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K Wakabayashi

Publications and source records attributed to K Wakabayashi.

At least 37 records · Page 2Linked to original sources
PubMed2003

A preliminary report on a computer-assisted dental cast analysis system used for the prosthodontic treatment.

To accomplish computerized 3D morphological analyses of maxillary and mandibular casts with malocclusions on the same co-ordinate system, a new reference co-ordinate located on soft tissue has been proposed consisting of the top of maxillary bilateral tubercles and incisive papilla on the maxillary cast. To test the validity of this co-ordinate system, the angles of the occlusal plane in this system were examined on 10 subjects with normal occlusion. In addition, to analyse maxillary and mandibular casts on the same co-ordinate system, a bite block was made under the intercuspal position. The maxillary cast was measured by 3D measuring system, then, the bite block was placed on maxillary casts, and measured similarly. To examine the position reproducibility of this method, 3D co-ordinates of the apex of the buccal cusp of the mandibular pre-molar in five bite blocks were determined. The angles formed of the occlusal plane were 1.3 +/- 1.3 degrees and 0.2 +/- 1.1 degrees on the sagittal and frontal base plane, respectively. This co-ordinate system had enough stability to replace the occlusal plane. By the measurement of bite blocks, the co-ordinates of the mandibular cusp tips were determined within the deviation of 0.2 mm.

Dental Casting Technique↗
PubMed2003

A COX-2 inhibitor, nimesulide, inhibits chemically-induced rat tongue carcinogenesis through suppression of cell proliferation activity and COX-2 and iNOS expression.

The modifying effects of a cyclooxygenase (cox)-2 selective inhibitor nimesulide on tongue carcinogenesis were investigated in male F344 rats initiated with 4-nitroquinoline-1-oxide (4-NQO). The cell proliferation activity measured by proliferating cell nuclear antigen (PCNA)-positive index and apoptotic index, and the immunohistochemical expression of COX-2, and inducible nitric oxide synthase (iNOS) in the tongue mucosa or neoplasms were also examined for mechanistic analysis of modifying effects of nimesulide on tongue carcinogenesis. All animals except those treated with nimesulide alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 1 week after the cessation of 4-NQO exposure, rats given 4-NQO were fed the experimental diets containing nimesulide (100 and 400 ppm) for 22 weeks. At week 32, the incidence of tongue squamous cell carcinoma was significantly reduced by feeding of the diet containing 400 ppm nimesulide. Feeding of nimesulide significantly decreased polyamine content and PCNA-labeling index in tongue carcinoma. Apoptotic index in tongue carcinoma was increased by feeding of nimesulide. In addition, nimesulide feeding reduced COX-2 and iNOS expression in the tongue dysplasia and neoplasms. These results suggest that 400 ppm nimesulide in diet, when given during the promotion phase, exerts chemopreventive ability against 4-NQO-induced tongue tumorigenesis through inhibition of cell proliferation activity in conjunction with modification of COX-2 and iNOS expression of the target lesions.

4-Nitroquinoline-1-oxide↗
PubMed2002

Office of Rare Diseases neuropathologic criteria for corticobasal degeneration.

A working group supported by the Office of Rare Diseases of the National Institutes of Health formulated neuropathologic criteria for corticobasal degeneration (CBD) that were subsequently validated by an independent group of neuropathologists. The criteria do not require a specific clinical phenotype, since CBD can have diverse clinical presentations, such as progressive asymmetrical rigidity and apraxia, progressive aphasia, or frontal lobe dementia. Cortical atrophy, ballooned neurons, and degeneration of the substantia nigra have been emphasized in previous descriptions and are present in CBD, but the present criteria emphasize tau-immunoreactive lesions in neurons, glia, and cell processes in the neuropathologic diagnosis of CBD. The minimal pathologic features for CBD are cortical and striatal tau-positive neuronal and glial lesions, especially astrocytic plaques and thread-like lesions in both white matter and gray matter, along with neuronal loss in focal cortical regions and in the substantia nigra. The methods required to make this diagnosis include histologic stains to assess neuronal loss, spongiosis and ballooned neurons, and a method to detect tau-positive neuronal and glial lesions. Use of either the Gallyas silver staining method or immunostains with sensitive tau antibodies is acceptable. In cases where ballooned neurons are sparse or difficult to detect, immunostaining for phospho-neurofilament or alpha-B-crystallin may prove helpful. Methods to assess Alzheimer-type pathology and Lewy body pathology are necessary to rule out other causes of dementia and Parkinsonism. Using these criteria provides good differentiation of CBD from other tauopathies, except frontotemporal dementia and Parkinsonism linked to chromosome 17, where additional clinical or molecular genetic information is required to make an accurate diagnosis.

