Search PubMed⌕ Search

Biomedical subjects

K Itoh

Publications and source records attributed to K Itoh.

At least 37 records · Page 2Linked to original sources

Stereospecific oxidation of the (S)-enantiomer of RS-8359, a selective and reversible monoamine oxidase A (MAO-A) inhibitor, by aldehyde oxidase.

In a previous paper by the authors on RS-8359, a new selective and reversible monoamine oxidase A (MAO-A) inhibitor, it was reported that the (S)-enantiomer of RS-8359 is rapidly eliminated from rats, monkeys and humans as a result of the formation of a 2-oxidative metabolite. The present study investigates the properties of the enzyme responsible for the 2-oxidation of RS-8359. Subcellular localization, cofactor requirement and the inhibitory effects of typical compounds were studied using rat liver preparations. In addition, the enzyme was purified from rat liver cytosol for further characterization. The enzyme activity was localized in the cytosolic fraction without the need for any cofactor and was extensively inhibited by menadione, chlorpromazine and quinacrine. The purified enzyme was also a homodimer with a monomeric molecular weight of 140 kDa and it had an A280/A450 ratio of 5.1 in the absorption spectrum. The results suggest that the enzyme responsible for the biotransformation of RS-8359 to give the 2-keto derivative is aldehyde oxidase (EC 1.2.3.1). The reaction of aldehyde oxidase is highly stereoselective for the (S)-configuration of RS-8359 and the (9R)-configuration of cinchona alkaloids.

Aldehyde Oxidase↗

Identification of differentially expressed genes in psoriasis using expression profiling approaches.

To identify differentially expressed genes which play causal roles in pathogenesis and maintenance for psoriasis, we used BodyMapping and introduced amplified fragment length polymorphism approaches. From the BodyMap database, we selected 2007 genes which specifically expressed in epithelial tissues. Among 2007 genes, we surveyed genes which differentially expressed in involved or uninvolved psoriatic lesional skin samples compared with atopic dermatitis, mycosis fungoides, and normal skin samples. As a result of surveying 2007 genes, 241 genes were differentially expressed only in involved psoriatic skin but not in the other samples. Hierarchical cluster analysis of gene expression profiles showed that 13 independent psoriatic-involved skin samples clustered tightly together, reflecting highly similar expression profiles. Using the same 2007 gene set, we examined gene expression levels in five serial lesions from distal uninvolved psoriatic skin to involved psoriatic plaque. We identified seven genes such as alpha-1-microglobulin/bikunin precursor, calnexin, claudin 1, leucine zipper down-regulated in cancer 1, tyrosinase-related protein 1, Yes-associated protein 1, and unc-13-like protein (Coleonyx elegans) which show high-expression levels only in uninvolved psoriatic lesions. These seven genes, which were reported to be related to apoptosis or antiproliferation, might have causal roles in pathophysiology in psoriasis.

Apoptosis↗

Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro-oesophageal reflux disease: randomized-controlled study of gastro-oesophageal reflux disease.

BACKGROUND: The epidemiology and pathophysiology of non-erosive gastro-oesophageal reflux disease differs from erosive gastro-oesophageal reflux disease. There is a possibility that non-erosive gastro-oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged. AIM: To investigate the efficacy of famotidine and omeprazole in the treatment of gastro-oesophageal reflux disease, especially non-erosive gastro-oesophageal reflux disease. PATIENTS AND METHODS: A randomized, open-label trial was conducted. Fifty-four gastro-oesophageal reflux disease patients were assigned to treatment with famotidine at a dosage of 20 mg twice daily; or omeprazole, 20 mg once daily, for a period of 8 weeks. The Short Form-36 Health Survey and Gastrointestinal Symptom Rating Scale administered at baseline and after 8 weeks of treatment as well as a symptom questionnaire were conducted daily. RESULTS: Short Form-36 revealed that gastro-oesophageal reflux disease has severe impact on health-related quality of life. Thirty-nine subjects (77%) were endoscopically diagnosed as non-erosive gastro-oesophageal reflux disease. The mean Gastrointestinal Symptom Rating Scale abdominal pain, and indigestion score of non-erosive gastro-oesophageal reflux disease significantly improved in famotidine-treated patients (P < 0.05), but not in the omeprazole. There was no significant change regarding improved heartburn symptoms of non-erosive gastro-oesophageal reflux disease between treatments in the daytime or night-time. CONCLUSION: Famotidine and omeprazole were both effective in improving symptoms of gastro-oesophageal reflux disease, particularly non-erosive gastro-oesophageal reflux disease.

