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Biomedical subjects

Y Terao

Publications and source records attributed to Y Terao.

At least 19 recordsLinked to original sources

Distribution of emm genotypes and superantigen genes of Streptococcus pyogenes isolated in Japan, 1994-9.

The purpose of this study was to examine characteristic profiles of Streptococcus pyogenes clinical isolates isolated in Japan during 1994-9. Genotyping of the M protein (emm typing) revealed that emm types 12 and 28 were the most common among 316 isolates. Most of the emm12 isolates were isolated from mucosa, while emm58 and emm89 were from skin. Moreover, the emm3 isolates were dominant in invasive infections. The distribution of 6 superantigen genes showed that all isolates harboured the mf gene and many had the speG gene. Invasive isolates were shown to have the ssa gene at a higher rate (76%) than noninvasive (37%). The distribution of superantigens was significantly different between emm types, but not between isolation sites. These results suggest that the distribution of emm types is related to isolation site, whereas superantigen distribution is related to clinical features of S. pyogenes infections.

Antigens, Bacterial↗

Growth-associated gene expression profiles by microarray analysis of trophoblast of molar pregnancies and normal villi.

We used microarray analysis to investigate expression profiles of 589 known genes committed to cell growth control to characterize regulatory circuitry for cell proliferation in complete moles (CMs). CMs are characterized by hyperplastic trophoblast and have a high propensity to give rise to choriocarcinoma. Characteristic alterations in gene expression profiles were observed when compared with normal villi. Fifty-seven genes were significantly up-regulated in CMs and involved the Ras-Map kinase 3, Jak-STAT5, and Wnt signal pathways, implicating growth factor or cytokine-mediated signal pathways in the trophoblastic hyperplasia of CMs. Several genes associated with anti-apoptosis, cell structuring, and/or cell attachment were also up-regulated in CMs. In contrast, relatively fewer genes were down-regulated and these involved IGFBPs, versican, interleukin-1, tumor necrosis factor receptor, CD44, and RAD52. Genes identified in this study may elucidate regulation mechanisms of trophoblastic proliferation and mechanisms causing a pathological phenotype in CMs.

Apoptosis↗

Interplay of the main chain, chiral side chains, and solvent in conformational transitions: poly([(R)-3,7-dimethyloctyl]-[(S)-3-methylpentyl]silylene).

Light scattering, sedimentation equilibrium, viscosity, circular dichroism (CD), and UV absorption (UV) measurements were made on dilute solutions of poly([(R)-3,7-dimethyloctyl]-[(S)-3-methylpentyl]silylene)(PRS) as functions of molecular weight. From light scattering and viscosity data, PRS is found to be a very stiff polymer of persistence length q as large as 103 nm at 25 degrees C, essentially a 7(3) helix found in the solid state; q increases only gradually with lowering temperature between -15 and 25 degrees C. The CD data show that PRS undergoes a conformational transition around 3 degrees C in isooctane (transition temperature T(c)). The CD signal is largely positive at low temperatures, passes through zero at T(c), and becomes largely negative at higher temperatures; T(c) is independent of sample's chain length N. This is a highly cooperative helix (M)-to-helix (P) transition depending remarkably on N, as PRS is substantially rodlike. The CD data are converted to the fraction f(P) of P helix as a function of N and analyzed successfully by a statistical mechanical theory based on a helix reversal model, where a polymer chain consists of M and P helices intervened by helix reversals, with the result that the free energy difference DeltaG(h) between P and M shows a temperature dependence similar to that of 2f(P) - 1, whereas the helix reversal energy is substantially constant at 1.2 x 10(4) J mol(-1); the latter value means that the helix reversal occurs only once in 100 Si units or less. This DeltaG(h) change and solvent dependence of T(c) are explained by a double-well potential for the rotation about Si-Si bonds, which incorporates into DeltaG(h) the solvent interactions with the helical grooves of side chains surrounding the main chain. Detailed features of UV absorption spectra at different temperature and molecular weights are also presented.

