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T Kobayakawa

Publications and source records attributed to T Kobayakawa.

At least 19 recordsLinked to original sources
PubMed2005

High-speed gas sensor for chemosensory event-related potentials or magnetic fields.

The observation of odor and air exchange with high temporal accuracy is necessary to obtain strict chemosensory event-related potentials (CSERPs) or magnetic fields, as proposed by Evans et al. [Evans W, Kobal G, Lorig T, Prah J. Suggestions for collection and reporting of chemosensory (olfactory) event-related potentials. Chem Senses, 1993; 18: 751- 6]. No suitable method for real time observation of gas stimuli, however, has been available until now. We have developed a technique to measure accurately gas molecule concentrations with a high temporal resolution. We determined that attenuation of sound amplitude varies in a manner dependent on the average molecular weight through which the sound wave passes. Based on this principle, we have designed a high-speed gas concentration sensor utilizing ultrasound. We investigated the practical potential of this sensor using a chemosensory stimulator (olfactometer); we succeeded in observing rapid gas exchange between air and nitrogen with a 2 kHz sampling rate. The signal/noise ratio of the stimulus was greater than 42 dB. In a 20 min experiment we determined that, for this olfactometer, the gas onset latency was 79 ms and the rise time was 16 ms. No significant artifact to magnetic fields was observed, even when the sensor was situated near a whole head magnetoencephalography (MEG) system. These results indicate that this sensor could be used for the observation of odor and air exchange, as well as, for real time monitoring of odor stimuli during actual experiments with a participant.

Algorithms↗
PubMed2005

Functional MRI detection of activation in the primary gustatory cortices in humans.

Magnetoencephalography (MEG) has recently revealed that the transitions between the parietal operculum (Pop) and the insula (area G) and the ventral end of the central sulcus (cs) were activated with the shortest latency by instrumental gustatory stimulation, which suggests that the location of the primary gustatory area is in these two regions. However, studies using other noninvasive brain-imaging methods such as positron-emission tomography or functional magnetic resonance imaging (fMRI) with manual application of tastants into the mouth have been unable to confirm this. The present study examined cortical activation by repetitive stimulation of the tongue tip with 1 M NaCl with a computer-controlled stimulator and used fMRI to detect it. In individual brains, activations were detected with multiple comparisons (false discovery rate) across the whole brain corrected (threshold at P < 0.05) at both area G and frontal operculum (Fop) in 8 of 11 subjects and at the rolandic operculum (Rop) in 7 subjects. Activations were also found at the ventral end of the cs (n = 3). Group analysis with random-effect models (multiple comparison using familywise error in regions of interest, P < 0.02) revealed activation at area G in both hemispheres and in the Fop, Rop, and ventral end of the cs on the left side. The present study revealed no activation on the gyrus of the external cerebral surface except for the Rop. Taking MEG findings into consideration, the present findings strongly indicate that the primary gustatory area is present at both the transition between the Pop and insula and the Rop including the gray matter within a ventral part of the cs.

Adult↗
PubMed2005

The disposition of oral amodiaquine in Papua New Guinean children with falciparum malaria.

AIMS: We assessed the disposition of oral amodiaquine (AQ) and CYP2C8 polymorphism in 20 children with falciparum malaria. METHODS: AQ and DEAQ concentrations were determined with SPE-HPLC method. CYP2C8 genotypes were assessed by PCR-RFLP method. RESULTS: AQ was not detectable beyond day 3 postdose. Cmax for DEAQ was reached in 3.0 days. The mean values for t1/2, MRT, and AUCtotal were 10.1 days, 15.5 days and 4512.6 microg l(-1) day, respectively. All the children were CYP2C8* homozygous. CONCLUSION: Our data are consistent with those previously reported, and the AQ regimen seems pharmacokinetically adequate in the absence of CYP2C8 polymorphism.

Administration, Oral↗
PubMed2003

High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi.

