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Biomedical subjects

S Yoshino

Publications and source records attributed to S Yoshino.

At least 19 recordsLinked to original sources
PubMed2001

Inhibition of pseudorabies virus replication by a dominant-negative mutant of early protein 0 expressed in a tetracycline-regulated system.

Pseudorabies virus (PRV) early protein 0 (EP0) consisting of 410 amino acids is a transactivator of viral genes. A mutant consisting of amino acids 1-113 exhibits dominant-negative properties. In order to assess the antiviral potential of the EP0 mutant, Vero cells were transformed with the EP0 mutant gene expressed in a tetracycline-regulated system. The transformed cell lines showed marked resistance to PRV infection when expression of the EP0 mutant gene was induced. In the transformed cell line infected with PRV, synthesis of the immediate-early protein (IE180) and of EP0 was inhibited, whereas the levels of IE and EP0 messenger RNA (mRNA) were not decreased, as compared with those of the control cell line. The present results suggest that the EP0 mutant may not alter the efficiency of the viral gene transcription but rather translation efficiency of the viral mRNA.

Animals↗
PubMed2001

Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igkappa leader sequence.

IL-18 is a novel cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL-18 cDNA linked with the Igkappa leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL- 18 vector and to evaluate IL-18--producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-gamma secretion was extremely high (40-140 pg/10(6) cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/10(6) cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells ( P< .01, by ANOVA and analysis of covariance). In addition, injection of colon 26 or Meth-A cells into mice immunized with a mature IL-18 transfectant revealed acquired immunity. Depletion of natural killer cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igkappa leader sequence may be a useful tumor vaccine.

Adenoviridae↗
PubMed2001

Phylogenetic investigation for the risk of hepatitis C virus transmission to surgical and dental patients.

Blood loss during treatment carries a potential risk for the transmission of blood-borne pathogens in hospital patients. To determine whether nosocomial transmission of hepatitis C virus (HCV) occurs in surgical wards and dental hospitals, we tested anti-HCV antibodies and HCV RNA in sera from these patients and analysed the hypervariable region 1 (HVR1) sequence of HCV phylogenetically in the HCV RNA-positive patients. Five of 83 patients from a surgical ward were positive for HCV RNA, and six patients from one dental hospital and nine patients from a second were found to be positive for HCV RNA during the examination period. The HVR1 sequences were amplified from these patients' serum, and after subcloning, multiple clones of the HVR1 sequence from each patient were determined. The phylogenetic analysis of these sequences showed that HVR1 species from each patient could be classified into one to three genetic clusters of HVR1 quasi-species and that these clusters were independent of each other among patients. Thus, there was no evidence of HCV transmission in our study, and unrecognized transmission of HCV may be a rare event in surgical and dental patients at university hospitals.

Adult↗
PubMed2000

Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6.

Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.

Administration, Oral↗
PubMed2000

Involvement of CD70-CD27 interactions in the induction of experimental autoimmune encephalomyelitis.

CD70/CD27 are cell surface molecules belonging to the TNF/TNF-receptor families. Ligation of CD27 by its ligand CD70 is thought to be important in T cell activation and T cell-B cell interaction. However, the in vivo function of these molecules during the establishment of cell-mediated immunity remains unclear. In this study, we examined the contribution of CD70-CD27 interactions to cell-mediated immunity by investigating the effect of anti-CD70 mAb on the development of experimental autoimmune encephalomyelitis (EAE). Treatment of SJL/J mice with anti-CD70 mAb prevented EAE induced by immunization with PLP(139-151). The preventive effect of anti-CD70 mAb was not due to the inhibition of T cell priming and antibody production from B cells, or immune deviation. However, TNF-alpha production was suppressed by treatment with anti-CD70 mAb, indicating that the ameliorating effect of anti-CD70 mAb appeared, at least in part, to be mediated by the inhibition of TNF-alpha production. These results indicate that the CD70-CD27 interaction plays a pivotal role in the development of cell-mediated autoimmune disease.

Animals↗
PubMed2000

Lymph node metastases identified with mediastinoscopy in a patient with superficial carcinoma of the esophagus.

