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Biomedical subjects

S Miyake

Publications and source records attributed to S Miyake.

At least 37 records · Page 2Linked to original sources
PubMed2001

CPT-11 may provide therapeutic efficacy for esophageal squamous cell cancer and the effects correlate with the level of DNA topoisomerase I protein.

CPT-11 is a potent anti-cancer drug and a specific inhibitor of DNA topoisomerase I (Topo I). In this study, we aim to evaluate the effects of CPT-11 on esophageal squamous cell cancers (ESCC) and to determine the correlation between the effects and the levels of Topo I expression. We examined the growth-inhibitory effect caused by SN-38, an active metabolite of CPT-11, in 14 human ESCC cell lines established from 10 primary and 4 metastatic lesions. CPT-11 was considered effective against 5 cell lines from primary lesions and one from metastatic lesions, and thus may show therapeutic efficacy against both primary and metastatic ESCC tumors. Although Topo I mRNA levels in these 14 ESCC cell lines, as quantitated by northern blot analysis, showed no correlation with the IC(50) values, Topo I protein levels, as quantitated by western blot analysis, showed an inverse correlation with the IC(50) values. Topo I protein levels could be an indicator of sensitivity to CPT-11. We also determined Topo I protein levels in 40 ESCC tumors and matched normal mucosae. Thirty-four tumors showed 1.2 - 22.3-fold increases in Topo I levels. Two patients receiving pre-operative chemotherapy and one receiving radiotherapy exhibited increased Topo I protein levels in their tumor lesions. It appeared that CPT-11 could provide selective therapeutic efficacy against ESCC tumors. CPT-11 may be effective for the treatment of metastatic ESCC tumors and as a second-line anti-cancer drug for ESCC.

Blotting, Western↗
PubMed2001

Natural killer type 2 bias in remission of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease characterized by clinical relapse and remission. Because of the potential role of natural killer (NK) cells in the regulation of autoimmunity, we have examined cytokine profile and surface phenotype of NK cells in the peripheral blood of MS. Here we demonstrate that NK cells in the remission of MS are characterized by a remarkable elevation of IL-5 mRNA and a decreased expression of IL-12Rbeta2 mRNA, as well as a higher expression of CD95. Moreover, the NK cells from MS in remission produced much larger amounts of IL-5 than did those from controls after stimulation with phorbol myristate acetate (PMA) and ionomycin. These features are reminiscent of those of NK type 2 (NK2) cells that can be induced in a condition favoring functional deviation of T cells toward Th2. Remarkably, the NK cells lose the NK2-like property when relapse of MS occurs, but regain it after recovery. We also found that NK2 cells induced in vitro inhibit induction of Th1 cells, suggesting that the NK2-like cells in vivo may also prohibit autoimmune effector T cells. Taken together, it is possible that NK cells play an active role in maintaining the remission of MS.

Adult↗
PubMed2001

[Clinical usefulness of antigen-captured ELISA method using mouse anti-Trichosporon asahii monoclonal antibody D-8 for diagnosis of summer-type hypersensitivity pneumonitis].

In the present study, we assessed the clinical usefulness of the antigen-captured ELISA method using mouse anti-Trichosporon asahii monoclonal antibody D-8 in 193 patients with summer-type hypersensitivity pneumonitis (SHP) and in 127 healthy volunteers. When the cut-off value was determined as 0.15, the diagnosis of SHP was accurately made by this method in 168 of 193 SHP patients. The sensitivity and specificity of the diagnosis of SHP determined by this method were 87.0% and 96.1%, respectively. We concluded that this ELISA method is a useful technique for the diagnosis of SHP when the possibility of SHP is recognized during the course of a case.

Alveolitis, Extrinsic Allergic↗
PubMed2001

[Recurrence of febrile convulsions after the first diphtheria-pertussis-tetanus vaccination and measles vaccination in children with febrile convulsions: a questionnaire survey in Takamatsu City].