Analysis of Variance↗

In vivo demonstration of T lymphocyte migration and amelioration of ileitis in intestinal mucosa of SAMP1/Yit mice by the inhibition of MAdCAM-1.

The aetiology of Crohn's disease (CD) remains unknown. Since SAMP1/Yit mice have been reported to develop CD-like spontaneous enteric inflammation, such mice have been studied as an animal model of CD. In this study, using this model we examined T lymphocyte migration in microvessels of intestinal mucosa in vivo and the expression of adhesion molecules by immunohistochemistry. Fluorescence-labelled T lymphocytes isolated from AKR/J (control) mice were injected into the tail veins of recipient mice, and T lymphocyte migration in the postcapillary venules of Peyer's patches, submucosal microvessels, and villus capillaries of the terminal ileum was monitored using an intravital microscope. Adhesion of T lymphocytes was significantly increased in 35 week old SAMP1/Yit mice compared with that in AKR/J or 15 week old SAMP1/Yit mice. Immunohistochemical study showed increased infiltration of CD4, CD8 and beta7-integrin-positive cells and increased expression of MAdCAM-1 and VCAM-1 in the terminal ileum of SAMP1/Yit mice. Antibodies against MAdCAM-1 and VCAM-1 significantly inhibited adhesion of T lymphocytes to microvessels of the terminal ileum, and anti-MAdCAM-1 antibody showed stronger suppressive effect than the anti-VCAM-1 antibody. Periodical administration of anti-MAdCAM-1 antibody twice a week for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice, but submucosal hypertrophy was not significantly suppressed. Anti-VCAM-1 antibody treatment failed to show significant resolution of ileitis. In addition, anti-MAdCAM-1 antibody treatment also attenuated established ileitis. The results demonstrate that, although MAdCAM-1 and VCAM-1 play an important role in T lymphocyte-endothelial cell interactions in SAMP1/Yit mice, MAdCAM-1 may be a more appropriate target for therapeutic modulation of chronic ileitis.

Animals↗

Species-specific oligonucleotide probes for the detection and identification of Lactobacillus isolated from mouse faeces.

AIMS: To develop species-specific monitoring techniques for rapid detection and identification of Lactobacillus isolated from mouse faeces. METHODS AND RESULTS: The specificity of oligonucleotide probes was evaluated by dot blot hybridization to 16S rDNA and 23S rDNA amplified by PCR from 12 Lactobacillus type strains and 100 strains of Lactobacillus isolated from mouse faeces. Oligonucleotide probes specific for each Lactobacillus species hybridized only with targeted rDNA. The Lactobacillus strains isolated from mouse faeces were identified mainly as Lactobacillus intestinalis, L. johnsonii, L. murinus and L. reuteri using species-specific probes. 16S rDNA of eight unidentified isolates were sequenced and two new probes were designed. Four of eight strains of unhybridized Lactobacillus were identified as L. johnsonii/gasseri group, and the remaining four strains as L. vaginalis. CONCLUSIONS: The species-specific probe set of L. intestinalis, L. johnsonii, L. murinus, L. reuteri and L. vaginalis in this study was efficient for rapid identification of Lactobacillus isolated from mouse faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: The oligonucleotide probe set for Lactobacillus species harboured in the mouse intestine, can be used for rapid identification of lactobacilli and monitoring of the faecal Lactobacillus community.

