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Biomedical subjects

K Ogawa

Publications and source records attributed to K Ogawa.

At least 55 records · Page 3Linked to original sources
PubMed2002

The diagnostic significance of the 3D-reconstructed MRI in vestibular schwannoma surgery: prediction of tumor origin.

In hearing preservation surgery for the treatment of vestibular schwannoma (VS), one of the important factors is the determination of the origin of VS. In this study, we investigated the diagnostic significance of using an MRI obtained by the three-dimensional Fourier transform fast spin-echo technique (3D-reconstructed MRI) in order to determine the origin of VS. The subjects consisted of 20 patients with mainly intra-canalicular sized VS who underwent tumor removal at our hospital. The origin of VS was determined from the 3D-reconstructed MRI findings and the results of the caloric test. These findings were then compared with the surgical findings. In 15 out of 20 patients, the MRI findings closely corresponded to the surgical ones, while the origin of VS hardly could be detected when a tumor filled up to the fundus acoustics on the MRI findings of the axial sections. On the other hand, 6 out of 15 patients (40%) whose tumor originated from the inferior vestibular nerve showed canal paresis. In conclusion, 3D-reconstructed MRI is considered to be helpful in obtaining more precise information regarding the origin of VS compared to the caloric test.

Caloric Tests↗
PubMed2002

Transient contribution of mast cells to pulmonary eosinophilia but not to hyper-responsiveness.

BACKGROUND: We have recently demonstrated that the transfer of interleukin (IL)-5-producing CD4+ T cell clones into unprimed mice is sufficient for the development ofeosinophilic inflammation in the bronchial mucosa upon antigen inhalation. OBJECTIVE: The aim of this study was to elucidate the possible contribution of mast cells in eosinophilic inflammation and bronchial hyper-responsiveness (BHR), and to discriminate between the roles of CD4+ T cells and mast cells. METHODS: Mast cell-deficient mice (WBB6F1-W/Wv) and their congenic normal littermates (WBB6F1-+/+) were immunized with ovalbumin and challenged by inhalation with the relevant antigen. RESULTS: Airway eosinophilia was induced with equivalent intensity in +/+ and W/Wv mice 6, 24, 96 and 216 h after antigen inhalation. In contrast, 48 h after antigen challenge, eosinophilic infiltration into the bronchial mucosa was significantly less pronounced in W/Wv mice than in +/+ mice. Anti-CD4 monoclonal antibody (mAb), anti-IL-5 mAb, and cyclosporin A were administered next, demonstrating that the airway eosinophilia of W/Wv mice induced 48 h after antigen challenge was almost completely inhibited by each of these three treatments, but that of +/+ mice was significantly less susceptible. Bronchial responsiveness to acetylcholine was increased 48 h after antigen challenge and was not significantly different between +/+ and W/Wv mice. Administration of anti-IL-5 mAb completely inhibited the development of BHR in both +/+ and W/Wv mice. CONCLUSION: These results indicate that, in mice, mast cells do have a supplemental role in the development of pulmonary eosinophilia but not BHR. CD4+ T cells totally regulate these responses by producing IL-5.

Administration, Inhalation↗
PubMed2002

Effects of rabeprazole, lansoprazole and omeprazole on intragastric pH in CYP2C19 extensive metabolizers.

AIM: To investigate the inhibitory effects on gastric acid secretion of three proton pump inhibitors, omeprazole, lansoprazole and rabeprazole, using a three-way crossover design in healthy Helicobacter pylori-negative,S-mephenytoin 4'-hydroxylase (CYP2C19) homo- and hetero-extensive metabolizers. METHODS: Eight healthy Japanese male volunteers were enrolled. After the administration of rabeprazole (10 mg/day), lansoprazole (30 mg/day) or omeprazole (20 mg/day), intragastric pH monitoring was commenced from 24 h before the first proton pump inhibitor dose, and continued for days 1-3 after proton pump inhibitor administration. The pH electrode was used for 48 h and changed just before pH monitoring on day 2. RESULTS: For the administration of 10 mg/day rabeprazole, the mean ratios of the 24-h pH > or = 3 holding time were 5.7 +/- 1.1%,13.6 +/- 2.2%, 35.3 +/- 2.7% and 62.8 +/- 3.1% for the pre-treatment day and days 1, 2 and 3, respectively. The same ratios for lansoprazole (30 mg/day) were 5.7 +/- 0.7%, 7.4 +/- 1.5%, 13.6 +/- 3.4% and 26.6 +/- 4.9%; the same ratios for 20 mg/day omeprazole were 5.9 +/- 0.9%, 6.1 +/- 1.2%, 11.4 +/- 2.8% and 16.4 +/- 4.6%. The mean ratio of the 24-h pH > or = 3 holding time of days 1-3 increased significantly compared to the pre-treatment day (P < 0.01) with the administration of rabeprazole and lansoprazole. The magnitude of inhibition of gastric acid secretion after rabeprazole administration was stronger than that after lansoprazole. A significant elevation of the mean ratio of the 24-h pH > or = 3 holding time was demonstrated on days 2 and 3 with omeprazole (P < 0.01). CONCLUSIONS: In H. pylori-negative CYP2C19 extensive metabolizers, rabeprazole (10 mg/day) shows a faster onset of rising intragastric pH and a stronger inhibition of gastric acid secretion than do lansoprazole (30 mg/day) or omeprazole (20 mg/day).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors.

