PubMed Health⌕ Search

Biomedical subjects

K Ogasawara

Publications and source records attributed to K Ogasawara.

At least 19 recordsLinked to original sources
PubMed2006

Novel cynomolgus macaque MHC-DPB1 polymorphisms in three South-East Asian populations.

Cynomolgus macaques (Macaca fascicularis, Mafa), alias the crab-eating monkeys or long-tailed macaques, live across a vast range of South-East Asia. These non-human primates have emerged as important animal models in infectious and chronic diseases and transplantation studies, necessitating a more extensive characterization of their major histocompatibility complex polymorphic regions. The current information on the polymorphic variation or diversity of the Mafa-DPB1 locus is largely limited in comparison with the more commonly studied rhesus macaque DPB1 locus. In this article, to better elucidate the degree and types of polymorphisms and genetic differences of Mafa-DPB1 locus among three South-East Asian populations and to investigate how the allele differences between macaques and humans might affect their respective immune responses, we identified 40 alleles within exon 2 of the Mafa-DPB1 locus by DNA sequencing using 217 individuals. We also performed evolutionary and population analyses using these sequences to reveal some population-specific alleles and trans-species allelic conservation between the cynomolgus macaques and the rhesus macaques. Of the 40 new alleles, eight belong to a newly identified lineage group not previously found in the rhesus macaque species. This allele information will be useful for medical researchers using the cynomolgus macaques in disease and immunological studies.

Alleles↗
PubMed2005

A ninety-day oral toxicity study of a new type of processed gum arabic, from Acacia tree (Acacia senegal) exudates, in F344 rats.

This study was designed to evaluate and characterize any subchronic toxicity of a new type of gum arabic (SUPER GUM [Acacia(sen)SUPER GUM]), a naturally processed polysaccharide exudate from gum acacia trees (Acacia senegal), when administered to both sexes of F344 rats at dietary levels of 0 (control), 1.25%, 2.5%, and 5.0% (10 rats/sex/group). During the study, the treatment had no effects on clinical signs, survival, body weights, and food and water consumption, or on findings of urinalysis, ophthalmology, hematology, or blood biochemistry. Gross pathology and histopathology exhibited no differences of toxicological significance between control and treated rats. Increased relative cecum (filled) weights, evident in both sexes of 5.0% group and females of 1.25% and 2.5% groups, were considered to be a physiological adaptation. Thus, the results indicated the toxic level of SUPER GUM to be more than 5.0%, and the no observed adverse effect level (NOAEL) was concluded to be 5.0% (3,117 mg/kg body weights/day for males, and 3,296 mg/kg body weights/day for males) from the present study.

Administration, Oral↗
PubMed2003

Comparative antimicrobial activities of gatifloxacin, sitafloxacin and levofloxacin against Mycobacterium tuberculosis replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines.

Mycobacterium tuberculosis (MTB) is capable of invading not only macrophages (Mphis) but also type II pneumocytes. In this study, we compared the antimicrobial activities of fluoroquinolones, including gatifloxacin, sitafloxacin and levofloxacin, against the MTB replication in the Mono Mac 6 human Mphi cell line (MM6-Mphis) and the A-549 human type II alveolar epithelial cell line (A-549 cells). When test quinolones were added at the MIC (0.125, 0.06 and 0.25 mg/l for gatifloxacin, sitafloxacin and levofloxacin, respectively) to the culture media of MTB-infected cells, these drugs exerted growth-inhibitory activity against intracellular organisms in the order of sitafloxacin > gatifloxacin > levofloxacin. On the other hand, when test quinolones were added at Cmax in the blood (1.7, 1.0 and 2.0 mg/l for gatifloxacin, sitafloxacin and levofloxacin, respectively), these drugs exhibited bactericidal activity against intracellular MTB in the order of gatifloxacin > sitafloxacin > or = levofloxacin. In addition, when test drugs were added at 1/8 C(max) to 1/2 C(max), the efficacy was in the order of sitafloxacin > gatifloxacin > levofloxacin. Thus, it appears that the MIC values of fluoroquinolones are not always predictive of their antimicrobial activity against intracellular MTB. In this context, it was also found that intracellular uptake of these quinolones by MM6-Mphis and A-549 cells was in the order of sitafloxacin > gatifloxacin > levofloxacin. This implies that the cellular permeability of these quinolones is an important factor that determines their efficacy to eliminate intracellular MTB organisms.

