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Biomedical subjects

S Nagaoka

Publications and source records attributed to S Nagaoka.

At least 19 recordsLinked to original sources
PubMed2007

Roxithromycin inhibits tumor necrosis factor-alpha-induced matrix metalloproteinase-1 expression through regulating mitogen-activated protein kinase phosphorylation and Ets-1 expression.

BACKGROUND AND OBJECTIVE: In periodontitis, matrix metalloproteinases (MMPs) are upregulated in response to locally released inflammatory cytokines, resulting in pathologic processes. Roxithromycin is a 14-membered ring macrolide antibiotic with broad-spectrum antibacterial effects against oral pathogens and immunomodulatory effects. Recently, we reported that roxithromycin inhibits tumor necrosis factor (TNF)-alpha-induced vascular endothelial growth factor expression in human periodontal ligament (HPDL) cell cultures. In the present study, we examined the effect of roxithromycin on TNF-alpha-induced MMP-1 production by HPDL cells. MATERIAL AND METHODS: Cultured cells were incubated with 1% fetal bovine serum for 24 h, followed by treatment with 10 ng/ml TNF-alpha, 10 microM roxithromycin, and mitogen-activated protein kinase inhibitor at various concentrations. Culture supernatants and sediments were collected at different time-points and used for enzyme-linked immunosorbent assays, and northern and western blot analyses. RESULTS: In HPDL cell cultures, roxithromycin strongly inhibited TNF-alpha-induced MMP-1 mRNA expression and production. The inhibition of MMP-1 gene expression by roxithromycin was dependent on de novo protein synthesis and was regulated at the transcriptional level. Roxithromycin significantly inhibited TNF-alpha-induced c-Jun N-terminal kinase activation (JNP) and marginally inhibited extracellular signal-regulated kinase (ERK) 1/2 activation, but not p38 mitogen-activated protein kinase activation. Furthermore, roxithromycin reduced the induction of Ets-1, one of the critical factors in MMP-1 transcription. CONCLUSION: Roxithromycin inhibits TNF-alpha-mediated MMP-1 induction through the downregulation of ERK1/2 and JNK activation and the subsequent reduction of Ets-1, suggesting that roxithromycin may have therapeutic use in periodontitis and other chronic inflammatory conditions involving MMP-1 induction.

Adult↗
PubMed2006

Plutonium isotopes derived from Nagasaki atomic bomb in the sediment of Nishiyama reservoir at Nagasaki, Japan.

The source of plutonium in sediments deposited at Nishiyama reservoir at Nagasaki was characterized by their (240)Pu/(239)Pu atom ratio. The average ratio was approximately 0.03, except in two layers. The main source of the plutonium was the Nagasaki atomic bomb. The plutonium continues to flow into the reservoir even now. The (240)Pu/(239)Pu atom ratios in two layers were higher than the average, which showed that plutonium in these layers were made of those of nuclear tests added to those of the atomic bomb.

Cesium Radioisotopes↗
PubMed2005

Preparation and characterization of spherical polymer packings from polybutadiene for size-exclusion chromatography.

Porous polymer spherical particles for column packings in nonaqueous size-exclusion chromatography (SEC) were prepared from 1,2-syndiotactic polybutadiene by suspension and evaporation method. The polymer microbeads obtained were crosslinked by radical reaction between 2-vinyl groups in polybutadiene with ultraviolet radiation, to render them insoluble. These microbeads have wider chromatographic separation width than polystyrene column packings. In addition, the polybutadiene microbeads did not show the excessive retention observed with commercial polystyrene columns for polycyclic aromatic compounds. Therefore, a close correlation between the elution volume and M, for polycyclic aromatic compounds was observed with polybutadiene microbeads columns.

Butadienes↗
PubMed2005

Plasma protein adsorption to nanofabricated fluorinated polyimide surface.

In this article, a series of fluorinated polyimides rubbed at different pressures was prepared, and the plasma protein adsorption on the rubbed polyimide films was evaluated using a micro-bicinchoninic acid protein assay. Interestingly, the amount of plasma protein adsorbed on the polyimide surface strongly depended on the rubbing pressure. The amounts of BSA and Fbg adsorbed on the rubbed polyimide film significantly decreased with an increase in the rubbing pressure. In contrast, the amounts of IgG adsorbed on the rubbed film dramatically increased with an increase in the rubbing pressure. In particular, it is interesting to note that a specific adsorption surface for IgG is formed by the rubbing process. We proposed that the nano-ordered hydrophilic and hydrophobic patternings formed on the top and bottom surfaces on the rubbed fluorinated polyimide film might have a significant influence on the plasma protein adsorption.

