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Biomedical subjects

Hiroyuki Nakamura

Publications and source records attributed to Hiroyuki Nakamura.

At least 37 records · Page 2Linked to original sources
PubMed2006

Effects of acute exercise on lung antioxidant enzymes in young and old rats.

The lung could be the target organ to cellular damage, since it is directly exposed to high concentrations of oxygen. Acute exercise and age would be an added challenge to the lung, and therefore, we investigated alterations of major lung antioxidant enzymes (manganese-superoxide dismutase, Mn-SOD; copper-zinc-SOD, Cu-Zn-SOD; glutathione peroxidase, GPX; catalase, CAT) activities and mRNA expressions in young (4 months old) and old (26 months old) male Wistar rats with exercise. Thioredoxin reductase (TrxR) activity was also investigated. Mn-SOD and Cu-Zn-SOD increased with age, but age did not affect GPX, CAT, or TrxR activity. Acute exercise in young animals increased the activities of Mn-SOD, Cu-Zn-SOD, and CAT. In contrast, only Mn-SOD increased significantly in the old animals. The mRNA expressions of Mn-SOD, Cu-Zn-SOD and GPX were not altered with age, while CAT mRNA expression decreased with age. Acute exercise had no significant effect on any of the antioxidant enzyme mRNA expression. Moreover, reactive carbonyl derivative increased with age, but no significant changes were detected after acute exercise in either group. In summary, antioxidant enzymes responsible for the removal of hydrogen peroxide were unable to increase their enzyme activities in the old animals with exercise.

Aging↗
PubMed2006

Synthesis and biological evaluation of boronic acid containing cis-stilbenes as apoptotic tubulin polymerization inhibitors.

A series of boronic acid containing cis-stilbenes as potent inhibitors of tubulin polymerization was synthesized by the introduction of boronic acid as an acceptor-type functional group into the aromatic ring B of the combretastatin framework. High cell-growth inhibition was observed with boron compounds 13 c and 13 d, in which a hydroxy group on the aromatic ring B of combretastatin A-4 was replaced with boronic acid; IC50 values toward B-16 and 1-87 cell lines are 0.48-2.1 microM. Compounds 13 c and 13 d exhibited significant inhibitory activity toward tubulin polymerization (IC50=21-22 microM). The carboxylic acid derivative 17, which can be considered as a mimic of boronic acid 13 c, did not show significant inhibition of cell growth or tubulin polymerization. According to the FACScan analysis using Jurkat cells, apoptosis was induced after incubation for 8 h with 13 c at a concentration of >10(-8) M. Growth inhibitory experiments against a panel of 39 human cancer cell lines revealed 13 c to inhibit growth differently than combretastatin A-4; the correlation coefficient (r) between the two compounds was 0.553 in the COMPARE analysis.

Animals↗
PubMed2006

Unusual Corynebacterium mucifaciens isolated from ear and nasal specimens.

OBJECTIVE: Corynebacterium mucifaciens was first proposed as a novel Corynebacterium species in 1997. This report describes our experience with the unexpectedly frequent isolation of C mucifaciens. STUDY DESIGN: By using agar supplemented with several antibiotics, microbiological studies were performed on specimens collected from the ear and nose. SETTING: A primary and secondary referral hospital. RESULTS: The organisms grew slowly. Five strains of C mucifaciens were found in specimens of middle ear effusion (MEE) from patients with otitis media with effusion (OME), and four strains were isolated from the nasal polyps and nasal discharge of patients with chronic sinusitis (CRS). CONCLUSIONS: C mucifaciens was isolated from nine otorhinological specimens. SIGNIFICANCE: This is the first report about the isolation of C mucifaciens from MEE, nasal polyps, and nasal discharge. Although its pathogenetic role is unknown, the characteristics of this microorganism might make it a potential cause of OME and/or CRS, so further studies are necessary. EBM RATING: C-4.

Adolescent↗
PubMed2006

Inhibition of the ATM/p53 signal transduction pathway by Kaposi's sarcoma-associated herpesvirus interferon regulatory factor 1.

Infected cells recognize viral replication as a DNA damage stress and elicit the ataxia telangiectasia-mutated (ATM)/p53-mediated DNA damage response signal transduction pathway as part of the host surveillance mechanisms, which ultimately induces the irreversible cell cycle arrest and apoptosis. Viruses have evolved a variety of mechanisms to counteract this host intracellular innate immunity. Kaposi's sarcoma-associated herpesvirus (KSHV) viral interferon regulatory factor 1 (vIRF1) interacts with the cellular p53 tumor suppressor through its central DNA binding domain, and this interaction inhibits transcriptional activation of p53. Here, we further demonstrate that KSHV vIRF1 downregulates the total p53 protein level by facilitating its proteasome-mediated degradation. Detailed biochemical study showed that vIRF1 interacted with cellular ATM kinase through its carboxyl-terminal transactivation domain and that this interaction blocked the activation of ATM kinase activity induced by DNA damage stress. As a consequence, vIRF1 expression greatly reduced the level of serine 15 phosphorylation of p53, resulting in an increase of p53 ubiquitination and thereby a decrease of its protein stability. These results indicate that KSHV vIRF1 comprehensively compromises an ATM/p53-mediated DNA damage response checkpoint by targeting both upstream ATM kinase and downstream p53 tumor suppressor, which might circumvent host growth surveillance and facilitate viral replication in infected cells.