Atrophy↗
PubMed2002

Maternal and developmental toxicity in mice by aminophenylnorharman, formed from norharman and aniline.

9-(4'-Aminophenyl)-9H-pyrido [3,4-b] indole (aminophenylnorharman, APNH) is a novel mutagenic heterocyclic amine, produced by the reaction of norharman with aniline in the presence of S9 mix. In the present study, the maternal and developmental toxicity of APNH were investigated in ICR mice administered oral doses of 0, 0.625, 1.25, 2.5 or 5 mg/kg/day on gestational days (GD) 6 through 15 or 0, 5, 10, or 20 mg/kg on GD 12. Maternal and foetal parameters were evaluated on day 18 of gestation. Foetuses of dams treated on GD 6-15 were examined for external and skeletal malformations and variations, and foetuses of dams treated on GD 12 were inspected for cleft palate. Maternal death occurred when APNH was administered at 5 mg/kg/day on GD 6-15. No significant decrease in body weight gain during the administration period was observed at doses of 2.5 mg/kg/day or less when applied on GD 6-15. Adverse changes in general condition of dams were observed in the groups treated at doses of 2.5 mg/kg/day and above on GD 6-15, whereas no adverse effects on dams were noted even when APNH was applied at a fairly high dose on GD 12. Intracytoplasmic vacuolation in hepatocytes, necrosis of proximal tubular epithelial cells and desquamation of necrotic epithelial cells in the tubular lumen were observed in dams treated with APNH at 2.5 or 5 mg/kg/day on GD 6-15. Increased preimplantation loss was observed at 5 mg/kg/day and post-implantation loss was observed at 2.5 mg/kg/day and above when applied on GD 6-15, or at 20 mg/kg when applied on GD 12. Foetal body weight was decreased by APNH in a dose-dependent manner. The frequency of external malformations (cleft palate) was significantly increased in the group treated with APNH at 2.5 mg/kg/ day on GD 6-15 compared to the controls. However, there were no foetuses with cleft palate even when APNH was given at 20 mg/kg on GD 12. No significant increases in skeletally malformed foetuses were found in any APNH-treated group. The frequency of lumbar ribs was increased dose dependently. This study demonstrated the developmental toxicity of a mutagenic compound, APNH, in mice at maternally toxic doses, and that cleft palate observed in term foetuses resulted from the adverse effect of APNH on the maternal environment during organogenesis. More detailed studies are warranted to assess the possible risks to pregnant women from exposure to APNH.

Aniline Compounds↗
PubMed2001

Interleukin-1beta stimulates galectin-9 expression in human astrocytes.

Galectin-9 is an eosinophil chemoattractant produced by activated T lymphocytes. We have addressed expression of galectin-9 in normal human astrocytes in culture. Expression of galectin-9 mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescent staining. Interleukin-1beta (IL-1beta) was found to enhance the galectin-9 expression in time- and concentration-dependent manners. Galectin-9 protein was detected in the membrane fraction, 105 000 x g precipitate, and immunofluorescent staining revealed diffuse cellular and perinuclear distributions. Dexamethasone pretreatment almost completely suppressed the production. We conclude that astrocytes produce galectin-9 in response to the stimulation with IL-1beta, and this may contribute to inflammatory reactions in the CNS.

Anti-Inflammatory Agents↗
PubMed2001

Synthesis of 2-phenylbenzotriazole-type mutagens, PBTA-5 and PBTA-6, and their detection in river water from Japan.

