Search PubMed⌕ Search

Biomedical subjects

T Kobayakawa

Publications and source records attributed to T Kobayakawa.

At least 19 recordsLinked to original sources
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↗
PubMed1999

High and variable frequencies of CYP2C19 mutations: medical consequences of poor drug metabolism in Vanuatu and other Pacific islands.

Cytochrome P450 (CYP) 2C19 is polymorphic with poor metabolizers representing 3-6% of Europeans and Africans, and 13-23% of Asians. Greater than 99% of the poor metabolizer alleles in Asian populations are defined by two single base pair mutations (CYP2C19*2 and CYP2C19*3). We have recently reported an unprecedentedly high prevalence (71%) of CYP2C19-related poor metabolizer genotype individuals and poor metabolism of proguanil on two malarious islands of Vanuatu in eastern Melanesia. To elucidate this further, a total of 5538 individuals from 24 populations on 16 different islands of Vanuatu were genotyped. Of these, 61% had a poor metabolizer genotype (*2/*2, *2/*3 or *3/*3) with substantial variation among the populations (38-79%). The overall frequencies of CYP2C19*1 (wild-type), CYP2C19*2, and CYP2C19*3 were 0.223, 0.633, and 0.144, respectively. A significant linear correlation was observed between heterozygosity and South latitude (r = 0.552, P < 0.05). The genotype frequencies of 21 of the 24 populations were consistent with Hardy-Weinberg expectations (P > 0.05). Comparisons of genetic, linguistic and geographical patterns among populations suggest that short range gene flow is largely responsible for the current distribution of CYP2C19 alleles in Vanuatu. Taken together with previous studies of nuclear genetic loci of Pacific island populations, these data predict that the poor metabolizer genotype is common throughout Polynesia and Micronesia and may be even more prevalent in western Melanesia than in Vanuatu. This suggests that the majority of Pacific Islanders metabolize a wide variety of clinically important drugs to a significantly lower degree than the average European.

Antimalarials↗
PubMed1998

Temporal process from receptors to higher brain in taste detection studied by gustatory-evoked magnetic fields and reaction times.

Using magnetoencephalography (MEG) and a taste stimulator with rapid-rise time, we previously located the primary gustatory area in the human cerebral cortex and also investigated the relation between the onset latency of the gustatory-evoked magnetic fields (GEM) and reaction times (RT) in different taste qualities. In the present study, we investigated the temporal process from receptors to the higher brain in taste detection based on the results of the GEM and RT of different tastes. We used 100 mM, 300 mM and 1 M NaCl and 3 mM saccharine. The duration of each stimulus was 400 ms. The interstimulus interval was approximately 30 s. The temperature of both taste solution and deionized water was maintained the same as that of the tongue. Four subjects participated in this experiment. The 64-channel whole-head SQUID system (CTF Systems Inc., Canada) was used to measure GEM. The sampling rate was 250 Hz, and the low-pass filter was 40 Hz. In each subject, GEM and RT to a given taste were measured separately by applying 40 trials of stimulation. After each trial of both measurements, subjects showed a perceived intensity by using their fingers. In the GEM study, the trials contaminated with eye movements were rejected and the remaining trials were averaged. Averaged GEM were super-imposed on the same sheet with all 64 channels to measure the onset latency of GEM from the stimulus onset. RT and onset latencies of GEM were longer for saccharine than NaCl, and the value of RT minus the onset latency of GEM from RT, presumably indicating the time for higher brain process plus motor process, did not differ between 3 mM saccharine and 1 M NaCl. With increased concentrations of NaCl, RT became shorter, but onset latencies of GEM remained constant. Sweet taste took a longer time than salty taste at receptor process including the time for diffusion to receptors.

Cerebral Cortex↗
PubMed1998

Malaria epidemiology, glucose 6-phosphate dehydrogenase deficiency and human settlement in the Vanuatu Archipelago.

