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Biomedical subjects

T Koga

Publications and source records attributed to T Koga.

At least 109 records · Page 6Linked to original sources

The role of vascular endothelial growth factor in human dental pulp cells: induction of chemotaxis, proliferation, and differentiation and activation of the AP-1-dependent signaling pathway.

Vascular endothelial growth factor (VEGF) is a potent mitogen in endothelial cells, but little is known about its activity in other cell types. To clarify the role of VEGF in human dental pulp cells and pulp tissue, we investigated the effects of VEGF on the chemotaxis, proliferation, and differentiation of human dental pulp cells. VEGF induced a strong chemotactic response in human dental pulp cells in a dose-dependent manner. VEGF also marginally enhanced the proliferation of human dental pulp cells and induced an increase in alkaline phosphatase in human dental pulp cells. However, these effects of VEGF were not observed in reference to human skin fibroblasts. Analyses by the reverse-transcription/polymerase-chain-reaction method and flow cytometry showed that the mRNAs of two VEGF receptors, fins-like tyrosine kinase and kinase insert domain-containing receptor, were expressed in human dental pulp cells, whereas only fms-like tyrosine kinase mRNA was expressed in human skin fibroblasts. VEGF induced the activation of activator protein 1 (AP-1) and c-fos mRNA expression in human dental pulp cells. The AP-1 inhibitor curcumin strongly inhibited VEGF-induced alkaline phosphatase production in human dental pulp cells. In addition, VEGF antisense oligonucleotide suppressed the production of VEGF and alkaline phosphatase in human dental pulp cells. These results suggest that VEGF produced by human dental pulp cells acts directly upon human dental pulp cells in an autocrine manner, and may promote the chemotaxis, proliferation, and/or differentiation of human dental pulp cells via the utilization of kinase insert domain-containing receptor and in part through AP-1 by increasing c-fos.

Alkaline Phosphatase↗

Catalytic properties for naphthoquinones and partial primary structure of rabbit heart acetohexamide reductase.

The catalytic properties of rabbit heart acetohexamide reductase (RHAR) for naphthoquinones were examined. RHAR efficiently reduced 1,4-naphthoquinone and juglone (5-hydroxy-1,4-naphthoquinone), whereas it had little or no ability to reduce menadione (2-methyl-1,4-naphthoquinone) or plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone). The structural requirements for these four naphthoquinones and one acetohexamide analog, and the kinetic mechanism for the inhibition of acetohexamide reduction by juglone led us to conclude that the 2-methyl group of menadione and plumbagin prevents access of the substrates to the catalytic site of RHAR. Five of six peptides derived from RHAR showed 30-42% residue identities with regions in the amino acid sequence of mouse lung carbonyl reductase (MLCR) belonging to the short-chain dehydrogenase/reductase (SDR) family. The catalytically important residues (Arg-39, Ser-136, Tyr-149 and Lys-153) of MLCR were found in the peptide sequences of RHAR, despite the low residue identities between the two enzymes. RHAR is probably best classified as a member of the SDR family similar to MLCR.

Acetohexamide↗

Residential randon exposure and lung cancer risk in Misasa, Japan: a case-control study.

In order to investigate an association between residential radon exposure and risk of lung cancer, a case-control study was conducted in Misasa Town, Tottori Prefecture, Japan. The case series consisted of 28 people who had died of lung cancer in the years 1976-96 and 36 controls chosen randomly from the residents in 1976, matched by sex and year of birth. Individual residential radon concentrations were measured for 1 year with alpha track detectors. The average radon concentration was 46 Bq/m3 for cases and 51 Bq/m3 for controls. Compared to the level of 24 or less Bq/m3, the adjusted odds ratios of lung cancer associated with radon levels of 25-49, 50-99 and 100 or more Bq/m3, were 1.13 (95% confidence interval; 0.29-4.40), 1.23 (0.16-9.39) and 0.25 (0.03-2.33), respectively. None of the estimates showed statistical significance, due to small sample size. When the subjects were limited to only include residents of more than 30 years, the estimates did not change substantially. This study did not find that the risk pattern of lung cancer, possibly associated with residential radon exposure, in Misasa Town differed from patterns observed in other countries.

