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M Tokuda

Publications and source records attributed to M Tokuda.

At least 19 recordsLinked to original sources
PubMed2007

Roxithromycin inhibits tumor necrosis factor-alpha-induced matrix metalloproteinase-1 expression through regulating mitogen-activated protein kinase phosphorylation and Ets-1 expression.

BACKGROUND AND OBJECTIVE: In periodontitis, matrix metalloproteinases (MMPs) are upregulated in response to locally released inflammatory cytokines, resulting in pathologic processes. Roxithromycin is a 14-membered ring macrolide antibiotic with broad-spectrum antibacterial effects against oral pathogens and immunomodulatory effects. Recently, we reported that roxithromycin inhibits tumor necrosis factor (TNF)-alpha-induced vascular endothelial growth factor expression in human periodontal ligament (HPDL) cell cultures. In the present study, we examined the effect of roxithromycin on TNF-alpha-induced MMP-1 production by HPDL cells. MATERIAL AND METHODS: Cultured cells were incubated with 1% fetal bovine serum for 24 h, followed by treatment with 10 ng/ml TNF-alpha, 10 microM roxithromycin, and mitogen-activated protein kinase inhibitor at various concentrations. Culture supernatants and sediments were collected at different time-points and used for enzyme-linked immunosorbent assays, and northern and western blot analyses. RESULTS: In HPDL cell cultures, roxithromycin strongly inhibited TNF-alpha-induced MMP-1 mRNA expression and production. The inhibition of MMP-1 gene expression by roxithromycin was dependent on de novo protein synthesis and was regulated at the transcriptional level. Roxithromycin significantly inhibited TNF-alpha-induced c-Jun N-terminal kinase activation (JNP) and marginally inhibited extracellular signal-regulated kinase (ERK) 1/2 activation, but not p38 mitogen-activated protein kinase activation. Furthermore, roxithromycin reduced the induction of Ets-1, one of the critical factors in MMP-1 transcription. CONCLUSION: Roxithromycin inhibits TNF-alpha-mediated MMP-1 induction through the downregulation of ERK1/2 and JNK activation and the subsequent reduction of Ets-1, suggesting that roxithromycin may have therapeutic use in periodontitis and other chronic inflammatory conditions involving MMP-1 induction.

Adult↗
PubMed2004

Synthesis of precursor of anti-inflammatory agents by using highly reactive zinc.

Highly reactive zinc metal was prepared by electrolysis of a N,N-dimethylformamide (DMF) solution containing naphthalene and a supporting electrolyte in a one-compartment cell fitted with a platinum cathode and a zinc anode. This highly reactive electrogenerated zinc (EGZn/Naph) was used for transformation of ethyl 2-bromoacrylate into the corresponding organozinc compound, which can not be achieved by the use of usual zinc metals. Reaction of the organozinc compounds thus prepared with various aryl halides in the presence of 5 mol% of palladium catalyst gave the corresponding cross-coupling products in high yields. These cross-coupling reactions were successfully applied to a synthesis of the precursor of anti-inflammatory agents such as ibuprofen, naproxen, cicloprofen and suprofen.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

pp60c-src activation in lung adenocarcinoma.

Nine src family members are known including c-Src, c-Yes, c-Lck, c-Fyn, c-Hck, c-Lyn, c-Blk, c-Fgr and c-Yrk. They encode proteins with molecular weights of 55-62 kilodaltons (kDa), which are either cytoplasmic or membrane-associated protein tyrosine kinases. A close correlation exists between an elevated pp60c-src tyrosine kinase activity and cell transformation. However, the level of activation of pp60c-src in non-small cell lung cancers (NSCLC) remains obscure. The aim of this study was to examine the level of activity of pp60c-src in NSCLC. pp60c-src expression and in vitro protein tyrosine kinase activity in lung cancer tissue samples were measured by western blotting and in vitro kinase assays and compared with those in the surrounding non-tumour lung tissue from the same patient. pp60c-src phosphorylation was assessed by two-dimensional tryptic phosphopeptide mapping. The kinase activity of pp60c-src was significantly activated in NSCLC, especially in adenocarcinomas. In addition, the pp60c-src kinase activity increased with the size of the adenocarcinoma. Two-dimensional tryptic phosphopeptide mapping showed dephosphorylation of pp60c-src at Tyr 530 in adenocarcinomas. The proto-oncogene product, pp60c-src, was activated in NSCLC, especially in adenocarcinomas, in part through the dephosphorylation of Tyr 530. Our results suggest that activation of pp60c-src might play an important role in the progression of lung adenocarcinomas.

