Biomedical subjects

Yoshifumi Takahashi

Publications and source records attributed to Yoshifumi Takahashi.

8 recordsLinked to original sources

PubMed2026

Progesterone Is Associated With Increased Vasohibin-2 Expression, Tubulin Detyrosination, and Paclitaxel Sensitivity in PR-Negative Ovarian Cancer Cells.

BACKGROUND: Progesterone induces rapid cellular responses in progesterone receptor (PR)-negative ovarian cancer cells that are consistent with non-genomic progesterone signaling. Vasohibin-2 (VASH2), originally identified as a pro-angiogenic factor, has recently been recognized as a tubulin carboxypeptidase involved in microtubule regulation. AIMS: This study investigated the association of progesterone treatment with VASH2-related molecular changes and paclitaxel sensitivity in ovarian cancer cells. METHODS: Two PR-negative ovarian cancer cell lines expressing membrane progesterone receptors (mPRs) were treated with progesterone. VASH2 mRNA expression was evaluated by RT-qPCR, whereas detyrosinated tubulin and cyclin B1 expression were assessed by western blotting. Paclitaxel and gemcitabine sensitivities were determined using WST-1 cell viability assays. RESULTS: Progesterone treatment was associated with increased VASH2 mRNA expression, enhanced tubulin detyrosination, cyclin B1 accumulation, and significantly reduced paclitaxel IC50 values in both cell lines. In contrast, progesterone had no significant effect on gemcitabine sensitivity. CONCLUSION: Progesterone treatment was associated with increased VASH2 expression, enhanced tubulin detyrosination, and increased paclitaxel sensitivity in PR-negative ovarian cancer cells. These findings provide in vitro evidence supporting further mechanistic and preclinical investigation of progesterone as a potential adjunct to paclitaxel therapy.

Humans↗

PubMed2003

Mutagenic activity and quantification of nitroarenes in surface soil in the Kinki region of Japan.

To clarify the mutagenic potential of surface soil in the Kinki region of Japan, particularly in Osaka and neighboring cities, 62 surface soil samples were collected and their organic extracts were examined by the Ames/Salmonella assay. All of the samples were mutagenic toward TA98 in both the presence and absence of a mammalian metabolic activation system (S9 mix). While all of the samples showed mutagenicity toward TA100 with S9 mix, only 45/62 (73%) were mutagenic without S9 mix. Fifty (81%) of the samples showed higher activity toward TA98 than TA100. The mean values of the mutagenicities of soil samples collected in Osaka prefecture (n=35) toward TA98 with and without S9 mix were 2315 and 1630 revertants per gram of soil, respectively, and these were 2.9 and 2.6 times as high as the values for samples from other prefectures (n=27), respectively. Three dinitropyrene (DNP) isomers, i.e. 1,3-, 1,6- and 1,8-DNP, and 3-nitrobenzanthrone (NBA) in the surface soil samples were quantified by fluorometric detection of the corresponding amino compounds, i.e. diaminopyrene isomers and 3-aminobenzanthrone, using high-performance liquid chromatography (HPLC). The three DNP isomers were detected in all of the soil samples (n=26) that were mainly collected in Osaka prefecture, and the amounts of 1,3-, 1,6- and 1,8-DNP were 6-1526, 11-1772 and 10-2092pg/g of soil, respectively. The contribution ratios of 1,3-, 1,6- and 1,8-DNP to the mutagenicity of soil extracts toward TA98 without S9 mix were 0.2-12, 0.3-12 and 0.5-27%, respectively. The amount of 3-NBA in soil samples (n=8) was 144-1158pg/g of soil, and the contribution ratio of 3-NBA to the mutagenicity of soil extracts was 2-38%. These results suggest that the surface soils in the Kinki region were highly polluted with mutagens and the pollution levels in Osaka prefecture were higher than those in other areas. DNP isomers and 3-NBA may be major mutagens that contaminate surface soil in this region.

Animals↗

PubMed2003

Placental transfer of mercury in pregnant rats which received dental amalgam restorations.