A questionnaire about convulsions and other adverse events after vaccination was sent to doctors who administered a diphtheria-pertussis-tetanus (DPT) vaccine (the first dose) or a measles vaccine between April 1, 1995 and December 31, 1997 in Takamatsu City to children with convulsions. DPT and measles vaccines were administered to 300 and 339 such children, respectively. Many of them had febrile seizures, the last of which had occurred before more than 1 year. Among them, 175 cases were administered with DPT and 180 with measles vaccine. There were recurrences of febrile convulsions after immunization in 2 (1.1%) of the cases given DPT and 3 (1.7%) of those given measles vaccination. According to the data of the Monitoring System for Adverse Events Following Immunization (the Ministry of Health and Welfare of Japan), the incidence of convulsion after immunization in healthy children between April 1, 1996 and September 30, 1997 was 0.4% after the first dose of DPT vaccination and 0.3% after measles vaccination. In comparison, the incidence was higher in children who had had febrile convulsions before more than one year. Especially, the rate of convulsions after measles vaccinations was significantly higher (p < 0.05) in children with febrile convulsions. These results suggest that the measles vaccination should be administered with caution to the children with previous febrile convulsions.

Child↗
PubMed2001

[A case of Churg-Strauss syndrome in which positive rheumatoid factor and MPO-ANCA preceded the development of clinical symptoms of vasculitis].

A 52-year-old man in whom bronchial asthma had been diagnosed in 1995 was admitted for the treatment of Churg-Strauss syndrome in June 1997. Positive tests MPO-ANCA and rheumatoid factor preceded the symptoms of vasculitis for several months. A skin biopsy revealed infiltration of eosinophils in the vessel walls, and the diagnosis of Churg-Strauss syndrome was confirmed. After systemic administration of corticosteroids, the symptoms other than mononeuritis improved markedly, and his MPO-ANCA and rheumatoid factor became negative. Rheumatoid factor and MPO-ANCA may be useful for the early diagnosis of Churg-Strauss syndrome in patients with bronchial asthma in which a well-controlled disease develops into an intractable condition.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population.

BACKGROUND: One of the most critical questions in immunosurveillance is whether differences between individuals with regards to natural immunological host defence can predict future development of cancer. Although this question has so far remained open, there are clear indications of significant roles of several naturally cytotoxic lymphocytes in preventing the development of cancer. We began a prospective cohort study among a Japanese general population in 1986, using various immunological and biochemical markers. METHODS: Natural cytotoxic activity of peripheral-blood mononuclear cells was assessed by isotope-release assay in 3625 residents of a Japanese population mostly older than 40 years of age, between 1986 and 1990. Immunological and biochemical markers were also measured, and participants were given a questionnaire on lifestyle. We did an 11-year follow-up survey of the cohort members looking at cancer incidence and death from all causes, and analysed the association between cytotoxic activity of peripheral-blood lymphocytes assessed at baseline and cancer incidence found in the subsequent follow-up. FINDINGS: 154 cancer cases were used in the analysis. When we categorised the cytotoxic activity of peripheral-blood lymphocytes by tertiles, age-adjusted relative risk of cancer incidence (all sites) was 0.72 (95% CI 0.45-1.16) for men with high cytotoxic activity, and 0.62 (0.38-1.03) for men with medium cytotoxic activity, taking the risk of those with low cytotoxic activity as reference. For women with high cytotoxic activity relative risk was 0.52 (0.28-0.95), and for those with medium cytotoxic activity 0.56 (0.31-1.01). For both sexes with high and medium cytotoxic activity risk was 0.63 (0.43-0.92) and 0.59 (0.40-0.87), respectively. INTERPRETATION: Our results indicate that medium and high cytotoxic activity of peripheral-blood lymphocytes is associated with reduced cancer risk, whereas low activity is associated with increased cancer risk suggesting a role for natural immunological host defence mechanisms against cancer.

Adult↗
PubMed2000

Phase-dependent responses of Per1 and Per2 genes to a light-stimulus in the suprachiasmatic nucleus of the rat.

Single brief and discrete light treatments are sufficient to reset the overt mammalian rhythms of nocturnal rodents. In the present study, we examined the phase-dependent response of the mammalian clock genes, Per1 and Per2, to a brief strong light-stimulus (1000 lux) in the circadian oscillator center, the suprachiasmatic nucleus (SCN) of rats. Light-induced elevation of Per1 mRNA was observed through the subjective night (CT16, CT20 and CT0 (=CT24)) with a marked peak at the subjective dawn (CT0). However, the light influence was very limited for the induction of Per2; only weak elevation of Per2 mRNA was detected at CT16. The effect of light-stimulus on the Per1 gene was transient, and the effect was restricted to ventrolateral SCN neurons in both CT0 and CT16 after light exposure. Since it is known that these rats show a light-induced behavioral phase-shift throughout the subjective night with being strongest at subjective dawn, the present results suggest that the transient induction of Per1 in ventrolateral SCN neurons is a critical step in the resetting of the biological clock to environmental light-dark schedule.