Animals↗

Effect of dentine conditioners on the bonding efficacy of one-bottle adhesives.

The bonding efficacy of four one-bottle adhesives (OptiBond Solo Plus, Gluma Comfort Bond, One Step and Prime & Bond NT) and a multi-step adhesive (Clearfil Photo Bond) as a control was evaluated. The dentine cavity wall was conditioned with phosphoric acid or ethylenediaminetetraacetic acid (EDTA) and the marginal integrity was estimated by measuring the wall-to-wall contraction gap width between the composite and the dentine cavity surface. In the positive control group, the adhesive was applied following glyceryl methacrylate (GM) priming. The analyses were performed by Kruskal-Wallis and Mann-Whitney U-tests. One-bottle adhesives were clearly inferior to the multi-step bonding system in marginal integrity when dentine was conditioned with EDTA. The present findings also suggested that the marginal sealing ability of ethanol-based one-bottle systems was better than acetone-based one-bottle systems when dentine surfaces were conditioned with EDTA. Nevertheless, further investigations are needed on the function of fillers in one-bottle adhesives for the prevention of contraction gaps.

Acid Etching, Dental↗

Herpes simplex esophagitis in the immunocompetent host.

We report here a case of herpes esophagitis with Mallory-Weiss syndrome in an immunocompetent host. A 26-year-old man was admitted to our hospital because of common cold symptoms and eruptions on the body. On day 2 after hospitalization, the patient showed high-grade fever, odynophagia and hematemesis. Upper gastrointestinal endoscopic examination showed multiple ulcerations throughout the mid- and distal esophagus. Bleeding from a Mallory-Weiss tear was also seen. Follow-up endoscopic examinations showed whitish exudates on day 5. Histological examination of biopsy specimens showed Cowdry type A intranuclear inclusion bodies in epithelial cells. Positive staining of a specific antibody against herpes simplex virus-1 (HSV-1) was seen in the nuclei of esophageal epithelial cells. Primary HSV-1 infection was suspected because ELISA titers of serum IgM antibody against HSV-1 were high and titers of serum IgG antibody against HSV-1 increased from an almost cut-off ratio. A diagnosis of herpes esophagitis in an immunocompetent host was made. Our case is the first report of herpes esophagitis with Mallory-Weiss syndrome in the immunocompetent host. It is important to remind herpes esophagitis in cases of severe odynophagia even in immunocompetent hosts.

Adult↗

Normalization of reversed bio-intact-PTH(1-84)/intact-PTH ratio after parathyroidectomy in a patient with severe secondary hyperparathyroidism.

The conventional intact-PTH assay detects both (1-84)-PTH and C-terminal fragments. The newer PTH assays, bio-intact-PTH assay and whole-PTH assay, use an antibody that binds only if the first amino acid is present, making it specific for the complete molecule, (1-84)-PTH. Thus, the intact-PTH concentrations are theoretically higher than bio-intact-PTH concentrations, and the ratio of bio-intact-PTH/intact-PTH is usually less than 1. These findings are observed in normal subjects and patients with primary and secondary hyperparathyroidism. Here we present a hemodialysis patient with severe secondary hyperparathyroidism who was found to have abnormally higher plasma bio-intact-PTH concentrations than intact-PTH concentrations, and the abnormally high biointact-PTH/intact-PTH ratio improved after parathyroidectomy (PTx). The patient was a 67-year-old man on maintenance hemodialysis since 1995. Since 2003, he was found to have high plasma intact-PTH concentrations and two swollen parathyroid glands in the neck. PTx with forearm autograft was performed in October 2003. Before PTx, an abnormally high ratio of bio-intact-PTH/intact-PTH was detected (840 pg/ml/770 pg/ml, > 1), while the same ratio was improved to normal range (100 pg/ml/200 pg/ml, < 1). Recently, a few patients with parathyroid carcinoma have been found to have higher (1-84)-PTH concentrations than intact-PTH concentrations with abnormally high (1-84)-PTH/intact-PTH ratio. Moreover, a new molecular form of PTH distinct from (1-84)-PTH was detected in these patients. We speculate that the resected parathyroid gland in our patient might have produced a new molecular form of PTH that was less well detected by the conventional intact-PTH assay.

