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Biomedical subjects

K Yoshii

Publications and source records attributed to K Yoshii.

At least 37 records · Page 2Linked to original sources

Open channel block of NMDA receptors by conformationally restricted analogs of milnacipran and their protective effect against NMDA-induced neurotoxicity.

We investigated the blocking effect of the conformationally restricted analogs of milnacipran on NMDA receptors by recording the whole-cell currents of Xenopus oocytes injected with rat brain mRNA and the single channel currents of cultured hippocampal neurons under voltage-clamp conditions. Their protective effect against excitotoxicity was also investigated on cultured cortex neurons. All conformationally restricted analogs examined blocked activated NMDA receptors, though their structures were quite different from known NMDA receptor blockers. The analogs with a (1S, 2R, 1'S)-configuration such as PPDC ((1S, 2R)-1-phenyl-2[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide+ ++) had lower IC50 values than those with other configurations. The empirical Hill coefficients for each compound were close to unity, indicating a 1:1 stoichiometry for the block. PPDC decreased the maximum responses to both N-methyl D-aspartate (NMDA) and glycine without altering their dissociation constants. The blocking effect was enhanced on hyperpolarization. PPDC had no effects on other glutamate receptor subtypes (AMPA, kainate, and metabotropic glutamate receptors) or other neurotransmitter receptors (GABA(A), 5HT2C, and AChM1 receptors) produced by the oocytes. PPDC decreased the mean open time of NMDA receptors without decreasing their elementary conductance. The microscopic blocking rate constant was 2.8x10(7) M(-1)s(-1). The macroscopic unblocking rate constant of PPDC was much faster than that of MK-801. Only the analogs with the (1S, 2R, 1'S)-configuration protected the cultures against NMDA-induced neurotoxicity, though they failed to protect against kainate-induced neurotoxicity. These results show that conformationally restricted analogs, at least PPDC, selectively blocked open channels of NMDA receptors.

Animals↗

[The effects of paid employment, social activities participation on women's health and comparison of role qualities].

PURPOSES: We examined how differences in employment status and social activities participation related to mental and physical health of women in middle age. Moreover we examined how the relation between employment status, social activities participation and health could be explained by the differences of role qualities between housework, paid work, and social activities. METHODS: The subjects were 640 women aged 35 to 44 in Tokyo, and the study was carried out with mailed questionnaires in 1997. RESULTS: 1. Women with full-time jobs had higher purpose-in-life scores than women with part-time jobs, or who didn't work, but they were also most fatigued physically. 2. Women who participated in social activities for 1 to 4 hours per week had lower depression scores and higher purpose-in-life scores than women who did not participate in any social activities, or who participated in social activities for more than 5 hours per week. 3. Women who weren't employed and didn't participate in any social activities were most depressed and had the lowest purpose-in-life scores. 4. Paid work and social activities were evaluated higher in 'fulfillment' and 'relation to society' than housework. Full-time job was evaluated higher in physical and mental 'workload' than housework, but social activities did not differ from housework in physical and mental 'workload'. 5. The role quality differences of housework from that of paid work and social activities, explained the relation between employment status, social activities participation and health.

Activities of Daily Living↗

Genetic analysis of wild polioviruses towards the eradication of poliomyelitis from the Western Pacific Region.

Since a laboratory network to eradicate poliomyelitis in the Western Pacific Region started in 1991, the Department of Virology II, National Institute of Infectious Diseases, has been functioning as a Regional Reference Laboratory. From 1992 to 1998, we examined 5453 stool samples collected from 3501 patients with acute flaccid paralysis in Cambodia, Vietnam, and Laos, and we isolated 392-type 1 and 10-type 3 wild polioviruses. As a result of the extensive immunization during this time in this area, the numbers of poliomyelitis cases by wild polioviruses have drastically decreased. In 1997, only nine type 1 wild polioviruses were isolated. Eight out of the nine cases were found in Cambodia, and one was in mid-Vietnam. Since then no wild polioviruses have been isolated in the Western Pacific Region for more than two years. A nucleotide sequence analysis of these 1997 isolates indicated that they all belonged to the same strain that has been prevailing in the Indochina area, suggesting the complete interruption of wild poliovirus transmission in the region.

Acute Disease↗

Phylogenic analysis of echovirus type 30 isolated from a large epidemic of aseptic meningitis in Japan during 1997-1998.

