Biomedical subjects

Y Totsuka

Publications and source records attributed to Y Totsuka.

At least 19 recordsLinked to original sources

PubMed2006

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗

PubMed2006

Static bone cavity of the mandible: Computed tomography findings with histopathologic correlation.

PURPOSE: To review computed tomography (CT) findings of histopathologically examined static bone cavities in order to determine whether an additional pathogenesis may play a role in this disease. MATERIAL AND METHODS: Four patients with histopathologically examined static bone cavities were included in this retrospective study. Location, appearance of bone remodeling, tissue characteristics, and contrast enhancement of the cavity were assessed on CT images. CT findings were then compared with the histopathological findings. RESULTS: Static bone cavity was found in the lingual molar region in three patients and in the lingual cuspid region of the mandible in one patient. Both fatty and soft tissues were present in the cavities of all four patients. Attenuation of the soft tissue in the cavities was found to be different from that of the submandibular gland. The soft tissue showed enhancement with contrast-enhanced CT in three patients. For all patients, the histopathologic content of the static bone cavity included fat, soft tissue, and abnormal vasculature. The thickened vein wall in the abnormal vasculature was observed. Aberrant tissue of the submandibular gland was not found in any of the static bone cavities. CONCLUSION: Contrast enhancement of the soft tissue on the contrast-enhanced CT images suggests the presence of vasculature in the cavities. Histopathological examination confirmed the presence of fatty tissue and dilated abnormal vessels, and the absence of salivary gland tissue in the cavities. These findings show that vascular structures are prominent in tissues found in static bone cavities.

Adult↗

PubMed2004

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗

PubMed2004

Search for electron neutrino appearance in a 250 km long-baseline experiment.

We present a search for electron neutrino appearance from accelerator-produced muon neutrinos in the K2K long-baseline neutrino experiment. One candidate event is found in the data corresponding to an exposure of 4.8 x 10(19) protons on target. The expected background in the absence of neutrino oscillations is estimated to be 2.4+/-0.6 events and is dominated by misidentification of events from neutral current pi(0) production. We exclude the nu(micro) to nu(e) oscillations at 90% C.L. for the effective mixing angle in the 2-flavor approximation of sin((2)2theta(microe)( approximately 1/2sin((2)2theta(13))>0.15 at Deltam(2)(microe)=2.8 x 10(-3) eV(2), the best-fit value of the nu(micro) disappearance analysis in K2K. The most stringent limit of sin((2)2theta(microe)<0.09 is obtained at Deltam(2)(microe)=6 x 10(-3) eV(2).

Journal Article↗

PubMed2004

Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.

A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)</=(3.6x10(-10))micro(B) at 90% C.L. by fitting to the Super-Kamiokande day-night spectra. The fitting took into account the effect of neutrino oscillation on the shapes of energy spectra. With additional information from other solar neutrino and KamLAND experiments constraining the oscillation region, a limit of micro(nu)</=(1.1x10(-10))micro(B) at 90% C.L. was obtained.

Journal Article↗

PubMed2004

Mutagens formed from beta-carbolines with aromatic amines.