Even though the existence of phosphodiesterase (PDE) 7 in T cells has been proved, the lack of a selective PDE7 inhibitor has confounded an accurate assessment of PDE7 function in such cells. In order to elucidate the role of PDE7 in human T cell function, the effects of two PDE inhibitors on PDE7A activity, cytokine synthesis, proliferation and CD25 expression of human peripheral blood mononuclear cells (PBMC) were determined. Recombinant human PDE7A was obtained and subjected to cyclic AMP-hydrolysis assay. PBMC of Dermatophagoides farinae mite extract (Df)-sensitive donors were stimulated with the relevant antigen or an anti-CD3 monoclonal antibody (MoAb). PBMC produced IL-5 and proliferated in response to stimulation with Df, while stimulation with anti-CD3 MoAb induced CD25 expression and messenger RNA (mRNA) synthesis of IL-2, IL-4 and IL-5 in peripheral T cells. A PDE inhibitor, T-2585, which suppressed PDE4 isoenzyme with high potency (IC50 = 0.00013 microM) and PDE7A with low potency (IC50 = 1.7 microM) inhibited cytokine synthesis, proliferation and CD25 expression in the dose range at which the drug suppressed PDE7A activity. A potent selective inhibitor of PDE4 (IC50 = 0.00031 microM), RP 73401, which did not effectively suppress PDE7A (IC50 > 10 microM), inhibited the Df- and anti-CD3 MoAb-stimulated responses only weakly, even at 10 microM. PDE7 may play a critical role in the regulation of human T cell function, and thereby selective PDE7 inhibitors have the potential to be used to treat immunological and inflammatory disorders.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2002

Transcriptional regulation of the IL-5 gene in peripheral T cells of asthmatic patients.

Mechanisms that underlie the regulation of IL-5 gene expression in human peripheral T cells remain incompletely defined because of the low efficiency of transfection of plasmid constructs into non-transformed T cells. To elucidate the cellular and molecular mechanisms of IL-5 production, concanavalin A (ConA)-stimulated blastocytes derived from peripheral blood lymphocytes of asthmatic patients were employed in this study. Transcriptional activity of the synthetic human IL-5 promoter in ConA-stimulated blastocytes correlated with the production of IL-5. Deletion analysis of the reporter gene showed that the cis-regulatory element located at - 119 to - 80 is critical for inducible IL-5 promoter activity. Electrophoretic mobility shift assay revealed that an oligonucleotide probe corresponding to the element (- 119 to - 90) gave two specific bands. The slower migrating band was absolutely dependent on stimulation and was composed of a co-operative complex of the transcription factors, nuclear factor of activated T cells (NFAT) and activating protein-1 (AP-1). The faster migrating band was also inducible and was identified as AP-1-less NFAT. Mutation of either the NFAT or AP-1 element abrogated the slower migrating band and at the same time abolished transcriptional activity of the human IL-5 promoter/enhancer gene. Cyclosporin A equivalently suppressed DNA-binding activity of the composite NFAT/AP-1 site, promoter activity and protein production of IL-5. In conclusion, these data suggests that the composite NFAT/AP-1 binding element (- 115 to - 100) plays a crucial role in IL-5 synthesis by peripheral T cells of asthmatic patients.

Adult↗
PubMed2002

Effects of N-alpha-methyl-histamine on human H(2) receptors expressed in CHO cells.

