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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 163 records · Page 9Linked to original sources
PubMed2001

Thymus-dependent modulation of Ly49 inhibitory receptor expression on NK1.1+gamma/delta T cells.

Major histocompatibility complex (MHC) class I-specific inhibitory receptors are expressed not only on natural killer (NK) cells but also on some subsets of T cells. We here show Ly49 expression on gamma/delta T cells in the thymus and liver of beta2-microglobulin-deficient (beta2m-/-) and C57BL/6 (beta2m+/+) mice. Ly49C/I or Ly49A receptor was expressed on NK1.1+gamma/delta T cells but not on NK1.1-gamma/delta T cells. The numbers of NK1.1+gamma/delta T cells were significantly smaller in beta2m+/+ mice than in beta2m-/- mice with the same H-2b genetic background. Among NK1.1+gamma/delta T cells, the proportions of Ly49C/I+ cells but not of Ly49A+ cells, were decreased in beta2m+/+ mice, suggesting that cognate interaction between Ly49C/I and H-2Kb is involved in the reduction of the number of Ly49C/I+ gamma/delta T cells in beta2m+/+ mice. The frequency of Ly49C/I+ cells in NK1.1+gamma/delta T cells was lower in both lethally irradiated beta2m+/+ mice transplanted with bone marrow (BM) from beta2m-/- mice and lethally irradiated beta2m-/- mice transplanted with BM from beta2m+/+ mice than those in adult thymectomized BM-transplanted chimera mice. These results suggest that reduction of Ly49C/I+ NK1.1+gamma/delta T cells in beta2m+/+ mice is at least partly due to the down-modulation by MHC class I molecules on BM-derived haematopoietic cells or radioresistant cells in the thymus.

Animals↗
PubMed2001

Accelerated DNA fragmentation of the denture-bearing mucosal epithelium in an animal model of diabetes.

This study examined the effect of masticatory pressure transmitted directly to the hard palate mucosa on the final stage of terminal differentiation of keratinizing system of rats with and without streptozotocin-induced diabetes mellitus. In the nondiabetic rats with masticatory pressure, the number of terminal-deoxynucleotidyl-transferase-mediated deoxyuridine-triphospate-biotin nick end labelling (TUNEL) positive cells tended to increase about twice as much as in the nondiabetic rats without pressure with and without denture. A similar tendency of increase was observed in the diabetic rats without pressure. The synergy of the mechanical pressure and diabetic condition for 2 weeks greatly accelerated the DNA fragmentation, showing 8-fold increase in TUNEL positive cells over the normal control, and caused exfoliation of the stratum corneum. A 4-week exposure of diabetics to the masticatory pressure induced laminar splitting in the midst of the spinosum. Some cells in the stratum granulosum exhibited a sign of DNA fragmentation when laminar splitting took place in the vital cell layer. Premature DNA fragmentation may disturb the adhesion between spinosum cells and prevent the maturation of stratum corneum. Increase in Bax protein-like immunoreactivity in these epithelial cells as revealed by immunocytochemistry may underlie the premature DNA fragmentation in the oral masticatory epithelium under pressure in diabetic patients.

Animals↗
PubMed2001

Histomorphometric analysis on bone dynamics in denture supporting tissue under masticatory pressure in rat.

The bone dynamics under denture base has not been clarified sufficiently. The purpose of this study was to evaluate histomorphometrically the bone dynamics in denture supporting tissue with relation to the intensity of the masticatory pressure. The removable denture bases, which exerted four different regulated masticatory pressures (0.0, 1.0, 20.0 or 40.0 kPa), were inserted to the hard palate of the molar region of 22-week-old rats. The palatal tissues were excised from 1 to 12 weeks after denture insertion at intervals of 1 week and embedded in methyl-methacrylate. No bone resorption was observed throughout the experimental period in the 0.0 and 1.0 kPa groups. In the 1.0 kPa group compared with the 0.0 kPa group, bone formation parameters except for bone formation rate significantly increased at 4 weeks, but there was no significant difference between these groups in the other experimental periods. In the 20.0 and 40.0 kPa groups, bone resorption was observed until 3 and 5 weeks, respectively, and the amounts of bone resorption (AoBR) were 45 +/- 25 and 104 +/- 21 microm, respectively. After bone resorption, bone formation parameters in these two groups showed transiently significant decrease compared with the 0.0 kPa group, but were the same time course as the 0.0 kPa group following this decrease. In conclusion, masticatory pressure caused different time courses of the bone dynamics in denture supporting tissue depending on the initial intensity of the pressure. The AoBR responded to the initial intensity of masticatory pressure. Bone formation following bone resorption did not cause equivalent recovery of the bone surface level to the level observed in the case without bone resorption in the present study.

