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Biomedical subjects

Satoshi Kawaguchi

Publications and source records attributed to Satoshi Kawaguchi.

At least 37 records · Page 2Linked to original sources
PubMed2003

Recognition by cellular and humoral autologous immunity in a human osteosarcoma cell line.

Because of the difficulty of developing pairs of osteosarcoma cell lines and cytotoxic T lymphocytes (CTLs), no osteosarcoma tumor antigens that are useful for antiosteosarcoma immunotherapy have yet been identified. In parallel with continuous attempts to develop such pairs from osteosarcoma, we employed serological identification using a recombinant expression cloning (SEREX) method to identify B cell-defined antigens. Consequently, a human osteosarcoma cell line, OS2000, was established from a primary osteosarcoma of a patient cured of hereditary retinoblastoma. Repetitious in vitro stimulations by OS2000 cells to the autologous peripheral T cells induced cytotoxic activity in the autologous osteosarcoma cells but not in the nontumor cells. The cytotoxicity was inhibited by anti-HLA class I monoclonal antibody. SEREX analysis revealed that autologous humoral immunity reacted to two proteins expressed in OS2000. One was the self HLA-Cw*0102 molecule, and the other was wild-type smooth muscle myosin light chain (SMMLC). However, no antigenicity of these proteins was seen versus the sera of the other patients. In conclusion, our results demonstrated the presence of host cellular and humoral immune responses to autologous osteosarcoma cells. This offered the opportunity to identify osteosarcoma antigens recognized by autologous immunity.

Antibody Formation↗
PubMed2003

Effect of steroid pulse therapy with and without orbital radiotherapy on Graves' ophthalmopathy.

PURPOSE: To report the effect of high-dose intravenous corticosteroid pulse therapy with and without orbital radiotherapy on Graves' ophthalmopathy. DESIGN: Nonrandomized clinical trial. METHODS: We selected 39 Japanese patients (age range, 22-64 years; mean, 48 years; 31 women, 8 men) who had active Graves' ophthalmopathy among 195 consecutive patients. In the first 20 patients, high-dose intravenous methylprednisolone pulse therapy (1 g per day for 3 successive days, repeated 3 times within 3 weeks) followed by 24-Gy orbital radiotherapy was performed. In the other 19 of the 39 patients, high-dose intravenous methylprednisolone pulse therapy without orbital radiotherapy was performed. Coronal computed tomography (CT) of the orbit and exophthalmometry were performed before the corticosteroid pulse therapy, and 1 and 6 months after the corticosteroid pulse therapy. The maximum coronal section area of the most hypertrophic rectus muscle in each eye was measured based on orbital CT imaging. RESULTS: Clinical findings at study entry were not significantly different between the two groups. No significant difference was found in the maximum coronal section area of the most hypertrophic rectus muscle and the results of exophthalmometry measurements in both groups before the therapy. Extraocular muscle hypertrophy was significantly reduced 1 month and 6 months after the therapy (P < .01) in both groups. However, no beneficial therapeutic effect on proptosis was observed in either group at 1 month and 6 months after the therapy. No significant difference in the therapeutic effect on extraocular muscle hypertrophy and proptosis was found between the two groups. CONCLUSIONS: Orbital irradiation after corticosteroid pulse therapy had no beneficial therapeutic effects on rectus muscle hypertrophy or proptosis of active Graves' ophthalmopathy during the 6-month follow-up period.

Adult↗
PubMed2003

Blood coagulation and fibrinolytic response after endovascular stent grafting of thoracic aorta.