Anti-Infective Agents↗
PubMed2003

Effect of calcium antagonist on cerebral blood flow and oxygen metabolism in patients with hypertension and chronic major cerebral artery occlusion: a positron emission tomography study.

To evaluate the effect of a calcium antagonist, nilvadipine, on cerebral blood flow and oxygen metabolism, we prospectively examined five ischaemic stroke patients, with both hypertension and chronic major cerebral artery occlusion, using positron emission tomography. The blood pressure showed a significant decrease after 3 months of nilvadipine treatment, the cerebral blood flow in the affected regions showed a significant increase and the oxygen extraction fraction showed a significant decrease. We conclude that nilvadipine is a safe and effective anti-hypertensive agent for patients with both hypertension and chronic major cerebral artery occlusion.

Aged↗
PubMed2002

Profiles of cell-to-cell interaction of Mycobacterium intracellulare-induced immunosuppressive macrophages with target T cells in terms of suppressor signal transmission.

Previously, we have found that immunosuppressive macrophages (M(phi)s) induced by Mycobacterium intracellulare-infection (MI-M(phi)s) required cell contact with target T cells to express their suppressor activity against concanavalin A (Con A)-induced T cell mitogenesis. In this study, we examined the profiles of cell-to-cell interaction of MI-M(phi)s with target T cells. First, MI-M(phi)s displayed suppressor activity in an H-2 allele-unrestricted manner, indicating that MHC molecules are not required for cell contact. The suppressor activity of MI-M(phi)s was reduced markedly by paraformaldehyde fixation or treatment with cytochalasin B or colchicine, indicating that vital membrane functions are required for their suppressor activity. Secondly, the suppressor activity of MI-M(phi)s was independent of cell-to-cell interaction via CD40 ligand/CD40 and M(phi)-derived indoleamine 2,3-dioxygenase, which causes rapid degradation of tryptophan in T cells. Thirdly, precultivation of splenocytes with MI-M(phi)s, allowing cell-to-cell contact, reduced Con A- or anti-CD3 antibody-induced mitogenesis but not phorbol myristate acetate/calcium ionophore A23187-elicited proliferation of T cells. In addition, co-cultivation of T cells with MI-M(phi)s caused marked changes in profiles of the tyrosine phosphorylation of 33 kDa, 34 kDa and 35-kDa proteins and, moreover, the activation of protein kinase C and its translocation to the cell membrane. It thus appears that suppressor signals of MI-M(phi)s, which are transmitted to the target T cells via cell contact, principally cross-talk with the early signalling events before the activation of PKC and/or intracellular calcium mobilization.

Animals↗
PubMed2002

Comparison of computer-based information support to clinical research in Chinese and Japanese hospitals: a postal survey of clinicians' views.

OBJECTIVES: The objectives of this research are to examine the current situation of computer-based information support of clinical research in hospitals and to determine the expectations of clinicians toward clinical research support functions of hospital information systems (HISs) in both China and Japan. METHODS: 172 clinicians from 42 major hospitals in China (2 groups), and 568 clinicians from 79 university hospitals in Japan (2 groups), were surveyed by postal questionnaire during July and August, 1999. The Kruskal-Wallis test was performed to analyze the differences among the groups. RESULTS: The total response rate was 66.9%. The result shows that 94.8% of the Japanese clinicians, 3.5 times more than those in China, use computers almost every day. High significance was shown for the frequency of non-HIS based information resources used by clinicians between China and Japan (p < 0.001), whereas no significance for the frequency of HIS use by clinicians between the China I and Japan I groups (p = 0.725) was found. 33.3% clinicians in China thought they could obtain 30-50% of the necessary patient data for clinical research from the HIS, about 2 times more than in Japan (p = 0.009). CONCLUSIONS: Although the degree of computer involvement among clinicians in Japan is much higher than in China, the computer-based hospital information systems have not been developed well for supporting clinical research in both countries. The clinicians expect comprehensive computerized patient records (CPRs) and full use of patient related information in the existing HISs to support their clinical research.

Attitude to Computers↗
PubMed2001

Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial.