Norharman, widely distributed in our environment such as cigarette smoke and cooked foods, is not mutagenic to Salmonella strains, but becomes mutagenic to Salmonella typhimurium TA98 and YG1024 with S9 mix in the presence of aromatic amines, including aniline and o-toluidine. Therefore, we have designated norharman as a "co-mutagen". Since, humans are simultaneously exposed to norharman and aromatic amines in daily life, it is important to clarify the mechanisms of its co-mutagenic action to further understanding of the potential genotoxic effects in humans. Regarding the mechanisms of this action of norharman with aniline, a mutagenic compound, 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole[aminophenylnorharman (APNH)] is produced by their interaction, and converted to the hydroxyamino derivative which eventually forms the DNA adduct, dG-C8-APNH through possible ultimate reactive forms with esterification, and this induces mutations. Also other aminophenyl-beta-carboline compounds, such as 9-(4'-amino-3'-methylphenyl)-9H-pyrido[3,4-b]indole[amino-3'-methylphenylnorharman (3'-AMPNH)], 9-(4'-amino-2'-methylphenyl)-9H-pyrido[3,4-b]indole [amino-2'-methylphenylnorharman (2'-AMPNH)], 9-(4'-aminophenyl)-1-methyl-9H-pyrido[3,4-b]indole[aminophenylharman (APH)] and 9-(4'-amino-3'-methylphenyl)-1-methyl-9H-pyrido[3,4-b]indole[amino-3'-methylphenylharman (AMPH)], have been found on reaction of norharman or harman with aniline or toluidine isomers. These compounds showed mutagenic and clastogenic actions in bacterial and mammalian cells. Among them, APNH demonstrated the most potent activity, and it was most extensively studied. When APNH was administered as a single dose to F344 rats, severe testicular toxicity was observed after 6 days. Moreover, liver preneoplastic lesions (GST-P-positive foci) in the liver clearly developed in animals fed 10-50 ppm of APNH in the diet for 4 weeks. Since, APNH was detected in 24 h urine of rats upon simultaneous administration with norharman and aniline by gavage, it is likely to be also produced from norharman and aniline in the human body. From these findings, it is suggested that aminophenyl-beta-carboline derivatives may be classified as one of the novel types of endogenous mutagens and carcinogens.

Amines↗

PubMed2003

Search for nu(e) from the sun at Super-Kamiokande-I.

We present the results of a search for low energy nu(e) from the Sun using 1496 days of data from Super-Kamiokande-I. We observe no significant excess of events and set an upper limit for the conversion probability to nu(e) of the 8B solar neutrino. This conversion limit is 0.8% (90% C.L.) of the standard solar model's neutrino flux for total energy=8-20 MeV. We also set a flux limit for monochromatic nu(e) for E(nu(e))=10-17 MeV.

Journal Article↗

PubMed2003

Search for supernova relic neutrinos at Super-Kamiokande.

A search for the relic neutrinos from all past core-collapse supernovae was conducted using 1496 days of data from the Super-Kamiokande detector. This analysis looked for electron-type antineutrinos that had produced a positron with an energy greater than 18 MeV. In the absence of a signal, 90% C.L. upper limits on the total flux were set for several theoretical models; these limits ranged from 20 to 130 macro nu(e) cm(-2) s(-1). Additionally, an upper bound of 1.2 macro nu(e) cm(-2) s(-1) was set for the supernova relic neutrino flux in the energy region E(nu)>19.3 MeV.

Journal Article↗

PubMed2003

Indications of neutrino oscillation in a 250 km long-baseline experiment.

The K2K experiment observes indications of neutrino oscillation: a reduction of nu(mu) flux together with a distortion of the energy spectrum. Fifty-six beam neutrino events are observed in Super-Kamiokande (SK), 250 km from the neutrino production point, with an expectation of 80.1(+6.2)(-5.4). Twenty-nine one ring mu-like events are used to reconstruct the neutrino energy spectrum, which is better matched to the expected spectrum with neutrino oscillation than without. The probability that the observed flux at SK is explained by statistical fluctuation without neutrino oscillation is less than 1%.

Journal Article↗

PubMed2003

Analysis of estrogenic activity of foodstuffs and cigarette smoke condensates using a yeast estrogen screening method.

Hormone mimics present in our environment are of concern because such agents could potentially reduce fertility and increase sexual dysfunction in wildlife and increase the risk of breast and reproductive organ cancers in man. Therefore, monitoring of the levels of estrogenic compounds in environmental materials is essential in order to prevent their exposure to man and to discover potential harmful effects on human health. In the present study, we analyzed estrogenic activity in 23 foodstuffs and cigarette smoke condensate samples extracted with an organic solvent, using the yeast estrogen screening (YES) system. Three soybean-related foodstuffs (soy sauce, tofu, miso), beer, coffee and cigarette smoke condensates showed clear estrogenic activity in the YES system. HPLC fractionations followed by the YES of these YES-positive samples revealed the presence of many estrogenic compounds in cigarette smoke condensates, whereas the other samples exerted estrogenic activities in only one or two fractions. Genistein was able to be isolated as the major active principle in soy sauce, tofu and miso, its concentration in these three foodstuffs ranging from 0.1 to 394 microg/g or ml. 8-Prenylnaringenin was also isolated from beer extracts as a major compound with estrogenic activity present at 0.22-4.0 ng/ml. Estrogenic activity of 8-prenylnaringenin with YES was 10-times as high as that of genistein, although it was 100-times less than that of 17beta-estradiol. Based on our results in vitro, 10 mg miso and 10 ml beer can be calculated to have similar estrogenic activity to 1 pmole 17beta-estradiol. It is very important that the effects of genistein and 8-prenylnaringenin on human health are elucidated.