Malawi changed its national policy for malaria treatment in 1993, becoming the first country in Africa to replace chloroquine by sulfadoxine and pyrimethamine combination (SP) as the first-line drug for uncomplicated malaria. Seven years after this change, we investigated the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations, known to be associated with decreased sensitivity to SP, in 173 asymptomatic Plasmodium falciparum infections from Salima, Malawi. A high prevalence rate (78%) of parasites with triple Asn-108/Ile-51/Arg-59 dhfr and double Gly-437/Glu-540 dhps mutations was found. This 'quintuple mutant' is considered as a molecular marker for clinical failure of SP treatment of P. falciparum malaria. A total of 11 different dhfr and dhps combinations were detected, 3 of which were not previously reported. Nineteen isolates contained the single Glu-540 mutant dhps, while no isolate contained the single Gly-437 mutant dhps, an unexpected finding since Gly-437 are mostly assumed to be one of the first mutations commonly selected under sulfadoxine pressure. Two isolates contained the dhps single or double mutant coupled with dhfr wild-type. The high prevalence rates of the three dhfr mutations in our study were consistent with a previous survey in 1995 in Karonga, Malawi, whereas the prevalences of dhps mutations had increased, most probably as a result of the wide use of SP. A total of 52 P. falciparum isolates were also investigated for pyrimethamine and sulfadoxine/pyrimethamine activity against parasite growth according to WHO in vitro standard protocol. A pyrimethamine resistant profile was found. When pyrimethamine was combined with sulfadoxine, the mean EC(50) value decreased to less than one tenth of the pyrimethamine alone level. This synergistic activity may be explained by sulfadoxine inhibition of dhps despite the double mutations in the dhps genes, which would interact with pyrimethamine acting to block the remaining folate despite dhfr mutations in the low p-aminobenzoic acid and low folic acid medium mixed with blood.

Adolescent↗
PubMed2001

Domain-domain interactions of HtpG, an Escherichia coli homologue of eukaryotic HSP90 molecular chaperone.

In the present study, we investigated the domain structure and domain-domain interactions of HtpG, an Escherichia coli homologue of eukaryotic HSP90. Limited proteolysis of recombinant HtpG, revealed three major tryptic sites, i.e. Arg7-Gly8, Arg336-Glu337 and Lys552-Leu553, of which the latter two were located at the positions equivalent to the major cleavage sites of human HSP90alpha. A similar pattern was obtained by papain treatment under nondenaturing conditions but not under denaturing conditions. Thus, HtpG consists of three domains, i.e. Domain A, Met1-Arg336; domain B, Glu337-Lys552; and domain C, Leu553-Ser624, as does HSP90. The domains of HtpG were expressed and their interactions were estimated on polyacrylamide gel electrophoresis under nondenaturing conditions. As a result, two kinds of domain-domain interactions were revealed: domain B interaction with domain A of the same polypeptide and domain C of one partner with domain B of the other in the dimer. Domain B could be structurally and functionally divided into two subdomains, the N-terminal two-thirds (subdomain BI) that interacted with domain A and the C-terminal one-third (subdomain BII) that interacted with domain C. The C-terminal two-thirds of domain A, i.e. Asp116-Arg336, were sufficient for the binding to domain B. We finally propose the domain organization of an HtpG dimer.

Amino Acid Sequence↗
PubMed2001

Enhancement of sweetness ratings of aspartame by a vanilla odor presented either by orthonasal or retronasal routes.

When taste stimuli are presented with specific odor stimuli, the perceived intensity of taste is enhanced, a phenomenon called odor-induced taste enhancement. There is a possibility, however, that the odor substances might have stimulated the taste receptors in the oral cavity as well as odor receptors in the nasal cavity because the odor substances were dissolved in the taste solutions in some preceding studies. Schifferstein and Verlegh (1996) found that the odor-induced taste enhancement effect was not found when the subjects wore a nose clip to prevent the olfactory perception. Thus, it was suggested that the odor-induced taste enhancement did not result from the stimulation of receptors in the oral cavity. To confirm and extend their study, we presented the odor stimuli simultaneously with, but not dissolved in, the taste stimuli with a more advanced approach to stimulus presentation. The participants reported enhancement of sweetness ratings for aspartame when the taste stimuli were presented with a vanilla odor. This odor induced taste enhancement was found when the gaseous odor stimuli were presented either by the retronasal route or by the orthonasal route. There was little possibility that the vanilla odor stimulated the taste receptors during the orthonasal stimulation because the odor stimuli were presented directly into the nasal cavity. Thus, we could show that the odor-induced taste enlancement is elicited by olfactory perception. These results also suggested that there is little functional difference between retronasal and orthonasal olfaction.

Administration, Oral↗
PubMed2000

Malaria eradication on islands.