Animals↗
PubMed2000

The 5' upstream region of mPer1 gene contains two promoters and is responsible for circadian oscillation.

The mPer1 gene is assumed to be a key molecule in the regulation and functioning of the mammalian circadian clock, which is based on the oscillation generated by a transcription-(post)translation feedback loop of a set of clock genes [1]. Robust circadian oscillation and acute light-elicited induction of mPer1 mRNA expression have been observed in the suprachiasmatic nucleus (SCN), the mammalian circadian center [2] [3]. To investigate the mechanism underlying the complex regulation of mPer1 expression, we isolated and characterized the 5' upstream region of the mPer1 gene. Unexpectedly, we identified two promoters, each followed by alternative first exons of mPer1. Consistent with the presence of multiple E-boxes in the promoters, exon-specific in situ hybridization of the SCN established that both promoters function in circadian oscillation and in light-induction of mPer1 expression. Transgenic mice carrying the 5' upstream region of the mPer1 gene fused to the luciferase gene demonstrated that a DNA fragment carrying both promoter regions is sufficient to elicit striking circadian oscillation in the SCN and responsiveness to light. Moreover, luminescence in the SCN accurately mirrored the mPer1 transcriptional activity. These transgenic mice will be very useful for monitoring clock-specific mPer1 expression in intact organisms and to follow the circadian clock in real time.

Animals↗
PubMed2000

Src family kinases negatively regulate platelet-derived growth factor alpha receptor-dependent signaling and disease progression.

We tested the hypothesis that Src family kinases (SFK) contribute to c-Cbl-mediated degradation of the platelet-derived growth factor (PDGF) alpha receptor (alphaPDGFR). Using either a receptor mutant that does not engage SFKs (F72/74), or cells that that lack SFKs, we found that SFKs contributed to degradation of the alphaPDGFR. Overexpression of c-Cbl also reduced the receptor half-life, but only if the receptor was able to engage SFKs. In cultured cells, prolonging the half-life of the receptor correlated with enhanced signaling and more efficient S phase entry, whereas accelerating receptor degradation had the opposite effect. Consistent with these tissue culture findings, there was a statistically significant increase in the onset of a proliferative retinal disease when animals were injected with cells expressing the F72/74 receptor, as compared with cells expressing the WT receptor. Our findings suggest that SFKs cooperate with c-Cbl to negatively regulate the alphaPDGFR, and that the SFK/c-Cbl suppression of alphaPDGFR output is relevant to the onset and progression of a proliferative disease.

3T3 Cells↗
PubMed2000

Use of gastrin-releasing peptide promoter for specific expression of thymidine kinase gene in small-cell lung carcinoma cells.

For specific transduction of herpes simplex virus thymidine kinase (HSV-tk) into human small-cell lung carcinoma (SCLC) cells, we explored the 5'-flanking region (-1.1 kb) of the gastrin-releasing peptide (GRP) gene as a lung cancer-specific promoter. RT-PCR analysis demonstrated expression of GRP mRNA in the SBC5 human SCLC cell line but not in the RERF human SCLC cell line, the A549 human lung adenocarcinoma cell line or the HeLa human uterine cervix epithelioid carcinoma cell line. A reporting vector containing the GRP promoter (pGL2-GRP) exhibited higher luciferase activity in SBC5 than in the other 3 cell lines. After transfecting an expression vector containing the GRP promoter-bound HSV-tk gene (pGRP-TK) into the cells, we measured their sensitivity to ganciclovir (GCV). In SBC5, pGRP-tk-transfected cells became about 100 times more sensitive to GCV than parental cells in vitro. In nude mice, tumors of pGRP-tk-transfected SBC5 regressed completely after i.p. administration of GCV. GRP promoter might be a good tool for tumor-specific transduction of suicide genes in GRP-expressing SCLC cells.

Animals↗
PubMed2000

Distribution and circadian expression of dbp in SCN and extra-SCN areas in the mouse brain.

The expression of dbp, a putative clock-controlled transcription factor, was investigated in the mouse brain by in situ hybridization using antisense cRNA probe. Positive dbp mRNA signals were detected in various parts of the brain, with the highest expression in the suprachiasmatic nucleus (SCN). The circadian expression profile was investigated in SCN and extra-SCN areas. In the SCN, dbp mRNA signals showed a peak at early daytime (ZT/CT4) and a trough at early nighttime (ZT/CT16) in both light-dark and constant dark conditions. In the cerebral cortex and the caudate-putamen, dbp mRNA was also expressed in a circadian manner, but the phase of dbp mRNA expression in these structures showed a 4-8 hr delay compared to that in the SCN. These findings indicate that the circadian expression profile of dbp in the extra-SCN brain areas is different from that in the SCN.