Chromatography, High Pressure Liquid↗

PubMed2003

Evaluation of static bone cavities with CT and MRI.

OBJECTIVES: To determine by CT and MRI the contents of static bone cavities (SBCs), which are thought to be formed by aberration of the submandibular gland. METHODS: Non-contrast-enhanced and contrast-enhanced CT was performed on 12 subjects (10 male and 2 female; age 18-64 years; mean age 57 years) in whom SBCs had been discovered incidentally on panoramic radiographs during routine dental treatment. MRI was also performed on 3 of the 12 subjects. RESULTS: No submandibular gland tissue was seen in the SBCs in any of the cases. However, fatty tissue of low attenuation was found in the SBCs in all cases on CT images. Blood vessels were seen in the SBCs in 10 cases, and enhanced soft tissue in contact with the bone cavity wall was seen in the SBCs in 2 cases. Blood vessels in the SBCs were observed on MR images in all three cases. Dilatation of the cavity blood vessels was seen in all 10 cases. Slight tortuosity of the blood vessels was seen in 4 of the 10 cases. CONCLUSIONS: Examination of contrast-enhanced CT images and MR images revealed that the contents of SBCs were not aberrations of the submandibular gland, as has generally been thought, but fatty tissue, blood vessels and soft tissue.

Adipose Tissue↗

PubMed2002

Electromyographic activity of the jaw-closing muscles during jaw opening--comparison of cases of masseter muscle contracture and TMJ closed lock.

Contracture of jaw-closing muscles is one of the causes of limitations of jaw opening. In contracture patients who have no history of trauma or infection, it is not easy to distinguish contracture from temporomandibular joint (TMJ) closed lock (TCL). The purpose of this study was to clarify whether there is any difference between electromyographic (EMG) activities of jaw muscles during jaw opening in patients with TCL and patients with masseter muscle contracture (MMC). The MMC-patient group consisted of one male and 11 females with no history of trauma or infection. The TCL-patient group consisted of one male and 11 females. Ten of the MMC patients showed certain types of EMG activities in masseter muscles (and eight in temporal muscles) during jaw opening. However, particular EMG activities were not observed in most of the TCL patients. The integral values in masseter muscles and in temporal muscles at the maximum opening position were significantly higher in the MMC-patient group than those in the TCL-patient group. These findings demonstrate that the EMG pattern of MMC patients without a history of trauma or infection is different from that of TCL patients. Therefore, EMG analysis of jaw-closing muscles during jaw opening is expected to be useful for differential diagnosis between MMC and TCL.

Adolescent↗

PubMed2002

A recurrent case of odontogenic ghost cell tumour of the mandible.

Odontogenic ghost cell tumour (OGCT), also referred to as dentinogenic ghost cell tumour, is an extremely rare tumour classified as a neoplastic variant of calcifying ondontogenic cyst (COC). To date, only 13 cases of OGCT arising in the maxilla or mandible have been reported. We describe an OGCT that recurred after segmental resection of the mandible in a 59-year-old man. Histopathological examination revealed tumour invasion of the surrounding cortical bone, areas containing numerous calcifying flaky cell nests, and dentinoid matrix near epithelial cell nests. No atypical mitosis was found. There has been no evidence of recurrence or metastasis in the 4 years after operation.

Dentin↗

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

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

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

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↗