During 1997 to 1998, a nationwide epidemic of aseptic meningitis occurred in Japan. More than 4,500 isolates from patients with aseptic meningitis were identified as echovirus type 30. To investigate the character of these isolates, we examined the nucleotide sequences of thirty-seven geographical representatives and compared them with 50 strains isolated during the past 20 years. The phylogenic analysis used partial sequences from either the VP1 or VP4-VP2 region of the viral capsid. This analysis revealed that the isolates were divided into six genomic groups. All isolates identified during 1997-1998 belonged to only two genomic groups; these two groups are thought to be the causative viral agents involved in the recent epidemic.

Enterovirus B, Human↗

[Sense of coherence, stressful life events and psychological health].

Aaron Antonovsky's Sense of Coherence (SOC), as a stable disposition of personality that serves as a major coping resource for the preservation of health, has been widely used in many studies. However, few empirical studies are conducted on the concept of SOC. We examined the stability of SOC and the buffering effect of SOC on the psychological health in dealing with stressful life events. The subjects were 200 adults randomly selected in Tokyo, and follow-up survey was conducted one year after the first survey. Goldberg's General Health Questionnaire (GHQ) was used for assessing psychological health. Antonovsky's SOC scale was translated into Japanese (and reverse translated) in this study. The test-retest reliability of SOC scale was 0.78. Cronbach's alpha was 0.91. The factors related to the SOC supported previous findings and Antonovsky's theory about the positive correlation with educational and economic status. In the follow-up survey, the subjects were also asked about the experience of 56 stressful life events (SLE) composed of four aspects of life during the previous year: personal, family, work and environment. The SLE was assessed through the total number and the weighted score. Contrary to the theory, the results showed that the SOC score has no intra-individual stability. The mean score of SOC in 1998 was 131.1 +/- 23.9, significantly lower than that in the previous year. When the subjects were divided into two groups based on a median 1997 score, the effect of SLE negatively affected SOC scores after one year among those who had a low SOC, although this effect was not observed among those who had a high SOC. The effect of SLE on changes of SOC was stronger among men compared to women. Also, the results showed the SOC was positively related to psychological health, and the buffering effect of SOC on the psychological health in dealing with stressful life events was only observed among men. Findings in this study suggest that SOC is variable for those with weak SOC if they experienced stressful life events. Also, the stressful life events differentially affect the SOC among men and women. The buffering effect was not sufficiently proven in this study. Methodological issues to confirm Antonovsky's theory are also presented.

Adult↗

Enterovirus 71 from fatal and nonfatal cases of hand, foot and mouth disease epidemics in Malaysia, Japan and Taiwan in 1997-1998.

Enterovirus 71 (EV71), one of the major causative agents for hand, foot and mouth disease (HFMD), is sometimes associated with severe central nervous system diseases. In 1997, in Malaysia and Japan, and in 1998 in Taiwan, there were HFMD epidemics involving sudden deaths among young children, and EV71 was isolated from the HFMD patients, including the fatal cases. The nucleotide sequences of each EV71 isolate were determined and compared by phylogenetical analysis. EV71 strains from previously reported epidemics belonged to genotype A-1, while those from recent epidemics could be divided into two genotypes, A-2 and B. In Malaysia, genotype A-2 was more prevalent, while in Japan and Taiwan, B genotype was more prevalent. Two isolates from fatal cases in Malaysia and one isolate from a fatal case in Japan were genotype A-2. However, all isolates from three fatal cases in Taiwan belonged to genotype B. The severity of the HFMD did not link directly to certain genotypes of EV71.

DNA Primers↗

A method for in-situ tight-seal recordings from single taste bud cells of mice.

In order to investigate taste transduction mechanisms, we developed a method to irrigate the receptor and basolateral membranes of mouse taste bud cells with different solutions under tight-seal recording conditions. A peeled tongue epithelium with taste bud cells was mounted on a recording platform designed to separate irrigating solutions for each membrane. The mucosal surface (receptor membrane side) of the peeled epithelium facing an inner chamber was always irrigated with deionized water or stimulating solutions, and the serosal surface (basolateral membrane side) was irrigated with a physiological saline solution. A recording electrode was placed on the basolateral membrane of a taste bud cell under an upright-microscope with a x 40-water-immersed objective. Investigated taste bud cells generated action potentials, and 1 M glucose, 200 mM NaCl, and 10 mM quinine elicited inward current. Irrigation with deionized water for more than 1 h had no effect. The resistance of the peeled tongue epithelium was 1570 +/- 343 omega cm2. These results show that the peeled tongue epithelium protects basolateral membranes from deionized water or stimulating solutions as the tongue epithelium does in situ and that this method is suitable to investigate the role of each membrane in taste transduction.