Adult↗

Measurements of Rn-222, Rn-220 and their decay products in the environmental air of the high background radiation areas in Yangjiang, China.

For the renewal of dose estimation from internal irradiation in the high background radiation areas (HBRA) of Yangjiang, the measurements of radon, thoron and their decay products in the environmental air were conducted, including: (1) integrating measurements of Rn-222 and Rn-220 concentrations; (2) eqilibrium factor F for Rn-222 and alpha-potential energy value of Rn-220; (3) external gamma radiation in places where radon measurements were undertaken; (4) cumulative exposure to indoor radon for each family in a case-control study on lung cancer. The Rn-Tn cup monitor method was used for the integrating measurement of Rn-222 and Rn-220 concentration. An alpha track detector was used for the integration measurement of Rn-222 concentration in the case-control study on lung cancer. The results of measurements show that although the investigated areas are located between the Equator and the Tropic of Cancer, and that people live in well-ventilated dwellings, the concentrations of radon, especially of Rn-220 are significantly higher in the indoor air of HBRA than those in the control area. The value of equilibrium factors for Rn-222, the alpha potential energy of decay products from Rn-222 and Rn-220 are determined.

Air↗

Dose measurement, its distribution and individual external dose assessments of inhabitants in the high background radiation areas in China.

As a part of the China-Japan cooperative research on natural radiation epidemiology, we have carried out a dose-assessment study to evaluate the external exposure to natural radiation in the high background radiation areas (HBRA) of Yangjiang in Guangdong province and in the control areas (CA) of Enping prefecture since 1991. Because of the difficulties in measuring the individual doses of all inhabitants directly by personal dosimeters, an indirect method was applied in which the exposed individual doses were estimated from the environmental radiation doses measured by survey meters and the occupancy factors of each hamlet. We analyzed the dose in the hamlets and the variation in the occupancy factors to obtain the parameters of dose estimation on the inhabitants in selected hamlets; Madi and several hamlets of different dose levels in HBRA and Hampizai hamlet in CA. With these parameters, we estimated individual dose rates and compared them with those obtained from direct measurement using dosimeters carried by selected individuals. The results obtained are as follows. 1) The environmental radiation doses are influenced by the natural radioactive nuclide concentrations in building materials, the age of the building and the arrangement of the houses in a hamlet. There existed a fairly large and heterogeneous distribution of indoor and outdoor environmental radiations. The indoor radiation doses were due to exposure from the natural radioactive nuclides in the building materials and were about two times as large as the outdoor radiation doses. The difference between indoor and outdoor doses was not observed in CA. 2) The occupancy factor was influenced by the age of individuals and by the season of the year. The occupancy factor was higher for infants and aged individuals than for other age groups. This lead to higher dose rates of exposure to those age groups. 3) A good correlation was observed between the dose assessed indirectly and that measured directly and the correlation factor was 0.97.

Background Radiation↗

Enzymatic synthesis of stable, odorless, and powdered furanone glucosides by sucrose phosphorylase.

Sucrose phosphorylase from Leuconostoc mesenteroides catalyzed transglucosylation from sucrose to 4-hydroxy-3(2H)-furanone derivatives. When 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) and 2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone or 5-ethyl-4-hydroxy-2-methyl-3(2H)-furanone (EHMF) were used as acceptors, their transfer ratios were more than 45%. In the case of glucosylation of HDMF, the major transfer product was identified as 2,5-dimethyl-3(2H)-furanone 4-O-alpha-D-glucopyranoside (DMF-G). In the case of glucosylation of EHMF, two major transfer products were obtained, and their structures were identified as 2-ethyl-5-methyl-3(2H)-furanone 4-O-alpha-D-glucopyranoside (2E5MF-G) and 5-ethyl-2-methyl-3(2H)-furanone 4-O-alpha-D-glucopyranoside (5E2MF-G) on the bases of spectrometric investigations. These glucosides were more stable than each aglycone. The glucosylated HDMF, DMF-G, was an odorless chemical, on the other hand, HDMF had a pineapple flavor. The glucosylated EHMF (EMF-G) were white odorless powders, though aglycone EHMF was a pale yellow syrup like a caramel with an intense sweet odor. Although DMF-G and EMF-G showed little radical-scavenging activity, hydrolyzates of these glucosides by an intestinal acetone powder from pigs had antioxidative activity as well as their aglycones. It was suggested that these glucosides improved some physical properties and may become prodrugs by glucosylation.