Adenocarcinoma↗
PubMed2003

Confirmation by DNA analysis that Contarinia maculipennis (Diptera: Cecidomyiidae) is a polyphagous pest of orchids and other unrelated cultivated plants.

The cytochrome oxidase subunit I gene in mitochondrial DNA of 53 larvae of Contarinia maculipennis Felt from flower buds of various host plants, collected from Hawaii, Japan and Thailand was analysed. Monophyly of the clade including C. maculipennis from Hawaii, Thailand and Japan was supported. There was no sequential variation within the specimens from Hawaii and Japan, which differed from one another by 6 bp (1.37%). Three haplotypes were recognized in specimens from Thailand but differences from Hawaiian and Japanese specimens were small. Overall, there were no differences in the 146 deduced amino acid residues. It is therefore concluded that C. maculipennis is a polyphagous species that can develop on plant hosts representing at least seven botanical families. This pest of Dendrobium flower buds in glasshouses is considered to have entered Hawaii, Florida and Japan from Southeast Asia, and was recently intercepted in the Netherlands. Infestations have established and spread in orchid glasshouses, causing concern about the possibility of more extensive damage to orchids and to crops, such as bitter gourd, grown in close proximity to orchid glasshouses in Japan. The potential usefulness of DNA analysis in determining host plant ranges of morphologically identical cecidomyiid species that are currently identified solely on differences of host plant is emphasized.

Animals↗
PubMed2002

Nonspecific interstitial pneumonia as pulmonary involvement of primary Sjögren's syndrome.

The pathologic patterns of lung involvement in nine patients with Sjögren's syndrome (SjS) are evaluated. The patients consisted of three males and six females, with a median age of 59 years. The SjS was diagnosed according to the criteria of the First International Seminar on SjS. In all patients, high-resolution computed radiographic scanning (HRCT) of the lungs was performed, and apparent honeycomb or microhoneycomb formation was observed in six patients. Pathologically, six patients were diagnosed with usual interstitial pneumonia (UIP), and three were diagnosed with nonspecific interstitial pneumonia/fibrosis (NSIP) (group II). There were no apparent honeycomb formations on HRCT in patients diagnosed with NSIP. In conclusion, NSIP is also a possible histologic classification of interstitial pneumonia associated with SjS.

Aged↗
PubMed2001

Cyclin D1-CDK4 complex, a possible critical factor for cell proliferation and prognosis in laryngeal squamous cell carcinomas.

Cyclin D1 and its catalytic partner CDK4 are known to play important roles in the G1/S checkpoint of the cell cycle. The complex formed by CDK4 and cyclin D1 has been strongly implicated in the control of cell proliferation and prognoses in human malignancies. We investigated the immunohistochemical expression of cyclin D1, CDK4 and proliferating cell nuclear antigen (PCNA) in 102 patients with laryngeal squamous cell carcinoma (LSCC). Cyclin D1 overexpression was observed in 59 cases (57.8%) of LSCC, and was significantly correlated with tumor site, tumor size, lymph node metastasis and advanced stage. CDK4 overexpression was observed in 48 cases (47.1%), and was significantly correlated with tumor size and advanced stage. Cyclin D1 and CDK4 expression was significantly associated with cell proliferation measured by PCNA (r = 0.812, p < 0.0001 and r = 0.725, p < 0.0001, respectively). The Kaplan-Meier analysis showed that cyclin D1 overexpression was significantly associated with disease-free survival and overall survival. CDK4 overexpression was significantly associated with overall survival. When cyclin D1 and CDK4 are combined, the patients with co-overexpression of cyclin D1-CDK4 revealed the poorest overall survival. Additionally, in early-stage (I-II) cases, co-overexpression of cyclin D1-CDK4 was also revealed to possess a significant prognostic role. By multivariate analysis, cyclin D1 overexpression, lymph node metastasis and advanced stage were independent prognostic factors for disease-free survival. Cyclin D1 overexpression, CDK4 overexpression, tumor grade, lymph node metastasis and advanced stage were independent prognostic factors for overall survival. These findings indicate that cyclin D1 and CDK4 overexpression and/or co-overexpression of these proteins may play a pivotal role in the biological behavior of LSCC and may provide a strong prognostic implication.

Adult↗
PubMed2001

Molecular cloning and characterization of a novel phospholemman-like protein from rat hippocampus.

A cDNA encoding a putative ion channel protein was isolated from a rat hippocampus library. This gene, termed phosphohippolin (Php), contains 318 bp open reading frame encoding a single transmembrane protein with a 5' signal peptide region. The deduced amino acid sequence shares 48.1% homology with phospholemman (Plm). Expression sequence tag database (dEST) search identified a mouse (AA521976) and human (AA209241) Php gene homologues. The tissue distribution studies of Php mRNA showed its abundant expression in rat brain and kidney, and in the brain, high expression was observed in hippocampus and cerebellum.