Mercury vapor released from one, two and four amalgam restorations in pregnant rats and mercury concentrations in maternal and fetal organs were studied. Dental treatment was given on day 2 of pregnancy. Mercury concentration in air samples drawn from each metabolism chamber with a rat were measured serially for 24 h on days 2, 8 and 15 of pregnancy. On each day of pregnancy, the amount of mercury in 24 h air samples was in proportion to the amalgam surface areas. Linear regression analysis showed relatively high correlation coefficients between the mercury content and amalgam surface areas, and the coefficients were statistically significant. A highly significant correlation was also found between the number of amalgam fillings and their surface areas. Mercury concentrations in major maternal organs with one, two and four amalgam fillings tended to increase with the increasing amalgam surface areas. Spearman's rank correlation test revealed significant correlations in the brain, liver, kidneys and placenta but not in the lung. Furthermore, significant correlations were also found between the mercury concentrations in all maternal organs and the amount of mercury in 24 h air samples on day 15 of pregnancy. Mercury concentrations in fetal brain, liver and kidneys were much lower than those of the dams but liver and kidneys showed positive correlations between the mercury content and maternal amalgam surface areas. Similar correlations were observed between the mercury concentrations in fetal organs and the amount of mercury in 24 h air samples on day 15 of pregnancy. In fetal brain, no significant correlations were found between either maternal amalgam surface areas or the amount of mercury in 24 h samples on day 15 of pregnancy but significant uptake of mercury was found in the samples from the dams given four amalgam fillings. The results of the present study demonstrated that mercury vapor released from the amalgam fillings in pregnant rats was distributed to maternal and fetal organs in dose-dependent amounts of the amalgam fillings.

Animals↗

PubMed2002

Seasonal fluctuation of the mutagenicity of river water in Fukui, Japan, and the contribution of 2-phenylbenzotriazole-type mutagens.

To clarify their mutagenic potential, samples of water from the Mawatari, Asuwa and Kitsune rivers, which flow through the central area of Fukui, Japan, were seasonally collected at six sites using blue rayon from July 1998 to August 2000. Forty-five of 52 (87%) of the water samples exhibited mutagenicity toward Salmonella typhimurium YG1024 and YG1029 with and without S9 mix, and the highest potencies were observed in YG1024 with S9 mix. The samples collected in summer and autumn tended to be more mutagenic than those collected in winter and spring. Fractionation using high-performance liquid chromatography (HPLC) suggests that several compounds are responsible for the mutagenicity of river water samples, and some of the major mutagens seem to be common among the samples. Three 2-phenylbenzotriazole (PBTA)-type mutagens, 2-[2-(acetylamino)-4-[(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-3), 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4) and 2-[2-(acetylamino)-4-[bis(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-6), were quantified in samples collected between July 1998 and April 1999. At least one of these PBTA-type mutagens was detected in 23/24 (96%) of the samples. The amounts of PBTA-3, -4 and -6 were <0.08-58.7, <0.1-15.0 and <0.07-467.9 ng/g of blue rayon, respectively, and high levels of PBTA congeners were detected in the samples collected from each river in July and November 1998. The contributions of these PBTA congeners to the mutagenicity of water samples were also high in July and November 1998. The highest total contribution was observed for samples from the Asuwa river (67.6%). These findings suggest that these three rivers were continually and heavily contaminated with mutagens, and PBTA congeners were some of the major mutagens in these rivers.

Cellulose↗

PubMed2002

Detection of large interaural delays and its implication for models of binaural interaction.

The interaural time difference (ITD) is a major cue to sound localization along the horizontal plane. The maximum natural ITD occurs when a sound source is positioned opposite to one ear. We examined the ability of owls and humans to detect large ITDs in sounds presented through headphones. Stimuli consisted of either broad or narrow bands of Gaussian noise, 100 ms in duration. Using headphones allowed presentation of ITDs that are greater than the maximum natural ITD. Owls were able to discriminate a sound leading to the left ear from one leading to the right ear, for ITDs that are 5 times the maximum natural delay. Neural recordings from optic-tectum neurons, however, show that best ITDs are usually well within the natural range and are never as large as ITDs that are behaviorally discriminable. A model of binaural crosscorrelation with short delay lines is shown to explain behavioral detection of large ITDs. The model uses curved trajectories of a cross-correlation pattern as the basis for detection. These trajectories represent side peaks of neural ITD-tuning curves and successfully predict localization reversals by both owls and human subjects.

Animals↗

PubMed2002

Manipulation of inhibition in the owl's nucleus laminaris and its effects on optic tectum neurons.