Vanuatu is located at the southeast margin of the malarious band extending from southeast Asia to eastern Melanesia. We analysed the malaria situation on different islands of Vanuatu, using passive case detection and malariometric survey data from 1985 to 1992, i.e. after the DDT residual programme ceased and before the impregnated bed-nets programme started on a larger scale. Malaria was mainly hypo-mesoendemic but with hyperendemic spots in certain years and on some islands. The transmission was generally more intense in the northern islands than in the south. In the late 1980s, annual parasite incidence per one thousand population (API) was around 180. The overall parasite rate was 11.9% with Plasmodium falciparum, P. vivax and P. malariae rate of 5.2, 6.7, and 0.1%, respectively. There was a seasonal fluctuation of P. falciparum incidence, whereas the P. vivax incidence was rather stable. Vivax malaria was confined to children less than 10 years old, while the intense in the northern islands than in the south. In the late 1980s, annual parasite incidence per one thousand population (API) was around 180. The overall parasite rate was 11.9% with Plasmodium falciparum, P. vivax and P. malariae rate of 5.2, 6.7, and 0.1%, respectively. There was a seasonal fluctuation of P. falciparum incidence, whereas the P. vivax incidence prevalence of P. falciparum only changed moderately with age. The mean rate of glucose 6-phosphate dehydrogenase (G6PD) deficiency among male subjects was in 7.4% but with a wide variation of 0-14.3% on different islands. A positive rank-order correlation was found between malaria incidence and G6PD deficiency rate on the different islands. A reasonable hypothesis is that malaria was introduced to the islands with the first human settlement 4000 years ago, with a geographical malaria distribution similar to the present situation. Different malaria endemicities possibly then selected different prevalences of G6PD deficiency over many generations.

Adolescent↗
PubMed1998

Effect of genetic background on Ea(d) transgene-mediated protection from murine lupus.

The expression of a transgenic encoding the I-E alpha-chain, Ea(d), is highly effective in the protection from systemic lupus erythematosus (SLE) in BXSB and (MRL x BXSB)F1 male mice, in which a mutant gene, Yaa (Y-linked autoimmune acceleration), plays a critical role. To gain further insight into the protective role of the Ea(d) transgene, we compared the effect of the transgene in two additional lupus-prone (NZB x BXSB)F1 and (NZW x BXSB)F1 hybrid mice, in which both F1 female mice develop typical SLE in the absence of the Yaa gene and their F1 males bearing the Yaa gene develop a more accelerated form of SLE. Comparative analysis of the clinical development of SLE in these F1 hybrid mice showed that Ea(d) transgene expression was much more effective in the protection from SLE occurring in the F1 females than in their male counterparts. Our results indicate that the Ea(d) transgene is capable of preventing SLE by inhibiting autoimmune responses, independently of the Yaa gene-accelerating effect, and that its protective capacity is strongly influenced by the genetic susceptibility to SLE in individual strains of lupus-prone mice. In addition, this autoimmune inhibitory effect was shown to be selective for IgG, but not IgM, anti-DNA autoantibody production, and is more specific for anti-gp70 autoantibody than for anti-DNA autoantibody. These results favour the hypothesis that the transgene expression may lead to the modulation of self-peptide presentation, thereby preventing excessive T-cell-dependent activation of autoreactive B cells.

Animals↗
PubMed1998

Role of neutrophils in murine cryoglobulinemia.

Murine IgG3 anti-IgG2a rheumatoid factor (RF) monoclonal antibodies (mAb) with cryoglobulin activity, are able to induce, in normal mice, skin leukocytoclastic vasculitis and lupus-like glomerulonephritis resembling 'wire-loop' lesions (subendothelial immune deposits). The development of glomerular, but not skin, lesions in immunoglobulin-deficient mice (lacking the corresponding IgG2a autoantigen) receiving IgG3 RF cryoglobulins indicates that the RF activity of IgG3 monoclonal cryoglobulins and subsequent formation of IgG3-IgG2a immune complexes play a critical role in the development of skin vasculitis. In contrast, nephritogenic activity is solely contributed by IgG3-associated cryoglobulin activity. Polymorphonuclear leukocyte (PMN) infiltration is one of the major pathologic changes observed in both types of lesions. Treatment with mAbs against the adhesion molecules leukocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) (both known for their involvement in PMN-endothelial cell interaction) inhibits the development of skin vascular lesions. However, it has no effect on the generation of glomerulonephritis. Apparently, adhesion molecule requirements for PMN interaction with glomerular capillary endothelial cells are different from those for PMN infiltration of the skin. However, the PMN depletion experiment has clearly shown that PMNs play an active role in the development of 'wire-loop' glomerular lesions. In the absence of the glomerular PMN infiltration, IgG3 RF cryoglobulins induce a different type of glomerular lesion, characterized by voluminous intracapillary thrombi and mesangial deposits, yet lacking subendothelial deposits. This is consistent with the fact that the latter lesions can be induced by certain IgG3 mAbs, which are unable to provoke glomerular PMN infiltration. Finally, the activation of the complement system does not appear to play a major role in either skin or glomerular lesions induced by IgG3 RF cryoglobulins.

Animals↗