Superficial esophageal cancers limited to the lamina propria are not associated with lymph node metastases. Mediastinoscopic transhiatal esophagectomy was planned in a patient with widespread superficial cancer of the midthoracic esophagus. Sampling of the upper mediastinal lymph nodes revealed metastases. The operation was converted to a transthoracic esophagectomy with radical lymphadenectomy. Histopathologic examination of the resection specimen showed three metastatic lymph nodes, despite local invasion limited to the lamina propria. This is the first report of a patient with superficial esophageal cancer and lymph node metastases.

Carcinoma, Squamous Cell↗
PubMed2000

Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis.

OX40 ligand (OX40L) and OX40 (CD134) are a pair of cell surface molecules belonging to the TNF/TNF receptor family. Interaction of OX40L with its receptor OX40 is thought to be important in T cell activation through T cell/antigen-presenting cell interaction. However, involvement of these molecules in the pathogenesis of rheumatoid arthritis (RA) remains unclear. To explore the contribution of OX40/OX40L interaction to the pathogenesis of RA in vivo, we evaluated the effect of a neutralizing anti-OX40L monoclonal antibody (mAb) on the development of collagen-induced arthritis (CIA) in DBA/1 mice as an animal model for RA. Administration of anti-OX40L mAb into type II collagen (CII) -immunized DBA/1 mice dramatically ameliorated the disease severity. In vivo treatment with anti-OX40L mAb did not inhibit the expansion of CII-reactive T cells, but suppressed IFN-gamma and anti-CII IgG2a production. Therefore, OX40/OX40L interaction appears to play a critical role in the development of CIA by enhancing Th1-type autoimmune response. In addition, T lymphocytes in synovial fluid and synovial tissue from RA patients expressed OX40, while OX40L was expressed on sublining cells in synovial tissue. These results indicate that OX40/OX40L interaction may play a critical role in the development of RA.

Animals↗
PubMed2000

Treatment of lupus in NZB/W F1 mice with monoclonal antibody against Fas ligand.

Since Fas ligand (FasL) can induce apoptosis of Fas-bearing cells, Fas/FasL interactions can play a critical role in maintaining self-tolerance. Fas/FasL interactions in lupus-like autoimmune disease have been well characterized in studies using either Fas or FasL mutant mice. However, the effect of the defective FasL-mediated signaling on the establishment of lupus in other mouse strains, such as NZB/W (B/W) F1, remains uncertain. In the present study, we examined the effect of anti-FasL monoclonal antibody (mAb) on the development of lupus. Treatment of B/W F1 mice with anti-FasL mAb augmented IgG1- and IgG2a-type anti-dsDNA Ab production. However, treatment of B/W F1 mice with anti-FasL mAb also significantly prevented the development of lupus nephritis. These results indicate that Fas/FasL interactions not only regulate IgG-type autoantibody production, but also influence the development of lupus nephritis in B/W F1 mice.

Animals↗
PubMed2000

The anti-rheumatic effect of multiple synovectomy in patients with refractory rheumatoid arthritis.

We assessed the anti-rheumatic effects of radical multiple synovectomy (RaMS) in patients with rheumatoid arthritis (RA) who did not respond to intensive medical treatment. The selection of patients into three groups, A, B or C, was randomised. Patients assigned to group A (n = 28) continued the prescribed pre-operative medication and had RaMS. Patients assigned to group B (n = 20) were started on a combination therapy with disease-modifying anti-rheumatic drugs (DMARDs) after radical multiple synovectomy. Nineteen RA patients who were started on the same combination therapy as group B but who did not undergo surgery served as controls (group C). The clinical and radiographic findings were assessed for at least 3 years after surgery. Patients in the surgically treated groups (groups A and B) showed a significant reduction in the number of swollen and painful joints and in their ESR and serum CRP levels, and this effect was maintained for at least 3 years. More than 40% of the patients remained in clinical remission during the observation period. The surgical outcome seemed to be superior to that of the controls and did not differ between group A and group B. Articular destruction (assessed by the carpal height ratio) did not progress in the patients who were in clinical remission.

