Biomedical subjects

Shoji Tanaka

Publications and source records attributed to Shoji Tanaka.

14 recordsLinked to original sources

PubMed2006

Direct identification of conformational isomers of adsorbed oligothiophene on Cu100.

A direct conformational analysis using scanning tunneling microscopy (STM) has been performed for individual adsorbed alpha-octithiophene molecules on Cu(100). s-cis and s-trans conformational isomers are induced by the rotational flexibility of individual thiophene rings. By adding bulky N-silyl substituents to octithiophene, we successfully identify the s-cis and s-trans conformational isomers using STM. The obtained relative abundances of the s-cis and s-trans conformations are analyzed using ab initio molecular orbital calculations.

Journal Article↗

PubMed2006

An ortho dimer of butylated hydroxyanisole inhibits nuclear factor kappa B activation and gene expression of inflammatory cytokines in macrophages stimulated by Porphyromonas gingivalis fimbriae.

Butylated hydroxyanisole, BHA, is widely used as a potent antioxidant, but its adverse effects such as carcinogenesis and proinflammatory activity have been reported, which are possibly due to the prooxidant property of this compound. We recently demonstrated that the dimer of 2-methoxyphenols exhibits cyclooxygenase-2 inhibition, because of lessening of its prooxidant property caused by the dimerization. In the present study, toward our goal of developing a chemopreventive agent for chronic periodontal diseases, we examined whether 2-BHA (2-tert-butyl-4-methoxyphenol) and its synthetic ortho dimer, bis-BHA (3,3'-di-tert-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol) could inhibit the Porphyromonas gingivalis fimbria-stimulated inflammatory reaction. The fimbria-induced expression of interleukin-1beta and neutrophil chemoattractant KC genes in RAW264.7 murine macrophages was strongly inhibited by bis-BHA. In contrast, 2-BHA showed only slight inhibition. bis-BHA also significantly inhibited the fimbria-stimulated phosphorylation-dependent degradation of the alpha inhibitor of nuclear factor-kappaB and the transcriptional activity of this factor in the cells. These findings suggest that bis-BHA possesses anti-inflammatory activity against chronic periodontal diseases.

Animals↗

PubMed2006

Site-specific phosphorylation of MCM4 during the cell cycle in mammalian cells.

MCM4, a subunit of a putative replicative helicase, is phosphorylated during the cell cycle, at least in part by cyclin-dependent kinases (CDK), which play a central role in the regulation of DNA replication. However, detailed characterization of the phosphorylation of MCM4 remains to be performed. We examined the phosphorylation of human MCM4 at Ser3, Thr7, Thr19, Ser32, Ser54, Ser88 and Thr110 using anti-phosphoMCM4 sera. Western blot analysis of HeLa cells indicated that phosphorylation of MCM4 at these seven sites can be classified into two groups: (a) phosphorylation that is greatly enhanced in the G2 and M phases (Thr7, Thr19, Ser32, Ser54, Ser88 and Thr110), and (b) phosphorylation that is firmly detected during interphase (Ser3). We present data indicating that phosphorylation at Thr7, Thr19, Ser32, Ser88 and Thr110 in the M phase requires CDK1, using a temperature-sensitive mutant of mouse CDK1, and phosphorylation at sites 3 and 32 during interphase requires CDK2, using a dominant-negative mutant of human CDK2. Based on these results and those from in vitro phosphorylation of MCM4 with CDK2/cyclin A, we discuss the kinases responsible for MCM4 phosphorylation. Phosphorylated MCM4 detected using anti-phospho sera exhibited different affinities for chromatin. Studies on the nuclear localization of chromatin-bound MCM4 phosphorylated at sites 3 and 32 suggested that they are not generally colocalized with replicating DNA. Unexpectedly, MCM4 phosphorylated at site 32 was enriched in the nucleolus through the cell cycle. These results suggest that phosphorylation of MCM4 has several distinct and site-specific roles in the function of MCM during the mammalian cell cycle.

Amino Acid Sequence↗

PubMed2006

The detection of Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans in tooth, tongue and buccal mucosa plaques in children, using immunoslot blot assay (IBA).

The present study was to investigate the distribution of typical periodontpathic bacteria (Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans) in tooth, tongue and buccal mucosa plaques in 3 to 17 Year old children. Clinical parameters (Rates of df, d, DMF, and D; plaque and gingival index) for each subject were determined prior to the collection of each site plaque. Three periodontopathic bacteria on each site samples were detected using IBA. The frequency of three bacteria for tooth plaque was higher than that for tongue or buccal mucosa plaque. The frequency of Porphyromonas gingivalis and Prevotella intermedia in supragingival plaques was significantly higher than that of corresponding ones in tongue or buccal mucosa plaques. The three bacteria also occurred more frequently in subjects aged between 10 and 14 years. Periodontopathic bacteria may be enhanced in circumpubertal children.