Action Potentials↗

Synthesis and biological activity of conformationally restricted analogues of milnacipran: (1S, 2R)-1-phenyl-2-[(R)-1-amino-2-propynyl]-N,N- diethylcyclopropanecarboxamide is a novel class of NMDA receptor channel blocker.

Conformationally restricted analogues of (+/-)-(Z)-2-aminomethyl-1-phenyl-N,N-diethylcyclopropanecarboxamide++ + [milnacipran, (+/-)-1] were designed on the basis of its characteristic cyclopropane structure and were synthesized enantioselectively to develop efficient NMDA receptor antagonists. Among these analogues, (1S,2R)-1-phenyl-2-[(R)-1-amino-2-propynyl]-N, N-diethylcyclopropanecarboxamide (2d) had one of the most potent affinities for the receptor, with a Ki value of 0.29 microM. The blockade of NMDA receptor channels expressed by Xenopus oocytes by 2d was investigated in detail, and 2d was identified as a new class of open channel blocker against this receptor.

Animals↗

Present status and performance of SPring-8 front ends.

SPring-8 front ends have a novel structure which makes it easy to rearrange them and exchange the components. The structure has a common support for all the components except X-ray beam-position monitors and lead collimators. The alignment of the common support as well as the components was carried out with an accuracy of 0.25 mm in the vertical and horizontal directions. Replaceable pumping systems have also been placed on the common support and have achieved a vacuum of 2 x 10(-8) Pa at the upstream part of the front ends without synchrotron radiation. During the commissioning with synchrotron radiation, the pumping systems displayed good pumping-down characteristics. Commissioning has been successfully performed for four standard in-vacuum X-ray undulators and three bending-magnet-beamline front ends up to July 1997. Measurements of temperature rise show that absorber, pre-slits and XY slits can handle the anticipated maximum heat load at a ring current of 100 mA.

Journal Article↗

Antagonism between the suppressive effects of NH3 and CO2 on bullfrog taste nerve responses to quinine.

The suppression mechanism of NH3 and CO2 on bullfrog taste nerve responses to 0.1 mM quinine was investigated by applying them directly on the tongue surface (surface application) or at the tongue interstices through the lingual artery (interstitial application). The surface application of NH3 and CO2 reversibly suppressed the taste nerve responses with IC50 values of 0.37 mM and 2.2 mM, respectively, whereas their hydrates were ineffective. The interstitial application of NH3 reversibly suppressed the taste nerve responses. The surface application of CO2 recovered the suppressed responses to quinine. The 4 s application of CO2 prior to that of 0.1 mM quinine had the maximum effect. These results show that NH3-induced alkalosis and CO2-induced acidosis of taste cells, taste nerve endings, or tongue interstices surrounding them suppressed the taste nerve responses, and that the neutralization of their intracellular pH recovered these responses. The time-dependent recovery suggests that the neutralization at a layer inside taste cells, taste nerve endings, or the interstices surrounding them is critical in taste transduction.

Ammonia↗

Liquid chromatography of guanidino compounds using a porous graphite carbon column and application to their analysis in serum.

The retention mechanism of guanidino compounds on a porous graphitic carbon seemed to be mainly hydrophobic interaction, according to the retention factors in buffer solutions and the results of an analysis by computational chemical calculation using molecular mechanics (MM2). The baseline separation of ten guanidino compounds was achieved by the addition of a hydrophobic counterion. The retention mechanism may be dynamic ion-exchange. The stable system was applied to the analysis of guanidino compounds in serum from nephritic patients. The effluent was monitored by a post-column labeling detection method using ninhydrin. The detection limit of guanidino compounds was a few picomoles; however, that of creatinine was one hundredth of those of the other compounds. The reproducibilities of the peak height and area of the ten guanidino compounds using gradient elution were quite high, and the standard deviations were within a few percent (n=5), except for creatinine. The recovery of the compounds from serum was more than 90% (n=5). The reproducibility of retention times was within 1% (n=5).

Buffers↗

[Internalized norms and social norms relating to negative health behaviors. The relationship of sociodemographic characteristics and reference groups].