Animals↗
PubMed2000

The evolutionarily conserved N-terminal region of Cbl is sufficient to enhance down-regulation of the epidermal growth factor receptor.

The mammalian proto-oncoprotein Cbl and its homologues in Caenorhabditis elegans and Drosophila are evolutionarily conserved negative regulators of the epidermal growth factor receptor (EGF-R). Overexpression of wild-type Cbl enhances down-regulation of activated EGF-R from the cell surface. We report that the Cbl tyrosine kinase-binding (TKB) domain is essential for this activity. Whereas wild-type Cbl enhanced ligand-dependent EGF-R ubiquitination, down-regulation from the cell surface, accumulation in intracellular vesicles, and degradation, a Cbl TKB domain-inactivated mutant (G306E) did not. Furthermore, the transforming truncation mutant Cbl-N (residues 1-357), comprising only the Cbl TKB domain, functioned as a dominant negative protein. It colocalized with EGF-R in intracellular vesicular structures, yet it suppressed down-regulation of EGF-R from the surface of cells expressing endogenous wild-type Cbl. Therefore, Cbl-mediated down-regulation of EGF-R requires the integrity of both the N-terminal TKB domain and additional C-terminal sequences. A Cbl truncation mutant comprising amino acids 1-440 functioned like wild-type Cbl in down-regulation assays. This mutant includes the evolutionarily conserved TKB and RING finger domains but lacks the less conserved C-terminal sequences. We conclude that the evolutionarily conserved N terminus of Cbl is sufficient to effect enhancement of EGF-R ubiquitination and down-regulation from the cell surface.

Amino Acid Sequence↗
PubMed2000

Preventive effects of drinking green tea on cancer and cardiovascular disease: epidemiological evidence for multiple targeting prevention.

The significance of drinking green tea in prevention of two of the main lifestyle-related diseases, cancer and cardiovascular disease, was demonstrated in terms of a prospective cohort study on a total of 8,552 general residents in Saitama Prefecture, Japan. On the basis of the follow-up study, we revealed decreased relative risk of cancer incidence for those consuming over 10 cups a day, compared with those consuming below 3 cups: 0.54 (95% confidence interval, 0.22-1.34) for men, 0.57 (0.34-0.98) for women, and 0.59 (0.35-0.98) for both sexes. Furthermore, a significant delay in cancer onset was associated with increased consumption of green tea. Next, decreased relative risk of death from cardiovascular disease was 0.58 (0.34-0.99) for men, 0.82 (0.49-1.38) for women, and 0.72 (0.60-1.04) for members of both sexes consuming over 10 cups a day. Finally, we evaluated the life-prolonging effects of drinking green tea on cumulative survival, using the life table.

Adult↗
PubMed2000

High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia.

High serum concentrations of soluble adhesion molecules are present in diabetics, but whether similar levels are present in patients with impaired glucose tolerance (IGT) is unclear. We measured serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin in 128 nondiabetic Japanese subjects. The concentrations of sICAM-1, sVCAM-1, and sE-selectin in IGT patients (n=47) were not different from those in subjects with normal glucose tolerance (NGT; n=81). IGT patients were subdivided into two groups by the results of 75 g OGTT, those with low- (hypoinsulinemia; n=23) or high-insulin (hyperinsulinemia; n=24). The levels of sICAM-1 and sVCAM-1 were not different among NGT and IGT with high-insulin or with low-insulin. However, sE-selectin concentrations were significantly higher in IGT patients with high-insulin than in NGT and IGT with low-insulin (61.1+/-3.4, 47.1+/-1.8 and 43.7+/-3.9 ng/ml, respectively, P<0.001). Adjustment for age and gender did not influence the results. Serum sE-selectin concentrations correlated significantly with the area under the curve of insulin (AUC(insulin)), AUC(glucose), diastolic blood pressure, and triglyceride levels (r=0.35, 0.26, 0.18 and 0.21, respectively), and negatively with HDL-cholesterol levels (r=-0.20). Multiple regression analysis showed that AUC(insulin) was the only independent factor that correlated with sE-selectin levels (P<0.001). Our results indicate that hyperinsulinemia/insulin resistance may be responsible for the elevation of sE-selectin levels.

E-Selectin↗