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Biomedical subjects

H Okamoto

Publications and source records attributed to H Okamoto.

At least 19 recordsLinked to original sources

Analysis of hepatitis B surface antigen mutations in Mongolia: molecular epidemiology and implications for mass vaccination.

Although the potential significance of hepatitis B surface antigen (HBsAg) mutants for failure of immunization has been studied in some endemic countries, whether the "a" determinant variants are responsible for vaccine failure in Mongolia remains unknown. Fifty-nine HBsAg-positive children (age: 8.8 +/- 0.9 years) who had been observed during the nationwide survey of vaccinated cohorts conducted in 2004 were subjected to molecular analyses of hepatitis B virus (HBV). Partial S gene sequences encoding amino acids (aa) 40-171 of HBsAg were determined in 57 children (96.6%) who had detectable HBV DNA. Phylogenetic analysis of the S gene sequences revealed that genotype D accounted for 93.0% and genotype A for 5.3%. Only one child (1.7%) had HBVs of genotypes A and D. HBsAg mutations were found in 17 (29.8%) children ranging from 1 to 4 aa per subject (mean +/- SD, 1.6 +/- 0.9 aa). Pro127Thr and Thr118Ala were the most common substitutions, which occurred in 6 (10.5%) and 3 (5.3%) subjects, respectively; none had Gly145Arg. There were no significant associations in the prevalence of HBsAg mutations with age, sex, residential area, or vaccination status against hepatitis B. Analysis of the deduced amino acid sequence of the entire preS1/preS2/S gene revealed that eight genotype D isolates and one genotype A isolate were quite similar to previously-reported wild-type isolates, suggesting that they are essentially wild-type, but not vaccine-induced mutants. In conclusion, the results demonstrate that hepatitis B surface gene mutants do not play a significant role in vaccination failure in Mongolia.

Amino Acid Sequence↗

Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine.

Reg I (regenerating gene product I) is a growth factor that plays a central role in the generation and regeneration of the gastric mucosal architecture. On the other hand, mouse Reg I mRNA is expressed at the highest levels in the small intestine among the gastrointestinal tissues. In the current study, with the aim to clarify the role of Reg I protein in the small intestine, the temporal and spatial pattern of Reg I expression and the phenotype of Reg I-knockout mice in the tissue were examined. In the wild-type mice, immunohistochemistry localized Reg I protein expression in absorptive cells located in the lower half of the intestinal villi. Reg I expression was undetectable until embryonic day 13 (E13), when the fetal intestine still lacks villous structure; however, it dramatically increased at E17 along with the formation and maturation of the fetal intestinal villi. In the small intestine of the adult Reg I-knockout mice, less densely packed, round-shaped aberrant morphology of the absorptive cells was observed light microscopically, and electron microscopical examination revealed a strikingly loose connection of these cells to the basement membrane. Antiproliferating cell nuclear antigen staining and anti-Ki67 staining demonstrated the marked decrease in the number of proliferating cells in the small intestinal mucosa of the knockout mice. The cell migration speed visualized by one shot labeling of 5-bromodeoxyuridine was significantly slower in the knockout mice. These phenotypes of Reg I-knockout mice emerged, in accordance with the temporal pattern of Reg I expression described above, from E17. Reg I was considered to be a regulator of cell growth that is required to generate and maintain the villous structure of the small intestine.

Animals↗

Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNbeta.

AIMS/HYPOTHESIS: The expression of IFNbeta in beta cells results in accelerated type 1 diabetes. The REG family of beta cell proliferation factors have been described as autoantigens in autoimmune diabetes. The aim of this study was to determine the effect of IFNbeta on Reg expression, and the implications of this in terms of autoimmunity. METHODS: Reg gene expression was determined in islets from non-obese diabetic (NOD) RIP-HuIFNbeta mice by cDNA microarray, quantitative real-time PCR and immunohistochemistry. The effect of IFNbeta on Reg1 and Reg2 expression was assessed in the NOD insulinoma cell line NIT-1. IL-6, known to induce Reg expression, was measured in the insulitis microenvironment. Morphological studies were carried out to determine islet enlargement in this model. RESULTS: Reg2 was upregulated in islets from the NOD RIP-HuIFNbeta mice at the onset of the autoimmune attack. IFNbeta upregulates Reg1 and Reg2 genes in NIT-1 cells. The expression of Il6 was increased in islets from transgenic mice and in NIT-1 cells exposed to HuIFNbeta. Moreover, islets from transgenic mice were enlarged compared with those from wild-type mice. CONCLUSIONS/INTERPRETATION: Reg overexpression correlates well with the acceleration of diabetes in this model. The upregulation of Reg suggests that islets try to improve hyperglycaemia by regenerating the cells lost in the autoimmune attack. Reg expression is regulated by several factors such as inflammation. Therefore, the overexpression of an IFNbeta-induced autoantigen (REG) in the islets during inflammation might contribute to the premature onset of diabetes.