Journal Article↗

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↗

Sodium butyrate induces growth arrest and senescence-like phenotypes in gynecologic cancer cells.

We demonstrated here the growth-suppressing effects of sodium butyrate (NaB) on human endometrial and ovarian cancer cells. The arrest of cells at the G1 checkpoint accounted for this effect. NaB-mediated p21 might arrest endometrial and ovarian cancer cells at the G0/G1 phase by eliciting pRb unphosphorylation. To demonstrate the role of pRb regulation by p21, we measured the sensitivity to NaB of cervical cancer cells in which pRb had been inactivated by HPV E7. The cervical cancer cells displayed a sensitivity in NaB-mediated G2/M arrest in addition to their sensitivity in G0/G1 arrest. Arrest at G0/G1 and G2/M accompanied induction of senescence-like phenotypes (SLPs). Most importantly, the effect of NaB on senescence induction was not coupled with the predominance of hypophosphorylated pRb forms in the cervical cancer cells. This suggested that NaB had the potential to elicit SLPs through p21-mediated withdrawal from cell cycle progression. The consequences of p21 induction were manifold. The effects of NaB on gynecologic cancer cell growth indicated its potential use in cancer treatment. NaB was effective even in the cancer cells with mutant p53 and/or Rb genes by eliciting cell senescence.

Animals↗

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↗

Identification of 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4) as a potent mutagen in river water in Kyoto and Aichi prefectures, Japan.

We have previously isolated five mutagens in blue rayon-adsorbed substances from water at a site below sewage plants in the Nishitakase River, in Kyoto, Japan, and identified two of them as 2-phenylbenzotriazole derivatives, 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-[(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2). In the present study, we collected adsorbed materials on blue cotton (3 kg x 9 times) at the same location, and isolated a sufficient amount (97 microg) of one of the remaining three mutagens other than PBTA-1 and PBTA-2, for structural analysis, by multiple column chromatography. The structure of mutagen, accounting for 12% of the total mutagenicity of the blue rayon-adsorbed substances, was determined to be a PBTA-1 analogue, 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4). PBTA-4 is a potent mutagen, inducing 190,000 and 7,800,000 revertants of Salmonella typhimurium TA98 and YG1024 per microgram, respectively, in the presence of S9 mix. In addition to the water of the Nishitakase River, PBTA-4 was detected in water samples from two rivers that flow through other regions where textile-dyeing industries have been developed. Like other PBTA analogues, PBTA-4 might also be produced from azo dyes during industrial processes in dyeing factories and treatment at sewage plants.

Animals↗

Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.

Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.

Amino Acid Sequence↗

Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor.

A DNA fragment encoding an amino acid sequence possessing common features to the G protein-coupled receptor (GPCR) superfamily was found in the human genomic sequence, and from this information, the full-length cDNA of a novel GPCR, designated SLT, was cloned from the human hippocampus cDNA library. SLT showed the highest homology to the melanin-concentrating hormone (MCH) receptor, SLC-1 (31.5% identity), and to a lesser extent, to the somatostatin (SST) receptor subtypes. MCH exhibited agonistic behavior when applied to the SLT-expressing CHO cells at subnanomolar doses whereas more than 200 known peptides, including SST and cortistatin, did not. These results indicated that MCH is the cognate ligand of the SLT receptor and that this newly cloned GPCR is the second subtype of the MCH receptor. Quantitative polymerase chain reaction analysis of the SLT gene expression in human tissues showed that the SLT receptor is expressed mainly in brain areas including the cerebral cortex, amygdala, hippocampus, and corpus callosum, as well as in a limited number of peripheral tissues. The distribution of the SLT nearly overlapped that of SLC-1, suggesting that some of the neural functions of MCH may be mediated by both of these receptor subtypes.

Amino Acid Sequence↗

Identification of co-mutagenic chlorinated harmans in final effluent from a sewage treatment plant.

