Biomedical subjects

Kazutaka Nishina

Publications and source records attributed to Kazutaka Nishina.

3 recordsLinked to original sources

PubMed2005

In vivo delivery of small interfering RNA targeting brain capillary endothelial cells.

Brain capillary endothelial cells (BCECs) play an important role in blood-brain barrier (BBB) functions and pathophysiologic mechanisms in brain ischemia and inflammation. We try to suppress gene expression in BCECs by intravenous application of small interfering RNA (siRNA). After injection of large dose siRNA with hydrodynamic technique to mouse, suppression of endogenous protein and the BBB function of BCECs was investigated. The brain-to-blood transport function of organic anion transporter 3 (OAT3) that expressed in BCECs was evaluated by Brain Efflux Index method in mouse. The siRNA could be delivered to BCECs and efficiently inhibited endogenously expressed protein of BCECs. The suppression effect of siRNA to OAT3 is enough to reduce the brain-to-blood transport of OAT3 substrate, benzylpenicillin at BBB. The in vivo siRNA-silencing method with hydrodynamic technique may be useful for the study of BBB function and gene therapy targeting BCECs.

Animals↗

PubMed2005

Escape from the interferon response associated with RNA interference using vectors that encode long modified hairpin-RNA.

In mammalian cells, siRNAs have been used to induce RNA interference (RNAi) in an attempt to prevent nonspecific effects (including the interferon (IFN) response) which are caused by long double-stranded RNAs (dsRNAs) of more than 30 bp. In this report, we describe a novel and simple strategy for avoiding activation of the IFN response by dsRNA. We show that modified hairpin-RNAs (mhRNAs) of more than 100 bp, with multiple specific point-mutations within the sense strand and transcribed from the U6 or tRNA(Val) promoters, can cause RNAi without inducing the IFN pathway genes. Moreover, we demonstrate that the 50-bp mhRNA vector could effectively suppress the replication of multiple hepatitis C viruses (the genomes of which differ slightly, thus the 21-bp siRNA vector failed to suppress one of them). Our findings should enhance the exploitation of RNAi in mammalian cells, especially in the field of RNAi therapy against pathogenic viruses.

Base Sequence↗

PubMed2004

[Medical treatment of dyskinesia].

Dyskinesia and dystonia are common complications of long-term levodopa therapy. Because peak-dose dyskinesia is due to excessive dopaminergic stimulation by anti-parkinsonian drugs, it is solved by reducing the whole dose or by taking frequent small doses of levodopa in order to keep relatively stable serum levels. It may be attenuated by dopamine receptor agonists or amantadine which acts as an N-methyl-D-aspartate (NMDA) receptor agonist. On the other hand, since early morning dystonia is related to the decline in the level of levodopa, it is initially treated by adding a small dose of levodopa in bedtime. Other patterns of dystonia are often treated accordingly to the treatment of wearing-off phenomenon.

Dyskinesia, Drug-Induced↗