BACKGROUND: Production of N-alpha-methyl-histamine (NAMH), a histamine H(3) receptor (H3R) agonist, is reportedly promoted in Helicobacter pylori infected human gastric mucosa. NAMH was suggested to act directly on histamine H(2) receptors (H2Rs) in animals to stimulate acid secretion and to be a H2R agonist. As H2Rs and H3Rs play different roles in gastric acid secretion, it is very important to verify that NAMH is a H2R agonist. AIMS: To determine whether NAMH is a H2R agonist, as well as a H3R agonist. METHODS: We used a Chinese hamster ovary (CHO) cell line expressing human H2Rs (CHO-H2R) and control CHO cells. Expression of human H2Rs was confirmed by tiotidine binding. cAMP production in CHO-H2R and control cells in response to histamine or NAMH was measured. cAMP production in response to 10(-7) M NAMH was also measured in the presence or absence of the H2R antagonist famotidine and the H3R antagonist thioperamide. RESULTS: NAMH dose dependently stimulated cAMP productions in CHO-H2R cells. This production was inhibited by famotidine but not by thioperamide. Control CHO cells were unresponsive to either histamine or NAMH. In addition, the effect of NAMH, in terms of cAMP production in CHO-H2R cells, was more potent than that of histamine-that is, with a lower EC(50) concentration and higher maximal cAMP production. Both NAMH and histamine, but not R-alpha-methyl-histamine, effectively inhibited [(3)H] tiotidine binding to CHO-H2R cells. CONCLUSIONS: NAMH, which is produced in the gastric mucosa by H pylori, is a potent H2R agonist as well as a H3R agonist.

Animals↗
PubMed2002

Bacterium-based heavy metal biosorbents: enhanced uptake of cadmium by E. coli expressing a metallothionein fused to beta-galactosidase.

We investigated the potential utility of a recombinant E. coli that expresses the human metallothionein II gene as a fusion protein with beta-galactosidase as a heavy metal biosorbent. E. coli cells expressing the metallothionein fusion demonstrated enhanced binding of Cd2+ compared to cells that lack the metallothionein. It was shown that the metallothionein fusion was capable of efficiently removing Cd2+ from solutions. Approximately 40% of the Cd2+ accumulated by the recombinant cells free in suspension was associated with the outer cell membrane, and 60% of that was present in the cytoplasm.

Biodegradation, Environmental↗
PubMed2002

Primary repair of pulmonary artery sling with double outlet right ventricle and distal tracheal stenosis.

The fate of patients with pulmonary artery sling depends on associated tracheal lesions. Distal tracheal stenosis involving the carina frequently results in lethal obstruction due to secretion or inflammatory edema. Further-more, associated complex cardiac anomalies with excessive pulmonary flow make the situation more complicated. We present a case of successful simultaneous one-stage repair of pulmonary artery sling, double outlet right ventricle and distal tracheal obstruction. Pulmonary artery sling was relieved by relocation of the left pulmonary artery (left pulmonary artery to main pulmonary artery) and a tracheoplasty (resection and end-to-end anastomosis). We advocate early aggressive simultaneous repair of pulmonary artery sling with tracheal stenosis and concomitant repair of intracardiac anomalies whenever possible.

Abnormalities, Multiple↗
PubMed2001

Possible role of organ-specific autoantigen for Fas ligand-mediated activation-induced cell death in murine Sjögren's syndrome.

Activation-induced cell death (AICD) is a well-known mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). In this study, we demonstrate that the administration of a soluble form of anti-FasL Ab, FLIM58, results in severe destructive autoimmune exocrinopathy in the murine model of human Sjögren's syndrome (SS), and we found that an organ-specific autoantigen may play an important role on down-modulation of AICD. A high titer of serum autoantibodies against 120-kDa alpha-fodrin autoantigen was detected in the FLIM58-treated mice, and splenic T cell culture supernatants contained high levels of IFN-gamma. In vitro T cell apoptosis assay indicated that FasL-mediated AICD is down-regulated by autoantigen stimulation in spleen cells from the murine SS model, but not from Fas-deficient MRL/lpr mice and FasL-deficient MRL/gld mice. FasL undergo metalloproteinase-mediated proteolytic processing in their extracellular domains, resulting in the release of soluble trimeric ligands (soluble FasL). We showed that the processing of soluble FasL occurs in autoantigen-specific CD4(+) T cells, and that a significant increase in expressions of metalloproteinase-9 mRNA was observed in spleen cells from SS model mice. These findings indicate that the increased generation of soluble FasL inhibits the normal AICD process, leading to the proliferation of effector CD4(+) T cells in the murine SS model.

Animals↗
PubMed2001

Invisible but common motion in organic crystals: a pedal motion in stilbenes and azobenzenes.

