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Biomedical subjects

M Torii

Publications and source records attributed to M Torii.

At least 19 recordsLinked to original sources

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↗

An online literature mining tool for protein phosphorylation.

A web-based version of the RLIMS-P literature mining system was developed for online mining of protein phosphorylation information from MEDLINE abstracts. The online tool presents extracted phosphorylation objects (phosphorylated proteins, phosphorylation sites and protein kinases) in summary tables and full reports with evidence-tagged abstracts. The tool further allows mapping of phosphorylated proteins to protein entries in the UniProt Knowledgebase based on PubMed ID and/or protein name. The literature mining, coupled with database association, allows retrieval of rich biological information for the phosphorylated proteins and facilitates database annotation of phosphorylation features.

Animals↗

Shear modulus and thermal properties of gutta percha for root canal filling.

The purpose of this investigation was to investigate the rheological properties of four commercially available gutta perchas for root canal filling. The relaxation modulus [Gr(0): instantaneous shear modulus] and specific volume of their materials were examined. In addition, the quantity of heat was also studied by differential scanning calorimeter. In a lower temperature range than the first-order transition temperature (melting point), the Gr(0) values of each material were almost identical. A marked decrease of Gr(0) was observed at the melting point, and the range of the first-order transition temperature at heating was from 42.0 to 60.0 degrees C. At higher temperatures than the first-order transition temperature of each material, a considerable difference in Gr(0) values was observed. The transition temperatures obtained by the results of the Gr(0), specific volume and quantity of heat agreed with one another. A marked specific volume change was observed at the first-order transition temperature. The technique using melted gutta percha may not be favourable compared with the conventional lateral condensation technique because melted gutta percha undergoes a large amount of shrinkage during setting.

Gutta-Percha↗

Hand-assisted laparoscopic resection of serous cystadenoma of the pancreas.

It is difficult to exclude the possibility of malignancy of pancreatic cystic tumors because a biopsy of the pancreas is hard to obtain. The indication of open surgery for those cystic tumors without evidence of malignancy is controversial. Therefore, laparoscopic or laparoscopically assisted procedure would be an adequate choice of treatment for cystic tumors of the pancreas. Hand-assisted laparoscopic distal pancreatectomy with preservation of the spleen and the splenic artery and vein was performed for two cases of pancreatic cystic tumors. Three ports and one hand port were used. After careful dissection and accurate hemostasis between the pancreas and splenic vessels, laparoscopic distal pancreatectomy was carried out using an endoscopic linear stapler. There were no perioperative complications. The pathological diagnoses were oligocystic serous cystadenoma and solitary cystic serous cystadenoma, respectively. Hand-assisted, spleen-preserving laparoscopic distal pancreatectomy with preservation of the splenic artery and vein is a feasible procedure for the treatment of benign or borderline-malignant cystic lesions of the distal pancreas.

Adult↗

[Studies on the antigens of invasive stages of Plasmodium yoelii and Plasmodium berghei].

OBJECTIVE: To detect the rhoptry and surface proteins of invasive stages of Plasmodium yoelii and P. berghei with monoclonal antibodies. METHODS: Subcellular localization of antigens was detected by IFA. The antigens of different stages of the two species malaria parasites were analyzed by Western blotting. RESULTS: The antigens of rhoptry are very complicated. There are similar epitopes of the rhoptry proteins detected between the two species of Plasmodium. The similar epitopes were also detected between ookinetes and merozoites of P. yoelii, and ookinete antigens between the two species. But there are different antigens detected between merozoites and ookinetes in P. yoelii. The sporozoite surface antigen of P. yoelii was not detected in the ookinetes and merozoites in the same species. CONCLUSION: There are similar epitopes in the rhoptry and surface antigens of different stages and different species of rodent malaria parasites. There are also distinct antigens among them.

Animals↗

von Willebrand Factor A domain-related protein, a novel microneme protein of the malaria ookinete highly conserved throughout Plasmodium parasites.

The mosquito-invasive form of the malarial parasite, the ookinete, develops numerous secretory organelles, called micronemes, in the apical cytoplasm. Micronemal proteins are thought to be secreted during midgut invasion and to play a crucial role in attachment and motility of the ookinete. We found a novel ookinete micronemal protein of rodent malarial parasite Plasmodium berghei, named P. berghei von Willebrand factor A domain-related protein (PbWARP), and report it here as a putative soluble adhesive protein of the ookinete. The PbWARP gene contained a single open reading frame encoding a putative secretory protein of 303 amino acids, with a von Willebrand factor type A module-like domain as a main component. Western blot analysis demonstrated that PbWARP was firstly produced 12 h after fertilization by maturing ookinetes as SDS-resistant complexes. Recombinant PbWARP produced with a baculovirus system also formed SDS-resistant high-order oligomers. Immuno-electron microscopic studies showed that PbWARP was randomly distributed in the micronemes. PbWARP homologues also exist in human malarial parasites, Plasmodium falciparum and Plasmodium vivax. Highly conserved primary structures of PbWARP homologues among these phylogenetically distant Plasmodium species suggest their functional significance and the presence of a common invasion mechanism widely utilized throughout Plasmodium parasites.