Animals↗
PubMed2006

[A case of small-cell lung cancer responding remarkably to CPT-11 and CDDP combination chemotherapy].

A 73-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and body weight loss. Chest X-ray film showed left-sided pleural effusion. Computed tomographic (CT) scan of the chest also demonstrated left-sided pleural effusion with lung tumor and lymphnode swelling. Repeated treatment with 60 mg/m(2) of cisplatin on day 1 followed by 80 mg/m(2) of irinotecan on days 1 and 8 were effective in this patient.

Aged↗
PubMed2006

Inhibition of transendothelial migration and invasion of human breast cancer cells by preventing geranylgeranylation of Rho.

Rho family GTPases are frequently overexpressed in breast cancers, which regulate cancer cell migration and invasion. They require prenylation, a lipid post-translational modification, for full biological functions. We examined the effects of 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (fluvastatin), a selective farnesyltransferase inhibitor (FTI-277) and a selective geranylgeranyltransferase type I inhibitor (GGTI-298) on in vitro invasive capacity of MDA-MB-231 human breast cancer cells into the endothelial cell monolayer in a transendothelial migration assay. Although, at a maximal dose of 5 microM, fluvastatin did not affect the integrity of endothelial cell monolayer, the transendothelial migration of MDA-MB-231 cells was inhibited potently by fluvastatin in a dose-dependent manner. The transendothelial migration of MDA-MB-231 cells was also inhibited potently by GGTI-298 in a dose-dependent manner but weakly by FTI-277. The inhibitory effects of fluvastatin, GGTI-298 and FTI-277 on MDA-MB-231 cell invasion were shown to correlate well with inhibition of the membrane localization of RhoA and RhoC, but not with Ras. These results suggest that geranylgeranylation step of RhoA and RhoC could be a good therapeutic target for the prevention of invasion and metastasis of breast cancer cells.

Alkyl and Aryl Transferases↗
PubMed2006

Analysis of the COL17A1 in non-Herlitz junctional epidermolysis bullosa and amelogenesis imperfecta.

Non-Herlitz junctional epidermolysis bullosa (nH-JEB) disease manifests with skin blistering, atrophy and tooth enamel hypoplasia. The majority of patients with nH-JEB harbor mutations in COL17A1, the gene encoding type XVII collagen. Heterozygotes with a single COL17A1 mutation, nH-JEB defect carriers, may exhibit only enamel hypoplasia. In this study, to further elucidate COL17A1 mutation phenotype/ genotype correlations, we examined two unrelated families with nH-JEB. Furthermore, we hypothesized that COL17A1 mutations might underlie or worsen the enamel hypoplasia seen in amelogenesis imperfecta (AI) patients that are characterized by defects in tooth enamel formation without other systemic manifestations. We therefore conducted COL17A1 mutational analysis in three patients from two AI families. One nH-JEB patient showed no COL17A1 expression and was a compound heterozygote for the novel premature termination codon (PTC) mutations 1285delA and Q1387X. In addition, reduced COL17A1 expression was found in a second nH-JEB patient who was homozygous for the novel PTC mutation 4335delC, the most carboxyl terminal PTC mutation thus far identified. Due to nonsense mediated mRNA decay, the position of these PTC mutations is thought not to influence the effect of COL17A1 transcript loss and hence the severity of the nH-JEB phenotype. This study is the first to suggest that type XVII collagen carboxyl PTC mutations lead to restoration of truncated polypeptide expression and to a milder clinical disease severity in nH-JEB. Conversely, we failed to detect any pathogenic COL17A1 defects in AI patients, in either exon or within the intron-exon borders of AI patients. This study furthers the understanding of mutations in COL17A1 causing nH-JEB, and clearly demonstrates that the mechanism of enamel hypoplasia differs between nH-JEB and AI diseases.

Adult↗
PubMed2006

[A case of AIDS-complicated lung infection mimicking acute eosinophilic pneumonia].