OBJECTIVE: Thrombosis is common in aneurysms immediately after stent-grafting, because of exclusion from systemic blood flow. We studied changes in blood coagulation and the fibrinolytic system in patients with thoracic aortic aneurysm or dissection after stent-grafting to examine risk for consumption coagulopathy. METHODS: Thirty-one thoracic aortic aneurysms were treated with stent-grafting (aneurysm group), and 29 aortic dissections were treated with entry closure with stent-grafting (dissection group). The stent-graft was constructed from a self-expanding Z stent and thin-walled woven polyester fabric. Platelet count, fibrinogen, antithrombin III (AT III), and thrombin-AT III complex were assayed as markers of coagulation. Plasminogen, alpha(2)-plasmin inhibitor, alpha(2)-plasmin inhibitor-plasmin complex, fibrin degradation products fragment E (FDP-E), and fibrin degradation products d-dimer were monitored as markers of fibrinolysis. Blood samples were collected before surgery and on postoperative days 1, 3, 7, and 14. RESULTS: In both groups platelet count significantly decreased on postoperative days 1 and 3, and increased on postoperative day 14. AT III significantly decreased on postoperative day 1, but recovered after postoperative day 7. FDP-E significantly increased on postoperative day 1 in both groups. There was significant correlation of aneurysm diameter with alpha(2)-plasmin inhibitor-plasmin complex, fibrin degradation products, and d-dimer in the dissection group on postoperative day 1. CONCLUSIONS: Activation of coagulation and fibrinolysis was observed after stent-grafting to treat thoracic aortic aneurysm and aortic dissection. However, no patients exhibited consumption coagulopathy postoperatively. Therefore we believe there is little risk for consumption coagulopathy after stent-grafting.

Adult↗
PubMed2003

Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer.

To establish an effective B7-based gene therapy against osteosarcoma, we transferred B7-1/Fas chimeric gene adenovirally into poorly immunogenic osteosarcoma cells. We found that adenovirus-mediated rat B7-1/Fas gene transfer induced (i) expression of rat B7-1/Fas chimeric molecules in osteosarcoma cells, (ii) activation of murine T cells, (iii) apoptosis of murine osteosarcoma cells in the presence of anti-rat B7-1 mAb in vitro, and (iv) therapeutic effects more prominently than B7-1 gene transfer on the development of pulmonary metastasis and survival of mice. These findings collectively support the therapeutic value of adenovirus-mediated B7-1/Fas gene transfer on poorly immunogenic osteosarcoma, which is resistant to a treatment protocol using transduction of B7-1 alone.

Adenoviridae↗
PubMed2003

Postoperative progression of pulmonary metastasis in osteosarcoma.

Early relapse with distant metastasis often is observed in patients with cancer after resection of the primary tumor. It is considered that resection of the primary tumor induces activation of systemic angiogenesis and enhances progression of remote metastasis. The authors show that resection of the primary osteosarcoma tumor enhances progression of pulmonary metastasis in animal osteosarcoma models. Matrigel plug neovascularization assay revealed that systemic angiogenic activity was elevated after primary tumor removal (tumor intact group, 1.61 +/- 0.21 g/dL; tumor removed group, 4.92 +/- 0.35 g/dL). In addition, serum concentration of the angiogenesis inhibitor, endostatin, decreased significantly after primary tumor removal. Treatment with the antiangiogenic reagent TNP-470 suppressed postoperative progression of pulmonary metastasis. These results indicate the possibility that activation of angiogenic activity after resection of osteosarcoma tumors enhances progression of pulmonary metastasis. The current data also suggest that administration of antiangiogenic reagents can prevent progression of pulmonary metastasis in osteosarcoma postoperatively.

Angiogenesis Inhibitors↗
PubMed2003

[Epidemic nosocomial keratoconjunctivitis caused by adenovirus type 4].