BACKGROUND: To be successful, a malaria control programme needs to be tailored to the local epidemiological characteristics. Vanuatu consists of 80 inhabited islands in the Southwest Pacific, with hypoendemic and mesoendemic malaria and suitable conditions for sustained parasite elimination. We aimed to assess whether malaria can be eliminated on isolated islands. METHODS: Weekly mass drug administration of chloroquine, pyrimethamine/sulfadoxine (Fansidar), and primaquine was carried out on the entire population of 718 inhabitants of Aneityum island for 9 weeks in 1991 before the onset of the rainy season. Simultaneously with the administration of drugs, permethrin-impregnated bednets were distributed to the entire population. Larvivorous fish were also introduced into several identified breeding sites of Anopheles farauti. Periodic malariometric monitoring has continued for the past 9 years. Two additional islands of Vanuatu, one with and one without malaria transmission, have been monitored for comparison. FINDINGS: High community involvement as measured by drug compliance (88.3%) and bednet provision (0.94 nets per villager) has resulted in sustained interruption of malaria transmission in Aneityum. The surveys showed complete absence of Plasmodium falciparum after mass drug administration, and P. vivax disappeared from 1996 onwards, with the exception of two instances of imported infections (one mixed infection in 1993 and one P. vivax infection in 1999). INTERPRETATION: Malaria can be eliminated on isolated islands with well-adapted short-term mass drug administration and sustained vector control if there is a high degree of community participation.

Adolescent↗
PubMed2000

Decline in taste and odor discrimination abilities with age, and relationship between gustation and olfaction.

It is important to learn about changes in both taste and odor perceptions with increasing age, because the taste of foods we encounter in our daily life is strongly affected by their smell. This study discusses the difference in qualitative taste and odor discrimination between the elderly and the young. Tastants and odorants used in this study were presented not as single stimuli but as a taste mixture (sucrose and tartaric acid) and an odor mixture (beta-phenylethyl alcohol and gamma-undecalactone). The results showed that quality discrimination abilities of the elderly subjects for both taste and odor were significantly lower than those of the young subjects, indicating a decline in quality discrimination abilities related to age. Also, a moderate but significant correlation was observed between the taste discrimination ability and the odor discrimination ability. We measured thresholds for single-taste and odor components in mixtures and compared them between the elderly and the young to investigate the cause for these findings.

Adult↗
PubMed1999

CD4+ and/or gammadelta+ T cells in the liver spontaneously produce IL-4 in vitro during the early phase of Leishmania major infection in susceptible BALB/c mice.

Numerous studies on the cytokine production profile in Leishmania major infected susceptible and resistant mice have been carried out to elucidate the mechanisms of healing or non-healing of this infection. However, many methods may have failed to detect the actual cytokine production in the inflammatory foci. To overcome this problems, the ELISPOT assay was used to examine the spontaneous production of IL-4 and IFN-gamma in vitro by mononuclear cells from the spleen, lymph nodes and liver in L. major-infected susceptible BALB/c and resistant C57BL/6 mice. None of these mononuclear cells spontaneously produced IFN-gamma in either mouse strains in vitro in the absence of the corresponding antigen(s). However, liver mononuclear cells from infected BALB/c mice spontaneously produced IL-4 in vitro in as early as 2 weeks after the infection, but this was not observed in C57BL/6 mice. The IL-4 producing liver lymphocytes consisted of CD4+ and/or gammadelta+ T cells and uncharacterized cells. These results suggest that liver lymphocytes play some role in the establishment of Th2 prevalence in susceptible BALB/c mice, based on the importance of IL.4 production in the early phase of L. major infection in establishing Th2 dominance in this parasite susceptible mouse.

Animals↗
PubMed1999

Immune response against protozoal and nematodal infection in mice with underlying Schistosoma mansoni infection.

Schistosoma mansoni infection induces T helper (Th) 2-dominant immune response in mice not only to S. mansoni itself but also to other coexisting antigens. In the present study, we challenged S. mansoni-infected mice with the intestinal nematode, Strongyloides venezuelensis, and the intracellular protozoa, Leishmania major to see whether such Th2-dominant immune responses alter susceptibility of the host to other concomitant parasitic infections. The recovery of S. venezuelensis adult worms from the small intestine was significantly decreased by S. mansoni infection, and the protection to S. venezuelensis appeared to act on migrating larvae. Antibodies elicited by S. mansoni infection showed cross-binding to third-stage larvae antigen of S. venezuelensis. On the other hand, S. mansoni infection did not affect the outcome of L. major infection in both susceptible BALB/c and resistant C57BL/6 mice. Popliteal lymph node cells of BALB/c mice expressed mRNA for interleukin (IL)-10 rather than IL-4, regardless of S. mansoni infection, and those of C57BL/6 mice expressed IFN-gamma mRNA upon L. major antigen stimulation, even in S. mansoni-infected mice. Our findings suggest that Th2-dominant immune response induced by S. mansoni protects mice from intestinal helminthic infections, whereas they do not always modulate protozoal infections.

Animals↗
PubMed1999

Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil.