Some molecules that have a molecular skeleton similar to stilbenes and azobenzenes are known to show an orientational disorder in the crystals. Some of the disorders are known to be dynamic and mediated by a pedal motion in crystals. Dynamic processes of (E)-stilbene (1) and (E)-3,3',4,4'-tetramethylazobenzene (2) in the crystals were investigated by X-ray diffraction analyses. The dynamic disorder and the pedal motion were detected at higher temperature, even in the molecules that showed no traces of the disorder at room temperature. The results demonstrated that the pedal motion should always be taken into account, even if no disorder is detected. The reasons for the nonoccurrence of the disorder and for the prevalence of the pedal motion are also discussed.

Journal Article↗
PubMed2001

The glutamate receptor agonist, AMPA, induces acetylcholine release in guinea pig cochlea; a microdialysis study.

Acetylcholine (Ach) has been considered a major neurotransmitter in the inner ear efferent nerve endings. A bioassay analysis has shown that the electrical stimulation of the crossed olivocochlear bundle increased the Ach-like activity in the perilymph. Applying in vivo microdialysis techniques and high-performance liquid chromatography to the perilymph, the change of Ach level was thus measured before and after alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), a glutamate receptor agonist, was added to the perfusate. Ach was only detectable when the perfusate contained an acetylcholinesterase inhibitor. The level of Ach increased 2-3-fold immediately after AMPA was administered. Our data suggest that the afferent stimulation, such as the administration of AMPA, may therefore induce the release of Ach from the efferent nerve endings.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Molecular cloning and characterization of a thioredoxin/nucleoside diphosphate kinase related dynein intermediate chain from the ascidian, Ciona intestinalis.

Flagellar outer arm dynein from the ascidian, Ciona intestinalis, contains five intermediate chains (IC1-5). Molecular cloning of C. intestinalis IC3 shows significant sequence homology to the dynein intermediate chain (IC1) from sea urchin and human NM23-H8 protein. The N-terminal thioredoxin-related region is well conserved in the C. intestinalis IC3, sea urchin IC1, and human NM23-H8 protein. Three NDP kinase (NDPK)-related sequences are present in middle portions of both C. intestinalis IC3 and sea urchin IC1, but the human NM23-H8 protein had only two. A large part of the C-terminal glutamic acid-rich region present in sea urchin IC1 was greatly reduced in C. intestinalis IC3 and completely lost in human NM23-H8. Thus, thioredoxin/NDPK-related dynein intermediate chains (TNDK-DIC) would be a characteristic of metazoan flagella and they have become smaller in size and less acidic during evolution.

Amino Acid Sequence↗
PubMed2001

Caveolar and intercellular channels provide major transport pathways of macromolecules across vascular endothelial cells.

Serum macromolecules are transported through the vascular endothelial layer to the interstitium via the caveolae and interendothelial clefts, but the nature of the permeability of these structures is unknown, and the manner of caveola-vesicle transport is controversial. We have developed a method of detecting macromolecular channels using an in situ HRP perfusion into arteries previously perfused with aldehyde and random conventional sectioning for electron microscopy. Using unbiased morphometry, 4.75% of the abluminal caveolae and 15.13% of the intercellular clefts were the tracer-positive in rat aortic endothelium. In rat aortas treated with N-ethylmaleimide, all caveolae and most free vesicles in the cytoplasm except those around the Golgi area were HRP-positive in the endothelial cells; 1.48% of abluminal caveolae were structurally recognized as caveolar channels through the endothelial layer in a plane of single section. The length density of the abluminal caveolae was decreased to about 80% to the physiological control level whereas the larger invaginations were more frequently observed. Moreover 96.17% of the intercellular clefts were HRP-positive. We suggest that a flexible channel-system functions extensively as a macromolecular transport pathway in the arterial endothelium in vivo because the tracer-labeled abluminal caveolae and intercellular clefts should be opened to the luminal surfaces methodologically. We therefore propose that caveolar channels, rather than transcytosis, provide a mechanism of caveola-vesicle transport in the endothelial cells, because free vesicles involved in transcytosis were few in number.

Animals↗
PubMed2001

Carrier-mediated processes in blood--brain barrier penetration and neural uptake of paraquat.