PURPOSE: To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis(EKC) occurring in the ophthalmology ward of Sapporo Medical University Hospital and to devise preventive measures for it. MATERIALS AND METHODS: We studied the symptoms and clinical course of 2 patients who had EKC and 16 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. RESULTS: The clinical symptoms of EKC were conjunctival hyperemia in 18 patients(100%), conjunctival follicles in 11 patients (61.1%), discharge in 8 patients(44.4%), superficial punctate keratopathy in 7 patients(38.9%), swelling of the eyelids in 3 patients(16.7%), and fever in 3 patients(16.7%). 72% were positive for Adeno-check. Adenovirus type 4 was isolated from the conjunctival swabs. We considered that the route of hospital infection was infection from the doctor's hands, from eye drops, and from contact lenses. We disclosed that nosocomical EKC had occurred in our hospital. The hospital infection was eliminated by closing the ophthalmology ward and sterilizing instruments and washing hands. CONCLUSIONS: The delay of proper measures increased the risk of nosocomical infection. We recognized the importance of careful observation of patients and immediate preventive efforts in nosocomical infection.

Adenovirus Infections, Human↗
PubMed2002

Improved generation of HLA class I/peptide tetramers.

As a tetrameric major histocompatibility complex (MHC) class I-peptide complex (tetramer) is capable of detecting antigen-specific cytotoxic T lymphocyte (CTL) by flow cytometry, significant information about the generation of in vivo immunity can be obtained. It is, however, difficult to make a soluble wild type of MHC class I heavy chain by the prokaryotic expression system. Therefore, we developed a new method for making soluble mutant HLA-A*2402 heavy chain. In this method, signal sequences were deleted, and the codon was changed to silent mutated nucleotide sequences that bacteria could use as preferable codon. When purified mutant HLA-A*2402 molecules were examined for the protein generation by SDS-polyacrylamide gel electrophoresis (PAGE) and western blotting using anti-HLA class I monoclonal antibody (mAb) as compared with wild type, a large amount of mutant heavy chain could be detected. In contrast, the expression of wild-type stable HLA-A*2402 heavy chain molecule was not detected in this system. Consequently, by using mutant HLA-A*2402/peptide tetramers, CTL precursors (CTLp) that specifically recognize antigenic peptide derived from the X;18 chromosomal translocations of synovial sarcoma were detected in patients' PBL.

Base Sequence↗
PubMed2002

Rhabdomyosarcoma arising from a dormant dumbbell ganglioneuroma of the lumbar spine: a case report.

STUDY DESIGN: A case report of a lumbar dumbbell tumor that showed a sequential change in histology from ganglioneuroma into rhabdomyosarcoma after long-term dormancy. OBJECTIVE: To present a case of non-neurogenic malignancy arising from ganglioneuroma. SUMMARY OF BACKGROUND DATA: Ganglioneuromas rarely form the dumbbell variety. Whereas conversion of ganglioneuroma into neurogenic malignancies occurs occasionally, between ganglioneuroma and mesenchymal malignancies it has so far been limited to a case in which ganglioneuroma developed after chemo- and radiotherapy for orbital rhabdomyosarcoma. METHODS: A 61-year-old man was referred with a recurrent retroperitoneal tumor that had been excised as ganglioneuroma. Using imaging, histologic, and immunohistochemical studies, a comparative analysis of the primary and recurrent tumors was performed. RESULTS: A total of 44 histologic sections were examined for the primary and the recurrent tumors that had been excised surgically, with an 8-month interval between resections. Histologic and immunohistochemical findings in the primary tumor were consistent with ganglioneuroma, whereas those in the recurrent tumor indicated rhabdomyosarcoma. CONCLUSIONS: It is assumed that the rhabdomyosarcoma arose from a dumbbell ganglioneuroma as a component of malignant ectomesenchymoma.

Disease Progression↗
PubMed2002

The Id2 gene is a novel target of transcriptional activation by EWS-ETS fusion proteins in Ewing family tumors.