We previously determined the chemical structures of four 2-phenylbenzotriazole mutagens (PBTA-1, -2, -3 and -4) in blue rayon-adsorbed material from the Nishitakase River in Kyoto prefecture and the Nikko River in Aichi prefecture in Japan. On the basis of a synthesis study, these four PBTA derivatives were deduced to have originated from corresponding dinitrophenylazo dyes by reduction and chlorination. 2-[(2-Bromo-4,6-dinitrophenyl)azo]-5-[bis(2-acetoxyethyl) amino]-4-methoxyacetanilide (Color Index Name, Disperse Blue 79:1; CAS Registry Number, 75497-74-4) is a very common dinitrophenylazo dye used in textile dyeing factories. In the present study, we synthesized 2-[4-[bis(2-acetoxyethyl)amino]-2-(acetylamino)-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-5) from Disperse Blue 79:1 by reduction with sodium hydrosulfite and subsequent chlorination with sodium hypochlorite. On hydrolysis of PBTA-5 with alkali, 2-[2-(acetylamino)-4-[bis(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-6) was obtained. Both PBTA-5 and -6 were potent mutagens, inducing 723,000 revertants and 485,000 revertants per microgram of Salmonella typhimurium YG1024, respectively, in the presence of S9 mix. To clarify whether PBTA-5 and -6 exist in the environment, water samples were collected from five rivers flowing through regions where textile dyeing industries are developed. PBTA-6 was detected at levels of 3-134 ng/g blue rayon in all water samples that were examined. On the other hand, the amount of PBTA-5 in the samples was less than the detection limit.

Adsorption↗
PubMed2001

Mono(ADP-ribosyl)ation of 2'-deoxyguanosine residue in DNA by an apoptosis-inducing protein, pierisin-1, from cabbage butterfly.

Pierisin-1 is a potent apoptosis-inducing protein derived from the cabbage butterfly, Pieris rapae. It has been shown that pierisin-1 has an A small middle dotB structure-function organization like cholera or diphtheria toxin, where the "A" domain (N-terminal) exhibits ADP-ribosyltransferase activity. The present studies were designed to identify the target molecule for ADP-ribosylation by pierisin-1 in the presence of beta-[adenylate-(32)P]NAD, and we found DNA as the acceptor, but not protein as is the case with other bacteria-derived ADP-ribosylating toxins. ADP-ribosylation of tRNAs from yeast was also catalyzed by pierisin-1, but the efficiency was around 110 of that for calf thymus DNA. Pierisin-1 efficiently catalyzed the ADP-ribosylation of double-stranded DNA containing dG small middle dotdC, but not dA small middle dotdT pairs. The ADP-ribose moiety of NAD was transferred to the amino group at N(2) of 2'-deoxyguanosine to yield N(2)-(alpha-ADP-ribos-1-yl)-2'-deoxyguanosine and its beta form, which were determined by several spectral analyses including (1)H- and (13)C-NMR and mass spectrometry. The chemical structures were also ascertained by the independent synthesis of N(2)-(D-ribos-1-yl)-2'-deoxyguanosine, which is the characteristic moiety of ADP-ribosylated dG. Using the (32)P-postlabeling method, ADP-ribosylated dG could be detected in DNA from pierisin-1-treated HeLa cells, in which apoptosis was easily induced. Thus, the targets for ADP-ribosylation by pierisin-1 were concluded to be 2'-deoxyguanosine residues in DNA. This finding may open a new field regarding the biological significance of ADP-ribosylation.

ADP Ribose Transferases↗
PubMed2001

Expression of beta-synuclein in normal human astrocytes.

Although alpha- and beta-synucleins are expressed predominantly in presynaptic nerve terminals, recent studies have demonstrated that alpha-synuclein is also expressed in cultured astrocytes and oligodendrocytes. We determined whether beta-synuclein might be expressed in astrocytes. Beta-synuclein mRNA and protein were detected in normal human astrocytes in culture, and immunofluorescent staining showed that beta-synuclein protein was expressed within the cytoplasm and nucleus. Furthermore, beta-synuclein immunoreactivity was present in astrocytes, but not in oligodendrocytes, in normal human brain tissues. Ultrastructurally, beta-synuclein immunoreactivity was found in the cytoplasm of astrocytes, in association with the plasma membrane, ribosomes, rough endoplasmic reticulum and the nuclear outer membrane. The novel expression of beta-synuclein in astrocytes may provide an important insight about the role of this protein.

Astrocytes↗
PubMed2001

Testicular toxicity in F344 rats by aminophenylnorharman, formed from norharman and aniline.