CONTEXT: The practice of administering weekly courses of antenatal corticosteroids to pregnant women at risk of preterm delivery is widespread, but no randomized trial has established the efficacy or safety of this practice. OBJECTIVES: To evaluate the efficacy of weekly administration of antenatal corticosteroids compared with a single course in reducing the incidence of neonatal morbidity and to evaluate potential complications of weekly treatment. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled intention-to-treat trial conducted in 13 academic centers in the United States from February 1996 through April 2000. PARTICIPANTS: A total of 502 pregnant women between 24 and 32 completed weeks' gestation who were at high risk of preterm delivery. INTERVENTION: All patients received a complete single course of antenatal corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for 4 doses). Participants who had not delivered 1 week after receipt of the single course were randomly assigned to receive either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks' gestation or delivery, whichever came first (n = 256), or a similarly administered placebo (n = 246). MAIN OUTCOME MEASURE: Composite neonatal morbidity (including severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death). RESULTS: Composite morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single-course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses was associated with a reduction in composite morbidity. CONCLUSIONS: Weekly courses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment. Weekly courses of antenatal corticosteroids should not be routinely prescribed for women at risk of preterm delivery.

Betamethasone↗
PubMed2001

Genes highly expressed in the early phase of murine graft-versus-host reaction.

Graft-versus-host reaction (GVHR) is a complex process initiated upon allorecognition. For detection of early molecular events in GVHR, we first assessed time courses with respect to symptoms and serum interferon (IFN)-gamma levels and then used the differential display method to compare gene transcript patterns during the early phase between acute lethal GVHR mice and syngeneic controls. In the GVHR mice, high expression levels of seven genes encoding the following molecules were detected: TGTP/Mg21 (an IFN-gamma-related signaling molecule), vitronectin, Nedd5 (a mammalian septin), manganese superoxide dismutase, activin betaC subunit, PRCC (a papillary renal cell carcinoma-associated molecule), and an uncharacterized gene corresponding to a mouse expressed sequence tag (EST). The expression levels of most genes peaked before the symptomatological onset and the peak of IFN-gamma levels. Thus, gene expression monitoring may characterize the inductive process of GVHR and aid in the development of gene-based diagnostics and therapies.

Animals↗
PubMed2001

Defective development of NK1.1+ T-cell antigen receptor alphabeta+ cells in zeta-associated protein 70 null mice with an accumulation of NK1.1+ CD3- NK-like cells in the thymus.

Development of natural killer 1.1+ (NK1.1+) CD3+ (NK1.1+ T) cells was analyzed in zeta-associated protein 70 (ZAP-70) null ((-/-)) mice. Both NK1.1+ TCRalphabeta+ and NK1.1+ TCRgammadelta+ cell populations were absent in the thymus and spleen. By contrast, the number of NK1.1+ CD3- cells was increased in these tissues. The NK1.1+ CD3- thymocytes in ZAP-70(-/-) mice had surface phenotypes in common with NK or NK1.1+ T cells. However, some of them were discordant either with NK cells or with NK1.1+ T cells. The NK1.1+ CD3- cells produced interferon-gamma upon stimulation with NK1.1 cross-linking in the presence of interleukin-2 and exhibited a substantial cytotoxicity against YAC-1 cells. Moreover, the generation of NK1.1+ T cells with invariant Valpha14Jalpha281 chains was induced from the NK1.1+ CD3- thymocytes following stimulation with phorbol myristate acetate and ionomycin in a neonatal thymic organ culture. An introduction of TCRalpha and beta transgenes to the ZAP-70(-/-) mice resulted in generation of an NK1.1+ TCRalphabeta(dim) population, whereas no substantial CD4+ CD8- or CD4- CD8+ population that expressed the introduced TCRalphabeta was generated in the mainstream T lineage. These findings demonstrate that ZAP-70 kinase is indispensable for the development of NK1.1+ T cells and that the unique NK1.1+ CD3- thymocytes in ZAP-70(-/-) mice contain immediate precursors of NK1.1+ T cells.

Animals↗
PubMed2001

Antiviral response by natural killer cells through TRAIL gene induction by IFN-alpha/beta.

Natural killer (NK) cells play an important role in early defense against viral infection. The cytotoxic activity of NK cells is increased by interferon-alpha/beta (IFN-alpha/beta), produced en masse in virally infected cells. However, the mechanism(s) by which IFN-alpha/beta contribute to the NK-cell-mediated antiviral response is not well understood. Here we provide evidence that the cytotoxicity of NK cells is enhanced by IFN-alpha/beta through induction of TNF-related apoptosis-inducing ligand (TRAIL). Isolation and analysis of the murine TRAIL promoter revealed the presence of an IFN-stimulated response element (ISRE), which binds to the transcription factor ISGF3 (interferon stimulated gene factor-3). This promoter is indeed activated by IFN-beta in ISGF3-dependent manner. We also show that virally infected cells, but not uninfected cells, are susceptible to TRAIL-mediated cytotoxicity in vitro, and that the TRAIL expressed in NK cells is indeed crucial in limiting virus replication in vivo. Thus, our study reveals a new molecular link between IFN-alpha/beta signaling and activation of NK cells in antiviral response of the host.