Amino Acid Sequence↗

The high molecular mass rhoptry protein, RhopH1, is encoded by members of the clag multigene family in Plasmodium falciparum and Plasmodium yoelii.

Malarial merozoite rhoptries contain a high molecular mass protein complex called RhopH. RhopH is composed of three polypeptides, RhopH1, RhopH2, and RhopH3, encoded by distinct genes. Using monoclonal antibody-purified protein complex from both Plasmodium falciparum and Plasmodium yoelii, peptides were obtained by digestion of RhopH1 and their sequence determined either by mass spectrometry or Edman degradation. In both species the genes encoding RhopH1 were identified as members of the cytoadherence linked asexual gene (clag) family. In P. falciparum the family members on chromosome 3 were identified as encoding RhopH1. In P. yoelii two related genes were identified and sequenced. One of the genes, pyrhoph1a, was positively identified as encoding RhopH1 by the peptide analysis and the other gene, pyrhoph1a-p, was at least transcribed. Genes in the clag family present in both parasite species have a number of conserved features. The size and location of the P. yoelii protein complex in the rhoptries was confirmed. The first clag gene identified on chromosome 9 was implicated in cytoadherence, the binding of infected erythrocytes to host endothelial cells; this study shows that other members of the family encode merozoite rhoptry proteins, proteins that may be involved in merozoite-erythrocyte interactions. We propose that the family should be renamed as rhoph1/clag.

Amino Acid Sequence↗

Regulation of interleukin-6 expression in human dental pulp cell cultures stimulated with Prevotella intermedia lipopolysaccharide.

Interleukin (IL)-6 expression in human dental pulp cell cultures after stimulation with Prevotella intermedia lipopolysaccharide (LPS) was investigated by Northern blot analysis, enzyme immunoassay, and bioassay. The IL-6 mRNA expression began to increase after 1 hr and continued after up to 8 hr of exposure on stimulation with 10 microg/ml of P. intermedia LPS. The bioactivity was dose-dependent on the concentration of P. intermedia LPS (0 to 100 microg/ml). The IL-6 mRNA expression was inhibited by actinomysin D and super-induced by cycloheximide. Anti-CD14 monoclonal antibody (MY4) inhibited the IL-6 mRNA expression when administered at a 0.5 microg/ml concentration before stimulation with P. intermedia LPS at 1 microg/ml. The immunoregulatory cytokines (interferon-gamma, IL-10, and IL-4) inhibited LPS-induced IL-6 production with a combined treatment. These results suggest the IL-6 expression by pulp cell cultures is CD14-dependent and regulated at the transcriptional level, and a combined treatment with immunoregulatory cytokines may be effective for control of pulpal inflammation due to P. intermedia LPS.

Antibodies, Monoclonal↗

Inhibition by carbapenem antibiotic imipenem of intestinal absorption of valproic acid in rats.

The concomitant use of carbapenem antibiotics with valproic acid has been prohibited because panipenem induced a decrease in plasma concentration of valproic acid in epileptic patients during valproic acid therapy. To clarify the possible mechanism of the carbapenem-valproic acid interaction, we investigated the effect of imipenem on the pharmacokinetic behaviour of valproic acid in rats. Co-administration of imipenem (30 mg kg(-1), i.v.) induced a decrease in the peak plasma concentration of valproic acid after oral administration. However, the imipenem-induced decrease in plasma concentrations of valproic acid was not observed within 60 min after intravenous injection of valproic acid. By utilizing in-situ vascular and luminal perfused small intestine, it was confirmed that absorption of valproic acid from the luminal to the vascular perfusate was decreased in the presence of imipenem (0.5 mM) in the vascular perfusate. The everted gut sac method was used to determine the effect of imipenem on active transport of valproic acid. The accumulation of valproic acid on the serosal side of the intestinal sac against the concentration gradient was reduced by lactic acid that inhibits the carrier-mediated transport of valproic acid across the intestinal brush-border membrane. However, imipenem did not affect the active transport of valproic acid. Therefore, the inhibition by imipenem of valproic acid absorption may be caused by a mechanism different from that of lactic acid. In conclusion, imipenem inhibits the intestinal absorption of valproic acid, which contributes to the decrease in plasma concentration of valproic acid after oral administration.

Administration, Oral↗

Development of a method for the in vitro production of Plasmodium vivax ookinetes.