Antirheumatic Agents↗
PubMed2000

Expression of kappa-opioid receptor mRNA in human peripheral blood lymphocytes and the relationship between its expression and the inflammatory changes in rheumatoid arthritis.

The expression of the kappa-opioid receptor on human peripheral blood cells (in rheumatoid arthritis cases and normal volunteers) was examined using reverse transcriptase polymerase chain reaction (RT-PCR), and the relationship between its expression and the inflammatory activity or chronic pain in patients with rheumatoid arthritis (RA) was determined. RT-PCR was performed on the peripheral blood cells obtained from 37 patients with RA and 13 healthy volunteers. kappa-Opioid receptor mRNA expression was exhibited on the blood cells of 37% of RA patients (14/ 37) and 54% of healthy volunteers (7/13) , and the levels of expression were lower in the RA patients than in the healthy volunteers. Regarding the relationship between the expression of kappa-opioid receptor mRNA and the symptoms in RA patients, it was noted that the expression of the receptor mRNA was significantly decreased in RA patients in whom erythrocyte sedimentation rate (ESR), Lansbury index, and visual analogue pain scores were high. The kappa-opioid receptor mRNA was expressed on four cell types, namely, T and B cells, macrophages, and natural killer (NK) cells in RA patients; however, it was expressed only on the T and B cells and macrophages (and not on NK cells) in the healthy volunteers. Our findings suggest that the levels of expression of kappa-opioid receptor mRNA were decreased in RA patients in comparison with those in healthy volunteers; and that they were significantly related to the inflammatory activity or chronic pain in the RA patients. The higher the mRNA expression level, the less severe the inflammatory changes of RA. The kappa-opioid receptor may thus play a role in the modulation of nociception and anti-inflammatory changes in chronic inflammatory disorders.

Adult↗
PubMed2000

Bone marrow CD34+ progenitor cells from rheumatoid arthritis patients support spontaneous transformation of peripheral blood B cells from healthy individuals.

We show that bone marrow (BM) CD34+ progenitor cells from rheumatoid arthritis (RA) patients have the capacity to support spontaneous transformation of peripheral blood B cells. CD34+ cells purified from BM blood from eight RA patients and eight osteoarthritis (OA) patients were expanded with granulocyte/macrophage colony stimulating factor (GM-CSF) for 4-6 weeks. GM-CSF-stimulated BM CD34+ cells from three of eight RA patients, but none from seven OA patients, gave rise to spontaneous transformation of highly purified B cells of Epstein-Barr virus (EBV)-seronegative healthy donors. GM-CSF-stimulated BM CD34+ cells from four of six RA patients and from one of four OA patients also supported the spontaneous transformation of peripheral blood B cells from EBV-seropositive healthy donors. All the transformed B cell lines were positive for EBV-DNA as determined by PCR. Neither GM-CSF-stimulated BM CD34+ cells alone nor highly purified B cells alone gave rise to spontaneously transformed B cell lines. These results suggest that the capacity of BM CD34+ cells to support survival of B cells might contribute to the pathogenesis of RA by sustaining abnormal B cell responses.

Antigens, CD19↗
PubMed2000

The role of lipopolysaccharide injected systemically in the reactivation of collagen-induced arthritis in mice.

1. We investigated the role of bacterial lipopolysaccharide (LPS) in the reactivation of autoimmune disease by using collagen-induced arthritis (CIA) in mice in which autoimmunity to the joint cartilage component type II collagen (CII) was involved. 2. CIA was induced by immunization with CII emulsified with complete Freund's adjuvant at the base of the tail (day 0) followed by a booster injection on day 21. Varying doses of LPS from E. coli were i.p. injected on day 50. 3. Arthritis began to develop on day 25 after immunization with CII and reached a peak on day 35. Thereafter, arthritis subsided gradually but moderate joint inflammation was still observed on day 50. An i.p. injection of LPS on day 50 markedly reactivated arthritis on a dose-related fashion. Histologically, on day 55, there were marked oedema of synovium which had proliferated by the day of LPS injection, new formation of fibrin, and intense infiltration of neutrophils accompanied with a large number of mononuclear cells. The reactivation of CIA by LPS was associated with increases in anti-CII IgG and IgG2a antibodies as well as various cytokines including IL-12, IFN-gamma, IL-1beta, and TNF-alpha. LPS from S. enteritidis, S. typhimurium, and K. neumoniae and its component, lipid A from E. coli also reactivated the disease. Polymyxin B sulphate suppressed LPS- or lipid A-induced reactivation of CIA. 4. These results suggest that LPS may play an important role in the reactivation of autoimmune joint inflammatory diseases such as rheumatoid arthritis in humans.