Mutations in human CYP2C19 and parasite dihydrofolate reductase (dhfr) genes, related to poor metabolism of proguanil and resistance to cycloguanil, respectively, have both been assumed to be associated with poor antimalarial effect by proguanil. To study this, 95 subjects with uncomplicated Plasmodium falciparum or Plasmodium vivax infections in Vanuatu received proguanil treatment for 3 days (adult relative dose of 300-500 mg/day) and were followed up for 28 days. A similarly high antimalarial efficacy against both infections was observed in 62 patients with CYP2C19-related poor metabolizer genotype and in 33 with extensive metabolizer genotype, even though blood cycloguanil was significantly more often detected in those with extensive metabolizer genotype than in those with poor metabolizer genotype. All 28 P. falciparum isolates had two dhfr mutations (residues 59 and 108), suggesting moderate resistance to cycloguanil. The results suggest that the parent compound proguanil has significant intrinsic efficacy against falciparum and vivax malaria independent of the metabolite cycloguanil.

Adolescent↗
PubMed1999

Perception of everyday odors--correlation between intensity, familiarity and strength of hedonic judgement.

In this study, 40 Japanese, 44 German and 39 Mexican women were presented with 18 everyday odorants. They were asked to rate them for intensity on a six-point scale from not detectable to very strong, for pleasantness on an 11-point scale from -5, to neutral at 0, to +5, and for familiarity on a six-point scale from completely unknown to extremely familiar. Consistent positive correlations were found between paired rating scores for the three measures, and although they were not particularly strong (r(s) range, 0.19-0.60), for most odorants all three correlations were significant. Similar results were obtained whether the data were analyzed on an individual or a national basis. Most notable were the consistent positive correlations between perceived intensity and ratings of familiarity and hedonic strength. It is suggested that the perceived intensity of the odorants depended not only on stimulus concentration but probably also on experience-dependent factors.

Adult↗
PubMed1999

Spatio-temporal analysis of cortical activity evoked by gustatory stimulation in humans.

Gustatory activated regions in the cerebral cortex have not been identified precisely in humans. In this study we recorded the magnetic fields from the brain in response to two tastants, 1 M NaCl and 3 mM saccharin. We estimated the location of areas activated sequentially after the onset of stimulation with magnetic source imaging. We investigated the primary gustatory area (area G) precisely, and found it at the transition between the parietal operculum and the insular cortex. The central sulcus was activated less frequently than area G but with almost the same latency in cases of NaCl stimulation. Following area G, we found activation in several cortical regions, e.g. both the frontal operculum and the anterior part of the insula, the hippocampus, the parahippocampal gyrus and the superior temporal sulcus.

Adult↗
PubMed1999

Proguanil disposition and toxicity in malaria patients from Vanuatu with high frequencies of CYP2C19 mutations.

The increasing resistance of falciparum malaria to common antimalarial drugs has renewed interest in the compound proguanil normally metabolized to cycloguanil, a strong dihydrofolate reductase inhibitor, via the cytochrome P450 isozyme CYP2C19. The relationship between CYP2C19 genotypes and proguanil metabolism was therefore studied in 100 uncomplicated malaria patients on Malakula island in Vanuatu, where a CYP2C19-related poor metabolizer genotype status was known to be frequent. The patients (median age, 7 years) with Plasmodium falciparum or P. vivax infections, received proguanil treatment for 3 days in daily doses corresponding to adult doses of 300-500 mg. Capillary blood samples were collected on filter paper for determining both human CYP2C19 mutations by polymerase chain reaction and mutation-specific restriction enzyme digestion and blood concentrations of proguanil and its metabolites by high-performance liquid chromatography. The frequencies of the defective alleles, CYP2C19*2 and CYP2C19*3, were 0.57 and 0.25, respectively. The patients were genotyped as 68 CYP2C19-related poor metabolizers and 32 extensive metabolizers. Proguanil concentrations were higher and cycloguanil and 4-chlorophenylbiguanide concentrations were lower in poor compared to extensive metabolizers. Among the extensive metabolizers, 27 were heterozygous and five were homozygous for unmutated alleles. The tendency of an intermediate degree of proguanil metabolism in heterozygous extensive metabolizers as compared to homozygous extensive metabolizers and poor metabolizers suggests the trend towards the existence of a gene dose effect. Mild adverse events (mainly gastro-intestinal symptoms) were often reported and positively correlated with proguanil concentrations. The incidence was, however, similar in poor and extensive metabolizers. In conclusion, our data demonstrate an association between CYP2C19 mutations and poor metabolism of proguanil.

Antimalarials↗