We report here that the Id2 (inhibitor of DNA binding 2) gene is a novel target of transcriptional activation by EWS-FLI1 and EWS-ERG, two fusion proteins that characterize Ewing family tumors (EFTs). To identify downstream targets of these EWS-ETS fusion proteins, we introduced EWS-ETS fusion constructs into a human fibrosarcoma cell line by retroviral transduction. cDNA microarray analysis revealed that Id2 expression was up-regulated by introducing the EWS-ETS fusion gene but not by the normal full-length ETS gene. An Id2 promoter-luciferase reporter assay showed that transactivation by EWS-ETS involves the minimal Id2 promoter and may function in cooperation with c-Myc within the full-length regulatory region. A chromatin immunoprecipitation assay revealed direct interaction between the Id2 promoter and EWS-FLI1 fusion protein in vivo. Significantly higher expression of Id2 and c-Myc was observed in all of the six EFT cell lines examined compared to six other sarcoma cell lines. Moreover, high levels of Id2 expression were also observed in five of the six primary tumors examined. Id2 is generally thought to affect the balance between cell differentiation and proliferation in development and is highly expressed in several cancer types. Considering these previous studies, our data suggest that the oncogenic effect of EWS-ETS may be mediated in part by up-regulating Id2 expression. doi:10.1038/sj.onc.1206025

Base Sequence↗
PubMed2002

Acral myxoinflammatory fibroblastic sarcoma: a report of five cases and review of the literature.

Five cases of acral myxoinflammatory fibroblastic sarcoma that occurred in the distal extremities within the subcutaneous tissue are described. In one case, recurrence and metastases were recognized rather rapidly, only 3 months after the first excision. There have been no reports of early recurrence or metastases, especially the latter. The predominant type of constituent cells, cellularity of the neoplastic cells and density of inflammatory cells varied microscopically among cases. However, characteristic ganglion-like cells, Reed-Sternberg-like cells, round mononuclear cells and myxoid stroma, sometimes only seen focally, were found in all cases. Positive immunoreaction for vimentin was present in all cases. There was no correlation between positivity of MIB-1 or p53 for the primary tumor and presence of recurrence or metastases. In conclusion, we should be more cautious about the possibility of recurrence or metastases in earlier phases of acral myxoinflammatory fibroblastic sarcoma. Identification of the atypical bizarre fibroblastic component as the manifestation of the malignant nature of this lesion is vital to correct diagnosis, and it is important to attend to the myxoid and hyalinized zones, the inflammatory infiltrate, the presence of ganglion-like cells and acral location as features of acral myxoinflammatory fibroblastic sarcoma.

Adolescent↗
PubMed2002

Detection and induction of CTLs specific for SYT-SSX-derived peptides in HLA-A24(+) patients with synovial sarcoma.

To investigate the immunogenic property of peptides derived from the synovial sarcoma-specific SYT-SSX fusion gene, we synthesized four peptides according to the binding motif for HLA-A24. The peptides, SS391 (PYGYDQIMPK) and SS393 (GYDQIMPKK), were derived from the breakpoint of SYT-SSX, and SS449a (AWTHRLRER) and SS449b (AWTHRLRERK) were from the SSX region. These peptides were tested for their reactivity with CTL precursors (CTLps) in 16 synovial sarcoma patients using HLA-A24/SYT-SSX peptide tetramers and also for induction of specific CTLs from four HLA-A24(+) synovial sarcoma patients. Tetramer analysis indicated that the increased CTLp frequency to the SYT-SSX was associated with pulmonary metastasis in synovial sarcoma patients (p < 0.03). CTLs were induced from PBLs of two synovial sarcoma patients using the peptide mixture of SS391 and SS393, which lysed HLA-A24(+) synovial sarcoma cells expressing SYT-SSX as well as the peptide-pulsed target cells in an HLA class I-restricted manner. These findings suggest that aberrantly expressed SYT-SSX gene products have primed SYT-SSX-specific CTLps in vivo and increased their frequency in synovial sarcoma patients. The identification of SYT-SSX peptides may offer an opportunity to design peptide-based immunotherapeutic approaches for HLA-A24(+) patients with synovial sarcoma.