A 34-year-old man was admitted with dyspnea and low grade fever. Chest radiograph and computed tomography (CT) showed bilateral, ground glass opacities and perihilar consolidation. Bronchoalveolar lavage (BAL) was performed. The percentage of eosinophils in the BAL fluid (BALF) was elevated (20.5%). BALF smear and culture showed normal flora. Acute eosinophilic pneumonia was diagnosed and steroid therapy was performed. Afterwards he was transferred to our hospital. The HIV antibody was positive and peripheral blood CD-4 positive lymphocytes decreased to 10/microl, cytomegalovirus (CMV) antigenemia was positive and beta-D-glucan increased. CMV infection and pneumocystis pneumonia (PCP) complicated with AIDS was diagnosed. Trimethoprim/sulfamethoxazole, ganciclovir, and antifungal drugs were administered, but he suffered pneumothorax on the 18th day after admission and died. Histopathologic findings from an autopsy lung specimen revealed CMV infection and PCP. It is known that the percentage of eosinophils in the BALF increases in some cases of PCP complicated with AIDS. We emphasize that it is necessary to consider PCP when the percentage of eosinophils in the BALF increase.

Acquired Immunodeficiency Syndrome↗
PubMed2006

[A case of squamous cell carcinoma of the lung with a high titer of proteinase 3 antineutrophil cytoplasmic antibody].

A 57-year-old man who had a history of sinusitis was admitted to Ryugasaki-Saiseikai hospital in April 2002 because of productive cough and bloody sputum. Chest radiographs and CT scans showed mediastinal lymphadenopathy and a solitary mass lesion with an irregular margin and cavity in the left lower lung field. Proteinase 3 antineutrophil cytoplasmic antibody (PR3 ANCA) was positive, and this is a sensitive and specific indicator of Wegener's granulomatosis. The pathological findings from transbronchial biopsy revealed squamous cell carcinoma of the lung, without the presence of vasculitis, accompanied by Wegener's granulomatosis. A partial response was finally obtained after three courses of paclitaxel and carboplatin. The serum level of PR3 ANCA decreased from 142 EU to 16 EU. This case appears to have had parallel time courses of progression of squamous cell carcinoma of the lung and changes in serum PR3 ANCA level. This is of importance in considering the relationship of lung cancer and paraneoplastic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

Phosphodiesterase 3 inhibition and cough in elderly asthmatics.

AIMS: Cough is a common symptom of bronchial asthma, a chronic inflammatory airway disease. Recently, the therapeutic effects of selective phosphodiesterase (PDE) inhibitors have been focused on bronchial asthma. This study was designed to investigate the clinical effect of PDE 3 inhibition on cough reflex sensitivity in elderly patients with bronchial asthma. METHODS: Effects of cilostazol, a PDE 3 inhibitor, on cough response to inhaled capsaicin were examined in 11 patients over 70 years with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. RESULTS: The cough threshold was significantly (p < 0.05) increased after two-week treatment with cilostazol (100 mg twice a day orally) compared with placebo [48.8 (GSEM 1.4) vs. 29.2 (GSEM 1.3) muM]. CONCLUSION: These findings indicate that PDE 3 inhibition may be a novel therapeutic option for elderly patients with asthma, especially for their cough symptoms.

Journal Article↗
PubMed2005

Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa.

Dystrophic EB (DEB) is clinically characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy, and is caused by mutations in the COL7A1 gene encoding type VII collagen. DEB is inherited in either an autosomal dominant (DDEB) or recessive (RDEB) fashion. DDEB basically results from a glycine substitution mutation within the collagenous domain on one COL7A1 allele, while a combination of mutations such as premature stop codon, missense, and splice-site mutations on both alleles causes RDEB. In this study, mutation analysis was performed in 20 distinct Japanese DEB families (16 RDEB and four DDEB). The result demonstrated 30 pathogenic COL7A1 mutations with 16 novel mutations, which included four missense, five nonsense, one deletion, two insertion, one indel, and three splice-site mutations. We confirmed that Japanese COL7A1 mutations were basically family specific, although three mutations, 5818delC, 6573 + 1G > C, and E2857X, were recurrent based on previous reports. Furthermore, the Q2827X mutation found in two unrelated families would be regarded as a candidate recurrent Japanese COL7A1 mutation. The study furthers our understanding of both the clinical and allelic heterogeneity displayed in Japanese DEB patients.

Adult↗
PubMed2005

Ventral lateral geniculate nucleus projects to the dorsal lateral geniculate nucleus in the cat.

The lamina C3 of the dorsal lateral geniculate nucleus of the cat does not receive retinal projections but instead receives visual information from the small subpopulation of W-type ganglion cells via the upper substratum of the stratum griseum superficiale of the superior colliculus. We herein report a projection from the lateral division of the ventral lateral geniculate nucleus into the lamina C3 of the dorsal lateral geniculate nucleus. As the lateral division receives projections from the contralateral retina and the ipsilateral upper stratum griseum superficiale of the superior colliculus, we suggest that these regions make up a small cell type W-cell neuronal network that provides visual information to layer I of the striate cortex via the lamina C3.

