Biomedical subjects

Masahiko Yanagita

Publications and source records attributed to Masahiko Yanagita.

5 recordsLinked to original sources

PubMed2006

Anti-fibrotic effects of theophylline on lung fibroblasts.

Theophylline has been used in the management of bronchial asthma and chronic obstructive pulmonary disease for over 50 years. It has not only a bronchodilating effect, but also an anti-inflammatory one conducive to the inhibition of airway remodeling, including subepithelial fibrosis. To date however, whether theophylline has a direct inhibitory effect on airway fibrosis has not been established. To clarify this question, we examined whether theophylline affected the function of lung fibroblasts. Theophylline suppressed TGF-beta-induced type I collagen (COL1) mRNA expression in lung fibroblasts and also inhibited fibroblast proliferation stimulated by FBS and TGF-beta-induced alpha-SMA protein. A cAMP analog also inhibited TGF-beta-induced COL1 mRNA expression in lung fibroblasts. A PKA inhibitor reduced the inhibitory effect of theophylline on TGF-beta-induced COL1 mRNA expression. These results indicate that theophylline exerts anti-fibrotic effects, at least partly, through the cAMP-PKA pathway.

Cell Line↗

PubMed2006

Disability and depression: investigating a complex relation using physical performance measures.

OBJECTIVE: The objective of this study was to examine the relation of physical performance measures with depressive symptoms in older men. METHOD: A cross-sectional, multivariate comparison of several measures of upper- and lower-extremity performance and their relation with depressive symptoms was performed in 2,856 older Japanese American men, aged 71-93 years, who participated in the fourth examination of the Honolulu Heart Program. Depressive symptoms were measured using an 11-item version of Center for Epidemiologic Studies Depression (CES-D) Scale. A score of at least 9 (from a maximum score of 33) is considered clinically significant. Timed functional performance tests, including walking and repeated chair stands, were used to assess lower-extremity performance; handgrip strength was used as an indicator of upper-extremity performance. RESULTS: Two hundred eighty-three participants (9.9%) had a score of 9 or greater on the 11-question CES-D Scale and were considered to be at high risk for depression. Time to walk 10 feet and time to complete five chair stands were significantly longer in those with depressive symptoms, whereas handgrip strength was significantly lower. Only the association of gait speed (time to walk 10 feet) and depressive symptoms remained significant when all physical performance measures were simultaneously included in a multivariate analysis. CONCLUSION: These results demonstrate physical performance measures, particularly gait speed, may be important potential correlates of depression in community-dwelling older men.

Aged↗

PubMed2005

Cigarette smoke extract induces endothelial cell injury via JNK pathway.

Cigarette smoking is the most crucial factor responsible for chronic obstructive pulmonary disease (COPD). The precise mechanisms of the development of the disease have, however, not been fully understood. Recently, impairment of pulmonary endothelial cells has been increasingly recognized as a critical pathophysiological process in COPD. To verify this hypothesis, we examined how cigarette smoke extract (CSE) damages human umbilical vein endothelial cells (HUVECs). CSE activated c-Jun N-terminal kinase (JNK), and treatment of HUVECs with SP600125, a specific inhibitor of the JNK pathway, significantly suppressed endothelial cell damage by CSE. In contrast, inhibition of the extracellular-regulated kinase or the p38 pathway did not affect the cytotoxicity of CSE. Furthermore, anti-oxidants superoxide dismutase and catalase reduced CSE-induced JNK phosphorylation and endothelial cell injury. These results indicate that CSE damages vascular endothelial cells through the JNK pathway activated, at least partially, by oxidative stress.

Animals↗

PubMed2004

Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide.

The goal of this study was to examine whether IL-6 could directly protect lung resident cells, especially alveolar epithelial cells, from reactive oxygen species (ROS)-induced cell death. ROS induced IL-6 gene expression in organotypic lung slices of wild-type (WT) mice. ROS also induced IL-6 gene expression in mouse primary lung fibroblasts, dose dependently. The organotypic lung slices of WT were more resistant to ROS-induced DNA fragmentation than those of IL-6-deficient (IL-6-/-) mice. WT resistance against ROS was abrogated by treatment with anti-IL-6 antibody. TdT-mediated dUTP nick end labeling stain and electron microscopy revealed that DNA fragmented cells in the IL-6-/- slice included alveolar epithelial cells and endothelial cells. In vitro studies demonstrated that IL-6 reduced ROS-induced A549 alveolar epithelial cell death. Together, these data suggest that IL-6 played an antioxidant role in the lung by protecting lung resident cells, especially alveolar epithelial cells, from ROS-induced cell death.

Animals↗

PubMed2002

[Chemotherapy for small-cell lung cancer (SCLC) patients with renal failure].

We administered chemotherapy in three cases of small-cell lung cancer (SCLC) with renal failure under different situations. Hemodialysis (HD) was used in 2 out of the 3 cases. Case 1 was complicated by acute renal failure from extensive bilateral tumor invasion. After chemotherapy (CBDCA + ETP) under HD, renal metastases regressed and renal function improved, although the final response was PD. In case 2, HD had been introduced for diabetic nephropathy. After 2 cycles of chemotherapy (CBDCA + ETP) under HD, the patient attained a PR. Case 3 is an example of paraneoplastic nephrotic syndrome with renal failure. Chemotherapy including CBDCA or CDDP was performed and the QOL of the patient improved. Pro-GRP and serum creatinine changed in parallel during the clinical course of 6 admissions. In conclusion, individualized therapy is necessary to increase survival time of SCLC patients with renal failure. Although chemotherapy is useful, further study is needed for the selection of suitable chemotherapeutic regimens, optimal dosage of each drug and the timing of HD.

Adult↗