Antioxidants↗

Time-Resolved fluorescence studies on the internal motion of chlorophyll a of light-harvesting chlorophyll a/b-protein complex in lipid membranes.

By analyzing the steady state and time-resolved fluorescence anisotropy, the internal motions of chlorophyll a of light-harvesting chlorophyll a/b-protein complex (LHCII) were characterized in a dimyristoylphosphatidylcholine (DMPC) liposome. Corresponding to the thermotropic phase of the membrane, chlorophyll a showed an unique internal motion in LHCII. At the gel phase, two motional components, one fast and the other slow, were observed, which would originate in the heterogeneity of the mutual orientation and the binding site of the chlorophyll a in LHCII. Interestingly, the faster motion was suppressed and only the slower segmental rotation with the larger motional amplitude was allowed on the phase transition to a liquid crystalline phase.

Animals↗

Induction of experimental periodontitis in mice with Porphyromonas gingivalis-adhered ligatures.

BACKGROUND: Little information is available on the colonization of periodontopathic bacteria and alveolar bone loss in a mouse system, because of the difficulty in establishing bacteria in the oral cavity. The aim of this study was to establish experimental periodontitis in mice by applying a Porphyromonas gingivalis-adhered ligature onto the molars. METHODS: Specific pathogen-free C3H/HeN mice were divided into 3 groups: 80 infected, 80 sham-infected, and 48 non-treated control mice. Sterile silk ligatures were preincubated with and without P. gingivalis 381 in vitro and then physically tied on the right maxillary first molar of infected and sham-infected mice, respectively. Ten mice from the infected and sham-infected groups and 6 from the control group were sacrificed at 2-week intervals for up to 15 weeks after infection. RESULTS: Plaque samples were collected at the time of sacrifice and alveolar bone loss was examined. The results indicated that P. gingivalis was recovered from the plaque samples in 95% of the infected mice after 1 week and then gradually dropped to 58% after 15 weeks of infection, whereas P. gingivalis was not isolated in either sham-infected or control mice throughout the experimental period. The infected mice showed significant P. gingivalis-induced bone loss at the sites where the ligature was tied weeks 13 to 15. A linear regression analysis revealed a significant positive correlation between the number of P. gingivalis recovered and alveolar bone loss at 15 weeks after infection (P <0.01). CONCLUSIONS: The use of a P. gingivalis-adhered ligature supported a long-lasting infection of P. gingivalis in mice, resulting in P. gingivalis-induced alveolar bone breakdown.

Alveolar Bone Loss↗

Good's syndrome presenting with cytomegalovirus pneumonia.

A 61-year-old woman who had undergone an operation for thymoma 17 years previously suddenly became dyspneic and showed bilateral pulmonary infiltrates on a chest radiograph. In the bronchoalveolar lavage fluid cells contained characteristic cytomegalic inclusion bodies, as well as cytomegalovirus DNA demonstrated by a polymerase chain reaction. Immunological findings included hypogammaglobulinemia, deficient numbers of circulating B cells, and impaired blast transformation of peripheral blood T cells in response to mitogens in vitro. Considering all of the findings, the patient was diagnosed with Good's syndrome presenting with cytomegalovirus pneumonia.

Agammaglobulinemia↗

Structural and immunochemical homologies between foxtail millet glutelin 60 kDa and starch granule-bound starch synthase proteins from rice, barley, corn and wheat grains.

