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Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 73 records · Page 4Linked to original sources

Interleukin (IL)-4/IL-9 and exogenous IL-16 induce IL-16 production by BEAS-2B cells, a bronchial epithelial cell line.

Previous studies have suggested that bronchial epithelial cells may perpetuate airway inflammation. We have reported that the bronchial epithelial cell line BEAS-2B can produce interleukin (IL)-16, a potent chemoattractant for CD4+ T cells. IL-16 is thought to regulate airway inflammation in asthmatics. Recent studies showed that IL-4 induces inflammatory cytokines in bronchial epithelial cells and that IL-9 is a candidate gene for development of asthma. The present study demonstrated that BEAS-2B cells produced specifically IL-16 by synergistic effects of IL-4 + IL-16, or IL-9 + IL-16, and that the synthesized IL-16 induced migration of CD4+ T cells. This study is a first report indicating that IL-16 production may be maintained by an autocrine machinery by epithelial cell-derived IL-16 with IL-4 and IL-9 in asthma.

Bronchi↗

alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity.

Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathogenesis of Alzheimer's disease (AD). Here we show the signal transduction mechanism involved in nicotinic receptor-mediated protection against beta-amyloid-enhanced glutamate neurotoxicity. Nicotine-induced protection was suppressed by an alpha7 nicotinic receptor antagonist (alpha-bungarotoxin), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002 and wortmannin), and a Src inhibitor (PP2). Levels of phosphorylated Akt, an effector of PI3K, and Bcl-2 were increased by nicotine. The alpha7 nicotinic receptor was physically associated with the PI3K p85 subunit and Fyn. These findings indicate that the alpha7 nicotinic receptor transduces signals to PI3K in a cascade, which ultimately contributes to a neuroprotective effect. This might form the basis of a new treatment for AD.

Amyloid beta-Peptides↗

Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins.

DEC1 is a basic helix-loop-helix (bHLH) protein related to Drosophila Hairy, Enhancer of split and HES, and involved in the control of proliferation and/or differentiation of chondrocytes, neurons, etc. We report here the identification and characterization of human, mouse and rat DEC2, a novel member of the DEC subfamily. DEC2 had high (97%) and moderate (52%) similarities in the bHLH region and the Orange domain with DEC1, respectively. However, DEC2, but not DEC1, had alanine and glycine-rich regions in the C-terminal half. Unlike Hairy, Enhancer of split and HES, DEC2 lacked the WRPW motif for interaction with the corepressor Groucho. The DEC2 gene was mapped to human chromosome 12p11.23-p12.1, mouse chromosome 6 G2-G3 and rat chromosome 4q43 distal-q4, where the conserved linkage homology has been identified among these species. Unlike DEC1, which was broadly expressed in many tissues, DEC2 showed a more restricted pattern of mRNA expression. The DEC subfamily proteins may play an important role in tissue development.

Amino Acid Sequence↗

Molecular characterization of the ERGIC-53 gene in two Japanese patients with combined factor V-factor VIII deficiency.

Combined deficiency of factor V and factor VIII is a distinct clinical entity and is an autosomal recessive disorder. Recently identification of the gene, the endoplasmic reticulum-Golgi intermediate compartment (ERGIC-53), responsible for combined factor V-factor VIII deficiency and mutations of the ERGIC-53 gene in affected patients have been reported. In this report we analyzed two Japanese patients with combined factor V-factor VIII deficiency by genomic polymerase chain reaction and sequencing analysis. In one patient we found a point mutation of C to T at nucleotide 604 in exon 5, resulting in a transition of arginine to stop codon, which was reported in previous reports. The DdeI digestion study demonstrated that this patient is homozygous for this nonsense mutation. In the other patient we found no mutation in the ERGIC-53 gene in analysis of the entire coding region and the intron/exon junctions, which is also consistent with the previous reports, suggesting the possibility of defects at other genetic loci.

Factor V Deficiency↗

Comparison of complete nucleotide sequences of genomic RNAs of four Soybean dwarf virus strains that differ in their vector specificity and symptom production.

