gamma. These findings collectively support the therapeutic value of adenovirus-mediated in vivo gene transfer on osteosarcoma, which is of greater simplicity than cell-based B7-1 vaccine, and represent an attractive strategy for therapy of patients with metastatic osteosarcama who acquired resistance to current therapeutic protocols.

Adenoviridae↗

Antegrade intramedullary K-wire fixation for distal radial fractures.

Manual reduction and antegrade intramedullary K-wire fixation were performed for 29 selected Colles-type distal radial fractures in 29 patients. Severely comminuted intra-articular fractures and Barton's fracture were not included in this study. The tips of the K-wires supported an articular surface of the distal radius. Except for 1 case of skin irritation in the forearm, there were no complications related to tendon or nerve injuries or reflex dystrophy. There was no pin loosening, but protrusion of sharp tips of K-wires into the wrist joint occurred in 3 patients. Average volar tilt, radial shortening, and step-off at follow-up evaluation were 5 degrees, 2.6 mm, and 0.2 mm, respectively. These radiologic results were consistent with values reported in other pinning studies; however, radial shortening was not controlled effectively. Fourteen (48%) of 29 patients had radial shortening >3 mm. The advantages of this surgical procedure are the low occurrence rate of soft-tissue complications and prevention of dorsal angulation of fractures.

Adult↗

Successful endografting with simultaneous visceral artery bypass grafting for severely calcified thoracoabdominal aortic aneurysm.

We present two cases of severely calcified thoracoabdominal aortic aneurysm treated by means of endografting with a retrograde aortomesenteric bifurcated bypass graft reconstructing the celiac axis and superior mesenteric artery. To avoid spinal ischemia, we monitored evoked spinal cord potential and performed an occlusion test of the intercostal arteries using a retrievable stentgraft. No change in evoked spinal cord potential was noted, and no endoleaks or complications, including paraplegia, were observed. This procedure is a feasible and less-invasive treatment for severely calcified thoracoabdominal aortic aneurysms.

Aged↗

Effect of high-dose intravenous steroid pulse therapy followed by 3-month oral steroid therapy for Graves' ophthalmopathy.

PURPOSE: To evaluate the effect of high-dose intravenous steroid pulse therapy followed by 3-month oral steroid therapy for Graves' ophthalmopathy. METHODS: We selected 41 Japanese patients (age range, 21-76 years; mean = 49 years) who had active Graves' ophthalmopathy among 205 consecutive patients examined at Sapporo Medical University Hospital between 1997 and 1999. In a prospective study, we investigated the effect on the 41 patients of high-dose intravenous methylprednisolone pulse therapy (1 g/day x 3 days x 3 times) followed by 3-month oral prednisone therapy. Coronal computed tomography (CT) of the orbit, exophthalmometry and monocular fixation field measured by Goldmann perimetry were carried out before the steroid pulse therapy, and 1 and 6 months after the steroid pulse therapy. The maximum coronal section area of the rectus muscle in each eye was measured using an orbital CT image. RESULTS: Extraocular muscle hypertrophy was significantly reduced 1 and 6 months after the pulse therapy (paired t-test, P <.01), and was not significantly different between 1 and 6 months after the pulse therapy. Proptosis was not significantly reduced by the pulse therapy. Monocular fixation fields were measured in 34 patients with diplopia, and limitation of eye movements was improved in 15 patients (44%) by the pulse therapy. In the other patients, improvement of the limitation was not detectable by the test of the monocular fixation field. CONCLUSIONS: The treatment in this study is effective for extraocular muscle hypertrophy, and relapse was minimum within 6 months. However, this treatment has limited effect on limitation of eye movements and less effect on proptosis.

Administration, Oral↗

Evaluation of thrombogenicity by indium-111 platelet scintigraphy in endografting for abdominal aortic aneurysms.

