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M Kaneko

Publications and source records attributed to M Kaneko.

At least 145 records · Page 8Linked to original sources
PubMed1999

Transient nuclear factor kappaB (NF-kappaB) activation stimulated by interleukin-1beta may be partly dependent on proteasome activity, but not phosphorylation and ubiquitination of the IkappaBalpha molecule, in C6 glioma cells. Regulation of NF-kappaB linked to chemokine production.

We previously reported that several stresses can induce cytokine-induced neutrophil chemoattractant expression in a nuclear factor kappaB (NF-kappaB)-dependent manner. In this study, we focused further on the regulation of NF-kappaB. The activation of NF-kappaB and the subsequent cytokine-induced neutrophil chemoattractant induction in response to interleukin-1beta (IL-1beta) were inhibited by proteasome inhibitors, MG132 and proteasome inhibitor I. Translocation of NF-kappaB into nuclei occurs by the phosphorylation, multi-ubiquitination, and degradation of IkappaBalpha, a regulatory protein of NF-kappaB. Nascent IkappaBalpha began to degrade 5 min after treatment with IL-1beta and disappeared completely after 15 min. However, IkappaBalpha returned to basal levels after 45-60 min. Interestingly, resynthesized IkappaBalpha was already phosphorylated at Ser-32. These results suggest that 1) the upstream signals are still activated, although the translocation of NF-kappaB peaks at 15 min; and 2) the regulated protein(s) acts downstream of IkappaBalpha phosphorylation. Western blotting showed that the resynthesized and phosphorylated IkappaB molecules were also upward-shifted by multi-ubiquitination in response to IL-1beta treatment. On the other hand, ATP-dependent Leu-Leu-Val-Tyr cleaving activity transiently increased, peaked at 15 min, and then decreased to basal levels at 60 min. Furthermore, the cytosolic fraction that was stimulated by IL-1beta for 15 min, but not for 0 and 60 min, could degrade phosphorylated and multi-ubiquitinated IkappaBalpha. These results indicate that the transient translocation of NF-kappaB in response to IL-1beta may be partly dependent on transient proteasome activation.

Animals↗
PubMed1999

Antithrombotic effect of SM-20302, a nonpeptide GPIIb/IIIa antagonist, in a photochemically induced thrombosis model in guinea pigs.

SM-20302, a synthetic inhibitor of the fibrinogen receptor of platelets, has been shown to inhibit the platelet aggregation induced by various stimuli. In the present study, we performed ex vivo platelet aggregation studies by using heparinized platelet-rich plasma (PRP) as well as citrated PRP and compared the antiaggregatory activity with the in vivo antithrombotic efficacy of SM-20302. The oral administration of SM-20302 (0.3-10 mg/kg) to guinea pigs completely inhibited the ADP-induced ex vivo platelet aggregation in citrated PRP. In heparinized PRP, SM-20302 (1-10 mg/kg) showed a dose-dependent inhibition of ex vivo platelet aggregation, and it exhibited complete inhibition at a dose of 3 and 10 mg/kg, respectively. The concentration of ionized calcium in the citrated samples was approximately 35 times lower than that in heparinized samples. Chelation of ionized calcium caused an enhancement of the antiaggregatory activity of SM-20302 in guinea pig heparinized PRP in vitro. And addition of CaCl2 to citrated PRP reversed the enhancement. Citrate therefore appeared to enhance the inhibitory activity of SM-20302 by lowering the ionized calcium levels. We also examined the in vivo efficacy of SM-20302 in a photochemically induced femoral artery thrombosis model in guinea pigs. The photochemical injury of the endothelium of femoral artery resulted in a progressive decline in the blood flow. The oral administration of SM-20302 (0.1-3 mg/kg) produced a dose-dependent maintenance of the femoral artery patency and significantly prolonged the time to occlusive thrombus formation at a dose of 1 and 3 mg/kg, respectively. These results suggest that SM-20302 may be an orally active antithrombotic agent, and its in vivo antithrombotic efficacy appeared to correlate well with the ex vivo platelet inhibition in PRP prepared from heparinized blood but not in PRP anticoagulated with citrate.

Adenosine Diphosphate↗
PubMed1999

Intracerebroventricular administration of nocistatin reduces inflammatory hyperalgesia in rats.

