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Biomedical subjects

T Kobayakawa

Publications and source records attributed to T Kobayakawa.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Differences in perception of everyday odors: a Japanese-German cross-cultural study.

There is a growing appreciation that experience with odors may strongly influence their perception. To further investigate this, the responses of 40 Japanese and 44 age-matched German women to everyday odorants were compared. Subjects were presented with 18 stimuli in squeeze bottles and asked to rate them according to intensity, familiarity, pleasantness and edibility, to describe associations elicited by them and, if possible, to name them. One-third of the odorants were presumed to be familiar to the Japanese only, one-third to the Germans and one-third to both populations. Significant differences were found between the two populations on all measures. Better performance by the Japanese in providing appropriate descriptors for 'Japanese' odorants and by the Germans for 'European' odorants supported the pre-selection of stimuli as culture-typical. Particularly clear differences between the two populations were found in pleasantness ratings. In general, a positive relationship was found between pleasantness and judgement of stimuli as edible, suggesting that culture-specific experiences-particularly of foods-may significantly influence odor perception. Somewhat unexpectedly, significant differences were also found between the two populations in intensity ratings for some odorants. These differences did not seem simply to be artefacts of the test situation and raise the possibility that experience may even influence such basic aspects of odor perception as stimulus intensity.

Cultural Characteristics↗
PubMed1998

[Primary health care in Thailand with community participation special reference to Japanese assistance].

The international health cooperation of Japan for developing countries has been mostly concentrated on matters such as improvement of hygienic environment, prevention of tropical infectious diseases, establishment of hospitals with modern medical instruments and devices, and dispatch of medical experts. PHC (Primary Health Care) activities based on voluntary participation of local inhabitants in developing countries have been largely neglected. In the field of health and medical care, sufficient effect may not be achieved unless the local health activity is based on voluntary participation of the inhabitants. The introduction of highly advanced modern medical techniques may be beneficial to some of the inhabitants, while most of the local inhabitants may not have the chance to receive such benefits, and additionally it is difficult to propagate modern medical care and technique widely to rural areas in Thailand. In Thailand, PHC activity based on community participation was started in 1985, with the following three items as main themes: (1) Training of Village Health Volunteers (VHV) and Village Health Communicators (VHC), and development of their activities. (2) Establishment and operation of Health Centers. (3) Establishment and operation of Drug Cooperative System (DC). Earlier, as one of PHC activities developed by Japan, "Thailand Local Health Activity Improvement Project" based on the program of Thailand-Japan Partnership was initiated in 1976 in rural areas of Chanthaburi Prefecture. From 1982, third country training programs have been carried out by Japan International Cooperation Agency (JICA). Since 10 years have elapsed the initiation of PHC activity in rural areas in Thailand under the cooperation of the Governments of Thailand and Japan, it seems to be time to reconsider and study again how PHC activity should be developed in future based on candid evaluation of achievements and results.

Attitude to Health↗
PubMed1996

The primary gustatory area in human cerebral cortex studied by magnetoencephalography.

Magnetic fields (MFs) from gustatory stimulation with 1 M NaCl and 3 mM saccharin were recorded from the human brain by using a whole-cortex SQUID system. The averaged onset latency of MFs was 93 ms for NaCl and 172 ms for saccharin and no response was obtained for water. A high correlation coefficient was noted between the difference of onset MFs latencies in two tastants and that of behavioral reaction times, and responses to saccharin were delayed or abolished after treatment of a subject's tongue with a sweet-suppressing agent. This finding indicates that the MFs obtained were caused by gustatory stimulation. By plotting the estimated current dipole on the magnetic resonance image, we could locate the primary gustatory area at the transition area between the operculum and insula, as reported in macaque monkeys.

Adult↗
PubMed1996

Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice.

To investigate the respective roles of Th1 and Th2 cells in the pathogenesis of lupus-like autoimmune disease, we have analyzed the spontaneous and antigen-induced productions of IgG1 vs IgG2a and IgG3 subclasses in relation to the mRNA expression of INF-gamma (Th1 cytokine promoting IgG2a and IgG3 production), IL-4 (Th2 cytokine promoting IgG1 production), and IL-10 (Th2 cytokine) in CD4+ T cells from lupus-prone MRL mice. For this purpose, two paired sets of MRL mice were chosen for the comparison of these parameters: (a) MRL-lpr/lpr (lpr for lymphoproliferation) and its recently described substrain with a prolonged survival, termed MRL-lpr/lpr.ll (ll for long lived) and (b) MRL male mice bearing the Yaa (Y-linked autoimmune acceleration) gene (MRL.Yaa) with an accelerated disease and their male counterparts lacking the Yaa gene. We demonstrate herein that the accelerated development of lupus-like autoimmune disease in MRL-lpr/lpr and MRL.Yaa mice, as compared with MRL-lpr/lpr.ll and MRL-+/+ mice, respectively, was correlated with an enhanced expression of IFN-gamma vs IL-4 and IL-10 mRNA in CD4+ T cells, which paralleled with an increase of spontaneous and foreign T cell-dependent antigen-induced productions of IgG2a and IgG3 vs IgG1 antibodies. These data suggest that an imbalance towards Th1 predominance may play a significant role in the acceleration of lupus-like autoimmune disease in MRL mice.

Animals↗
PubMed1995

The function of 5-HT3 receptors on colonic transit in rats.