Animals↗
PubMed2001

Schistosoma japonicum egg granuloma formation in the interleukin-4 or interferon-gamma deficient host.

The roles of interleukin (IL)-4 and interferon (IFN)-gamma in Schistosoma japonicum egg granuloma formation were investigated in cercariae-infected (infection model) or after implantation of laid parasite eggs (egg implantation model) in cytokine deficient mice. Two weeks after hepatic egg-implantation, a markedly decreased mononuclear cell infiltration and lack of multinuclear cell formation were characteristic features in IL-4 deficient mice. By 4 weeks (late stage), the cellular reactions around the eggs were negligible in the deficient mice. Compared to the controls, there was a drastic reduction in the production of the Th2 cytokines, IL-4, IL-5 and IL-13. MCP-1 levels were also significantly lowered. In mice experimentally infected with cercariae, granuloma cellularity in both the wild-type and IL-4 deficient mice at 45 days and 10 weeks postinfection was analogous to the egg implantation model at 2 and 4 weeks. Overall, the effects of IFN-gamma deficiency on granuloma induction differed markedly from the IL-4 results. Two weeks after egg implantation, IFN-gamma deficient mice showed suppressed neutrophil response and hepatic necrosis with confluent mononuclear cell infiltration along the outer layer of granulomas. By 4 weeks, there was a decrease in cell infiltration, fibrosis and MCP-1 production while IL-10 production increased. While these early characteristic features for IFN-gamma deficiency were common to both the egg implantation (at 2 and 4 weeks) and cercariae infection model (at 45 days), there was a surprising difference, i.e. marked fibrosis was found in the late stages (at 10 weeks postinfection) of cercariae-infected mice, but not in parasite egg implanted mice. Furthermore, while IL-13 levels were unchanged, both MCP-1 and IL-4 production were significantly lower at 10 weeks in comparison with wild-type. The present study clearly demonstrates the importance of both Th1 and Th2 cytokine responses in S. japonicum egg-induced granuloma formation.

Animals↗
PubMed2001

Effect of nitric oxide synthase inhibition on Schistosoma japonicum egg-induced granuloma formation in the mouse liver.

Nitric oxide (NO) plays diverse roles in a variety of pathological processes. We investigated the role of NO in Schistosoma japonicum egg-induced granuloma formation in a mouse hepatic model. Immunohistological analysis revealed that there is the most intense and extensive inducible nitric oxide (iNOS) expression 2 weeks after egg implantation, and thereafter it decreased considerably with time. Treatment with nitric oxide synthase inhibitors, NIL (L-N6- (iminoethyl)-lysine) or N(omega)-nitro-L-arginine methyl ester (L-NAME), resulted in two different types of unusual granulomas at 2 weeks. One type showed suppressed fibrosis, while another showed foreign body-type multinuclear cell formation which frequently appeared particularly when 50 microg/ml NIL was given. At 3 weeks following treatment, fibrotic granulomas with scanty peripheral cellularity was obvious. However, there were no apparent changes after this period (at 4 weeks). Cytokine analysis in NIL-treated mice showed a significant increase of IL-4 and IL-13 production at 2 weeks. These findings indicated that nitric oxide contributes to granuloma development during the early stages, probably through the regulation of Th2 cytokine production.

Animals↗
PubMed2001

A novel heat stress-responsive gene in the marine diatom Chaetoceros compressum encoding two types of transcripts, a trypsin-like protease and its related protein, by alternative RNA splicing.

We investigated the change of mRNA expression patterns in the laboratory-grown diatom Chaetoceros compressum under heat-stress conditions by mRNA arbitrarily primed (RAP) RT-PCR. Cells grown at 20 degrees C were subjected to heat treatment at 30 degrees C for 15 min and subsequently maintained at 20 degrees C for 8 h. Four genes including HI-5 were detected as heat stress-responsive genes by fingerprint analysis of RAP RT-PCR. Cloning for full-length cDNA sequences of HI-5 transcripts and related genomic DNA analysis revealed that two types of mRNA, HI-5a and HI-5b, were transcribed from the single HI-5 gene. While the HI-5a protein contained a catalytic domain characteristic to trypsin-like proteases, the HI-5b protein lacked this domain due to an insertion in the associated mRNA of 112 nucleotides; this insertion sequence contained a stop codon near the central region. Quantitative RT-PCR was performed to investigate the changes in expression levels of the two types of mRNA following heat treatment. The HI-5b transcripts were constitutively expressed in both unstressed and heat-stressed cells. In contrast, the number of HI-5a transcripts markedly increased in cells immediately after heat stress, reaching levels 19-fold higher at 8 h after heat stress than that in unstressed cells. These results suggest that RNA splicing plays a key role in heat stress-dependent expression of the HI-5a and HI-5b transcripts from the single HI-5 gene in the diatom.