Aged↗

Identification of Fabry's disease by the screening of alpha-galactosidase A activity in male and female hemodialysis patients.

BACKGROUND: Although previous studies reported that the prevalence of Fabry's disease was 0.16 - 1.2% in hemodialysis (HD) patients based on measurement of a-galactosidase A (alpha-Gal A) activity, few reports detected female patients by the screening for alpha-Gal A. Here we determined the prevalence of Fabry's disease not only in male but also in female HD patients by measuring alpha-Gal A. METHODS: Plasma alpha-Gal A was measured in 696 consecutive males (n = 401) and females (n = 295) on HD. Patients with low plasma alpha-Gal A were examined for leukocyte alpha-Gal A, and patients with low leukocyte alpha-Gal A underwent alpha-Gal A gene sequence analysis for possible mutations, and family survey. RESULTS: Among 15 patients with low plasma alpha-Gal A activity, 4 male patients with low leukocyte alpha-Gal A and 1 female patient revealing low plasma alpha-Gal A were detected in 696 HD patients (0.7% of total patients). 3 of these 5 patients were already diagnosed to have the classical type of Fabry's disease. The other 2 patients were newly diagnosed as Fabry's disease, and did not have typical manifestations of Fabry's disease other than renal failure and left ventricular hypertrophy. DNA analysis of these 2 newly diagnosed patients revealed that each had an alpha-Gal missense mutation, previously identified (E66Q, M2961). CONCLUSION: Fabry's disease should be considered in the etiology of unexplained end-stage renal disease. Not only affected males but also affected females undergoing HD patients can be readily diagnosed by alpha-Gal A activities and gene analysis. These patients and their family members may benefit from enzyme replacement therapy for Fabry's disease.

Adult↗

Intestinal flora of animal models of human diseases as an environmental factor.

Genetically-engineered animals are known to be useful in clarifying the functions of many genes and as animal models for human diseases. However, it has been widely reported that pathophysiology is not expressed in these animals when they become germfree or SPF animals, i.e., the pathophysiology is not the result of genes alone and a combination of gene function and intestinal flora as an environmental factor are necessary. It is important to determine the roles of each of these two factors by pathophysiological analysis. Gnotobiotic mice were produced by establishment of specified bacterial species in germfree animals to form the intestinal flora of SPF animals and they were placed in barrier facilities. Measures have been taken against infections by bacteria such as Pseudomonas aeruginosa and Enterobacter cloacae. In addition, gnotobiotic mice with a highly normal physiology are required. Analysis of the effects of each bacterial species and combinations of bacteria on in vivo functions, i.e., the cross-talk between the host and intestinal flora, is essential in the creation of better laboratory animals. Monitoring of the intestinal flora, a key factor in the colonies produced, is a topic for future research.

Animals↗

Evidence for direct CP violation in B0-->K+pi- decays.

We report evidence for direct CP violation in the decay B0-->K+pi(-) with 253 fb(-1) of data collected with the Belle detector at the KEKB e(+)e(-) collider. Using 275x10(6) BB pairs we observe a B-->K+/-pi(-/+) signal with 2140+/-53 events. The measured CP violating asymmetry is A(CP)(K+pi(-))=-0.101+/-0.025(stat)+/-0.005(syst), corresponding to a significance of 3.9sigma including systematics. We also search for CP violation in the decays B+-->K+pi(0) and B+-->pi(+)pi(0). The measured CP violating asymmetries are A(CP)(K+pi(0))=0.04+/-0.05(stat)+/-0.02(syst) and A(CP)(pi(+)pi(0))=-0.02+/-0.10(stat)+/-0.01(syst), corresponding to the intervals -0.05<A(CP)(K+pi(0))<0.13 and -0.18<A(CP)(pi(+)pi(0))<0.14 at 90% confidence level.