Animals↗
PubMed2001

Implication of malignancy and prognosis of p27(kip1), Cyclin E, and Cdk2 expression in epithelial ovarian tumors.

OBJECTIVE: The aim of this study was to further evaluate whether the expression of p27(kip1), cyclin E, and cdk2 is related to the malignancy of ovarian tumors and whether their expressions, alone or in combination, are associated with prognosis in epithelial ovarian carcinoma. METHODS: Immunohistochemical analysis using anti-p27(kip1), anti-cyclinE, and anti-cdk2 antibodies was carried out for 103 cases consisting of benign, borderline, and malignant ovarian tumors, and Western blot analysis and cdk2 activity assay were performed in 26 fresh ovarian tumor samples. RESULTS: p27(kip1) expression was reduced in ovarian carcinomas in contrast to benign and borderline tumors. The expression of cyclin E and cdk2 gradually increased from benign to borderline to malignant tumors. Kaplan-Meier survival analysis showed that patients with p27(kip1) expression had a high overall survival rate. Patients with cyclin E overexpression had a low overall survival rate. When the combination of these proteins was analyzed, patients with the p27(kip1) (-)/cyclin E (++)/cdk2 (++) phenotype were significantly associated with the poorest overall survival. In multivariate Cox regression analysis, the combined phenotype of p27(kip1) (-)/cyclin E (++)/cdk2 (++) was independently related to poor prognosis. CONCLUSIONS: Our results suggest that loss of p27(kip1) expression and overexpression of cyclin E or cdk2 were significantly associated with malignancy in ovarian tumors. p27(kip1) and cyclin E proteins may be valuable prognostic factors for epithelial ovarian carcinoma patients. Furthermore, the combined evaluation of p27(kip1)/cyclin E/cdk2 may provide the most important prognostic implication.

Adolescent↗
PubMed2001

Lung cancer associated with several connective tissue diseases: with a review of literature.

The association between connective tissue disease (CTD) and malignancy has been an area of debate. Whether this relation is casual or causal, it would seem that the importance of their possible relationship is twofold. The purpose of this study is to describe the clinical features of lung cancer associated with several CTDs. Patients with CTD associated with lung cancer were retrospectively evaluated. A review of the clinical features of 153 reported cases from 1944 to the present was conducted. There were 82 females and 71 males, with a median age of 58. Histological types of lung cancer were as follows, bronchioloalveolar cell carcinoma (39 cases), adenocarcinoma (36), squamous cell carcinoma (28), small cell lung cancer (27), large cell carcinoma (6), others (8), and unknown (10). There was a relationship between smoking and development of lung cancer in patients with rheumatoid arthritis (RA) and polymyositis/dermatomyositis (PM/DM). The majority of patients with progressive systemic sclerosis (PSS) who developed lung cancer were female, with underlying interstitial fibrosis, and most tumors were of bronchioloalveolar cell or adenocarcinoma cell type. Patient characteristics were significantly different among the various groups of CTD associated with lung cancer.

Adenocarcinoma↗
PubMed2001

Lymphocyte subsets in lung tissues of interstitial pneumonia associated with untreated polymyositis/dermatomyositis.

This study was designed to evaluate the distribution of lymphocyte subsets in lung specimens obtained by surgical lung biopsy from 12 patients with interstitial pneumonia associated with untreated polymyositis/dermatomyositis (PM/DM). Differences of histological findings and distributions of lymphocyte subsets between PM and DM were also evaluated. Distributions of B lymphocytes, CD4-positive T lymphocytes, and CD8-positive T lymphocytes were evaluated immunohistochemically. Interstitial pneumonia was pathologically classified as basically nonspecific interstitial pneumonia (NSIP) in all patients. Immunohistochemically, the distribution of B lymphocytes was mostly restricted to inside and/or around lymphoid follicles. The CD4-positive T lymphocytes were distributed diffusely in fibrotic areas and unrelated to lymphoid follicles. Most CD8-positive T lymphocytes were diffusely distributed, especially in relatively normal alveoli. There were no significant differences in the distribution of lymphocyte subsets between PM and DM. Although the distribution of B lymphocytes and CD4- and CD8-positive T lymphocytes in the lung were different, there were no significant differences in distributions of lymphocyte subsets between PM and DM.

Aged↗
PubMed2001

Primary lung cancer associated with polymyositis/dermatomyositis, with a review of the literature.