So-called "negative health behaviors" (e.g. smoking, excessive eating/drinking), which are related to morbidity and mortality, are generally well known to the public. However there are many who undertake negative health behaviors despite knowing of their negative health effects. Using a mail survey of subjects aged 25 to 54, we examined reasons and justifications for engaging in negative health behaviors and their related factors from the lay person's perspective. Concerning the reasons for negative health behaviors, we hypothesized seven concepts (work priority, group harmony priority, the contribution to relaxation, tools for communication, prior orientation focused on the present, individualistic priority, and appearance), and devised multiple questions for each concept. The results are as follows. 1. Compared to females, males tended to support of the five concepts about the internalized norms concerned with negative health behaviors (e.g. the tendency of each individual to approve or disapprove of the reasons for negative health behaviors). In females, the younger generation and those that were married expressed more support than the older and the unmarried. There were differences in males according to occupation. 2. Concerning which reference groups had the largest influence on the social norms concerned with negative health behaviors (e.g. the perceptions as to what degree a group regards the reasons about negative health behaviors as desirable), most perceived that the "office" and "friends" groups would be more supportive of reasons for negative health behaviors than the "family" groups. 3. The health behaviors, which correlated with the internalized norms or the social norms concerned with negative health behaviors, were eating breakfast, smoking, and drinking (frequency and amount). In particular, drinking behavior was influenced most by the internalized norms and the social norms.

Adult↗

In situ tight-seal recordings of taste substance-elicited action currents and voltage-gated Ba currents from single taste bud cells in the peeled epithelium of mouse tongue.

We investigated the taste responses of single taste-bud cells (TBCs) in mice by applying stimuli only on receptor membranes acclimated to deionized water under tight-seal cell-attached voltage-clamp conditions, while their basolateral membranes were irrigated with a physiological saline solution. For this irrigation, we developed a new method: a peeled-tongue epithelium with TBCs mounted on a recording chamber where the peeled epithelium separated the irrigating solutions for each membrane as it separated in situ. Although no quinine-elicited action potentials had been reported, TBCs elicited a long-lasting train of biphasic currents derived from the action potentials in response to 10 mM quinine, in addition to responses to 10 mM HCl, or 200 mM NaCl dissolved in deionized water. These results indicate that quinine as well as HCl and NaCl depolarizes TBCs and generate action potentials. Under whole-cell recording conditions, TBCs generated action potentials, and voltage-gated currents such as LVA and HVA Ca currents, TTX-sensitive Na currents, and TEA/4-AP-sensitive K currents on depolarization. These voltage-gated channels were shown to exist predominantly on the basolateral membranes. We discussed the receptor mechanisms and the role of taste substance-elicited action potentials.

Action Potentials↗

NH3- and CO2-induced suppression of taste nerve responses in clawed toads and eels.

We investigated the effects of intracellular pH values (pHi) on taste nerve responses of clawed toads and eels. (1) CO2, NH3 or trimethylamine reversibly suppressed the taste nerve responses of clawed toads to various amino acids, CaCl2 and caffeine. IC50 values of the suppression of the responses to 0.1 mM L-proline were as follows: approximately 10 mM for CO2, approximately 0.3 mM for NH3, approximately 0.2 mM for trimethylamine. (2) Cross-adaptation experiments showed that L-proline, caffeine and CaCl2 stimulated different receptor sites from each other, indicating the suppressive effect was non-specific. (3) Although CO2, NH3 or trimethylamine yielded the charged molecules, HCO3-, CO3(2-), NH4+ or trimethylammonium on hydration, none of these charged species suppressed taste responses. (4) NH3 increased the threshold concentration of L-proline by e-fold per 0.37 mM NH3 and decreased the maximum response to L-proline with increasing NH3 concentration. (5) The taste nerve responses of eels to 0.1 mM L-arginine, a potent stimulus on eel taste receptors, were similarly suppressed by NH3 with an IC50 value of approximately 0.3 mM. (6) These results indicated that these uncharged species changed pHi, which suppressed the taste responses. CO2-induced acidosis and NH3- or trimethylamine-induced alkalosis are likely to inhibit activities of ion channels or enzymes involved in taste transduction mechanisms.

Ammonia↗

Two major strains of type 1 wild poliovirus circulating in Indochina.

Two hundred ninety-four isolates from 329 patients with acute flaccid paralysis in Cambodia and Vietnam during 1992-1995 were identified as type 1 wild polioviruses. Among these isolates, 85 were selected as geographic representatives and were examined by determining the nucleotide sequences of their genome in the VP1 region. The phylogenic analysis revealed that all of the isolates examined were classified into groups A and B. Isolates belonging to group A had been found only in northern Vietnam until 1993 but not in 1994 and 1995. Group B isolates were located in both northern and southern Vietnam and Cambodia. In 1994 and 1995, however, only group B isolates were found in the Mekong Delta area in southern Vietnam and Cambodia. Isolates of groups A and B were genetically different from strains previously isolated in other Asian countries. One of the two indigenous wild polioviruses still remains to be eliminated in this area.

Antigens, Viral↗