Obstruction of the endograft limb by thrombosis has often been reported and may cause fatal complications such as leg necrosis or myonephropathic metabolic syndrome. The purpose of this study was to evaluate endograft antithrombogenicity by indium-111 platelet scintigraphy. Seventeen patients with abdominal aortic aneurysms were treated by endografting. Thirteen patients were treated with conventional open surgery using an artificial graft. The endograft was constructed from a self-expanding Z-shaped stent and woven polyester fabric. Autologous platelets labeled with indium-111 were injected at 2 weeks postoperatively. At 24 hours and 72 hours postinjection, the ratio of scintillation count of the endograft or graft to that of the native artery was calculated to assess platelet deposition. The normalization ratio was calculated as follows: (scintillation count per pixel of endograft or graft/circumference)/(scintillation count per pixel of the native femoral artery). Platelet factor 4 and beta-thromboglobulin were measured to evaluate the systemic platelets activity at 2 weeks postoperatively. There was no significant difference in platelet counts or labeling efficiency between the groups. The ratio was significantly higher in the endografting group than in the open surgery group at 72 hours postinjection (2.5-0.7 vs 3.9-1.1, P<.001). There was no significant difference in platelet factor 4 and beta-thromboglobulin between the groups. Although there was no difference in systemic platelet activity, endografting was associated with lower antithrombogenicity. It remains unclear whether lower antithrombogenicity causes thromboembolism as a complication of the procedure. The authors recommend the administration of antiplatelet drugs to prevent endograft obstruction in patients with very narrow iliac arteries.

Aged↗

In vivo immunogenicity of osteosarcoma cells that express B7-1a, an alternatively spliced form of B7-1.

BACKGROUND: B7 family members play a central costimulatory role in T cell activation. We have previously identified B7-1a, an alternatively spliced form of B7-1. The function of B7-1a in induction of anti-tumor immunity remains uncertain. MATERIALS AND METHODS: The cDNAs of murine B7-1, B7-1a and B7-2 were introduced into a murine osteosarcoma cell line, LM8. The ability of B7 transfectants to elicit in vivo anti-tumor immunity was comparatively analyzed with respect to tumorigenecity, pulmonary metastasis and survival time. RESULTS: LM8 cells expressing B7-1, B7-1a, or B7-2 all elicited immunological responses in immunocompetent C3H/He mice. Notably, the anti-tumor effects were most obvious in mice inoculated with B7-1a-transfected LM8 cells. Such a difference among B7-transfectants became indistinguishable in immunodeficient nude mice. CONCLUSION: These findings indicate that B7-1a serves as a more efficacious costimulatory molecule than B7-1 or B7-2 in the induction and maintenance of anti-tumor immune responses against a poorly immunogenic osteosarcoma cell line.

Alternative Splicing↗

Intrinsic and extrinsic manipulation of B7/CTLA-4 interaction for induction of anti-tumor immunity against osteosarcoma cells.

BACKGROUND: B7 family members play a central costimulatory role in T cell activation. We identified B7-1a, an alternatively spliced form of B7-1. The therapeutic efficacy of B7-1a-expressing tumor vaccine remains uncertain. MATERIALS AND METHODS: The murine osteosarcoma cell line, LM8, was engineered to express equivalent levels of B7-1 (B7-1-LM8) and B7-1a (B7-1a-LM8). The therapeutic efficacy of B7-transfected cells and anti-CTLA-4 blocking mAb was evaluated by the mixing experiments on the primary tumor, pulmonary metastasis and survival time. RESULTS: (i) a mixture of B7-1-LM8 or B7-1a-LM8 cells inhibited growth of the subcutaneous LM8 tumors and augmented the therapeutic effects of anti-CTLA-4 mAb and (ii) a combination of B7-1a-LM8 cells and anti-CTLA-4 mAb most significantly eradicated pulmonary metastasis and prolonged the survival time of mice. CONCLUSION: These findings suggest that intrinsic (lack of IgC-like domain in B7-1a) and extrinsic (anti-CTLA-4 mAb) manipulations of B7/CTLA-4 interaction synergistically improve the therapeutic efficacy of B7-based osteosarcoma vaccines.

Abatacept↗