Adsorption↗
PubMed2004

Expression of IAP family proteins in colon cancers from patients with different age groups.

Members of the inhibitor of apoptosis protein (IAP) family including survivin, are expressed in many tumors. However, age-related changes in their expression in cancer have not been clarified. Thus, we investigated the expression of mRNA-coding for IAP family proteins in colon cancer samples from young (<70 years of age) and elderly (>70 years) patients by real-time quantitative RT-PCR. Samples were collected from cases with well-differentiated adenocarcinoma or moderately differentiated adenocarcinoma and their adjacent normal epithelial tissue. Well-differentiated adenocarcinoma tended to express higher levels of survivin than normal mucosa, and expression in moderately differentiated adenocarcinoma was significantly greater than in normal mucosa in samples from both groups of patients ( p<0.05, respectively). When samples were compared between the different age groups, the normal mucosa exhibited similar levels of survivin expression. However, samples from older patients showed a significantly higher level of expression than those from younger patients in well and moderately differentiated adenocarcinomas ( p<0.05, respectively). In contrast, the levels of expression of cIAP1, cIAP2, and NAIP in the cancerous tissues were lower than those found in normal mucosa regardless of age. As for age-related changes, the expression of cIAP2 in normal mucosa and moderately differentiated adenocarcinoma was stronger in the elderly group than the young group ( p<0.05, respectively), and NAIP expression in well-differentiated adenocarcinoma was higher in the young group than the elderly group ( p<0.05). XIAP expression was similar in normal and cancerous tissues in both the young and elderly groups. These results suggest that the expression of IAP family proteins, especially survivin, is associated with the age-related biological characteristics of colon cancer.

Adenocarcinoma↗
PubMed2003

Competitive plasma protein adsorption onto fluorinated polyimide surfaces.

A series of fluorinated polyimides cured at different temperatures was prepared, and plasma protein adsorption and platelet adhesion onto the polyimide films were evaluated in vitro using scanning electron microscopy, a micro-bicinchoninic acid protein assay, and a gold-colloid-labeled immunoassay. In particular, we focused on competitive plasma protein adsorption onto polyimide film because elucidation of the competitive adsorption mechanism is needed for a good understanding of in vivo biocompatibility of polyimide. Interestingly, the trend of IgG adsorption onto the polyimide surface measured in human plasma was completely contrary to that observed with IgG dissolved in PBS, and the adsorption increased with an increase in the curing temperature. We propose that the human plasma F(c) region in IgG might selectively adsorb onto polyimide film cured at high temperatures because of competitive plasma protein adsorption to the surface.

Adsorption↗
PubMed2003

Chemical modification of manganese porphyrins with biomolecules for new functional antioxidants.

Superoxide dismutase (SOD), which catalyzes the reduction of O2*- to H2O2, is the key enzyme for the protection of oxidative stress. Here we have chemically modified manganese (Mn) porphyrins with biomolecules for new functional antioxidants. The Mn-porphyrins were conjugated with the following biochemical functional molecules: (1) catalase, to catalyze reduction of H2O2 to H2O. The resulting conjugate showed dual functions of SOD and catalase; (2) a carbohydrate, to facilitate receptor binding and, hence, active targeting. The resulting conjugate showed both SOD activity and carbohydrate recognition. These results suggest that the antioxidants promise the application to biomedical fields.

Animals↗
PubMed2003

Interaction between fibroblast cells and fluorinated polyimide with nano-modified surface.

In this study, we investigated the effect of surface nano-modification of aromatic fluorinated polyimide (6FDA-6FAP) derived from 2,2'-bis (3,4-dicarboxyphenyl) hexafluoropropane dianhydride (6FDA) and 2,2'-bis (4-aminophenyl) hexafluoropropane (6FAP) on the interaction with proteins and cells. The surface of 6FDA-6FAP was modified by surface-rubbing showed nano-ordered stripes along the rubbing direction. The rat fibroblast FR cells formed multicellular spheroids with high cell density on the rubbed surface then expressed excellent collagen production similarly in vivo, while on the non-modified surface the cells formed two-dimensional monolayers and the collagen production was negligible. The modulation of cell function by the surface nano-modification along with surface micro-modification may be one of the most important considerations during the design and manufacture of novel biochips or tissue engineering materials.

Animals↗
PubMed2002

Biocompatibility of fluorinated polyimide.