Animals↗
PubMed2005

Immobilization of enzymes on a microchannel surface through cross-linking polymerization.

A novel and facile method for the preparation of an enzyme-immobilized microreactor has been developed in which enzymes are immobilized as an enzyme-polymer membrane formed on the inner wall of the microchannel by a cross-linking polymerization method; the resulting microreactor shows excellent reaction performance and stability against denaturating agents.

Biosensing Techniques↗
PubMed2005

Coexpression of CD40 and CD40 ligand in Epstein-Barr virus-infected T and NK cells and their role in cell survival.

We investigated the role that CD40-CD40 ligand (CD40L) signaling plays in survival of Epstein-Barr virus (EBV)-infected T and NK cells. EBV-infected T and NK cell lines derived from patients with either chronic active EBV infection (CAEBV) or nasal T/NK cell lymphoma, as well as virus-infected peripheral T cells freshly isolated from a patient with CAEBV, were shown to express both CD40 and CD40L on their surface. Apoptosis of these cells was enhanced by blockade of CD40-CD40L signaling by a fusion protein of CD40 and immunoglobulin G (CD40Ig). Expression of CD40 was induced in human CD40L-positive Jurkat T cells after experimental EBV infection, and apoptosis of infected cells was enhanced by CD40Ig. These results suggest that CD40-CD40L signaling promotes survival of EBV-infected T and NK cells and, thus, plays an important role in the pathogenesis of T/NK lymphoproliferative disorders associated with the virus.

CD40 Antigens↗
PubMed2005

Involvement of p38 MAP kinase-mediated cytochrome c release on sphingosine-1-phosphate (S1P)- and N-monomethyl-S1P-induced cell death of PC12 cells.

d-erythro-Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, affects various neuronal functions including cell fate. S1P appears to have contradictory effects in PC12 cells, a neuronal model cell line; neurite retraction and cell survival/differentiation. In the present study, we examined whether S1P induces cell death in undifferentiated PC12 cells. Culture with S1P at 20 microM for 4 h caused lactate dehydrogenase leakage 24 h later. The response was reduced by an inhibitor of caspases and accompanied by the release of cytochrome c and DNA fragmentation. S1P caused the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) within 10 min. An inhibitor of p38 MAPK (10 microM SB203580) inhibited both the release of cytochrome c and DNA fragmentation induced by S1P. Treatment with nerve growth factor or pertussis toxin (PTX) decreased S1P-induced phosphorylation of p38 MAPK and cell death. These findings suggest that S1P-activated p38 MAPK acts as a death signal upstream of the release of cytochrome c. N-Monomethyl-S1P (MM-S1P), a weak agonist in cells expressing S1P1 receptors, had marked effects (phosphorylation of p38 MAPK, release of cytochrome c and DNA fragmentation) at lower concentrations than S1P and in a PTX-sensitive manner. These findings show that the activation of S1P receptors by S1P and MM-S1P causes cell death accompanied by DNA fragmentation via the p38 MAPK pathway-mediated release of cytochrome c in PC12 cells. The potential of S1P and MM-S1P to act as agonists of S1P receptors and as intracellular messengers is discussed.

Animals↗
PubMed2005

Specific molecule localization in microchannel laminar flow and its application for non-immobilized-probe analysis.

Microfluidic systems enable superior control of fluidics. We have developed a novel size-separation method utilizing secondary flow within a microchannel. Using confocal fluorescence microscopy and computer simulation, we confirmed that separation occurred as a result of specific molecular localization in the curving part of the microchannel. Maximum separation efficiency was achieved by optimizing microchannel design and flow rate for individual separation targets. In addition, more effective separation was achieved by use of plural microchannel curves. This method was used for sequence-selective DNA sensing. Double-stranded DNA formed by hybridization between target DNA and a complementary probe had different elution profiles from those of the single-stranded non-complementary sequence. Moreover, the response depends on the length of the DNA molecules. This method does not require immobilization of either probe or target DNA, because all reactions occurred in the solution phase. Such features may reduce experimental error and the difference between data from different operators.

Biosensing Techniques↗
PubMed2005

Controllable polymerization of N-carboxy anhydrides in a microreaction system.

We have developed a microfluidic system for polymerization of amino acid N-carboxyanhydride and compared the properties of the products with those obtained by batchwise system under various experimental conditions. It was found that the microreactor produced polymers with narrower molecular weight distribution compared with polymers obtained by the batchwise system. Also, the molecular mass of the polymer produced using the microreactor was simply governed by the flow (pumping) rate. These results indicated that the microreactor could be a model for synthesis of amino acid polymer with highly controllable average molecular weight and molecular weight distribution.

Journal Article↗