Animals↗
PubMed2001

Brain PET and technetium-99m-ECD SPECT imaging in Lhermitte-Duclos disease.

Two patients with Lhermitte-Duclos disease were evaluated by brain positron emission tomography (PET) and technetium-99m-ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT). In the lesions in both patients, hyperperfusion was detected on cerebral blood flow images obtained by PET, and hyperactivity by standard 99mTc-ECD SPECT. Dynamic 99mTc-ECD SPECT images demonstrated a plateau of activity in each lesion. These findings suggest that lesions in Lhermitte-Duclos disease have a retention mechanism for 99mTc-ECD equivalent to that of normal neural tissue.

Adolescent↗
PubMed2001

Recombination and gene conversion-like events may contribute to ABO gene diversity causing various phenotypes.

We identified five different alleles, tentatively named ABO*O301, *0302, *R102, *R103, and *A110, in Japanese individuals possessing the blood group O phenotype. These alleles lack the guanine deletion at nucleotide position 261 which is shared by a majority of O alleles. Nucleotide sequence analysis revealed that *0301 and *0302 had single nonsynonymous substitutions compared with *A101 or *A102 responsible for the A1 phenotype. Analysis of intron 6 at the ABO gene by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing revealed that *R102 and *R103 had chimeric sequences of A-02 and B-02, respectively, from exons 6 to 7. In the analysis of five other chimeric alleles detected in the same manner, we identified a total of four different recombination-breakpoints within or near intron 6. When 510 unrelated Japanese were examined, the frequency of the chimeric alleles generated by recombination in intron 6 or exon 7 was estimated to be 1.7%. In addition, we found that *O301, *A110, *C101, *A111, and 35% of *A102 had a unique A-B-A chimeric sequence at intron 6, presumed to originate from a gene conversion-like event. We had previously established that *A110 also had an A-O2-A chimeric sequence around nucleotide position 646 in exon 7. Thus this allele has an A-B-A-O2-A chimeric sequence from intron 6 to exon 7 probably generated by two different gene conversions. Similar patchwork sequences around nucleotide position 646 in exon 7 were observed in two other new alleles responsible for the Ax and B3 phenotypes. Thus, the site is presumably a hotspot for gene conversion. These results indicate that both recombination and gene conversion-like events play important roles in generating ABO gene diversity.

ABO Blood-Group System↗
PubMed2001

Combination of early and delayed SPET imaging using technetium-99m ethyl cysteinate dimer immediately after local intra-arterial thrombolysis.

The aim of this study was to investigate the prognostic utility of post-treatment technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission tomography (SPET) for predicting ischemic tissue outcome in cases involving embolic middle cerebral artery occlusion treated with local intra-arterial thrombolysis. We examined twenty-five patients with a moderately ischemic area determined using pretreatment technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) SPET, and with complete recanalization within 6 h. Post-treatment 99mTc-ECD SPET studies, consisting of scanning for 0.5-6.5 min (early scan) and 15-21 min (delayed scan) after tracer injection, were performed immediately after thrombolysis. The extent of the affected area outlined on pretreatment 99mTc-HMPAO SPET was used for the post-treatment early and delayed 99mTc-ECD SPET images, and the AR/CE ratio (ratio of affected regional activity to cerebellar activity) was calculated. The washout index of 99mTc-ECD in the affected area was also calculated by dividing the difference between the AR/CE ratio in the early and delayed images by the AR/CE ratio in the early image. Twelve patients without infarction or with small subcortical/basal ganglial infarction, ten with medium or large cortical infarction, and three with hemorrhage were identified by follow-up computed tomography. Although the AR/CE ratio in post-treatment early 99mTc-ECD SPET images was significantly higher in the hemorrhagic group than in the cortical infarction group, this value did not differentiate the reversible ischemia group from either the cortical infarction or the hemorrhagic group. The AR/CE ratio in post-treatment delayed 99mTc-ECD SPET images statistically differentiated the reversible ischemia group from both the cortical infarction and the hemorrhagic group. However, the difference between the cortical infarction and hemorrhagic groups was not statistically significant. The washout index of 99mTc-ECD statistically differentiated all three groups. This study demonstrated that a combination of early and delayed 99mTc-ECD SPET imaging performed immediately after thrombolysis predicts ischemic tissue outcome.

Adult↗