Contact between blood and biomaterial triggers a complex series of events including protein adsorption, leukocyte adhesion and activation, and complement activation. In this article, a series of fluorinated polyimides cured at a different temperatures was prepared, and the biocompatibility of the membranes was evaluated using in vitro protein adsorption, neutrophil adhesion, and complement activation experiments under static conditions. We found that protein adsorption, neutrophil adhesion, and complement activation for the polyimides significantly depends on the curing temperature and decreases with an increase in the temperature and that the polyimide has a good biocompatibility compared with poly(styrene) and polydimethylsiloxane. We concluded that the rearrangement of molecules such as CF(3), sulfone, and ketone at the outermost surface occurs because of curing, which induces an increase in the hydrophobicity and that the cured polyimide suppresses protein adsorption, neutrophil adhesion, and complement activation because of its high hydrophobicity and low surface free energy.

Adsorption↗
PubMed2002

Aquatic animal research in space station and its issues--focus on support technology on nitrate toxicity.

We studied the effects of accumulated nitrate in water on the spawning, hatching and development of medaka using a simple nitrifying filter and a combined filter having both nitrifying and denitrifying capabilities. A nitrate concentration of 100 mg NO3(-)-N/L was clearly of lethal toxicity to fish when they were exposed to nitrate in both adult and the growing phases. A nitrate concentration of 75 mg NO3(-)-N/L reduced the fertilization rate, delayed the hatching time and reduced the hatching rate of the eggs laid by adults and decreased the growth rate of juveniles. In addition, nitrate accumulations as low as 50 mg NO3(-)-N/L remarkably retarded spawning and lowered the number of eggs laid by fish exposed in the juvenile phase. The effects on the reproduction system may be initiated by a low concentration, approximately 30 mg NO3(-)-N/L.

Animals↗
PubMed2002

LET distributions from CR-39 plates on Space Shuttle missions STS-84 and STS-91 and a comparison of the results of the CR-39 plates with those of RRMD-II and RRMD-III telescopes.

The LET distributions during the Space Shuttle missions STS-84 (altitude 270-412 km, average 375 km; inclination angle, 51.6 degrees) and STS-91 (altitude 328-397 km, average 373 km; inclination angle, 51.6 degrees) were measured using CR-39 plastic nuclear track detectors. A correction for the dip-angle dependence of the track-formation sensitivity of the CR-39 plates was applied to the data analysis. The absorbed doses and the dose equivalents around RRMD Detector Units, estimated from the LET distributions in the LET region of 4-200 keV/micrometers, fluctuated with standard deviations of +/- 21% to +/- 35% in both flight experiments. The LET distributions obtained from the CR-39 plates agreed well with that obtained from RRMD-II in STS-91. However, the particle fluxes obtained from RRMD-III in STS-84 and STS-91 were two or three times higher than those obtained from RRMD-II and the CR-39 plates. It was concluded that the LET distributions obtained from RRMD-II and the CR-39 plates in the present flight experiments did not include the contribution of target-fragmented secondary heavy particles produced by low-LET particles, such as relativistic or semi-relativistic protons and helium ions, whereas RRMD-III was able to detect these secondary particles because of its low triggering level.

Cosmic Radiation↗
PubMed2001

Identification of novel hypocholesterolemic peptides derived from bovine milk beta-lactoglobulin.

This study was designed to clarify the mechanisms of hypocholesterolemic action of beta-lactoglobuline tryptic hydrolysate (LTH) and to identify the novel hypocholesterolemic peptide derived from LTH by screening using Caco-2 cells and animal studies. Serum and liver cholesterol levels were significantly lower in rats fed LTH than in those fed casein tryptic hydrolysate (CTH). The present study suggests that the inhibition of micellar solubility of cholesterol which causes the suppression of cholesterol absorption by a direct interaction between cholesterol mixed micelles, and LTH in the jejunal epithelia is part of the mechanism underlying the hypocholesterolemic action of LTH. Though no one could trace the hypocholesterolemic peptide to any protein origin, we identified, for the first time, a novel hypocholesterolemic peptide, Ile-Ile-Ala-Glu-Lys (IIAEK). Surprisingly, the present study provides the first direct evidence that a new hypocholesterolemic peptide derived from beta-lactoglobuline can powerfully influence serum cholesterol levels and exhibit a greater hypocholesterolemic activity in comparison with that of medicine, beta-sitosterol, in animal studies.

Administration, Oral↗
PubMed2001

Cell death by reactive oxygen species generated from water-soluble cationic metalloporphyrins as superoxide dismutase mimics.