Nocistatin is a biologically active peptide derived from prepronociceptin, and its intrathecal administration has been reported to reduce nociceptin- or prostaglandin E2-induced hyperalgesia and allodynia in mice. In this study, we investigated the effects of intracerebroventricular (i.c.v.) administration of nocistatin on the inflammatory hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin in the rat paw-pressure test. Intracerebroventricular administration of nocistatin (0.5-50 pmol/rat) dose-dependently reduced carrageenan/kaolin-induced hyperalgesia, which peaked at 15-30 m. However, i.c.v. administration of nocistatin (50 pmol/rat) had no effect on the nociceptive threshold of non-inflamed rats. These results indicate that nocistatin has anti-hyperalgesic effects on the inflammatory hyperalgesia induced by carrageenan/kaolin at the supraspinal level.

Animals↗
PubMed1999

Possible involvement of p38 MAP kinase in HSP70 expression induced by hypoxia in rat primary astrocytes.

The aim of this study was to elucidate the possible mechanism of HSP induction in response to hypoxia in rat primary astrocytes. Treatment with SB203580, a selective p38 MAP kinase (p38 MAPK) inhibitor, attenuated the increase in HSP70 in a concentration-dependent manner. p38 MAPK was activated in response to hypoxic treatment. These results suggest that p38 MAPK positively regulates hypoxia-induced HSP70 expression in astrocytes.

Animals↗
PubMed1999

Temporary and partial inhibition of platelets by SM-20302 prevents coronary artery thrombosis in a chronic canine model.

We proposed that temporary and partial platelet inhibition by a GPIIb/IIIa receptor antagonist, SM-20302, would provide sustained antithrombotic efficacy in a chronic model of coronary artery thrombosis. Instrumented, conscious dogs received vehicle (Group I, n = 7), low dose SM-20302 (30 microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group II, n = 7), or high dose SM-20302 (100 microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group III, n = 7). Thrombosis was initiated by electrolytic injury to the circumflex coronary artery. Coronary blood flow was monitored for 6 h on day 1 and days 2-6. Platelet aggregation was performed in platelet-rich plasma prepared from citrated or heparinized blood. At 6 h, both doses of SM-20302 inhibited adenosine diphosphate-induced platelet aggregation completely (> 90%) in citrated platelet-rich plasma, but incompletely (57-59%) in heparinized platelet-rich plasma. Platelet reactivity returned to baseline values at 24 h. Control animals developed thrombotic occlusion on Day 1. Both doses of SM-20302 maintained vessel patency during the infusion period (Day 1) and the subsequent 5 days. Myocardial infarct size and mortality in the drug treated groups were reduced compared to the vehicle group. Thus, temporary inhibition of platelet reactivity by SM-20302 is associated with sustained prevention of primary thrombus formation, and reduction in infarct size and mortality.

Animals↗
PubMed1999

Latent infection and reactivation of human herpesvirus 6 in two novel myeloid cell lines.

It has been reported that reactivation of human herpesvirus-6 (HHV-6) causes a failure of hematopoiesis. To clarify the mechanisms of bone marrow suppression induced by HHV-6 infection, it is necessary to establish an in vitro model of HHV-6 infection in hematopoietic progenitor cells. We have established two novel Philadelphia chromosome-positive myeloid cell lines, SAS413 and SAS527, which possess different hematologic characteristics and show distinct susceptibility to infection by HHV-6, from a patient with blast crisis of chronic myelogenous leukemia (CML). HHV-6 subgroup A (HHV-6A) showed marked replication in SAS413, forming syncytia and inducing cell lysis in short-term culture. On the other hand, HHV-6A-inoculated SAS527 continued to proliferate without cell lysis and only a few cells showed HHV-6 antigen expression. In contrast to HHV-6A infection, inoculation with HHV-6 subgroup B (HHV-6B) did not induce any cytopathic effect (CPE) or viral antigen expression in either of the cell lines. Although HHV-6B replication was undetectable, the presence of the HHV-6 genome in both cell lines was shown by polymerase chain reaction (PCR) during culture for more than 10 months, suggesting that HHV-6B latently infected SAS413 and SAS527. Phorbol ester treatment of SAS527 latently infected with HHV-6B resulted in reactivation of HHV-6, as shown by the appearance of a CPE, positive reactivity for the HHV-6 antigen, and isolation of infectious HHV-6. These novel cell lines should be useful for studying the mechanisms of HHV-6-induced hematopoietic failure and HHV-6 latency and reactivation, as well as differentiation, of the myeloid cell lineage.

Adult↗
PubMed1999

Induction of human leukocyte antigen (HLA)-A2-restricted and MAGE-3-gene-derived peptide-specific cytolytic T lymphocytes using cultured dendritic cells from an HLA-A2 esophageal cancer patient.