Alternative Splicing↗
PubMed2001

A survey on the drug therapy for delirium.

Delirium, which is experienced by 10-30% of inpatients, is commonly seen in daily practice. A survey was conducted of the delirium medications, and results were obtained from 28 psychiatric departments and related facilities. Haloperidol was used in 67% cases for the treatment of delirium. Ninety-seven per cent of facilities considered haloperidol as the drug of first choice, while 57% thought this drug had few side-effects and was easy to use. However, because the use of this drug is not covered by health insurance in Japan, its use is limited. We expect that this study on medication for the treatment of delirium will be a first step in increasing the approved indications for drugs used for the treatment of delirium, and to reduce off-label use.

Antipsychotic Agents↗
PubMed2001

Association between birthweight and body mass index at 3 years of age.

BACKGROUND: Obesity in children is one of the risk factors for adulthood obesity, which then leads to the development of chronic diseases such as hypertension, hyperlipidemia and diabetes. In this study, we identified significant factors associating with the body mass index (BMI) at 3 years of age from the perinatal characteristics of children. METHODS: A total of 588 children were included in the study. The BMI at 3 years of age was examined in conjunction with the possible variables such as parents' smoking status during pregnancy, parents' age at birth, gestational age, sibling number and live birth order, sex, birthweight, BMI at 1 month of age, weight gain during the first month of life and feeding method at 1 month of age. RESULTS: Univariate analysis showed that birthweight (P<0.0001), weight gain during the first month of life (P=0.0012) and BMI at 1 month of age (P<0.0001) were significantly associated with the BMI at 3 years of age. Of these factors, birthweight and weight gain during the first month of life were the independent factors correlating with the BMI at 3 years by multivariate analysis (P<0.0001 and P=0.0095, respectively). CONCLUSIONS: Infants with higher birthweight and/or greater weight gain during the first month of life may have a risk of being overweight at 3 years of age.

Age Factors↗
PubMed2001

Association of IFN-gamma and IFN regulatory factor 1 polymorphisms with childhood atopic asthma.

BACKGROUND: IFN-gamma and related molecules play important roles in the differentiation and function of TH2 cells. OBJECTIVE: We sought to determine whether IFNG and related genes contribute to any susceptibility to atopic asthma, a representative TH2-dominant disorder. METHODS: We investigated the association of IFNG (CA repeat polymorphism within the first intron), IRF1 (GT repeat polymorphism within the intron 7), IFNGR1 (Val 14 Met), and IFNGR2 (Gln 64 Arg) gene polymorphisms with atopic asthma in the Japanese child population. RESULTS: A significant association (P =.0018) was observed between IFNG gene polymorphism and atopic asthma. The tendency was more prominent in patients with age of onset of 3 years or younger (P =.0004) or patients with a family history of allergic diseases (P =.0038). Furthermore, there was a significant association between IRF1 gene whole-allele distribution and atopic asthma (P =.044). The tendency was more prominent in patients with onset at 3 years of age or less (P =.0058). On the other hand, IFNGR1 and IFNGR2 gene polymorphisms showed no association with atopic asthma. CONCLUSION: These results suggested that among IFNG and related genes, IFNG and IRF1 genes confer genetic susceptibility to atopic asthma in Japanese children.

Adolescent↗
PubMed2001

Effect of erythromycin on matrix metalloproteinase-9 and cell migration.

Erythromycin (EM) has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To investigate the mechanism of this anti-inflammatory effect, we studied the relationship between the concentration of EM and matrix metalloproteinase-9 (MMP-9) activity, which is important in cell migration. We showed that EM suppressed the gelatinolytic activity of U937 cell-derived MMP-9 by using gelatin zymography, showed that expressions of MMP-9 protein and MMP-9 mRNA were down-regulated by EM in a dose-dependent manner, and showed that U937 migration was also suppressed by EM. We also demonstrated that EM treatment suppressed the gelatinolytic activity of MMP-9 in spleen macrophages. These findings suggest that the suppressive effect of EM on MMP-9 activity is one of the anti-inflammatory mechanisms that inhibit the migration of inflammatory cells into the inflammatory site.

Anti-Bacterial Agents↗
PubMed2001

Clinical studies of enteritis caused by methicillin-resistant Staphylococcus aureus.