Soybean dwarf virus (SbDV) is divided into four strains, namely YS, YP, DS and DP. YS and YP cause yellowing in soybeans, while DS and DP cause dwarfing. YS and DS are transmitted by Aulacorthum solani, while YP and DP are transmitted by Acyrthosiphon pisum. To clarify the taxonomic relationship between the four strains and to classify SbDV into an appropriate genus in the Luteoviridae, we determined the complete nucleotide sequences of genomic RNAs of four isolates belonging to each of the strains. The genomes of the four isolates had a chimeric form between Barley yellow dwarf virus-PAV and poleroviruses, and the genome organizations were similar to the Australian isolate SbDV Tas-1. In all of the non-coding regions and ORFs, nucleotide and deduced amino acid sequence identity between the same symptom-type strains was higher than that between the different symptom-type strains. However, in the N-terminal half of the readthrough domain (RTD) the deduced amino acid identity between the same aphid transmissibility-type strains was higher than that between the different aphid transmissibility-type strains. These data suggest that the N-terminal half of the RTD is closely related to the aphid transmission specificity, and that the present strains were generated from ancestral Y and D strains by mutations and strong selection pressures of efficient aphid transmission. Therefore, we propose that SbDV should be classified into a new genus in the family Luteoviridae and that the four strains described should be regarded as different strains of the same virus, rather than as distinct virus species.

Amino Acid Sequence↗

Regulation of hyaluronan synthase gene expression in human periodontal ligament cells by tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma.

Accumulation and fragmentation of hyaluronic (HA) accompanies the inflammatory changes in the periodontium and gingival crevicular fluid are involved in periodontitis, but the mechanism for this is unknown. Recently, three human hyaluronan-synthase (HAS1, 2, and 3) genes have been cloned and characterised as synthesising hyaluronans of different molecular weights. Both HAS1 and HAS2 synthesise high molecular-weight HA, whereas HAS3 produces lower molecular weight HA. In the present study the regulation of HAS genes by cytokines in cultured human periodontal ligament (PDL) cells was investigated using a novel real-time fluorescence polymerase chain reaction detection system. Human PDL cells derived from premolars were cultured with or without tumour necrosing factor (TNF)-alpha (1-100 ng/ml), interleukin (IL)-1beta (0.1-10 ng/ml) and interferon (IFN)-gamma (1-100 ng/ml). Expression of HAS mRNA was assessed in cultured cells treated with these cytokines for 0-24 h. The expression of HAS2 mRNA was enhanced about 4.5- and 2.2-fold at maximum after 3-h stimulation with 10 ng/ml TNF-alpha and 1 ng/ml IL-1beta, respectively, whereas IFN-gamma exerted little effect on HAS2 or HAS3 mRNA expression during the experiment. Expression of HAS3 mRNA was increased by about 14- and 10-fold after 3-h stimulation with 10 ng/ml TNF-alpha and 1 ng/ml IL-1beta, respectively. These results suggest that TNF-alpha and IL-1beta regulate HAS expression, and consequently may result in an accumulation of HA and an increase in HA of a lower molecular-weight.

Cells, Cultured↗

Oligoclonal expansion of alphabeta T lymphocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with abnormal karyotypes.

We observed a fatal case of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) with an abnormal karyotype. Increased levels of alphabeta T cells of the patient were investigated using an inverse polymerase chain reaction (PCR) of the T-cell receptor variable region gene, followed by Jbeta-PCR and single-strand conformation polymorphism (SSCP) to confirm the clonality of specific alphabeta-T cell subsets. A high frequency (>15%) was recognized in Vbeta9 at onset, but not in any Vbeta and Valpha families 2 weeks after chemotherapy. High levels (>20%) of some Jbeta genes were detected in all Vbeta families investigated, and the predominant bias of the Jbeta2 gene relative to the Jbeta1 gene (86.1% versus 13.9% at onset, and 77.4% versus 23.5% after chemotherapy) was recognized in pan-alphabeta T cells. When each Vbeta-Jbeta fragment was compared among the samples at onset and after chemotherapy by SSCP analysis, several distinct bands were observed that indicate a clonal evolution. Thus, the findings suggest that some of the alphabeta T cell clones could be associated with abnormal karyotypes in EBV-HLH. The present findings provide molecular evidence of the presence of oligoclonal T cells in pan-alphabeta-T cells and clonal evolution during a short clinical course in EBV-HLH with abnormal karyotypes.