We investigated the effect on cell death of reactive oxygen species induced by water-soluble cationic metalloporphyrins with superoxide dismutase (SOD) activity. The SOD activity of 5,10,15,20-tetrakis(4-N-methylpyridyl)]porphine (MPy(4)P) containing Fe, Mn or Cu was measured using a cytochrome c assay by the xanthine/xanthine oxidase system and stopped-flow kinetic analysis. Cell viability of four cell lines treated with metalloporphyrins, mitomycin c (MMC), or cisplatin was estimated by a trypan blue exclusion assay. FeMPy(4)P with a high SOD activity showed a significant cytotoxicity compared with MMC and cisplatin, while CuMPy(4)P without SOD activity exhibited no cytotoxicity. However, MnMPy(4)P showing an SOD activity as high as that of FeMPy(4)P did not indicate cytotoxicity. These findings suggest that FeMPy(4)P as SOD mimic converts intracellular O2(*-) to H(2)O(2) and that it rapidly reacts with H(2)O(2) to form *OH, causing DNA damage and inducing cell death. On the other hand, MnMPy(4)P did not participate in the Fenton reaction, so that DNA damage in the cells treated with MnMPy(4)P was not observed. In addition, the cytotoxicity by the metalloporphyrin was inversely correlated with the SOD activity of the cells and the selective damage at cellular and DNA levels was confirmed. We believe that for an anticancer drug with antioxidant ability O(2)(*-) is useful as a target molecule to induce selective cell death between cancer and normal cells and that metalloporphyrins showing SOD activity and Fenton-like reaction are a new class of anticancer agents.

Animals↗
PubMed2001

Differentiation of Dictyostelium discoideum vegetative cells into spores during Earth orbit in space.

We reported previously that emerged amoebae of Dictyostelium (D.) discoideum grew, aggregated and differentiated to fruiting bodies with normal morphology in space. Here, we investigated the effects of space radiation and/or microgravity on the number, viability, kinetics of germination, growth rate and mutation frequency of spores formed in space in a radiation-sensitive strain, gamma s13, and the parental strain, NC4. In gamma s13, there were hardly spores in the fruiting bodies formed in space. In NC4, we found a decrease in the number of spores, a delay in germination of the spores and delayed start of cell growth of the spores formed in space when compared to the ground control. However, the mutation frequency of the NC4 spores formed in space was similar to that of the ground control. We conclude that the depression of spore formation might be induced by microgravity and/or space radiation through the depression of some stage(s) of DNA repair during cell differentiation in the slime mold.

Animals↗
PubMed2001

The effects of microgravity on induced mutation in Escherichia coli and Saccharomyces cerevisiae.

We examined whether microgravity influences the induced-mutation frequencies through in vivo experiments during space flight aboard the space shuttle Discovery (STS-91). We prepared dried samples of repair-deficient strains and parental strains of Escherichia (E.) coli and Saccharomyces (S.) cerevisiae given DNA damage treatment. After culture in space, we measured the induced-mutation frequencies and SOS-responses under microgravity. The experimental findings indicate that almost the same induced-mutation frequencies and SOS-responses of space samples were observed in both strains compared with the ground control samples. It is suggested that microgravity might not influence induced-mutation frequencies and SOS-responses at the stages of DNA replication and/or DNA repair. In addition, we developed a new experimental apparatus for space experiments to culture and freeze stocks of E. coli and S. cerevisiae cells.

Alkylating Agents↗
PubMed2001

Alkylating agent (MNU)-induced mutation in space environment.

In recent years, some contradictory data about the effects of microgravity on radiation-induced biological responses in space experiments have been reported. We prepared a damaged template DNA produced with an alkylating agent (N-methyl-N-nitroso urea; MNU) to measure incorrect base-incorporation during DNA replication in microgravity. We examined whether mutation frequency is affected by microgravity during DNA replication for a DNA template damaged by an alkylating agent. Using an in vitro enzymatic reaction system, DNA synthesis by Taq polymerase or polymerase III was done during a US space shuttle mission (Discovery, STS-91). After the flight, DNA replication and mutation frequencies were measured. We found that there was almost no effect of microgravity on DNA replication and mutation frequency. It is suggested that microgravity might not affect at the stage of substrate incorporation in induced-mutation frequency.

Alkylating Agents↗
PubMed2001

Measurements of LET-distribution, dose equivalent and quality factor with the RRMD-III on the Space Shuttle Missions STS-84, -89 and -91.

Dosimetric measurements on the Space Shuttle Missions STS-84, -89 and -91 have been made by the real-time radiation monitoring device III (RRMD-III). Simultaneously, another dosimetry measurement was made by the Dosimetry Telescope (DOSTEL) on STS-84 and by the tissue-equivalent proportional counter (TEPC) on STS-91. First, the RRMD-III instrument is described in detail and its results summarized. Then, the results of DOSTEL and TEPC are compared with those of the RRMD-III. Also, the absorbed doses obtained by TLD (Mg2SiO4) and by RRMD-III on board STS-84 and -91 are compared.

Atlantic Ocean↗