OBJECTIVE: To study the clinical features of methicillin-resistant Staphylococcus aureus (MRSA) enteritis in our surgical ward. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 16 men and 1 woman who developed MRSA enteritis from January 1995 to October 1999. MAIN OUTCOME MEASURES: Causes and treatments. RESULTS: The underlying diseases were as follows: gastric cancer (n = 13), colorectal cancer (n = 2), recurrent cancer (n = 1) and bowel obstruction following gastrectomy (n = 1). 16 patients were operated on. Two cases were treated with histamine H2 receptor blockers. The mean age of patients was 65 years (range 50-80). In 13 cases MRSA enteritis developed within 6 days of operation. 10 strains of MRSA were isolated from stools, 8 from gastric juice, and 3 from intra-abdominal exudate. 10 patients were treated with vancomycin given through a nasogastric tube and 2 through a nasogastric tube and by drip intravenous infusion. 15 patients survived and 2 died. CONCLUSIONS: Patients who are given broad-spectrum antibiotics and whose gastric secretion is reduced are at high risk of MRSA enteritis. In the surgical ward, early diagnosis, treatment, and isolation are essential for patients with MRSA enteritis.

Aged↗
PubMed2001

Membrane-type 1 matrix metalloproteinase is induced in decidual stroma without direct invasion by trophoblasts.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) in endometrium and decidua may greatly affect attachment of the embryo to the epithelium, invasion of the trophoblast into the stroma, and extracellular matrix remodelling in the endometrium and decidua. We investigated the expression of this enzyme in normally cycling endometrium and in decidua associated with normal and tubal pregnancies at both the gene and protein level. Localization of expression (but not the overall level of expression), differed between endometrium and decidua parietalis and tubal pregnancy decidua. MT1-MMP mRNA was expressed mainly in epithelium and only faintly in stroma throughout the menstrual cycle, while in decidua parietalis and tubal pregnancy decidua, this mRNA was expressed predominantly in stromal cells. MT1-MMP protein was detected in the epithelium alone throughout the menstrual cycle, while in decidua parietalis and tubal pregnancy decidua, it was detected in stromal cells as well as the epithelium. Since decidua showed altered expression in the absence of trophoblastic contact, trophoblast invasion may not directly affect MT1-MMP gene expression.

Adult↗
PubMed2001

Side chain effect on ion channel characters of Aib rich peptides.

As models of ion channel proteins and naturally occurring pore-forming peptides, we designed a series of Aib rich peptides [Ac-(Aib-Xxx-Aib-Ala)(5)-NH(2) (Xxx = Lys, Glu, Ser, and Gly: BXBA-20)] to investigate the effects of the side chains of the amino acid residues Lys, Glu, Ser, and Gly on the conformation and electrophysiological properties of ion channels. The conformation of peptides and their affinity for phospholipid membranes were evaluated by CD spectroscopy. Patch-clamp experiments revealed that all BXBA-20 peptides form ion channels in DPhPC bilayers exhibiting clearly resolved transitions between the open and closed states. The channel forming frequency was in the order BKBA-20>BEBA-20>BSBA-20>BGBA-20. In the case of BKBA-20 and BEBA-20, the self-assembled conductive oligomers expressed homogeneous and voltage-independent single channel conductances. In contrast, heterogeneous conductance was observed in BSBA-20 and BGBA-20 ion channels under similar experimental conditions. From these results, we conclude that peptides with a high degree of helical conformation, high amphipathicity, high affinity for lipid membranes, and self-associating characters in vesicles are most suitable for inducing ion channels with a high frequency of occurrence. Moreover, BEBA-20, BSBA-20, and BGBA-20 channels were cation-selective, whereas the BKBA-20 channel was non-selective.

Aminoisobutyric Acids↗
PubMed2001

Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population.

OBJECTIVE: Systemic lupus erythematosus (SLE) in a multisystem autoimmune disorder characterized by multiorgan pathology and autoantibodies against a variety of autoantigens. The CD28 and CTLA-4 genes might be candidate genes for SLE, because costimulation signals from CD80/CD86 to CD28/CTLA-4 have been suggested to play an important role in the activation or inactivation of T lymphocytes. METHODS: We investigated three polymorphic regions within the CTLA-4 gene, a C/T base exchange in the promoter region -318 (CTLA-4 -318C/T), an A/G substitution in the exon 1 position 49 (CTLA-4 49A/G), an (AT)(n) repeat polymorphism in the 3' untranslated region of exon 4 [CTLA-4 3' (AT)(n)], and a CD28 gene polymorphism, a T/C substitution in the intron 3 position +17 (CD28 IVS3+17T/C), in SLE patients and controls. RESULTS: SLE patients had significantly higher frequencies of the CTLA-4 49G allele (P=0.003) and of the CTLA-4 (AT)(n) 106 bp allele (P=0.0008) than controls. We also found a strong linkage disequilibrium between the A allele of CTLA-4 49A/G and the 86 bp allele of CTLA-4 3' (AT)(n). On the contrary, no association was found between SLE and CTLA-4 -318C/T or CD28 IVS3 +17T/C. CONCLUSION: We conclude that the CTLA-4 gene appears to play a significant role in the development of SLE in the Japanese population.