Animals↗
PubMed2000

Bacterial lipopolysaccharide acts as an adjuvant to induce autoimmune arthritis in mice.

We investigated the ability of lipopolysaccharide (LPS) as an adjuvant to induce autoimmune arthritis. LPS from Escherichia coli was intraperitoneally injected into DBA/1J mice together with the joint cartilage component type II collagen (CII) on day 0. Thereafter, the injection of CII and LPS was continued every 2 weeks up to day 56. The results showed that mice injected with CII plus LPS had signs of arthritis on day 55 and the joint inflammation reached a peak on day 75. Injection of CII or LPS alone induced no arthritis. Histologically, marked oedema of synovium and intense infiltration of inflammatory cells, including neutrophils, were observed 3 days after the onset of joint inflammation. Twenty-one days later, there were marked proliferation of synovial tissues with many mononuclear cells and destruction of cartilage. Anti-CII immunoglobulin G (IgG) and IgG2a antibodies were markedly produced in mice injected with CII plus LPS. Pronounced secretion of cytokines, including interleukins-12 and -1beta, interferon-gamma and tumour necrosis factor-alpha, was also observed in these animals. Arthritis was passively transferred into naive syngeneic mice with sera but not with lymphoid cells from mice given CII with LPS. Other types of LPS from Salmonella enteritidis, Salmonella typhimurium and Klebsiella pneumoniae as well as lipid A from E. coli, induced inflammation in joints when administered with CII. Polymixin B sulphate mixed with LPS or lipid A blocked the induction of joint inflammation. These results indicate that LPS appears to play an important role as an adjuvant in the induction of arthritis in which autoimmunity to CII is involved.

Adjuvants, Immunologic↗
PubMed2000

Detection of telomerase activity in peritoneal lavage fluid from patients with gastric cancer using immunomagnetic beads.

Cytologic examination of peritoneal lavage fluid is a useful predictor of peritoneal recurrence in gastric cancer. However, this technique is not overly sensitive and requires special abilities in the cytologist. In this study, telomerase activity was used to detect free cancer cells in peritoneal lavage fluid from patients with gastric cancer. In the first part, 12 lavage-fluid samples obtained from 12 patients with gastric cancer were analysed using the conventional telomeric repeat amplification protocol (TRAP) assay. Three of five patients with early gastric cancer had positive telomerase activity. These false-positive results may have been due to lymphocyte contamination. Furthermore, polymerase chain reaction inhibitors were also detected in the lavage-fluid samples. Therefore, we developed a novel method for elimination of haematopoietic cell and Taq polymerase inhibitors to increase the accuracy of the TRAP assay using immunomagnetic beads, which bind to most normal and neoplastic human epithelial cells. Telomerase activity was found in 10 of 20 (50%) lavage-fluid samples from patients with serosal or subserosal invasion. Cytologic examination was positive in nine of 20 (45%) samples. Both the telomerase activity and cytology were negative in all 14 patients without serosal or subserosal invasion. These results suggest that the TRAP assay combined with immunomagnetic beads might be useful for detection of free cancer cells in the peritoneal space in gastric cancer without the aid of an experienced cytologist.

Adenocarcinoma↗
PubMed2000

Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells: possible association with Na(+), K(+)-ATPase.