It has been suggested that lung cancer is frequently associated with polymyositis/dermatomyositis (PM/DM). The purpose of this study was to describe the clinical features of primary lung cancer associated with PM/DM. We first describe the clinical features of two cases treated in our hospital, and then provide a review of the literature. Finally, 24 patients (five females and 19 males) with primary lung cancer associated with PM/DM are retrospectively evaluated. Histological types of lung cancer were as follows: small cell lung cancer (n = 7), squamous cell carcinoma (n = 5), adenocarcinoma (n = 2), others (n = 5), and unknown (4). The onset of PM/DM is frequently observed before the detection of lung cancer. This is the first report to describe the clinical features of lung cancer associated with PM/DM.

Adult↗
PubMed2001

Clinical features of polymyositis/dermatomyositis associated with silicosis and a review of the literature.

There are few reports which describe the association of polymyositis/dermatomyositis (PM/DM) and silicosis. The purpose of this study is to describe the clinical features of PM/DM associated with silicosis. We first describe clinical features of two cases and provide a review of the literature. Finally, seven patients with PM/DM associated with silicosis are retrospectively evaluated. There were one female and six males. Histological specimens were obtained by open lung biopsy in five cases and not examined in two. The mechanism of the association between silicosis and PM/DM is discussed.

Biopsy, Needle↗
PubMed2001

Overexpression of cyclin E and cyclin-dependent kinase 2 is correlated with development of hepatocellular carcinomas.

Mammalian cell cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (CDKs) and CDK inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address the role of these cell cycle proteins in hepatocellular carcinomas, we analyzed the expression of cyclin E and CDK2. A panel of livers with human hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis were used as a human experimental system. The inbred LEC (Long-Evans with a cinnamon-like coat color) rats were used as an animal experimental HCC model. Immunohistochemical staining of serial paraffin sections was performed using antibodies to cyclin E and CDK2. The results showed that cyclin E and CDK2 were concurrently overexpressed in hepatocellular carcinomas both in human and rat livers. Western blot analysis and CDK2 kinase assay demonstrated expression levels of cyclin E and CDK2 and CDK2 kinase activity, respectively, and both were shown to increase along with the development of hepatocellular carcinomas. Analysis of the correlation between expression of cyclin E and CDK2 and clinicopathological parameters revealed a significant correlation between expression of cyclin E and tumor grade (P=0.013), and PCNA index (P=0.006) as well as CDK2 expression (P=0.015). Overexpression of CDK2 tended to be associated with poorly differentiated HCCs. The results suggest that overexpression of cyclin E and CDK2 plays an important role in the development of hepatocellular carcinoma.

Journal Article↗
PubMed2001

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Journal Article↗
PubMed2001

Regulation of interleukin-6 expression in human dental pulp cell cultures stimulated with Prevotella intermedia lipopolysaccharide.

Interleukin (IL)-6 expression in human dental pulp cell cultures after stimulation with Prevotella intermedia lipopolysaccharide (LPS) was investigated by Northern blot analysis, enzyme immunoassay, and bioassay. The IL-6 mRNA expression began to increase after 1 hr and continued after up to 8 hr of exposure on stimulation with 10 microg/ml of P. intermedia LPS. The bioactivity was dose-dependent on the concentration of P. intermedia LPS (0 to 100 microg/ml). The IL-6 mRNA expression was inhibited by actinomysin D and super-induced by cycloheximide. Anti-CD14 monoclonal antibody (MY4) inhibited the IL-6 mRNA expression when administered at a 0.5 microg/ml concentration before stimulation with P. intermedia LPS at 1 microg/ml. The immunoregulatory cytokines (interferon-gamma, IL-10, and IL-4) inhibited LPS-induced IL-6 production with a combined treatment. These results suggest the IL-6 expression by pulp cell cultures is CD14-dependent and regulated at the transcriptional level, and a combined treatment with immunoregulatory cytokines may be effective for control of pulpal inflammation due to P. intermedia LPS.

Antibodies, Monoclonal↗
PubMed2001

Non-specific interstitial pneumonia as pulmonary involvement of systemic sclerosis.

The pathological features of lung disease in nine patients with systemic sclerosis (SSc) were evaluated. The patients comprised one man and eight women, with a median age of 58 years. SSc was diagnosed according to the criteria of the American Rheumatism Association. In all patients, high resolution computed radiographic scanning of the lungs (HRCT) was performed, and apparent honeycomb formation was seen in four patients. Pathologically, four patients were diagnosed with usual interstitial pneumonia (UIP), three with non-specific interstitial pneumonia (NSIP) group II, one NSIP group II-III, and one NSIP group II with diffuse alveolar damage. HRCT showed no apparent honeycomb formations in patients diagnosed with NSIP. This is the first report describing NSIP as a pulmonary complication of SSc.

Adult↗