Foxtail millet glutelin 60 kDa (MG60) was purified by preparative SDS-PAGE, and the N-terminal amino acid sequence was determined within 20 residues. The result demonstrated that the primary structure at N-terminal of MG60 was almost identical to those of the granule-bound starch synthase (GBSS) proteins from rice, barley, corn, wheat and potato. The existence of common epitopes among MG60 and GBSS proteins from these starch-storing cereals were corroborated by immunoblot analysis using antisera raised against MG60. These facts strongly suggest a close relationship between MG60-like glutelins and GBSS proteins.

Amino Acid Sequence↗

Efficient extraction and some properties of storage proteins (prolamin and glutelin) in ancient rice cultivars.

Two typical storage proteins (prolamin and glutelin) in a total of 14 samples of ancient rice cultivars were examined for their accumulation in the endosperms during days after flowering (DAF), extraction efficiency with various solvents, and variations in polypeptide components or amino acid compositions. There was little difference in accumulation profiles between this and previous observations, in which glutelin appeared on 5-7 DAF and prolamin on 7-9 DAF. As for the extraction of prolamin and glutelin, it was most effectively attained by sequential usage of 55% propanol and 21% SDS. As a result of SDS-PAGE, prolamin and glutelin proved to be composed mainly of a single polypeptide with a molecular weight (MW) of 15 kDa and two subunits with MWs of 21 kDa (alpha) and 32 kDa (beta), respectively. A comparison between the ancient and modern rice cultivars revealed the same physicochemical properties in either case of prolamin or glutelin. Additionally, a good relationship was observed on the total protein and glutelin (but not prolamin) contents in the ancient rice cultivar.

Electrophoresis, Polyacrylamide Gel↗

Structural and functional properties of apolipoprotein A-I mutants.

Apolipoprotein (apo) A-I is composed of 243 amino acid residues that fold into amphipathic helixes, and plays a central role in the high density lipoprotein (HDL) metabolism. Familial apoA-I deficiency is a rare metabolic disorder of which three cases have been characterized at a molecular level in western Japan. However, in subjects with apoA-I deficiency, coronary artery disease was not always present. One apo A-I deficiency was compound heterozygous apoA-I mutant for a TATA box mutation and a structural nonsense mutation. To date, screening analysis in our laboratory has identified nine genetically-determined structural mutations of apo A-I. We have also characterized these apo A-I mutations, including apoA-I (Glu235del) Nichinan. Few structural mutations were associated with altered HDL cholesterol levels.

Apolipoprotein A-I↗

Clinicopathological features and overexpression of matrix metalloproteinases in intramucosal gastric carcinoma with lymph node metastasis.

Endoscopic mucosal resection, which has been widely accepted for the treatment of intramucosal gastric carcinoma (IMGC) because of the minimal invasiveness of the procedure and the sustained quality of life it provides, can only be used on the premise that the carcinoma has no lymph node metastasis. We evaluated the clinicopathological and biological features of IMGC with lymph node metastases in relation to matrix metalloproteinase (MMP) expression. Fifteen cases of lymph node metastasis-positive [n(+)] IMGC and 59 cases of lymph node metastatic-negative [n(-)] IMGC were obtained. The expression of MMP-2 and MMP-9 was investigated with immunohistochemical methods. Clinicopathologically, n(+)-IMGCs were more likely to be of a larger size, to be of poorly differentiated adenocarcinoma, to have had lymphatic permeation [ly(+)], and to have ulcerations within the lesion compared to n(-)-IMGCs. The incidence of the positive expression of MMP-9 in n(+)-IMGCs (67%) or ly(+)-IMGCs (86%) was significantly higher than that in n(-)-IMGCs (32%) or ly(-)-IMGCs (34%). Even in IMGCs, carcinoma cells may produce MMPs that can degrade the basement membrane, allowing them to permeate the lymph capillary. Ulcerations within the lesion may also facilitate the interchange of lymphatic flow between the mucosa and the submucosa, promoting the development of lymph node metastases.

Carcinoma↗

Late onset systemic lupus erythematosus with lichen planus-like eruption and cardiac tamponade.