Child↗

The sulphydryl reagent, N-ethylmaleimide, disrupts sleep and blocks A1 adenosine receptor-mediated inhibition of intracellular calcium signaling in the in vitro ventromedial preoptic nucleus.

To explore the neuronal signaling mechanisms underlying sleep regulation in the rat, the present study examined continuous intra-third ventricle infusion of N-ethylmaleimide (NEM), a sulphydryl reagent that inhibits G(i/o) protein-coupled receptor-mediated signaling pathways. The diurnal infusion of NEM (0.01-10 micromol/10 h) dose-dependently inhibited both non-rapid eye movement sleep and rapid eye movement sleep. A maximal dose of NEM (10 micromol/10 h) dramatically inhibited day-time sleep (-57% for non-rapid eye movement sleep and -89% for rapid eye movement sleep) with a compensatory increase of sleep during the subsequent night-time (+33% for non-rapid eye movement sleep and +259% for rapid eye movement sleep). The day-time brain temperature was also increased by NEM, demonstrating effects of NEM on both sleep and body temperature levels. Immunostaining of the rat hypothalamus with a monoclonal antibody against the A1 adenosine receptor (A1R) was used to explore the distribution of a sleep-related G(i/o) protein-coupled receptor. Robust A1R-like immunoreactivity was found in the ventromedial preoptic nucleus and the supraoptic nucleus. Fura-2-based Ca(2+) imaging analysis of acute hypothalamic slices further demonstrated that the A1R agonist N(6)-cyclopentyladenosine (CPA; 200 nM) inhibited spontaneous Ca(2+) oscillations and high potassium (80 mM)-induced Ca(2+) flux in the ventromedial preoptic nucleus, while NEM (100-300 microM) and an A1R antagonist 8-cyclopentyl-dipropylxanthine (300 nM) blocked the CPA actions and increased the high potassium-induced Ca(2+) flux. From these results we suggest that NEM-sensitive G protein-coupled receptor(s) may play an important role in the regulation of sleep and body temperature in the rat and one possible mechanism is an A1R-mediated regulation of intracellular Ca(2+) concentrations in the ventromedial preoptic nucleus.

Adenosine↗

Application of in situ PCR to diagnose pneumonia in medico-legal autopsy cases.

In situ polymerase chain reaction (in situ PCR) can detect specific sequences of DNA, such as those of micro-organisms in human tissue samples. In forensic medicine, there are many cases implicated with infection, and pneumonia is an especially common finding in autopsy cases. In the present study, we tried to detect the presence of bacterial infections in lung tissue samples. The experiment was performed with ten paraffin-embedded lung tissue samples, including three non-pneumonia cases using specific primers for Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus equisimilis, and a DIG Oligonucleotide 3'-End Labeling Kit (Boehringer Mannheim). The findings showed that at least one or all three species of bacterial flora in the alveoli could be detected in all seven pneumonia cases, and that some leukocyte cytoplasms, after antigen-antibody and color emission chemical reactions, were also observed to have changed color due to phagocytosis. Detection of bacterial DNA in the leukocyte cytoplasm is a sign of vital reaction and differentiates between antemortem and postmortem infection. The present findings revealed that in situ PCR had the advantage that it helped identifying specific bacteria in the lung tissues with pneumonia.

Journal Article↗

Synergistic effects of pegylated recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor on mobilization of hematopoietic progenitor and stem cells with long-term repopulating ability into peripheral blood in mice.