Adolescent↗
PubMed2002

Chemokine profile of herniated intervertebral discs infiltrated with monocytes and macrophages.

STUDY DESIGN: Herniated lumbar disc specimens were analyzed using reverse transcriptase-polymerase chain reaction to determine the profile of chemokine expression. OBJECTIVE: To investigate the mechanism underlying the recruitment of inflammatory cells into herniated discs during the process of spontaneous regression. SUMMARY OF BACKGROUND DATA: Spontaneous regression of herniated intervertebral discs has been increasingly reported. Although macrophages are suggested to play a central role in this process, it remains unclear how these macrophages accumulate in the herniated discs. METHODS: RNA was extracted from 36 surgical specimens of the herniated lumbar disc, a disc specimen of idiopathic scoliosis and pyogenic spondylitis, and activated peripheral blood mononuclear cells of a normal donor. The RNA was reverse transcribed, and the resultant cDNA was amplified by PCR using primer pairs specific to the CXC chemokines (IL-8, MGSA-alpha, IP-10, MIG), the CC chemokines (MCP-1, MCP-2, MCP-3, MCP-4, MIP-1alpha, MIP-3alpha, RANTES, STCP-1), the C chemokine (lymphotactin), and the glyceraldehyde phosphate housekeeping gene. Thin cryostat sections also were made from the disc specimens and stained with hematoxylin and eosin. RESULTS: All the chemokines examined except MCP-4 were expressed by activated peripheral blood mononuclear cells. Glyceraldehyde phosphate was detected in 8 of 36 herniated discs and in 1 disc specimen each of idiopathic scoliosis and pyogenic spondylitis. Chemokine expression was examined for these 10 disc specimens. From among the 13 chemokines examined, MCP-3, MCP-4, RANTES, and IP-10 were detected in the disc from the idiopathic scoliosis, and MCP-3, MCP-4, RANTES, IP-10, MIG, and MGSA-alpha were detected in the infected or herniated discs. Histologic analysis showed infiltration of inflammatory cells in the infected disc and all 8 herniated discs. CONCLUSIONS: The findings suggest that chemoattractive properties exist in a selected population of human intervertebral discs, and that unique sets of chemokinesplay a role in spontaneous regression of these herniated disc tissues.

Adult↗
PubMed2002

A quantitative analysis of sensory function in lumbar radiculopathy using current perception threshold testing.

STUDY DESIGN: Peripheral sensory functions in patients with radiculopathy resulting from lumbar disc herniation and in control individuals were analyzed using current perception threshold testing. OBJECTIVE: To evaluate the severity of sensory disturbance quantitatively in patients with lumbar radiculopathy. SUMMARY OF BACKGROUND DATA: Subjective evaluation of the severity of sensory disturbance associated with spinal disorders using conventional methods often is difficult. Current perception threshold evaluation is a recently proposed method for studying peripheral nerve dysfunction. This is a quantitative sensory test for analyzing functions of A-beta, A-delta, and C fibers. METHODS: In this study, 48 patients with lumbar radiculopathy resulting from lumbar disc herniation were examined. The mean age of the patients was 37.9 years. All the patients had pain distribution from the compression of one lumbar nerve root (L5 or S1), and unequivocal unilateral disc herniation of the corresponding level was shown by magnetic resonance imaging. Eleven healthy volunteers were used as control subjects. Their mean age was 38.2 years. Current perception threshold evaluation using a Neurometer device was performed at three frequencies: 2000, 250, and 5 Hz. The stimulus sites were located on the dorsal side of the first metatarsus (the L5 dermatome) and the dorsal side of the fifth metatarsus (the S1 dermatome). These sites were investigated on both legs in all the patients and control subjects. The intensity of pain was scored using a visual analog scale. RESULTS: In the control group, there were no significant differences in current perception threshold values at any frequency between the left and right legs. In the patient group, the current perception threshold values in the affected legs were significantly higher than those in the contralateral legs at all frequencies. The current perception threshold values in the affected legs in the patient group were significantly higher than those in the control subjects at 2000 and 250 Hz, whereas there were no significant differences at 5 Hz. The current perception threshold values in the affected legs were significantly higher in patients with hypesthesia than in those without hypesthesia at 2000 and 250 Hz, and in patients with severe pain than in those with less pain at 5 Hz. CONCLUSIONS: Current perception threshold testing showed that the functions of A-beta, A-delta, and C fibers deteriorated in patients with lumbar radiculopathy. This technique may be useful for quantifying sensory nerve dysfunction in patients with radiculopathy.