A 71-year-old Japanese woman is reported as a case of late onset systemic lupus erythematosus (SLE) with lichen planus (LP)-like eruption and cardiac tamponade. As an initial symptom, our patient had cutaneous lesions clinically and histologically resembling LP, and then the passage of time allowed for the development of additional criteria (lymphopenia, pericarditis) until the diagnosis of SLE could be made. Our case suggests that LP-like eruptions may be one of the unusual variations of late onset SLE and elderly patients with LP-like eruptions should be carefully followed until a final diagnosis can be clearly made.

Age Factors↗

Application of quantitative RT-PCR using "TaqMan" technology to evaluate the expression of CK 18 mRNA in various cell lines.

Reverse transcriptase polymerase chain reaction (RT-PCR) is often used for sensitive detection of micrometastasis in peripheral blood, lymph nodes and bone marrow. While the utility of this method has been documented, it also has limitations in the detection of micrometastasis. The mRNA of target genes can be detected in healthy donors or in samples used for negative control, therefore the non-quantitativeness of conventional RT-PCR has been called into question. We analyzed the expression level of cytokeratin (CK) 18 mRNA in established esophageal and gastrointestinal carcinoma cell lines and non-epithelial cells, using quantitative RT-PCR, based on real time 'TaqMan TM' technology. CK 18 mRNA is more highly expressed in carcinoma cells than in non-epithelial cells. However, the expression level in non-epithelial cells was easily detected using conventional RT-PCR and agarose gel electrophoresis. In an analysis of CK 18 mRNA expression in peripheral venous blood in 13 healthy volunteers, we found that CK 18 mRNA was much less expressed than in cancer cell lines. However, the expression in all samples was at a level which was also detected using conventional RT-PCR. It would thus seem that not only qualitative, but also quantitative analysis, of the target mRNA is important to detect micrometastasis. Quantitative RT-PCR methods will make comparisons of the possible differences in expression levels of the target gene. For clinical applications, much further study is needed.

Adult↗

Genetic analysis of the gene cluster responsible for synthesis of serotype e-specific polysaccharide antigen in Actinobacillus actinomycetemcomitans.

A gene cluster associated with the biosynthesis of the serotype e-specific polysaccharide antigen (SPA) of Actinobacillus actinomycetemcomitans IDH1705 belonging to serotype e was cloned and sequenced. This cluster consisted of 18 open reading frames. Escherichia coli produced the polysaccharide that reacts with the serotype e-specific antiserum when transformed with a plasmid containing the cluster. Comparing the structure of the gene cluster with similar clusters from A. actinomycetemcomitans strains Y4 (serotype b) and NCTC9710 (serotype c) revealed that a 5.3-kb region containing the distal half of one gene and two entire genes in the cluster from strain IDH1705 replaced a 6.2-kb region containing eight genes in the cluster from strain Y4, and a 4.7-kb region containing four genes in the cluster from strain NCTC9710. These results suggest that this region is essential to the antigenic specificity of serotype e A. actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans↗

Effects of Helical Sense and Macrodipole on Helix Interaction in Poly(glutamic acid) Monolayers at the Air-Water Interface.

The effect of the helical sense and the helical macrodipole moment of poly(glutamic acid) (PGA) amphiphiles on miscibility in their binary surface monolayers was examined by means of the surface pressure-area isotherm and spectroscopic measurements. Four types of PGA amphiphiles, having different chirality (l or d) and two long alkyl chains at the C- or N-terminus (1 or 2), were successfully prepared by polymerization of the corresponding NCAs. In acidic solutions, these amphiphiles were found to take right-handed or left-handed helical conformation, depending upon the chirality of the glutamic acid unit, and are dispersed in water molecularly without aggregation. On the other hand, the binary mixed monolayer of 1L and 1D provided a marked positive deviation from an ideal mixing curve, while that of the combination of 1L and 2L gave a much smaller negative deviation, suggesting that helical sense would play a more important role in monolayer miscibility. Copyright 1999 Academic Press.

Journal Article↗