We developed a method for the in vitro production of mature Plasmodium vivax ookinetes. Gametocytemic blood was collected from 98 P. vivax-infected patients reporting to malaria clinics in Maesod and Maekasa Districts, Tak Province, Thailand. Briefly, gametogenesis was induced using xanthurenic acid and parasites were separated by density gradient centrifugation and then cultured in RPMI-1640, pH 7.8-8.2. At the same time that blood was collected, 200 Anopheles dirus mosquitoes were allowed to feed on each patient. Mosquito midguts were removed 2-36 hr postfeeding, and gut contents were smeared onto glass slides, as were cultured samples from varying time points. Slides were stained with Giemsa, and the in vitro and mosquito development of ookinetes compared. Mature ookinetes were produced in 48.0% (47/98) of in vitro cultures, with a total yield ranging from 10 to 248,500 (mean = 15,523, median = 600) ookinetes produced per 5 ml blood. The temporal development and the morphology of the P. vivax ookinetes produced in vitro was similar to that observed in the A. dirus mosquitoes. The method that we describe is simple, can be used at remote sites without sophisticated equipment, and yields high numbers of clean ookinetes. This method of producing mature P. vivax ookinetes will be a useful tool for studies on ookinetes in P. vivax endemic regions.

Animals↗

Twenty-six-week carcinogenicity study of sulfamethoxazole in CB6F1-Tg-rasH2 mice.

Sulfamethoxazole (SMX), a hormone-mediated rodent-specific nongenotoxic carcinogen, was administered to CB6F1 mice carrying a human prototype c-Ha-ras gene (Tg-rasH2) at doses of 0, 25, 100 or 400 mg/kg/day and to the wild-type mice at a dose of 400 mg/kg/day in feed for 26 weeks to evaluate the carcinogenicity and to validate the Tg-rasH2 model. N-Methyl-N-nitrosourea was administered at an intraperitoneal dose of 75 mg/kg to Tg-rasH2 as a positive control and the experimental system was confirmed to be valid. Histopathological examination revealed adenomas of the lung and Harderian gland and hemangiosarcoma of the spleen at low frequencies in the Tg-rasH2 treated with SMX; however, no statistically significant differences were observed either in the onset or prevalence rates of these neoplasms compared with that in the control group. Between the wild-type mice and Tg-rasH2, the onset rate and prevalence of the neoplasms were not significantly different, but the neoplasms tended to be more frequent in Tg-rasH2 mice showing a sensitivity to tumorigenicity. Follicular epithelial cell hyperplasia was observed in the thyroid gland in the groups of Tg-rasH2 given 100 mg/kg SMX or more, but no neoplastic lesion was observed. SMX was judged to be negative for carcinogenic potential in Tg-rasH2 in the present study.

Animals↗

Polymerization contraction stress of resin composite restorations in a model Class I cavity configuration using photoelastic analysis.

PURPOSE: An important factor that contributes to deterioration of resin composite restorations is contraction stress that occurs during polymerization. The purpose of this article is to familiarize the clinician with the characteristics of contraction stress by visualizing the stresses associated with this invisible and complex phenomenon. MATERIALS AND METHODS: Internal residual stresses generated during polymerization of resin composite restorations were determined using micro-photoelastic analysis. Butt-joint preparations simulating Class I restorations (2.0 mm x 5.0 mm, 2.0 mm in depth) were prepared in three types of substrates (bovine teeth, posterior composite resin, and transparent composite resin) and were used to examine contraction stress in and around the preparations. Three types of composite materials (a posterior composite, a self-cured transparent composite, and a light-cured transparent composite) were used as the restorative materials. The self-cured composite is an experimental material, and the others are commercial products. After treatment of the preparation walls with a bonding system, the preparations were bulk-filled with composite. Specimens for photoelastic analysis were prepared by cutting sections perpendicular to the long axis of the preparation. Fringe patterns for directions and magnitudes of stresses were obtained using transmitted and reflected polarized light with polarizing microscopes. Then, the photoelastic analysis was performed to examine stresses in and around the preparations. RESULTS: When cavity preparations in bovine teeth were filled with light-cured composite, a gap was formed between the dentinal wall and the composite restorative material, resulting in very low stress within the restoration. When cavity preparations in the posterior composite models were filled with either self-cured or light-cured composite, the stress distribution in the two composites was similar, but the magnitude of the stress was greater in the light-cured material. When preparations in the transparent composite models were filled with posterior composite and light-cured transparent composite material, significant stress was generated in the preparation models simulating tooth structure, owing to the contraction of both restorative materials. CLINICAL SIGNIFICANCE: Polymerization contraction stress is an undesirable and inevitable characteristic of adhesive restorations encountered in clinical dentistry that may compromise restoration success. Clinicians must understand the concept of polymerization contraction stress and realize that the quality of composite resin restorations depends on successful management of these stresses.