Adolescent↗
PubMed2002

ErbB2 expression is correlated with increased survival of patients with osteosarcoma.

BACKGROUND: Elevated ErbB2 expression and gene amplification have been shown to be associated with poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. By contrast, a previous study showed that the expression of ErbB2 declines in individual osteosarcomas as they become metastatic. In the current study, the authors determined the relation between ErbB2 status and outcome in a large number of selected patients with high-grade osteosarcoma. METHODS: ErbB2 status was determined immunohistochemically in biopsy specimens of osteosarcoma of the extremities from 81 patients who were treated with surgery and chemotherapy. None of the patients had metastatic disease at presentation (Stage II), and all were followed-up for at least five years. The ErbB2 status was analyzed in relation to the lengths of event-free and overall survival. RESULTS: Of the 81 tumors examined, 51 (61%) demonstrated high levels of ErbB2 expression. The presence of increased levels of ErbB2 in osteosarcoma was significantly associated with the increased probability of event-free (72.2% v. 45.6% at 5 years, P = 0.03) and overall survival (79.7% v. 58.2% at 5 years, P = 0.03). Cox multivariate analysis showed that the risk of adverse events and death was increased substantially (rate ratio: 2.24 and 2.54; 95% confidence interval, 1.07-4.72 and 1.09-5.67, respectively) among patients with decreased levels of ErbB2 protein in tumor cells, as compared with patients who had increased levels of ErbB2 in tumor cells. CONCLUSIONS: In patients with high-grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased levels of ErbB2 in tumor cells is associated with a significantly increased probability of event-free and overall survival. Further data are needed before this marker can be used in making clinical decisions.

Adolescent↗
PubMed2002

Complications associated with bone cementing for the treatment of giant cell tumors of bone.

Aretrospective review was conducted of giant cell tumors treated between 1984 and 1998 using the technique of aggressive curettage through a large bone window followed by acrylic cement reconstruction. Fifteen patients with a mean follow-up time of 46 months (range, 24-188 months) were identified. One patient had a local recurrence 24 months postoperatively. All the patients showed a radiolucent zone at the bone-cement interface up to 2.5 mm in width during the first 6 months after operation. However, the radiolucent zones were nonprogressive and did not affect the stability of the bone cement. Osteoarthritis of the knee joint occurred 14 years postoperatively in one patient with an intraarticular fracture at presentation. A stress fracture occurred in one patient who had the largest tumor in the distal femur. Acrylic cement reconstruction is a safe and effective procedure that provides local adjuvant therapy. Giant cell tumors with an associated intraarticular fracture remain a challenging problem to treat.

Adolescent↗
PubMed2002

Endovascular stent grafting of the descending thoracic aorta after arch repair in acute type A dissection.

An endovascular stent graft was successfully deployed to the primary entry site in the proximal descending thoracic aorta after total aortic arch replacement using the "elephant trunk" technique in acute type A aortic dissection. The residual false lumen of the descending aorta was thrombosed completely after stent grafting. The elephant trunk was feasible for a proximal landing zone for stent grafting of the descending aorta. Stent grafting in combination with aortic arch replacement was a safe and effective procedure, and may be an alternative choice in carefully selected patients with type A aortic dissection.

Aortic Dissection↗