Journal Article↗

Identification of zonal flows in a toroidal plasma.

This Letter presents experimental confirmation of the presence of zonal flows in magnetically confined toroidal plasma using an advanced diagnostic system--dual heavy ion beam probes. The simultaneous observation of an electric field at two distant toroidal locations (approximately 1.5 m apart) in the high temperature (approximately 1 keV) plasma provides a fluctuation spectrum of electric field (or flow), a spatiotemporal structure of the zonal flows (characteristic radial length of approximately 1.5 cm and lifetime of approximately 1.5 ms), their long-range correlation with toroidal symmetry (n=0), and the difference in the zonal flow amplitude with and without a transport barrier. These constitute essential elements of turbulence-zonal flow systems, and illustrate one of the fundamental processes of structure formation in nature.

Journal Article↗

Identification of parathyroid hormone-related protein-derived peptides immunogenic in human histocompatibility leukocyte antigen-A24+ prostate cancer patients.

Parathyroid hormone-related protein (PTHrP) is a key factor in the development of bone metastases, which are a major barrier in treating prostate cancer patients. In this study, we attempted to identify PTHrP-derived peptides immunogenic in human histocompatibility leukocyte antigen (HLA)-A24(+) prostate cancer patients. Among four different PTHrP peptides carrying the HLA-A24 binding motif, both the PTHrP(36-44) and PTHrP(102-111) peptides efficiently induced peptide-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) prostate cancer patients. Peptide-stimulated PBMCs showed cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. Experiments using antibodies and cold inhibition targets confirmed that their cytotoxicity was dependent on PTHrP peptide-specific and CD8(+) T cells. Immunoglobulin G reactive to the PTHrP(102-111) or PTHrP(110-119) peptide was frequently detected in the plasma of prostate cancer patients, suggesting that the PTHrP(102-111) peptide is able to elicit cellular and humoral immune responses in cancer patients. These results indicate that the PTHrP could be a promising target molecule for specific immunotherapy of HLA-A24(+) prostate cancer patients with metastases.

CD8-Positive T-Lymphocytes↗

Pole dynamics for the flierl-petviashvili equation and zonal flow.

Using the method of positions of the complex singularities, we identify a class of new, exact solutions of the Flierl-Petviashvili equation. The solutions are periodic and have the geometry of the zonal flow. We examine the physical properties and find that the solution can reproduce data from experimental observations and numerical simulations.

Journal Article↗

Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2(+) cancer patients.

Epidermal growth factor receptor (EGFR) is one of the most appropriate target molecules for cancer therapy because of its relatively high expression in about one-third of all epithelial cancers in correlation with neoplasmic progression. With respect to EGFR-targeted therapies, antibodies and tyrosine-kinase inhibitors have been intensively studied, a novel EGFR-tyrosine-kinase inhibitor ZD1839 has been approved as an anticancer drug, and many other agents are now under clinical trial. In addition, cytotoxic T lymphocyte (CTL)-directed epitope peptides could be another class of compounds useful in EGFR-targeted therapies. However, there is presently no information on CTL-directed peptides of EGFR. Therefore, from the viewpoint of development of peptide-based cancer therapy, this study was intended to determine the EGFR-derived peptides recognised by both cellular and humoral immunities in HLA-A2(+) epithelial cancer patients. We herein report finding of two such types of EGFR-derived peptides at position 479-488 and 1138-1147, both of which were recognised by the majority of patients' sera (IgG), and also possessed the ability to induce HLA-A2-restricted peptide-specific CTLs against EGFR-positive tumour cells in peripheral blood mononuclear cells (PBMCs) of epithelial cancer patients. These results may provide a scientific basis for the development of EGFR-based immunotherapy for HLA-A2(+) cancer patients.

Antibody Formation↗