We investigated the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on peripheral blood progenitor cell (PBPC) mobilization and the combined effect of PEG-rHuMGDF plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) in C57BL/6 mice. Treatment of mice with PEG-rHuMGDF increased the numbers of day 8 and day 12 spleen colony-forming units (CFU-S), and pre-CFU-S in the PB. Ten days administration of PEG-rHuMGDF could mobilize higher numbers of days 8 and day 12 CFU-S than 5 days administration. An optimal dose of PEG-rHuMGDF mobilized a higher number of committed progenitor cells (day 8 CFU-S) and a lower number of immature progenitor cells (pre-CFU-S) into PB than rhG-CSF. The combined administration of optimal or suboptimal doses of PEG-rHuMGDF and rhG-CSF induced synergistic effects on mobilization of CFU-S and pre-CFU-S into PB compared to either factor alone. Four months after sex-mismatched PBPC transplantation, long-term donor-derived engraftment was observed in all recipients that had been transplanted with PBPCs mobilized by rhG-CSF and/or PEG-rHuMGDF, as determined by Y-chromosome polymerase chain reaction (PCR) analysis. Our data suggest that cytokine-induced pathways for PBPC mobilization may be different between PEG-rHuMGDF and rhG-CSF and indicate that PEG-rHuMGDF alone or the combination with rhG-CSF may be useful in effective PBPC mobilization.

Animals↗

Thickening of the glenoid fossa in osteoarthritis of the temporomandibular joint. An autopsy study.

OBJECTIVE: To evaluate the thickness of the roof of the glenoid fossa of the temporomandibular joint (TMJ) in relationship to the stage of internal derangement from autopsy material. MATERIAL AND METHODS: The minimum thickness of the roof of the glenoid fossa was measured with a caliper in 61 TMJ autopsy specimens. Based on macroscopic examination the joints were categorized as normal (30 joints), disk displacement (eight joints), disk displacement with osteoarthritis (12 joints) and osteoarthritis with perforation of the disk or posterior attachment (11 joints). The relationship between thickness of roof of the glenoid fossa and status of the joint was analysed. RESULTS: The roof of the glenoid fossa was on the average 0.6 mm in normal joints, 1.1 mm in joints both with disk displacement and disk displacement with osteoarthritis and 2.6 mm in joints with osteoarthritis and perforation. The difference between the normal joints and those with perforation was significant (P<0.01). CONCLUSION: Progressive remodeling with thickening of the roof of the glenoid fossa seems to be associated with perforation of the disk or posterior attachment.

Adult↗

High risk of Helicobacter pylori infection in young Japanese dentists.

BACKGROUND AND AIM: The route of person-to-person transmission of Helicobacter pylori may be either fecal-oral or oral-oral, because the bacterium is found in both dental plaque and feces. We assessed the prevalence of H. pylori seropositivity, which reflects present or past infection, in Japanese dentists exposed occupationally to dental plaque. METHODS: We examined the sera of 60 dentists (34 who were 20-29 years or older, and 26 who were over 30 years of age) and 60 age-matched controls by using quantitative ELISA for antibodies of the immunoglobulin G class to H. pylori. RESULTS: The proportion of dentists seropositive for H. pylori (42 of 60, 70%) was higher than in controls (23 of 60, 38%). The odds ratio for H. pylori seropositivity (3.8; 95% CI, 1.76-8.02) was high in the dentists. When dentists were classified in terms of the length of their practice, the odds ratio for seropositivity (10.4; 95% CI, 3.26-32.85) was high in the dentists practising for fewer than 4 years. The proportion of dentists in their 20s who were seropositive was greater than that in the group of age-matched controls. CONCLUSION: Japanese young dentists are at a high risk for H. pylori infection, with the oral-oral transmission route being possibly the most common.

Adult↗

Spatio-temporal EEG power spectral patterns during a short daytime nap.

This is an approach to investigate topographic changes in electroencephalographic (EEG) spectral power during pre- and post-nap wakefulness as well as stages 1 (S1) and 2 (S2) NREM sleep in 12 subjects. Delta- and theta-band power significantly increased in the frontal and central regions during S1 and S2 with an increase in inter- and intra-hemispheric correlations. Beta-band power significantly increased in the frontal, central and parietal regions during S2 with an increase in interhemispheric correlation. In contrast, alpha-band power significantly decreased in the parietal-occipital regions during S1 and S2 with a decrease in interhemispheric correlation. Thus, daytime nap modulated spatio-temporal patterns of EEG power spectral patterns in wide scalp regions.

Adult↗

Myxoid adrenal cortical adenoma.