9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole [aminophenylnorharman (APNH)] is a novel mutagenic heterocyclic amine, produced by the reaction of norharman with aniline in the presence of S9 mix. In the present study, the acute toxicity of this compound was investigated in male F344 rats. Ten-week-old animals were treated with a single intragastric injection of APNH at doses of 45 or 90 mg/kg body wt and euthanized 1, 3, or 6 days afterward. When APNH was administered at a dose of 90 mg/kg, vacuolation of Sertoli cells in the testis was seen at 1 day after treatment. The testicular damage had markedly progressed by day 6, with multinucleated giant cells and loss of round spermatids in the seminiferous tubules observed in groups 1 and 2 of the four histological categories of spermatogenesis. Numbers of spermatogonia were also decreased by APNH treatment. No toxic changes were observed in Leydig cells under these conditions and serum follicle-stimulating hormone and luteinizing hormone concentrations were also unchanged from control values. Such severe testicular damage was not observed at any time point at the 45 mg/kg dose level of APNH. Moreover, neither norharman nor aniline alone exerted acute testicular toxicity at doses equivalent to 90 mg/kg of APNH. In addition to the testicular lesions, erosive changes of urinary bladder, thymic atrophy, and panmyelophthisis were evident in rats given APNH at 90 mg/kg.

Administration, Oral↗
PubMed2001

Oxidative DNA damage by an N-hydroxy metabolite of the mutagenic compound formed from norharman and aniline.

Norharman (9H-pyrido[3,4-b]indole), which is a heterocyclic amine included in cigarette smoke or cooked foodstuffs, is not mutagenic itself. However, norharman reacts with non-mutagenic aniline to form mutagenic aminophenylnorharman (APNH), of which DNA adducts formation and hepatocarcinogenic potential are pointed out. We investigated whether N-OH-APNH, an N-hydroxy metabolite of APNH, can cause oxidative DNA damage or not, using 32P-labeled DNA fragments. N-OH-APNH caused Cu(II)-mediated DNA damage. When an endogenous reductant, beta-nicotinamide adenine dinucleotide (NADH) was added, the DNA damage was greatly enhanced. Catalase and a Cu(I)-specific chelator inhibited DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). Typical -*OH scavenger did not inhibit DNA damage. These results suggest that the main reactive species are probably copper-hydroperoxo complexes with DNA. We also measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation by N-OH-APNH in the presence of Cu(II), using an electrochemical detector coupled to a high-pressure liquid chromatograph. Addition of NADH greatly enhanced 8-oxodG formation. UV-VIS spectra and mass spectra suggested that N-OH-APNH was autoxidized to nitrosophenylnorharman (NO-PNH). We speculated that NO-PNH was reduced by NADH. Cu(II) facilitated the redox cycle. In the presence of NADH and Cu(II), very low concentrations of N-OH-APNH could induce DNA damage via redox reactions. We conclude that oxidative DNA damage, in addition to DNA adduct formation, may play an important role in the expression of genotoxicity of APNH.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Marked reduction of Helicobacter pylori-induced gastritis by urease inhibitors, acetohydroxamic acid and flurofamide, in Mongolian gerbils.

Urease has been suggested to be essential for colonization and pathogenesis of Helicobacter pylori infection. In the present study, we evaluated the effects of urease inhibitors [acetohydroxamic acid (AHA) and flurofamide (FFA)] on H. pylori-induced gastritis in Mongolian gerbils. Animals were orally inoculated with H. pylori, and given urease inhibitors in their diet throughout the experimental period of six weeks or four weeks, starting from two weeks after H. pylori inoculation. With the administration of AHA at doses of 100, 500, and 2500 ppm throughout the experimental period, H. pylori-induced gastritis in animals was decreased in a dose-dependent manner, significantly so at 2500 ppm. Suppression of gastric lesions was also evident in animals administered 2500 ppm AHA after the H. pylori infection. Bacterial infection rates were reduced to 40-50% of the control value of 100%, by the highest dose of AHA. The potent urease inhibitor, FFA, also caused marked amelioration of H. pylori-associated gastritis on administration at 100 ppm throughout the six-week experimental period or for four weeks after H. pylori infection. Animals treated with FFA had few visible gastric lesions, and the proportion infected with H. pylori was reduced to less than 10%. Since antibiotic-resistant strains of H. pylori have become a serious problem, nonantibiotic urease inhibitors may be very useful to control H. pylori-associated gastroduodenal disease.

Administration, Oral↗
PubMed2001

Expression of alpha-synuclein in a human glioma cell line and its up-regulation by interleukin-1beta.