Previously, we showed that expression of nm23-H1 is associated inversely with sensitivity to cisplatin in human oesophageal squamous cell carcinoma (OSCC). The present study was undertaken to investigate the association of nm23-H1 expression with cisplatin-induced DNA damage in OSCC using antisense nm23-H1 transfectants. YES-2/AS-12, an antisense nm23-H1-transfected OSCC cell line, showed significantly reduced expression of intracellular nm23-H1 protein compared with that in parental YES-2 cells and YES-2/Neo transfectants. Surface expression of nm23-H1 protein was not observed in any of the three cell lines. PCR analysis for DNA damage demonstrated that YES-2/AS-12 cells were more resistant to nuclear and mitochondrial DNA damage by cisplatin than were YES-2/Neo cells. In addition, mitochondrial membrane potentials and DNA fragmentation assays confirmed that YES-2/AS-12 was more resistant than YES-2/Neo to apoptosis induced by cisplatin. In contrast, YES-2/AS-12 was more sensitive to ouabain, a selective inhibitor of Na(+), K(+)-ATPase, than YES-2 and YES-2/Neo. Pre-treatment with ouabain resulted in no differences in cisplatin sensitivity between the three cell lines examined. Intracellular platinum level in YES-2/AS-12 was significantly lower than that in YES-2 and YES-2/Neo following incubation with cisplatin, whereas ouabain pre-treatment resulted in no differences in intracellular platinum accumulations between the three cell lines. Our data support the conclusion that reduced expression of intracellular nm23-H1 in OSCC cells is associated with cisplatin resistance via the prevention of both nuclear and mitochondrial DNA damage and suggest that it may be related to Na(+), K(+)-ATPase activity, which is responsible for intracellular cisplatin accumulation.

Antineoplastic Agents↗
PubMed2000

Translational regulation of platelet-derived growth factor B chain (c-sis) mRNA by short open reading frames in the 5'-untranslated region.

Platelet-derived growth factor B chain (PDGF-B/c-SIS), the product of c-sis proto-oncogene, is a potent mitogen and chemoattractant for cells of mesenchymal origin. Expression of PDGF-B/c-SIS is regulated at the translational level, in addition to at the transcriptional level. The 5'-untranslated region (5'-UTR) of PDGF-B/c-sis mRNA is known to inhibit translation of the downstream coding sequences. The 5'-UTR contains putative influential elements, such as GC-rich elements, stem-loop structures and short open reading frames (SORFs). To clarify the inhibition mechanism of PDGF-B/c-sis mRNA translation, effects of three SORFs in the 5'-UTR on the translational regulation were investigated in transient expression assays. Introducing point mutation(s) in the initiation codons of SORFs affected the reporter gene expression in several cell lines (COS-1, U-2, JEG-3). Abrogation of three SORFs resulted in an increase of the reporter gene expression both in beta-galactosidase assay and Western blot analysis. These results suggest that SORFs in the 5'-UTR sequences have inhibitory effects on the translation of the downstream coding sequences.

5' Untranslated Regions↗
PubMed2000

Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis.

OBJECTIVE: To examine whether different combinations of disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX), salazosulphapyridine (SASP) and dexamethasone (DEX; a steroid), act by inhibiting the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cultured synoviocytes, causing a decrease in their serum concentrations in patients with rheumatoid arthritis (RA). METHODS: The VEGF and bFGF concentrations in cultured synoviocytes and peripheral blood from patients with RA were measured by enzyme-linked immunosorbent assay and their serum concentrations were measured at two time points. RESULTS: BUC and GST inhibited VEGF production even when given alone, and a combination of BUC, GST and MTX with DEX also inhibited VEGF production. None of the DMARDs or DEX inhibited bFGF production when given alone, but a combination of SASP and GST inhibited the production of bFGF in cultured synoviocytes. Serum VEGF concentrations were significantly decreased 6 months after the commencement of medication compared with their concentrations before medication. CONCLUSION: Our results show that the effects of a combination of DEX with any two of BUC, GST, SASP and MTX on the production of VEGF and bFGF in cultured synoviocytes and on the serum concentrations of VEGF in patients with RA may be based on synergistic or additive effects of the drugs.

Anti-Inflammatory Agents↗