Animals↗

Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers.

Methods to permit more precise delineation of astrocytomas of different grades may have therapeutic utility. The authors selectively microdissected pure populations of cells from normal brain and astrocytomas. They performed two-dimensional protein gel electrophoresis (2DGE) followed by protein sequencing. Differential expression was confirmed immunohistochemically. 2DGE identified proteomic patterns and proteins that differentiated normal brain from tumor and distinguished astrocytomas of increasing grade.

Astrocytoma↗

Coherent control of charge and lattice dynamics in a photoinduced neutral-to-ionic transition of a charge-transfer compound.

Coherent control of a charge-lattice coupled oscillation associated with the neutral (N)-ionic (I) transition was successfully demonstrated for a charge-transfer (CT) compound, tetrathiafulvalene-p-chloranil, with use of double femtosecond laser pulses. By changing the interval of the two laser pulses, amplitude of the oscillation in the reflectivity for the intramolecular transition band sensitive to the degree of CT was periodically changed. With increase of the pump intensity, the oscillation amplitude was dramatically enhanced. Such an enhancement is discussed in terms of the cooperative nature of the N-I transition.

Journal Article↗

Ultrafast photoinduced melting of a spin-Peierls phase in an organic charge-transfer compound, K-tetracyanoquinodimethane.

Ultrafast photoinduced phase transition in a spin-Peierls (SP) system of K-tetracyanoquinodimethane (K-TCNQ) was studied by femtosecond (fs) reflection spectroscopy. Photocarriers destabilize the SP phase, resulting in a decrease in molecular dimerization within 400 fs. Such a melting of the SP phase drives three kinds of coherent oscillations. By comparing the oscillations with the Raman bands activated by the dimerization, we show that the oscillation of 20 cm-1 is due to an LO phonon, and it plays an important role for the stabilization of the SP phase.

Journal Article↗

Utilization of personal digital assistants (PDA) for intraoperative naming tasks in awake surgery.

The naming task, one of the most important tasks for screening essential language function, is widely used in awake surgery. We employed personal digital assistants (PDA) for the display of objects in three patients performing the naming task during awake surgery for gliomas adjacent to the language area in the left hemisphere. The compact, light-weight, self-illuminated instrument can easily be held close to the patient's face. None had difficulty seeing the screen despite the presence of the surgical drape around the face. The examiner could easily change the displayed objects with a click. However, the PDA screen is too small for use in auditory comprehension tasks such as the Token Test.

Brain Mapping↗

Transient appearance of hepatic natural killer cells with high cytotoxicity and unique phenotype in very young mice.

There were few natural killer (NK) cells in the liver in very young mice at the age of 1-2 weeks. This was because the cell yield from the liver of young mice was low. The percentage of NK cells in the liver of young mice, however, was almost comparable with that in the liver of adult mice. Lymphocytes were isolated from the liver and spleen of C57BL/6 (B6) mice, and NK cytotoxicity and phenotype were herein examined in this study. NK cytotoxicity was extremely high in the liver of very young mice. This phenomenon was seen in the liver of various normal mouse strains. In contrast, the appearance of high cytotoxicity was not seen in NK cells of the spleen, irrespective of mouse strains. The quality of NK cells in the liver of young mice was different from that in adult mice. NK cells in the liver of young mice were mainly CD69(+)Mac-1(-) Fas ligand(+), whereas those in the liver of adult mice were CD69(-)Mac-1(+) Fas ligand(-). These results revealed that the quality of hepatic NK cells changes in the process of ageing. Namely, liver NK cells in very young mice temporarily show the highest NK cytotoxicity and a unique activated phenotype. Physiological meaning of the present phenomenon was discussed.