Due to the structural similarity to N-methyl-4-phenyl pyridinium (MPP(+)), paraquat might induce dopaminergic toxicity in the brain. However, its blood--brain barrier (BBB) penetration has not been well documented. We studied the manner of BBB penetration and neural cell uptake of paraquat using a brain microdialysis technique with HPLC/UV detection in rats. After subcutaneous administration, paraquat appeared dose-dependently in the dialysate. In contrast, MPP(+) could not penetrate the BBB in either control or paraquat pre-treated rats. These data indicated that the penetration of paraquat into the brain would be mediated by a specific carrier process, not resulting from the destruction of BBB function by paraquat itself or a paraquat radical. To examine whether paraquat was carried across the BBB by a certain amino acid transporter, L-valine or L-lysine was pre-administered as a co-substrate. The pre-treatment of L-valine, which is a high affinity substrate for the neutral amino acid transporter, markedly reduced the BBB penetration of paraquat. When paraquat was administered to the striatum through a microdialysis probe, a significant amount of paraquat was detected in the striatal cells after a sequential 180-min washout with Ringer's solution. This uptake was significantly inhibited by a low Na(+) condition, but not by treatment with putrescine, a potent uptake inhibitor of paraquat into lung tissue. These findings indicated that paraquat is possibly taken up into the brain by the neutral amino acid transport system, then transported into striatal, possibly neuronal, cells in a Na(+)-dependent manner.

1-Methyl-4-phenylpyridinium↗
PubMed2001

Two consecutive zinc fingers in Sp1 and in MAZ are essential for interactions with cis-elements.

The zinc finger proteins Sp1 and Myc-associated zinc finger protein (MAZ) are transcription factors that control the expression of various genes. Regulation of transcription by these factors is based on interactions between GC-rich DNA-binding sites (GGGCGG for Sp1 and GGGAGGG for MAZ) and the carboxyl-terminal zinc finger motifs of the two proteins. Sp1 and MAZ have three and six zinc fingers, respectively, and the details of their interactions with cis-elements remain to be clarified. We demonstrate here that Sp1 and MAZ interact with the same GC-rich DNA-binding sites, apparently sharing DNA-binding sites with each other. We found that the DNA binding activities of Sp1 and MAZ depended mainly on consecutive zinc fingers, namely the second and third zinc fingers in Sp1 and the third and fourth zinc fingers in MAZ. Furthermore, the interactions of the zinc finger proteins with the same cis-elements appear to play a critical role in the regulation of gene expression. It seems plausible that two consecutive zinc finger motifs in a zinc finger protein might be essential for interaction of the protein with DNA.

3T3 Cells↗
PubMed2001

Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1.

Heme controls expression of genes involved in the synthesis of globins and heme. The mammalian transcription factor Bach1 functions as a repressor of the Maf recognition element (MARE) by forming antagonizing hetero-oligomers with the small Maf family proteins. We show here that heme binds specifically to Bach1 and regulates its DNA-binding activity. Deletion studies demonstrated that a heme-binding region of Bach1 is confined within its C-terminal region that possesses four dipeptide cysteine-proline (CP) motifs. Mutations in all of the CP motifs of Bach1 abolished its interaction with heme. The DNA-binding activity of Bach1 as a MafK hetero-oligomer was markedly inhibited by heme in gel mobility shift assays. The repressor activity of Bach1 was lost upon addition of hemin in transfected cells. These results suggest that increased levels of heme inactivate the repressor Bach1, resulting in induction of a host of genes with MARES:

Amino Acid Sequence↗
PubMed2001

Quantitative comparison of two types of planar lipid bilayers--folded and painted--with respect to fusion with vesicles.

Two major types of planar lipid bilayers, painted and folded, were compared with respect to vesicle fusion using one chamber for the preparation of both bilayers. Liposomes containing ion channels composed of nystatin and ergosterol were used as the vesicle sample. Fusion of the liposome to either bilayer elicited a spike-like current change, which corresponds to a fusion event. The lag time between the first fusion event and the addition of the vesicles is an index of the ease with which the vesicles fuse with the bilayers. The lag time in the painted bilayer at a KCl concentration (cis) of 450 mM was 1.58+/-1.18 min, similar to that in the folded bilayer (1.65+/-0.64 min). The lag time decreased with increase of the osmotic difference across the painted bilayer, whereas this change was small in the folded bilayer. The fusion of the liposomes to the painted bilayer was markedly reduced by stopping the stirring in the cis compartment, whereas the fusion to the folded bilayer was not affected significantly. These results imply that no practical difference exists in the ability of vesicles to fuse with the painted and folded bilayers. For the study of single channel behavior, the painted bilayer could have an advantage because simply stopping the stirring prevents excess fusion.

Animals↗