Myxoid adrenal cortical adenoma is a rare tumor and, to our knowledge, only 16 cases have been reported. We present the case of a 56-year-old Japanese man who was admitted to hospital because of a right adrenal mass that was discovered during a routine physical examination. The resected mass was well circumscribed and contained canary yellow multinodular regions that were surrounded by a brown gelatinous region. Histologically, the multinodular regions resembled a conventional adrenal cortical adenoma, being composed of solid aggregates of large clear or eosinophilic cells. In the gelatinous region, anastomosing small eosinophilic or vesicular cells were visible within a myxoid stroma that contained large amounts of acidic mucopolysaccharides. Light-microscopic findings were consistent with a diagnosis of adenoma. Immunohistochemical staining revealed that a small number of tumor cells were positive for vimentin, and the MIB-1 labeling index was less than 1%. Flow cytometry demonstrated that cells were diploid. At the ultrastructural level, many fat droplets were found in the large clear cells in the multinodular regions. Small eosinophilic cells in the myxoid region contained many mitochondria but few fat droplets. There were no findings suggestive of malignancy. Although the adrenal cortex might have the potential to produce connective tissue-type mucin as a consequence of its mesodermal origin, the mechanism of production of acidic mucopolysaccharides in a myxoid adrenal cortical tumor remains to be clarified.

Adrenal Cortex Neoplasms↗

Ortho cubic super-high resolution computed tomography: a new radiographic technique with application to the temporomandibular joint.

OBJECTIVE: The purpose of this study was to present a newly developed ortho cubic super-high resolution computerized radiographic technique (Ortho-CT) and its application to the temporomandibular joint. METHOD AND PATIENTS: A prototype was assembled on a Scanora (Soredex Findent Co) with the use of a 4-inch image intensifier instead of film. Data were collected from a single 360 degrees scan and a cylinder 32 mm in height and 38 mm in diameter. Images were reconstructed with a software program on a personal computer. Imaging data consisted of 240 (height) x 280 (diameter) cubic voxels, each with a dimension of 0.136 mm. With this small voxel size, the image resolution was high and was the same in any direction. Three patients with temporomandibular joint disease (trauma, pain and dysfunction, fibroosseous ankylosis) were evaluated with Ortho-CT, and the images were compared to routine radiographic films. CONCLUSION: Preliminary clinical experience with Ortho-CT demonstrates subjectively superior image quality compared to panoramic and conventional tomographic images. The images were similar to conventional computed tomography, but this new radiographic technique is less expensive, takes less space, and gives a lesser patient dose.

Adult↗

Clinical and endoscopic features of nonsteroidal anti-inflammatory drug-induced colonic ulcerations.

OBJECTIVE: Clinical and endoscopic features of nonsteroidal anti-inflammatory drug (NSAID)-induced colonic ulcerations have not been fully investigated. METHODS: During a 3-yr period from April 1996 to March 1999, 6076 subjects underwent total colonoscopy at our institutions. Among them, the diagnosis of NSAID-induced colonic ulceration was made by their clinical and colonoscopic findings. All patients diagnosed as having this disease underwent upper endoscopy and follow-up colonoscopy. Clinical features, serial changes in colonoscopic findings, and upper GI lesions were analyzed. RESULTS: Among the subjects, 14 patients were diagnosed as having NSAID-induced ulcerations. Seven patients were complicated by renal failure. Three patients had gastric ulcers concurrently. Eleven patients had colonic lesions in the ileocecal region. In 13 of 14 patients, initial colonoscopy demonstrated sharply demarcated, semilunar or circumferential ulcers without stricture formation. After discontinuance of NSAIDs, improvement of the ulcers without stricture or inflammatory polyps could be confirmed 3-10 wk later. In one patient with diaphragm-like stricture, follow-up colonoscopy performed 2 yr later demonstrated resolution of circumferential ulcer. CONCLUSIONS: NSAID-induced colonic ulceration may occur more frequently than previously recognized. Frank ulcerations, rather than stricture formation, seem to be the typical colonoscopic signs of NSAID-induced colonic ulceration.

Anti-Inflammatory Agents, Non-Steroidal↗