Adolescent↗

PubMed2005

Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages.

o-Methoxyphenols such as eugenol and isoeugenol exhibit anti-oxidant and anti-inflammatory activities, but at higher concentrations act as oxidants and potent allergens. We recently demonstrated the eugenol dimer bis-eugenol to be an efficient inhibitor of lipopolysaccharide (LPS)-induced inflammatory cytokine expression in macrophages without cytotoxicity. This result suggested that dimer compound of o-methoxyphenols may possess anti-inflammatory activity. Thus, we further synthesized dehydrodiisoeugenol and alpha-diisoeugenol from isoeugenols, and investigated whether these dimers could inhibit LPS-stimulated nuclear factor kappa B (NF-kappaB) activation and cyclooxygenase (COX)-2 gene expression, both of which are closely involved in inflammation and mutagenesis. The expression of the COX-2 gene was strongly inhibited by dehydrodiisoeugenol in RAW264.7 murine macrophages stimulated with LPS. In contrast, isoeugenol and alpha-diisoeugenol did not inhibit it. Dehydrodiisoeugenol also significantly inhibited LPS-stimulated phosphorylation-dependent proteolysis of inhibitor kappaB-alpha and transcriptional activity of NF-kappaB in the cells. These findings suggest that dehydrodiisoeugenol acts as a potent anti-inflammatory agent.

Animals↗

PubMed2005

Interleukin-6 negatively regulates Porphyromonas gingivalis fimbria-stimulated fibronectin expression in human gingival fibroblasts.

Our previous study demonstrated that fibronectin (FN) is a negative regulator of Porphyromonas gingivalis fimbria-induced pathogenesis in the initiation and development of chronic periodontal diseases. We show herein the regulatory action of interleukin-6 (IL-6) on FN expression in fimbria-treated human gingival fibroblasts. Interestingly, the decrease in FN expression in the cells treated with fimbriae at a high dose (8 microg of protein ml(-1)) was negated by treatment with anti-IL-6 antibody. Also, the increase in FN expression in cells treated with fimbriae at a low dose (1 microg of protein ml(-1)) was inhibited by exogenous IL-6. These results suggest that P. gingivalis fimbria-stimulated FN expression in human gingival fibroblasts is negatively regulated by endogenous IL-6.

Adult↗

PubMed2003

Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.

Achondroplasia is the most common genetic form of human dwarfism, for which there is presently no effective therapy. C-type natriuretic peptide (CNP) is a newly identified molecule that regulates endochondral bone growth through GC-B, a subtype of particulate guanylyl cyclase. Here we show that targeted overexpression of CNP in chondrocytes counteracts dwarfism in a mouse model of achondroplasia with activated fibroblast growth factor receptor 3 (FGFR-3) in the cartilage. CNP prevented the shortening of achondroplastic bones by correcting the decreased extracellular matrix synthesis in the growth plate through inhibition of the MAPK pathway of FGF signaling. CNP had no effect on the STAT-1 pathway of FGF signaling that mediates the decreased proliferation and the delayed differentiation of achondroplastic chondrocytes. These results demonstrate that activation of the CNP-GC-B system in endochondral bone formation constitutes a new therapeutic strategy for human achondroplasia.

Achondroplasia↗

PubMed2003

Preventive effect of bis-eugenol, a eugenol ortho dimer, on lipopolysaccharide-stimulated nuclear factor kappa B activation and inflammatory cytokine expression in macrophages.

Eugenol exhibits antioxidant and anti-inflammatory activities, but at higher concentrations acts as an oxidant and potent allergen. It was earlier shown that bis-eugenol synthesized by the oxidation of eugenol was less cytotoxic and more highly antioxidative than eugenol. But its anti-inflammatory mechanism remains yet unclear. Since nuclear factor-kappa B (NF-kappa B) is a key transcriptional factor in the expression of inflammatory cytokines, we examined whether eugenol and bis-eugenol are inhibitors of NF-kappa B activation. We observed that bis-eugenol, but not eugenol, clearly inhibited the degradation of inhibitory kappa B-alpha in RAW264.7 murine macrophages stimulated with lipopolysaccharide and, consequently, the transcriptional activity of the stimulated NF-kappa B in the cells. In addition, bis-eugenol actually inhibited LPS-stimulated expression of inflammatory cytokines at both gene and protein levels. These findings suggest that bis-eugenol acts as a potent inhibitor of NF-kappa B.

Animals↗

PubMed2002

First systematic band-filling control in organic conductors.