BACKGROUND AND OBJECTIVES: Using peripheral blood mononuclear cells (PBMCs) from a 10-year survivor with established human leukocyte antigen (HLA)-A2(+) and MAGE-3(+) esophageal cancer cell line (KYSE-170), we examined the induction of HLA-A2-restricted and MAGE-3-gene-derived peptide (FLWGPRALV, amino acids 271-279)-specific cytolytic T lymphocytes (CTLs). METHODS: Autologous dendritic cells (DCs) cultured with granulocyte-macrophage colony stimulating factor and interleukin-4 were used as antigen presenting cells. PBMCs were stimulated by peptide-pulsed DCs in vitro. RESULTS: PBMC cocultured with FLWGPRALV-pulsed DCs could induce the relevant peptide-specific CTLs, which had tumor necrosis factor production and specific cytotoxicity against relevant peptide-pulsed autologous DCs (34%, effector:target ratio = 40:1). Moreover, they showed specific cytotoxicity against the autologous esophageal cancer cell line KYSE-170 (17%, effector:target ratio = 40:1). CONCLUSIONS: These results suggest that FLWGPRALV-pulsed cultured DCs would be a potent candidate for peptide vaccine against HLA-A2(+) and MAGE-3(+) esophageal cancer.

Antigen-Presenting Cells↗
PubMed1999

1q23 gain is associated with progressive neuroblastoma resistant to aggressive treatment.

Neuroblastoma is one of the most common malignant tumors of childhood and is characterized by regressive and progressive disease. Genetic factors that define progression of neuroblastomas are still unknown. We performed comparative genomic hybridization (CGH) on 27 neuroblastomas and dual-color fluorescence in situ hybridization (FISH) to identify genetic aberrations associated with progressive neuroblastoma showing resistance to aggressive treatment. 17q21-q25 gains and MYCN amplification were associated with stage 4 neuroblastomas; however, these genetic aberrations had no significant relation to the progression of stage 4 neuroblastomas. A novel chromosomal gain at 1q21-q25 was found in 8 of 16 cases (50%) of stage 4 neuroblastoma. Gain of 1q21-q25 was observed in all of the progressive cases (8/8), which showed resistance to chemotherapy, including 5 fatal neuroblastomas in stage 4, whereas 1q21-q25 gain was not found in any of the 8 remission cases in stage 4. Survival analysis also showed that 1q21-q25 gain was associated with a poor outcome. High xenotransplantability in nude mice was observed for the tumors with 1q21-q25 gain (4/5; 80%). These data show that 1q21-q25 gain is strongly associated with progression of stage 4 neuroblastoma. Furthermore, by dual-color FISH analysis using cosmid clones, the 1q21-q25 gain was narrowed to increase in DNA copy number on 1q23 in the fatal type of stage 4 neuroblastoma showing this gain. These results suggest that DNA amplification at 1q23 may play a role in the development of progressive neuroblastoma in an advanced stage.

Animals↗
PubMed1999

Establishment and characterization of nurse cell-like stromal cell lines from synovial tissues of patients with rheumatoid arthritis.

OBJECTIVE: To investigate the features of synovial stromal cells established from patients with rheumatoid arthritis (RA), and to define these cells as nurse cells. METHODS: Synovial nurse-like stromal cell lines (RA-SNCs) were established from patients with RA. These cell lines were examined for morphology, pseudoemperipolesis activity, cell surface markers, and cytokine production. The interaction between these RA-SNCs and a synovial tissue B cell clone was also examined. RESULTS: RA-SNCs had nurse cell activity. They spontaneously produced interleukin-6 (IL-6), IL-8, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Furthermore, they produced IL-1beta and tumor necrosis factor alpha and expressed higher levels of the other cytokines after coculture with the B cell clone. Proliferation and Ig production by the B cell clone were dependent on direct contact with RA-SNCs. CONCLUSION: These results indicate that the RA-SNCs were nurse cells. The findings suggest that RA-SNCs may play an important role in the pathogenesis of RA by producing large amounts of cytokines and maintaining infiltrating lymphocytes.

Antibodies, Monoclonal↗
PubMed1999

Suppressed severity of collagen-induced arthritis by in vivo transfection of nuclear factor kappaB decoy oligodeoxynucleotides as a gene therapy.