Harman (1-methyl-9H-pyrido[3,4-b]indole) reacted readily with sodium hypochlorite in an aqueous medium to give the mono-chlorinated derivatives, which reportedly have greater co-mutagenic activity than harman in the presence of o-toluidine toward Salmonella typhimurium TA 98 with S9 mix. Mono-chlorinated harmans were detected by concentration using blue rayon (BR) and GC/MS analysis in the final effluent from a sewage treatment plant in Shizuoka, Japan. The amounts adsorbed for 24h were 1-45ng/gBR for mono-chlorinated harman and 110-730ng/gBR for harman.

Biotransformation↗

Interhemispheric facilitation of the hand motor area in humans.

1. We investigated interhemispheric interactions between the human hand motor areas using transcranial cortical magnetic and electrical stimulation. 2. A magnetic test stimulus was applied over the motor cortex contralateral to the recorded muscle (test motor cortex), and an electrical or magnetic conditioning stimulus was applied over the ipsilateral hemisphere (conditioning motor cortex). We investigated the effects of the conditioning stimulus on responses to the test stimulus. 3. Two effects were elicited at different interstimulus intervals (ISIs): early facilitation (ISI = 4-5 ms) and late inhibition (ISI > or = 11 ms). 4. The early facilitation was evoked by a magnetic or anodal electrical conditioning stimulus over the motor point in the conditioning hemisphere, which suggests that the conditioning stimulus for early facilitation directly activates corticospinal neurones. 5. The ISIs for early facilitation taken together with the time required for activation of corticospinal neurones by I3-waves in the test hemisphere are compatible with the interhemispheric conduction time through the corpus callosum. Early facilitation was observed in responses to I3-waves, but not in responses to D-waves nor to I1-waves. Based on these results, we conclude that early facilitation is mediated through the corpus callosum. 6. If the magnetic conditioning stimulus induced posteriorly directed currents, or if an anodal electrical conditioning stimulus was applied over a point 2 cm anterior to the motor point, then we observed late inhibition with no early facilitation. 7. Late inhibition was evoked in responses to both I1- and I3-waves, but was not evoked in responses to D-waves. The stronger the conditioning stimulus was, the greater was the amount of inhibition. These results are compatible with surround inhibition at the motor cortex.

Conditioning, Psychological↗

Hemispheric lateralization in the cortical motor preparation for human vocalization.

To investigate the cortical information processing during the preparation of vocalization, we performed transcranial magnetic stimulation (TMS) over the cortex while the subjects prepared to produce voice in response to a visual cue. The control reaction time (RT) of vocalization without TMS was 250-350 msec. TMS prolonged RT when it was delivered up to 150-200 msec before the expected onset of voice (EOV). The largest delay of RT was induced bilaterally over points 6 cm to the left and right of the vertex (the left and right motor areas), resulting in 10-20% prolongation of RT. During the early phase of prevocalization period (50-100 msec before EOV), the delay induced over the left motor area was slightly larger than that induced over the right motor area, whereas, during the late phase (0-50 msec before EOV), it was significantly larger over the right motor area. Bilateral and simultaneous TMS of the left and right motor areas induced delays not significantly different from that induced by unilateral TMS during the early phase, but induced a large delay well in excess of the latter during the late phase. Thus, during the cortical preparation for human vocalization, alternation of hemispheric lateralization takes place between the bilateral motor cortices near the facial motor representations, with mild left hemispheric predominance at the early phase switching over to robust right hemispheric predominance during the late phase. Our results also suggested involvement of the motor representation of respiratory muscles and also of supplementary motor cortex.

Adult↗

Identification and quantification of chlorinated bisphenol A in wastewater from wastepaper recycling plants.