The systematic study of band-filling control for four kinds of organic conductors with various kinds of ground states has succeeded. (1) By partial substitution of (GaCl(4))(-) by (MCl(4))(2-) [M = Co, Zn] in the anion blocking layer of lambda-ET(2)(GaCl(4))(-) [ET = bis(ethylenedithio)tetrathiafulvalene], single crystals of lambda-ET(2)(GaCl(4))(-)(1-x)(MCl(4))(2-)(x) [x = 0.0, 0.05, 0.06] have been obtained. The resistivity at room temperature decreases from 3 Omega cm (x = 0.0) to 0.1 Omega cm (x = 0.06) by doping to the antiferromagnet with an effective half-filled band (x = 0.0). (2) Another 2:1 (donor/anion) salt, delta'-ET(2)(GaCl(4))(-), which is a spin gap material, has been doped as delta'-ET(2)(GaCl(4))(-)(1-x)(MCl(4))(2-)(x) [x = 0.05, 0.14]. The resistivity is lowered from 10 Omega cm (x = 0.0) to 0.3 Omega cm (x = 0.14). For both 2:1 salts, the semiconducting behaviors have transferred to relatively conductive semiconducting ones by doping. (3) As for alpha-type 3:1 salts, the parent material is in a charge-ordering state such as alpha-(ET(+)ET(+)ET(0))(CoCl(4))(2-)(TCE), where the charge-ordered donors are dispersed in the two-dimensional conducting layer. Although the calculation of alpha-ET(3)(CoCl(4))(2-)(TCE) shows a band-insulating nature, and the crystal structure analysis indicates that this material is in a charge-ordering state, the metallic behavior down to 165 K has been observed. With doping of (GaCl(4))(-) to the alpha-system, isostructural alpha-ET(3)(CoCl(4))(2-)(1-x)(GaCl(4))(-)(x)(TCE) [x = 0.54, 0.57, 0.62] have been afforded, where the pattern of the horizontal stripe-type charge ordering changes with an increase of x. (4) By doping (GaCl(4))(-) to the 3:2 gapless band insulator which is isostructural to beta'-ET(3)(MCl(4))(2)(2-) [M = Zn, Mn], the obtained beta'-ET(3)(CoCl(4))(2-)(2-x)(GaCl(4))(-)(x) [x = 0.66, 0.88] shows metallic behavior down to 100 and 140 K, respectively. They are the first metallic states in organic conductors by band-filling control of the gapless band insulator. These systematic studies of band-filling control suggest that the doping to the gapless band insulator with a pseudo-1/2-filled band is most effective.

Journal Article↗

PubMed2002

Frequency of reactivity for Porphyromonas gingivalis and Prevotella spp. in supra- and subgingival plaques, and periodontal clinical parameters according to subject age.

BACKGROUND: The present study was conducted to assess the association between selected clinical parameters and the distribution of Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Prevotella nigrescens (Pn), and Prevotella melaninogenica (Pm) in supra- and subgingival plaque samples measured by an immunoslot blot assay (IBA) using their monoclonal antibodies. METHODS: Plaque samples from 299 patients aged 6 to 69 randomly chosen from a group of dental outpatients were examined. Plaque index, gingival index, and probing depths were evaluated according to the criteria of positive (cell number > or = 10(6)) or negative (<106) reactivity to the 4 different monoclonal antibodies. RESULTS: An increase in probing depth in subjects exhibiting either a positive or negative reaction for the 4 test bacteria was associated with increasing age. Comparing bacteria-positive subgingival plaque samples to their corresponding bacteria-negative counterparts, we found an increased plaque index in children positive for any of the 4 bacteria; in addition, that for Pg and Pi was increased in subjects 40 to 49 years old. The gingival index increased with increasing amount of Pi and Pn, but not with Pg and Pm in those 20 to 29 years of age. The frequency of Pg reactivity in subgingival plaque was markedly enhanced in subjects older than 30 to 39 years of age, and was significantly higher than that in supragingival plaque. The frequency of Pi and Pn reactivity was significantly increased in adults aged 20 to 29 and plateaued at older ages. The frequency of Pm reactivity was relatively low and independent of subject age. CONCLUSIONS: The increase in probing depth with increasing age was not affected by the occurrence of periodontopathic bacteria. The high rate of occurrence of Pg, together with Pi and Pn, in subgingival plaque of the adult age groups was suggested to be associated with the high frequency of periodontal disease in the older age groups (above 30 to 49 years of age). The IBA appears to be useful for the efficient and rapid detection of periodontopathic bacteria.

Adolescent↗

PubMed1999

Architecture and dynamics of the primate prefrontal cortical circuit for spatial working memory.