OBJECTIVE: In both rheumatoid arthritis and collagen-induced arthritis (CIA), the nuclear factor kappaB (NF-kappaB) transcription factor plays a pivotal role in the coordinated transactivation of many cytokines related to pathogenesis. This study investigated whether synthetic double-stranded DNA that show a high affinity for NF-kappaB could be introduced in vivo as "decoy" cis elements to bind the transcription factor and block the activation of such proinflammatory cytokine genes as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha), and thus suppress the severity of joint destruction. METHODS: NF-kappaB decoy oligonucleotides (ODN) were introduced by an intraarticular injection into the bilateral hind ankle joints of CIA rats using the hemagglutinating virus of Japan (HVJ)-liposome method. Joint destruction was evaluated by histology and radiography. IL-1 and TNFalpha levels were assessed by enzyme-linked immunosorbent assay and Northern blot analysis. RESULTS: Using the HVJ-liposome method, the presence of fluorescein isothiocyanate-labeled ODN in the synovium was confirmed until 28 days after intraarticular injection. In vivo transfection of NF-kappaB decoy ODN by an intraarticular injection into CIA rats decreased the severity of hind-paw swelling. Histologic and radiographic studies showed a marked suppression of joint destruction treated by NF-kappaB decoy ODN transfection. This treatment method also suppressed the production of IL-1 and TNFalpha in the synovium of arthritic joints. CONCLUSION: The present results demonstrate that administration of NF-kappaB decoy ODN in arthritic joints of rats with CIA led to an amelioration of arthritis. These findings suggest that intraarticular transfection of NF-kappaB decoy ODN may provide a useful therapeutic approach for the treatment of inflammatory arthritis.

Animals↗
PubMed1999

Treatment of life-threatening huge atrial myxoma: report of two cases.

We herein report two patients with left atrial myxoma who needed an emergency operation. Case 1 was a 48-year-old woman who was injured in a traffic accident and underwent an operation for a right leg fracture. Just after the operation she developed cardiac and respiratory arrest with complaints of chest pain. She was successfully resuscitated and diagnosed to have a left atrial myxoma by echocardiography. Emergency surgery was performed and a giant left atrial myxoma was thus removed from the atrial septum. Case 2 was a 54-year-old housewife who was transferred to our department under the diagnosis of a left atrial myxoma by echocardiography. She complained of dyspnea and chest discomfort. By angiography, the tumor was seen to be partially incarcerated at the diastolic phase. A huge myxoma was removed from the atrial septum which was secured by a patch closure. Cardiac echocardiography can help rule out left atrial myxoma if it is highly suspected. As early surgical mortality is low and the long-term results are good, we strongly believe that patients with cardiac myxoma should be operated on as early as possible, once a diagnosis is made.

Echocardiography↗
PubMed1999

Extensive epidural teratoma in early infancy treated by multi-stage surgery.

We report a rare case of extensive extradural teratoma successfully treated by multi-stage laminotomy and thoracotomy. A 34-day-old, dyspneic infant had a large posterior mediastinal mass identified on a chest X-ray radiograph. Imaging studies disclosed that the mass originated from the extradural space at the level of the lower thoracic spine, extending cephalad to C4 and caudad to L4 and severely compressing the spinal cord anteriorly, causing paraplegia. The tumor expanded bilaterally through the intraspinal foramina, coalescing to form a huge mediastinal mass. The upper half of the teratoma was removed utilizing a laminotomy from T3 through T9; 2 months later the lower half was excised via a laminotomy from T11 to L3. An additional procedure was required to resect recurrent tumor through a laminotomy from T8 to T12. The reconstructed vertebral arches were well-preserved in shape, with an almost normal spinal canal.

Epidural Neoplasms↗
PubMed1999

High cervical disc lesions in elderly patients--presentation and surgical approach.

The incidence of high cervical disc lesions is extremely rare, and the mechanism of their development is unclear. We report these three cases, and discuss the possible mechanisms. We also describe surgical strategies for these lesions. The first and second cases were an 82-year-old male and an 84-year-old male with retro-odontoid disc hernia. The third was an 83-year-old female with a herniated disc at C2/C3. To investigate Aetiological mechanisms of these lesions, we examined the findings on cervical images in extension and flexion, and compared the results in a younger than 80-year-old group and an older than 80-year-old group. The patients underwent surgery via a posterolateral intradural approach. Wide laminectomy and incision of the dentate ligaments enabled access to the ventral space of the upper cervical spinal canal and sufficient decompression. All patients became ambulatory postoperatively without special fixation of the cervical spine. In the younger group, the level mostly loaded during cervical movement was C5/6, however, the levels in the older group were C2/3 and C3/4. In elderly patients, less mobilization of the middle and/or lower cervical spine due to spondylotic change causes overloading at higher levels resulting in high cervical disc lesions. Retro-odontoid disc lesions can be caused by a herniated disc at C2/C3, which migrates upward. Regarding surgical strategy, the posterolateral intradural approach is less invasive and more advantageous for these lesions.