The function of serotonin (5-HT)3 receptors on colonic transit was investigated in unanesthetized rats. The colonic transit was accelerated by 5-HT (10 mg/kg, s.c.), 2-methyl-5-HT (30 mg/kg, s.c.), neostigmine (0.03-0.1 mg/kg, s.c.), corticotropin releasing factor (CRF; 1 microgram intracerebroventricular administration) and restraint stress (for 45 minutes). A potent and selective 5-HT3 receptor antagonist, azasetron (+/-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro- 4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide monohydrochloride ; 0.01-10 mg/kg, p.o. inhibited the 5-HT-, CRF- and stress-accelerated colonic transit in a dose-dependent manner. Ondansetron (10 mg/kg, p.o.) and granisetron (1 mg/kg, p.o) also inhibited the stress-accelerated colonic transit, but azasetron was more effective than these two drugs. Atropine methylbromide (0.1 mg/kg, s.c.) and tetrodotoxin (0.01 mg/kg, s.c.) inhibited the accelerated colonic transit under stress conditions, but methysergide (10 mg/kg, s.c.), SDZ205-557 (10 mg/kg, s.c.), domperidone (30 mg/kg, p.o.), trimebutine (300 mg/kg, p.o.), did not. Azasetron (10 micrograms) administered intracerebroventricularly did not inhibit the stress-induced acceleration. These results suggest that endogenous 5-HT which is released through stress accelerates the colonic transit via the 5-HT3 receptors and finally a cholinergic mechanism. It is considered that azasetron inhibits colonic transit particularly under stress conditions through the blockade of the peripheral 5-HT3 receptors. Azasetron may improve bowel function in stress-related colonic dysfunction like irritable bowel syndrome.

Animals↗
PubMed1993

Ghana/JICA/WHO training course in polio diagnostic procedures and vaccine potency testing.

The Ghana/Japan International Cooperation Agency/WHO training course in polio diagnostic procedures and vaccine potency testing was initiated at the Noguchi Memorial Institute for Medical Research in Ghana for 5 consecutive years from 1992. The purpose of the course is to create virologists and technicians competent in the laboratory methods to support the polio eradication initiative in Africa. The participants are invited mainly from anglophone countries in the region.

Curriculum↗
PubMed1991

[MRI and arthrography in the evaluation of TMJ disorders].

Arthrosis of the temporomandibular joint (TMJ) is a noninfectious, noninflammatory condition characterized by joint pain, noise (clicking) and abnormal motion. It contains various disease processes, such as abnormalities in the menisci or masticating muscles, subluxation of the condyle and degenerative joint disease. Analysis of the morphology and dynamics of TMJ by means of imaging modalities has become highly advanced since the development of arthrography in the late 1970s. Magnetic resonance imaging (MRI) has become the modality of choice in the evaluation of TMJ owing to the development of surface coils. We retrospectively studied MRI and inferior joint compartment arthrography in the evaluation of TMJ disorders. Nineteen joints of 14 patients included 15 with internal derangement, two with osteoarthrosis and two normal joints. Sagittal MR images were routinely obtained in a resting position and in positions with the mouth half open, and also with the mouth fully open on balanced images. Although perforation of the menisci was difficult to evaluate, MRI and arthrography were equally useful in identifying the shape and position of the meniscus. However, MRI was more reliable in depicting TMJ abnormalities than arthrography. MR is considered to be the modality of choice in screening arthrosis of TMJ, making the definitive diagnosis of internal derangement and monitoring conservative therapy for arthrosis.

Adult↗
PubMed1987

Recovery from immunesuppression in mice infected with Schistosoma japonicum by treatment of praziquantel.

To learn the possible alteration of immune response, hemolytic plaque-forming cells (PFC) produced in the spleen of Schistosoma japonicum infected mice treated with Praziquantel and untreated group were counted. There was no significant difference in the immunesuppression percentage between the treated and untreated groups 1 and 3 weeks after treatment. In 5 weeks after treatment, however, the immunesuppression percentage in the treated mice was markedly reduced in comparison with that of the untreated group. Recovery from immunesuppression appears to be associated with elimination or impairment of adult worms.

Animals↗
PubMed1986

Protection against hepatic injury by a novel spiropiperidine derivative.

The evaluation of a novel hepatoprotective agent, Y-8845 (8(2-dimethylaminoethyl)-3-oxo-4-phenyl-1-thia-4,8-diazaspiro [4,5]decane dihydrochloride monohydrate), against carbon tetrachloride (CCl4)- and endotoxin-induced acute and chronic hepatic injury was carried out in rats. This compound, in a dose-dependent way, markedly reduced the increases in serum transaminase activities, the extent of liver cell necrosis, and the delay in indocyanine green (ICG) disappearance produced by a single toxic dosage of CCl4. This protective effect was observed even at doses of Y-8845 lower than 10 mg/kg po. It was also shown to protect the liver against injury induced by endotoxin. Furthermore, in the chronic liver injury induced by repeated administrations of CCl4 for 12 weeks, significant reductions of the increases in serum enzyme activities, liver fibrosis, and liver enlargement, and improvement in the ICG retention rate, were recognized in the Y-8845-treated groups at 10 mg/kg po or less. These findings indicate that this new agent has a remarkable protective effect, and possibly a therapeutic effect on liver injury.

Alanine Transaminase↗