In the experimental protocol of working memory tasks using a monkey as a subject, tuned activity of the prefrontal cortical neurons that is sustained during the delay period is a neuronal substrate of the working memory. This study addresses the question as to how this tuned activity is formed and maintained in the prefrontal cortex by means of computer simulations of the dynamics of a model prefrontal cortical circuit. The model assumes that pyramidal cells receive two types of intracortical inhibition, "parallel" and "anti-parallel", in accordance with recent experimental findings. The parallel and anti-parallel refer to the relationship between the preferred directions of presynaptic interneurons and postsynaptic pyramidal cells. The following three factors are suggested to be crucial for the formation and maintenance of spatial working memory: cortical amplification of the activity due to excitatory closed-loop circuitry, suppression of excessive excitation by the parallel inhibition, and sharpening of the activity profile by the anti-parallel inhibition.

Journal Article↗

PubMedDate not supplied

Dopamine controls fundamental cognitive operations of multi-target spatial working memory.

This study addresses computationally how the prefrontal cortical circuit performs operations of multiple items in spatial working memory. The basic idea is that dopamine controls the circuit dynamics for the operations by changing the ratio of the NMDA-channel transmission to the AMPA-channel transmission. There is evidence that this ratio is a function of dopamine D1 receptor activation. The simulation shows that the model circuit performs several different operations of multi-target spatial working memory depending on this ratio. When the ratio is low, 'replacement' occurs from the previously loaded target to a new one. In intermediate levels of the ratio, a new target is 'added' to the previously loaded target, resulting in the coexistence of more than one target. For higher ratios, the circuit 'rejects' other succeedingly received target stimuli. This study suggests four important issues: First, the cortical circuit can perform operations of multi-target spatial working memory. Second, the circuit can switch the modes of the operations by changing the NMDA-to-AMPA ratio. Third, dopamine would have major roles in the operations of multi-target spatial working memory. Fourth, the intracortical inhibition (especially of the cross-directional) plays an important role in regulating the competition between targets.

Animals↗

PubMedDate not supplied

The detection of Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans in the supragingival plaque of children with and without caries.

PURPOSE: The present study was undertaken to determine the presence of 3 periodontopathic bacteria in the supragingival plaques of 3- to 16-year-old children with different oral health conditions. METHODS: DMFT and dft, PMA index (P=papillary gingivitis, M=marginal gingivitis, and A=attached gingivitis), OHI (oral hygiene index), and oral malodor of each subject were determined prior to the collection of supragingival plaques. Periodontopathic bacteria (P. gingivalis, P. intermedia, and A. actinomycetemcomitans) in supragingival plaques were detected using an immunoslot blot assay with monoclonal 3 periodontopathic bacteria in the 2 subject groups (children with and without caries). P. gingivalis-positive subjects, but not their P. intermedia or A. actinomycetemcomitans counterparts, were correlated to oral malodor. Oral malodor was also correlated to debris index, a component of OHI. RESULTS: The group with the higher OHI showed a higher prevalence of periodontopathic bacteria. For the 3 periodontopathic bacteria in the subjects tested, P. gingivalis-, P. intermedia-, and A. actinomycetemcomitans-positive plaques were not age related. CONCLUSIONS: The supragingival plaques in children can harbor periodontopathic bacteria such as P. gingivalis, P. intermedia, and A. actinomycetemcomitans.

Adolescent↗

PubMedDate not supplied

Preventive effect of ortho dimer of butylated hydroxyanisole on activator protein-1 activation and cyclooxygenase-2 expression in macrophages stimulated by fimbriae of Porphyromonas gingivalis, an oral anaerobe.

Butylated hydroxyanisole (BHA; a mixture of 2- and 3-BHA) is widely used as a potent antioxidant, but is reported to have adverse effects, such as carcinogenesis and pro-inflammatory activity, possibly due to the pro-oxidant property of this compound. 2-Methoxyphenol dimers derived from ferulic acid were recently demonstrated to inhibit the expression of lipopolysaccharide-stimulated cyclooxygenase-2 (COX-2) via redox-sensitive transcription factors such as nuclear factor kappa B or activator protein-1 (AP-1), due to a weakening of its pro-oxidant property by dimerization. To develop anti-inflammatory and/or anticancer drugs for the prevention of oral diseases, such as leukoplakia and destructive chronic periodontitis, whether 2-BHA (2-tert-butyl-4-methoxyphenol) and its synthetic ortho dimer, bis-BHA (3,3'-di-tert-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol) can inhibit AP-1 transcriptional activity stimulated by Porphyromonas gingivalis fimbriae was examined. The fimbria-stimulated AP-1 activation of RAW 264.7 murine macrophages was markedly inhibited by bis-BHA. However, BHA showed slight inhibition. Furthermore, bis-BHA significantly inhibited fimbria-induced COX-2 gene expression, which is closely involved with inflammation and carcinogenesis. These findings suggest that bis-BHA may possess a potent anti-inflammatory effect against oral diseases.

Animals↗