Abatacept↗
PubMed2001

Sevoflurane protects stunned myocardium through activation of mitochondrial ATP-sensitive potassium channels.

UNLABELLED: We sought to determine the hemodynamic and cardioprotective effects of sevoflurane in canine stunned myocardium. Forty-nine dogs were allocated to one of seven groups (n = 7 for each). In six separate groups, dogs received vehicle, glibenclamide (a nonselective adenosine triphosphate-dependent potassium [K(ATP)] channel antagonist) (0.3 mg/kg IV) or 5-hydroxydecanoic acid (a mitochondrial K(ATP) channel antagonist) (5 mg/kg IV) in the presence or absence of 1 minimum alveolar concentration (1 MAC) sevoflurane. In an additional group, dogs received 1 MAC sevoflurane with hemodynamic correction. Regional myocardial contractility was evaluated with segment shortening. Measurements were made before and during 15-min ischemia and 90-min reperfusion. Recovery of segment shortening 90 min after reperfusion was significantly improved in the dogs anesthetized with sevoflurane either with or without hemodynamic correction (70.1 +/- 4.2 and 75.9 +/- 3.1% of baseline, respectively), whereas the recovery was poor in control and glibenclamide or 5-hydroxydecanoic acid pretreated dogs (33.3 +/- 4.3, 33.8 +/- 6.8, and 45.0 +/- 5.5% of baseline, respectively). Regional myocardial perfusion showed no significant difference among groups. The results indicate that sevoflurane has a cardioprotective effect mediated through activation of mitochondrial K(ATP) channels and independent of coronary blood flow or reduction in cardiac work. IMPLICATIONS: Sevoflurane exerts a cardioprotective effect that is mediated via activation of adenosine triphosphate-sensitive potassium channels in ischemic canine hearts.

Adenosine Triphosphate↗
PubMed2001

Activation of Akt/protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus.

Apoptosis plays an important role in delayed neuronal cell death after cerebral ischemia. Activation of Akt/protein kinase B has been recently reported to prevent apoptosis in several cell types. In this article the authors examine whether induction of ischemic tolerance resulting from a sublethal ischemic insult requires Akt activation. Sublethal ischemia gradually and persistently stimulated phosphorylation of Akt-Ser-473 in the hippocampal CA1 region after reperfusion. After lethal ischemia, phosphorylation of Akt-Ser-473 showed no obvious decrease in preconditioned gerbils but a marked decrease in nonconditioned gerbils. Changes in Akt-Ser-473 phosphorylation were correlated with changes in Akt activities, as measured by an in vitro kinase assay. Intracerebral ventricular infusion of wortmannin before preconditioning blocked both the increase in Akt-Ser-473 phosphorylation in a dose-dependent manner and the neuroprotective action of preconditioning. These results suggest that Akt activation is induced by a sublethal ischemic insult in gerbil hippocampus and contributes to neuroprotective ischemic tolerance in CA1 pyramidal neurons.

Androstadienes↗
PubMed2001

Clinical characteristics of acute hemorrhagic rectal ulcer.

BACKGROUND: Acute hemorrhagic rectal ulcer (AHRU) occurs suddenly with painless, massive, fresh rectal bleeding in elderly, bed-ridden patients who have a serious primary disease. There have been several reports on AHRU in Japan, but in Western countries, there have been none. We examined the clinical characteristics of four cases, and we report on AHRU in Western countries. STUDY: The medical records and endoscopic findings in four patients with AHRU seen during a 3-year period were reviewed. The diagnosis of AHRU was established by clinical symptoms, endoscopic examination, and other methods. RESULTS: All of the patients were elderly and bed-ridden and all had sudden onset of massive, fresh rectal bleeding without pain. Sigmoidoscopic examination of all patients showed a shallow or irregular bleeding ulcer in the lower rectum. In three cases, the clinical course was uneventful. In the other case, massive, fresh rectal bleeding recurred but transanal ligation was effective. CONCLUSIONS: When painless, massive, fresh rectal bleeding occurs in elderly and bed-ridden patients, it is important to carefully examine the lower rectum, as there is a strong possibility of AHRU.

Aged↗