Age Factors↗

Muscarinic cationic current in gastrointestinal smooth muscles: signal transduction and role in contraction.

1 The muscarinic receptor plays a key role in the parasympathetic nervous control of various peripheral tissues including gastrointestinal tract. The neurotransmitter acetylcholine, via activating muscarinic receptors that exist in smooth muscle, produces its contraction. 2 There is the opening of cationic channels as an underlying mechanism. The opening of cationic channels results in influxes of Ca2+ via the channels into the cell and also via voltage-dependent Ca2+ channels which secondarily opened in response to the depolarization, providing an amount of Ca2+ for activation of the contractile proteins. 3 Electrophysiological and pharmacological studies have shown that the cationic channels as well as muscarinic receptors exist in many visceral smooth muscle cells. However, the activation mechanisms of the cationic channels are still unclear. 4 In this article, we summarize the current knowledge of the muscarinic receptor-operated cationic channels, focusing on the receptor subtype, G protein and other signalling molecules that are involved in activation of these channels and on the molecular characteristics of the channel. This will improve strategies aimed at developing new selective pharmacological agents and understanding the activation mechanism and functions of these channels in physiological systems.

Acetylcholine↗

Raised monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebrospinal fluid of patients with neuropsychiatric lupus.

BACKGROUND: An imbalance in cytokine homoeostasis is thought to have a key role in the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), and recently, a role for chemokines has been noted. OBJECTIVE: To compare concentrations of monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebral spinal fluid (CSF) of patients with SLE, and with and without neuropsychiatric symptoms. METHODS: CSF was obtained from 185 patients with SLE: 96 with NPSLE and 89 patients with SLE without neuropsychiatric symptoms (non-NPSLE patients). MCP-1/CCL2 concentrations were measured with an ELISA. RESULTS: The average concentration of CSF MCP-1/CCL2 in patients with NPSLE was 1959 pg/ml, and in non-NPSLE patients 712 pg/ml. The average MCP-1/CCL2 concentration was significantly higher in the NPSLE group than in the non-NPSLE group (p<0.001). In one representative patient with NPSLE, MCP-1/CCL2 levels in the CSF decreased in parallel with a decline in neuropsychiatric symptoms. CONCLUSIONS: CSF MCP-1/CCL2 levels are higher in patients with NPSLE than in non-NPSLE patients. MCP-1/CCL2 may have an important role in the expression of NPSLE. These results indicate that CSF MCP-1/CCL2 reflects an inflammatory activity in the brain, suggesting that it might be used as a diagnostic tool and a monitor for therapeutic responses in patients with NPSLE.

Adolescent↗

Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage from patients with rheumatoid arthritis.

OBJECTIVES: To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells. METHODS: Human articular cartilage specimens were obtained from joints from RA and osteoarthritis (OA) patients and normal joints (controls). Transcript levels of MCP-4 in cartilage were determined by real-time polymerase chain reaction. Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast-like synoviocytes (FLS) were treated with various concentrations of recombinant MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay. RESULTS: The gene expression of MCP-4 was significantly higher in cartilage from RA patients than in that from OA patients (P = 0.00902) and in normal cartilage (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients (mean 94.7 +/- 37.6 pg/ml) was significantly higher than in serum from OA patients (mean 49.2 +/- 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 +/- 23.9 pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid from RA patients (mean 247.2 +/- 161.2 pg/ml) was also significantly higher than in that from OA patients (mean 29.6 +/- 50.5 pg/ml, P = 0.000019). Moreover, MCP-4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner. CONCLUSIONS: MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and activates the proliferation of rheumatoid synovial cells, thereby leading to joint destruction in RA.

Arthritis, Rheumatoid↗

Direct observation of excitons and a continuum of one-dimensional Mott insulators: a reflection-type third-harmonic-generation study of Ni-halogen chain compounds.

The third-harmonic-generation (THG) spectrum was measured for a NiBr-chain compound, which is a one-dimensional Mott insulator, in a reflection configuration. A sharp peak and a shoulder structure in the THG spectrum are attributed to three-photon resonance to an exciton and a continuum, respectively. The band-edge energy, the exciton binding energy, and the spectral weights for the exciton and the continuum were determined from comparative studies of linear absorption, THG, and electroreflectance spectra. The excitonic effect is more pronounced in the NiCl chain than in the NiBr chain.

Journal Article↗