Animals↗

Micronemal transport of Plasmodium ookinete chitinases to the electron-dense area of the apical complex for extracellular secretion.

Plasmodium ookinetes secrete chitinases to penetrate the acellular, chitin-containing peritrophic matrix of the mosquito midgut en route to invasion of the epithelium. Chitinases are potentially targets that can be used to block malaria transmission. We demonstrate here that chitinases of Plasmodium falciparum and P. gallinaceum are concentrated at the apical end of ookinetes. The chitinase PgCHT1 of P. gallinaceum is present within ookinete micronemes and subsequently becomes localized in the electron-dense area of the apical complex. These observations suggest a pathway by which ookinetes secrete proteins extracellularly.

Animals↗

Antibodies to malaria vaccine candidates Pvs25 and Pvs28 completely block the ability of Plasmodium vivax to infect mosquitoes.

Transmission-blocking vaccines are one strategy for controlling malaria, whereby sexual-stage parasites are inhibited from infecting mosquitoes by human antibodies. To evaluate whether the recently cloned Plasmodium vivax proteins Pvs25 and Pvs28 are candidates for a transmission-blocking vaccine, the molecules were expressed in yeast as secreted recombinant proteins. Mice vaccinated with these proteins adsorbed to aluminum hydroxide developed strong antibody responses against the immunogens, although for Pvs28, this response was genetically restricted. Antisera against both recombinant Pvs25 and Pvs28 recognized the corresponding molecules expressed by cultured sexual-stage parasites isolated from patients with P. vivax malaria. The development of malaria parasites in mosquitoes was completely inhibited when these antisera were ingested with the infected blood meal. Pvs25 and Pvs28, expressed in Saccharomyces cerevisiae, are as yet the only fully characterized transmission-blocking vaccine candidates against P. vivax that induce such a potent antiparasite response.

Amino Acid Sequence↗

Prostaglandin E2 predominantly induces production of hepatocyte growth factor/scatter factor in human dental pulp in acute inflammation.

Hepatocyte growth factor (HGF), which is also known as the scatter factor, is a broad-spectrum and multifunctional cytokine, mediates epithelial-mesenchyme interaction, and is shown to be involved in the development and regeneration of various tissues, including tooth. Here, we report that HGF was present in adult human dental pulps, and its levels increased during acute inflammation of the tissue. Levels of HGF mRNA in dental pulps also increased with inflammation, as determined by reverse-transcription/polymerase chain-reaction. The production of HGF in fibroblasts from dental pulps in culture was dose-dependently stimulated by inflammatory cytokines such as interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha, and by prostaglandin (PG) E2, as determined by an enzyme-linked immunosorbent assay. We also showed that indomethacin did not affect the increase in HGF production by the cells with IL-1alpha, TNF-alpha, and PGE2. The levels of HGF mRNA in the cells were simultaneously increased by these stimulants, as determined by Northern blotting. Since the production of PGs is known to increase at the beginning of inflammation, PGE2 may be involved in the regeneration of dental pulps by the induction of HGF expression after inflammation.

Adolescent↗

Antibacterial activities and release kinetics of a newly developed recoverable controlled agent-release system.

We attempted to develop a resin with a recoverable antibacterial activity based on the desorption/adsorption of a cationic bactericide by the ion-exchange mechanism. The aims of this study were to investigate the release kinetics of the agent and the antibacterial activity of this newly designed resin system. An experimental resin was prepared by the addition of methacrylic acid as a cation-exchanger and a cationic antibacterial agent, cetylpyridinium chloride (CPC), to triethyleneglycol dimethacrylate. The amount of CPC desorbed from the experimental resin into buffer solutions at pH 4-8 was measured. The adsorption of CPC to control resin and re-adsorption of CPC to the experimental resin, which had once desorbed the agent, were also determined. The antibacterial activity of experimental resin against Streptococcus mutans was evaluated, and the relationship between bacterial acid production and antibacterial effect was assessed. The experimental resin desorbed CPC at pH < or = 6, and the amount of agent desorbed increased with increasing acidity. The control resin adsorbed CPC when immersed in CPC aqueous solution at a rate determined by the concentration of the agent and immersion time. The experimental resin, once desorbed CPC, could re-adsorb the bactericide by being exposed to a solution of the agent. Less plaque formed on the experimental resin, and the growth and survival of S. mutans was inhibited in the condition in which acid was produced. These results demonstrate that the resin system proposed was able to desorb and re-adsorb the cationic bactericide by an ion-exchange mechanism and could show an inhibitory effect on S. mutans growth and plaque formation.

Adsorption↗