Differences in arrival time and intensity (or level) of sound between the ears serve as cues for localization of sound in many animals. Barn owls use interaural time difference (ITD) and interaural level difference (ILD) for localization in azimuth and elevation, respectively. The owl's brain processes these two cues in separate pathways. The nucleus laminaris is the first site that detects ITDs by methods of delay lines and coincidence detection. The nucleus ventralis lemnisci lateralis, pars posterior is the first site of processing ILDs. The two pathways merge in the inferior colliculus to give rise to sensitivity to combinations of ITD and ILD. This selectivity is relayed to the optic tectum where neurons are sensitive to both visual and auditory stimuli. The present paper reports the results of manipulating inhibition in the nucleus laminaris and its effects on the optic tectum neurons. Injection of GABA or muscimol (a GABA(A) receptor agonist) in the nucleus laminaris reduces the responses of its neurons to ITD. This finding proves that GABA(A) receptor-mediated inhibition acts on the nucleus laminaris neurons. The same treatment did not affect the neurons of the nucleus ventralis lemnisci lateralis, pars posterior, whereas it reduced the response of the optic tectum neurons to ITD-ILD pairs. We conclude that although the two pathways are independent, the process of combining ITD and ILD creates a new relationship in which the output of the neuron varies with the amplitude of either input. This conclusion is consistent with the recent finding that the combination sensitivity is due to a multiplication of ITD and ILD inputs.

Animals↗

PubMed2002

Mutagenicity of two 2-phenylbenzotriazole derivatives, 2-[2-(acetylamino)-4-(diethylamino)-5-methoxyphenyl]-5-amino- 7-bromo-4-chloro-2H-benzotriazole and 2-[2-(acetylamino)-4-(diallylamino)-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole and their detection in river water in Japan.

We recently detected five 2-phenylbenzotriazole (PBTA)-type mutagens (PBTA-1, PBTA-2, PBTA-3, PBTA-4 and PBTA-6) in concentrates from several rivers that flow in geographically different areas in Japan containing textile-related industries. On the basis of synthesis studies, these five PBTA derivatives were deduced to have originated from the corresponding dinitrophenylazo dyes, which are industrial chemicals used in textile dyeing, via reduction and chlorination. 2-[(2-Bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)-4-methoxyacetanilide (Color Index name Disperse Blue 291, CAS registry no. 56548-64-2) and 2-[(2-bromo-4,6-dinitrophenyl)azo]-5-(diallylamino)-4-methoxyacetanilide (Color Index name Disperse Blue 373, CAS registry no. 51868-46-3) are used in textile dyeing and have 2-[(2-bromo-4,6-dinitrophenyl)azo]-4-methoxyacetanilide moieties in their structures, which are thought to be essential for their conversion to mutagenic PBTA derivatives. In the present study we have synthesized 2-[2-(acetyl-amino)-4-(diethylamino)-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-7) and 2-[2-(acetylamino)-4-(diallylamino)-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-8) from Disperse Blue 291 and Disperse Blue 373, respectively, by reduction with iron powder and subsequent chlorination with sodium hypochlorite. Both PBTA-7 and PBTA-8 exerted strong mutagenicity in Salmonella typhimurium TA98 and YG1024 in the presence of S9 mix (43 000 and 1 430 000 revertants/nmol for PBTA-7 and 40 700 and 2 213 000 revertants/nmol for PBTA-8 in TA98 and YG1024). To clarify whether PBTA-7 and PBTA-8 exist in the environment, water samples were collected at seven sites in six rivers flowing through two different regions where textile dyeing industries are located. All water samples were mutagenic in Salmonella typhimurium YG1024 with S9 mix and their potencies ranged from 108 000 to 1 990 000 revertants/g blue rayon. PBTA-7 and PBTA-8 were detected in water samples from both regions at levels of <0.1-101.4 ng/g blue rayon and <0.1-48.9 ng/g blue rayon, respectively. In some samples PBTA-7 and PBTA-8 could contribute up to 15% of the water mutagenicity.

Aniline Compounds↗

PubMed2002

[Audiological assessment of hearing-impaired children under age 3 and their later pure tone audiometry].

We analyzed the first audiological assessment and latest pure tone audiometry (PTA) in 29 hearing-impaired children (58 ears) visiting Osaka University for their first audiological assessment at the ages of 0, 1, and 2. We evaluated their hearing thresholds with PTA during follow-up and compared them to their first assessments. We combined auditory brain-stem response (ABR), behavioral audiometry, and conditioned orientation reflex (COR) for audiological evaluation of infants. Hearing thresholds assessed by 2 or 3 of these methods were sufficiently precise for hearing aid fitting. Thresholds of recorded ABR waves in 14 ears at loud sound pressure correlated well with later pure tone thresholds at high frequencies. Pure tone thresholds of those in whom no ABR waves were observed at 100 dB, were often out of scale at high frequencies--14% at 4000 Hz and 73% at 8000 Hz. Because of residual hearing at low frequencies, 4-frequency-averaged hearing at 500 Hz, 2 x 1000 Hz, 2000 Hz was better than 100 dB in 7 of 44 ears (16%), and 4 of 22 children (18%) did not fit the severest rank, 2, of the Disabled Persons, Welfare Law in Japan.

Audiometry, Pure-Tone↗