Aged↗
PubMed1999

Endoscopic septotomy: a new surgical approach to infantile hydrometrocolpos with imperforate hemivagina and ipsilateral renal agenesis.

The authors propose a new surgical approach for neonates and infants with hydrometrocolpos caused by double vagina and imperforate hemivagina. Usually for these patients, laparotomy is a common approach used to decompress the obstructed hemivagina. The authors compared the characteristics of three options used to relieve obstruction of the hemivagina using endoscopic, transvaginal, and laparotomy approaches. An endoscopic septotomy (colposcopic approach) using the Storz neonatal resectoscope is less invasive and less expensive than other methods. We emphasize that endoscopic septotomy is a feasible surgical method to relieve the obstructive symptoms related to imperforate hemivagina.

Endoscopy↗
PubMed1999

Enhanced metastasis after local therapy in a murine model using C-1300 neuroblastoma.

BACKGROUND/PURPOSE: In the treatment of advanced neuroblastoma, the role of surgery has been controversial. This study was carried out to determine the effect of surgery, irradiation, and chemotherapy in inhibiting or promoting distant metastases. METHODS: Transplanted C-1300 neuroblastomas in hind legs of syngeneic mice were treated by surgery, radiation, and chemotherapy. The liver was evaluated 18 days after each treatment modality for metastases. RESULTS: Mice developed no liver metastasis when leg tumors received no treatment or chemotherapy. In the mice who had the tumor resected, liver metastases were found in 8 of 16 mice that had 7-mm tumors. One hundred percent of the mice that had 9- or 12-mm tumors presented with metastases to the liver. In mice who received radiation therapy, 100% had liver metastases. CONCLUSIONS: Local control by surgery and single-dose radiation induced liver metastasis in a murine model. Surgery to remove tumors should be used in conjunction with chemotherapy to prevent secondary liver metastases.

Amputation, Surgical↗
PubMed1999

Accelerated recovery from cyclophosphamide-induced leukopenia in mice administered a Japanese ethical herbal drug, Hochu-ekki-to.

The effect of a Japanese ethical herbal drug, Hochu-ekki-to (HOT), on recovery from leukopenia induced by cyclophosphamide (CY) was investigated. Daily oral administration of 1000 mg/kg HOT into CY-treated mice significantly prevented decrease of leukocyte numbers in the peripheral blood and accelerated recovery from leukopenia. Ginsenoside Rgl extracted from Ginseng radix, a major herb of HOT, was one of the active ingredients. HOT increased numbers of neutrophils and monocytes in the peripheral blood compared with CY-treated control. Moreover, HOT augmented the resistance against Pseudomonas aeruginosa infection. The number of colony-forming units in the spleen (CFU-S) also increased in HOT-treated mice. The frequencies of IL-3-, GM-CSF- and IFN-gamma-producing cells increased in the spleen, bone marrow, liver and IEL on HOT treatment, and HOT clearly augmented the expressions of IL-3, GM-CSF and IFN-gamma mRNA in the spleen, bone marrow, liver and IEL except IL-3 and IFN-gamma mRNA in the IEL. These results suggest that HOT enhances the production of hematopoietic lymphokines, stimulates the proliferation of hematopoietic progenitor cells and consequently accelerates recovery from leukopenia in CY-treated mice. Additionally, IFN-gamma which HOT-augmented the production may contribute the protective effect against the bacterial infection by activating of phagocyte cells.

Animals↗
PubMed1999

Evaluation of a clinic-based screening program for lung cancer with a case-control design in Kanagawa, Japan.

A case-control study was performed in Kanagawa Prefecture, Japan, which introduced lung cancer screening, by family physicians, to determine if this program was effective. The subjects were persons who died from lung cancer, restricted to those between 40 and 74 years old at death, and National Health Insurance (NHI) holders. A total of 193 lung cancer deaths meeting the criteria were selected for the case group. Three controls for each case were selected at random from living NHI holders matched by residence, gender and year of birth (+1 year). Smoking adjusted odds ratios were calculated using a multiple logistic regression model. The odds ratios of dying from lung cancer for screening participants within 12 months compared with non-participants was 0.535 which was statistically significant (95% CI, 0.337-0.850). The odds ratio in the 12-24-month period before diagnosis was 0.638 (0.302-0.967), which was also significant. The results demonstrated that screening for lung cancer by family physicians can reduce the lung cancer mortality, and that a clinic-based screening program by family physicians is effective.

Adult↗