Although alpha-synuclein is expressed primarily in neurons, it is a major component of oligodendroglial and astrocytic inclusions in several neurodegenerative diseases. Recent study has further demonstrated that alpha-synuclein is expressed in cultured rat oligodendrocytes. We determined whether alpha-synuclein might be expressed in astrocytic cells. alpha-Synuclein mRNA and protein were detected in U251 human astrocytic glioma cells and normal human astrocytes, and the levels were increased in the former, but not in the latter, by stimulation with interleukin-1beta in a time- and concentration-dependent manner. Serum deprivation also led to an increase of alpha-synuclein mRNA and protein in U251 cells. Immunofluorescent staining confirmed the cell-associated alpha-synuclein. These findings suggest that human astrocytes can produce alpha-synuclein in culture and that certain inflammatory cytokines and cell stress increase alpha-synuclein expression.

Astrocytes↗
PubMed2001

Chromosomal effects of newly identified water pollutants PBTA-1 and PBTA-2 and their possible mother compounds (azo dyes) and intermediates (non-ClPBTAs) in two Chinese hamster cell lines.

We performed the in vitro micronucleus (MN) test on 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[N-(2-cyanoethyl)-ethylamino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2), which are newly identified water pollutants from the Nishitakase river in Kyoto, Japan, and on their possible mother compounds (AZO DYE) and intermediates (non-ClPBTAs). We tested these compounds in the absence and presence of S9 mix in two Chinese hamster cell lines CHL and V79-MZ and scored MN, polynuclear and karyorrhectic (PN), and mitotic (M) cells. PBTA-2 in the absence of S9 mix induced the strongest responses in both cell lines. It was also a strong inducer of binucleate cells in PN cells in both cell lines, which suggested that it induced polyploidy. PBTA-1 showed clear positive results only in the absence of S9 mix and only in V79-MZ cells, inducing aneuploidy. In CHL cells AZO DYE-1 significantly induced MN cells in the presence of S9 mix, and AZO DYE-2 induced MN and PN cells, including binucleate cells and cells with a multilobed nucleus, in the absence of S9 mix. In V79-MZ cells, AZO DYE-1 and -2 induced primarily M cells in the presence of S9 mix. 9% of the M cells treated with 50 microg/ml AZO DYE-1 showed endoreduplication. AZO DYE-2 at 200 microg/ml condensed the chromatin in 100% of the cells. The non-ClPBTAs were a bit more cytotoxic than the other compounds and induced a slight increase in MN cells in both cell lines. Some of the chemicals tested induced a characteristic karyomorphology that might reflect abnormal cell division. Abnormalities of cell division could be detected in PN and M cells as well as in MN cells. Structure-activity relationships have also been discussed.

Animals↗
PubMed2001

Structures of mutagens produced by the co-mutagen norharman with o- and m-toluidine isomers.

Norharman, abundantly present in cigarette smoke and cooked foods, is not mutagenic to Salmonella typhimurium strains. However, norharman shows mutagenicity to S. typhimurium TA98 and YG1024 in the presence of S9 mix when coexisting with aromatic amines, including aniline, o- and m-toluidines. We previously reported that the mutagenicity from norharman and aniline in the presence of S9 mix was due to the formation of a mutagenic compound, 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorharman). In the present study, we analyzed the mutagens produced by norharman with o- or m-toluidine in the presence of S9 mix. When norharman and o-toluidine were reacted at 37 degrees C for 20 min, two mutagenic compounds, which were mutagenic with and without S9 mix, respectively, were produced, and these were isolated by HPLC. The former mutagen was deduced to be 9-(4'-amino-3'-methylphenyl)-9H-pyrido[3,4-b]indole (amino-3'-methylphenylnorharman) on the basis of various spectral data, and this new heterocyclic amine was confirmed by its chemical synthesis. The latter mutagen was identified to be the hydroxyamino derivative. Amino-3'-methylphenylnorharman induced 41,000 revertants of TA98, and 698,000 revertants of YG1024 per microg with S9 mix. Formation of the same DNA adducts was observed in YG1024 when amino-3'-methylphenylnorharman or a mixture of norharman plus o-toluidine was incubated with S9 mix. These observations suggest that norharman reacts with o-toluidine in the presence of S9 mix to produce amino-3'-methylphenylnorharman, and this compound is metabolically activated to yield its hydroxyamino derivative. After activation by O-acetyltransferase, it might bind to DNA and exert mutagenicity in S. typhimurium TA98 and YG1024. When norharman and m-toluidine were reacted in the presence of S9 mix, 9-(4'-amino-2'-methylphenyl)-9H-pyrido[3,4-b]indole (amino-2'-methylphenylnorharman) was identified as a mutagen. Thus, the mutagenicity of norharman with m-toluidine may follow a mechanism similar to that with o-toluidine.

Animals↗