Chlorinated derivatives of bisphenol A were detected in the final effluents of eight paper manufacturing plants in Shizuoka, Japan, where thermal paper and/or other printed paper is used as the raw material. Their amounts were determined by gas chromatography/mass spectrometry (GC/MS) after treatment with N, O-bis(trimethylsilyl)trifluoroacetamide, and ranged from traces to 2.0 microg/l. They are likely produced by chlorination of bisphenol A, which was released into the effluents from the pulping process of wastepaper, during or after bleaching with chlorine.

Benzhydryl Compounds↗

A single motor unit recording technique for studying the differential activation of corticospinal volleys by transcranial magnetic stimulation.

The purpose of this method is to establish a single motor unit recording technique to study the differential activation of corticospinal volleys by various types of transcranial magnetic stimulation (TMS). TMS is performed with various coil orientations over the hand or leg motor areas and surface EMG, and single motor unit recordings are made either from the studied hand or leg muscle. Transcranial electrical stimulation (TES) is also performed over the motor cortex as well as at the foramen magnum level to determine the latency of D waves. The intensity of stimulation is set just above the motor threshold for each type of stimulation. This method makes it possible to activate some I volleys (especially I1 and I3 waves) preferentially, if not selectively, from the hand and leg motor areas. The obtained results accord well with recent epidural recording studies, which lends support to the validity of this method.

Differential Threshold↗

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex.

OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.

Action Potentials↗

Fba, a novel fibronectin-binding protein from Streptococcus pyogenes, promotes bacterial entry into epithelial cells, and the fba gene is positively transcribed under the Mga regulator.

In infection by Streptococcus pyogenes, fibronectin (Fn)-binding proteins play important roles as adhesins and invasins. Here, we present a novel Fn-binding protein of S. pyogenes that exhibits a low similarity to other Fn-binding proteins reported. After searching the Oklahoma Streptococcal Genome Sequencing Database for open reading frames (ORFs) with an LPXTG motif, nine ORFs were found among those recognized as putative surface proteins, and one of them was designated as Fba. The fba gene was found in M types 1, 2, 4, 22, 28 and 49 of S. pyogenes, but not in other serotypes or groups of streptococci. Fba, a 37.8 kDa protein, possesses three or four proline-rich repeat domains and exhibits a high homology to FnBPA, the Fn-binding protein of Staphylococcus aureus. Recombinant Fba exhibited a strong binding ability to Fn. In addition, Fba-deficient mutants showed diminished invasive capabilities to HEp-2 cells and low mortality in mice following skin infection. The fba gene was located downstream of the mga regulon and analysis using an mga-inactivated mutant revealed that it was transcribed under the control of the Mga regulator. These results indicate that Fba is a novel protein and one of the important virulence factors of S. pyogenes.

Adhesins, Bacterial↗

Activation of alveolar phospholipase A2 after hydrochloric acid aspiration in rats.

PURPOSE: The present study was carried out to determine phospholipase A2 (PLA2) activity in the bronchoalveolar lavage fluid (BALF) in rats subjected to HCI aspiration. MATERIALS AND METHODS: Rats were allocated into one of five groups. Groups H-1 and H-3 received instillation of HCI into lungs. Groups S-1 and S-3 received saline instead of HCI. Group C received no instillation. BAL was performed according to the protocol, that is, 1 hour after the instillation in groups H-1 and S-1, 3 hours after the instillation in groups H-3 and S-3, and arbitrarily in group C. Obtain BALF was analyzed for the protein concentration, PLA2 activity, and the molecular mass of PLA2. RESULTS: The protein concentration in BALF showed an increase in groups H-1 and H-3. PLA2 activity decreased in group H-1, but increased in group H-3, compared with groups S-1 and S-3, respectively. PLA2 in groups C and H-1 revealed a high molecular mass (HM), but that in group H-3 revealed a low molecular mass (LM). CONCLUSIONS: There is an increase in the alveolar LM-PLA2 at inflammatory phase after HCI aspiration, suggesting the pathophysiologic role of LM-PLA2 in the acute lung injury.

Animals↗