Biomedical subjects

Shigeru Kohno

Publications and source records attributed to Shigeru Kohno.

345 records · Page 20Linked to original sources

PubMedDate not supplied

Evaluation of theophylline or pranlukast, a cysteinyl leukotriene receptor 1 antagonist, as add-on therapy in uncontrolled asthmatic patients with a medium dose of inhaled corticosteroids.

A few studies compared the additional effects of oral controller medicines on pulmonary function in asthmatic patients on a moderate dose of inhaled steroids. The aim of this study was to compare the additional effects of two oral asthma controllers, a leukotriene receptor antagonist and a sustained released theophylline (Theo), with a moderate dose of inhaled steroid on peak expiratory flow (PEF) and asthma-related symptoms. A total of 67 adult asthmatic patients with PEF < 80% predicted during a 2-week run-in period with 800 microg/day of beclomethasone dipropionate were randomized to receive either pranlukast, 450 mg/day (n = 33), or sustained released Theo, 200 mg/day (n = 34), for 4 weeks. Pranlukast and Theo did not significantly alter the symptom scores, use of rescue beta2-agonist, and daily PEF variability. However, both agents significantly increased both morning and evening PEF compared with the run-in periods. The effects of both medications were comparable. For asthmatic patients even on a moderate dose of inhaled steroids, the addition of either leukotriene receptor antagonist or sustained released Theo does not improve asthma-related symptoms but significantly and equally increases PEF.

Administration, Inhalation↗

PubMedDate not supplied

Gene transfer using nonviral delivery systems.

In peritoneal dialysis, loss of peritoneal function is a major factor in treatment failure. The alterations in peritoneal function are related to structural changes in the peritoneal membrane, including peritoneal sclerosis with increased extracellular matrix. Although peritoneal sclerosis is considered reversible to some extent through peritoneal rest, which improves peritoneal function and facilitates morphological changes, there has been no therapeutic intervention and no drug against the development and progression of peritoneal sclerosis. Using recent biotechnological advances in genetic engineering, a strategy based on genetic modification of the peritoneal membrane could be a potential therapeutic maneuver against peritoneal sclerosis and peritoneal membrane failure. Before this gene therapy may be applied clinically, a safe and effective gene delivery system as well as the selection of a gene therapy method must be established. There are presently two kinds of gene transfer vectors: viral and nonviral. Viral vectors are used mainly as a gene delivery system in the field of continuous ambulatory peritoneal dialysis research; however, they have several problems such as immunogenicity and toxicity. On the other hand, nonviral vectors have several advantages over viral vectors. We review here gene transfer using nonviral vector systems in the peritoneum: electroporation, liposomes, and cationized gelatin microspheres. In the field of peritoneal dialysis, gene therapy research using nonviral vectors is presently limited. Improvement in delivery methods together with an intelligent design of targeted genes has brought about large degrees of enhancement in the efficiency, specificity, and temporal control of nonviral vectors.

Gene Transfer Techniques↗

PubMedDate not supplied

Antiproliferative effects of gefitinib are associated with suppression of E2F-1 expression and telomerase activity.

BACKGROUND: Gefitinib (Iressa, ZD1839) is a selective epidermal growth factor receptor tyrosine kinase inhibitor. E2F-1 is a critical determinant in cell cycle. Growth signals up-regulate telomerase activity. The effects of gefitinib on E2F-1 and telomerase in A549, H23 and A431 cells were examined. MATERIALS AND METHODS: Cell proliferation and cell cycle progression were measured by the WST-1 assay and flow cytometry. The expression of E2F-1 and cyclin-dependent kinase inhibitors was evaluated, and hTERT mRNA expression and telomerase activity were analyzed. RESULTS: In the A431 and A549 cells, treatment with gefitinib inhibited cell proliferation and was associated with an increase in G1-phase. In both cell types, gefitinib decreased the expression of E2F-1 mRNA and protein, followed by the suppression of hTERT mRNA and telomerase activity. In the H23 cells, gefitinib did not affect cell proliferation. CONCLUSION: The antiproliferative effects of gefitinib may be, at least in part, due to the inhibition of E2F-1 expression and telomerase activity.

Adenocarcinoma↗