Institution
Hokkaido University
Education•Sapporo, Hokkaidô, Japan•
About: Hokkaido University is a education organization based out in Sapporo, Hokkaidô, Japan. It is known for research contribution in the topics: Population & Catalysis. The organization has 53925 authors who have published 115403 publications receiving 2651647 citations. The organization is also known as: Hokudai & Hokkaidō daigaku.
Topics: Population, Catalysis, Gene, Transplantation, Virus
Papers published on a yearly basis
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TL;DR: The regulation of mitochondrial oxidative stress or manipulation of TFAM protein may provide a novel therapeutic strategy of HF.
Abstract: The excessive reactive oxygen species (ROS), produced by the electron leak in mitochondria of failing myocardium, play an important role in development and progression of heart failure (HF) and cardiac remodeling, which is associated with induction of myocyte hypertrophy and apoptosis and activation of matrix metalloproteinases. Furthermore, ROS can damage mitochondrial DNA(mtDNA), and thus lead to mitochondrial dysfunction and additional ROS generation. Recently, we found that the overexpression of mitochondrial transcription factor A (TFAM), which is essential for mtDNA transcription and replication, ameliorates cardiac remodeling and failure. Therefore, the regulation of mitochondrial oxidative stress or manipulation of TFAM protein may provide a novel therapeutic strategy of HF.
357 citations
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TL;DR: Type III but not type I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-ε region of HBV pregenomic RNA.
356 citations
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TL;DR: In this article, the Lyapunov analysis is used to study the high-dimensional chaotic states of a class of delay-differential equations with time delayed feedback such as nonlinear optical resonators.
355 citations
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TL;DR: 2-AG is identified as the major endocannabinoid mediating retrograde suppression at excitatory and inhibitory synapses of MS neurons, and CB1 cannabinoid receptor, the main target of 2-AG, was present at high levels on GABAergic axon terminals of MS neuron and parvalbumin-positive interneurons and at low levels on excitatories corticostriatal afferents.
Abstract: Endogenous cannabinoids (endocannabinoids) mediate retrograde signals for short- and long-term suppression of transmitter release at synapses of striatal medium spiny (MS) neurons. An endocannabinoid, 2-arachidonoyl-glycerol (2-AG), is synthesized from diacylglycerol (DAG) after membrane depolarization and Gq-coupled receptor activation. To understand 2-AG-mediated retrograde signaling in the striatum, we determined precise subcellular distributions of the synthetic enzyme of 2-AG, DAG lipase-α (DAGLα), and its upstream metabotropic glutamate receptor 5 (mGluR5) and muscarinic acetylcholine receptor 1 (M1). DAGLα, mGluR5, and M1 were all richly distributed on the somatodendritic surface of MS neurons, but their subcellular distributions were different. Although mGluR5 and DAGLα levels were highest in spines and accumulated in the perisynaptic region, M1 level was lowest in spines and was rather excluded from the mGluR5-rich perisynaptic region. These subcellular arrangements suggest that mGluR5 and M1 might differentially affect endocannabinoid-mediated, depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE) in MS neurons. Indeed, mGluR5 activation enhanced both DSI and DSE, whereas M1 activation enhanced DSI only. Importantly, DSI, DSE, and receptor-driven endocannabinoid-mediated suppression were all abolished by the DAG lipase inhibitor tetrahydrolipstatin, indicating 2-AG as the major endocannabinoid mediating retrograde suppression at excitatory and inhibitory synapses of MS neurons. Accordingly, CB1 cannabinoid receptor, the main target of 2-AG, was present at high levels on GABAergic axon terminals of MS neurons and parvalbumin-positive interneurons and at low levels on excitatory corticostriatal afferents. Thus, endocannabinoid signaling molecules are arranged to modulate the excitability of the MS neuron effectively depending on cortical activity and cholinergic tone as measured by mGluR5 and M1 receptors, respectively.
355 citations
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TL;DR: Administration of infliximab in patients with Behçet's disease with refractory uveoretinitis suppressed the frequency of ocular attacks, and multiple administration was well tolerated, suggesting that inflIXimab is effective for this condition.
Abstract: OBJECTIVE: Behcet's disease (BD) with uveoretinitis is a chronic refractory disease accompanied by ocular attacks. As the decrease in visual acuity due to ocular attack is seriously life-threatening, development of a new drug is anticipated. Since tumor necrosis factor-a (TNF-a) is involved in the symptoms of BD, particularly the activity of ocular symptoms, suppression of TNF-a might be effective in treating BD with uveoretinitis. We conducted a clinical trial of infliximab, an anti-TNF-a chimeric monoclonal antibody, in patients with BD. METHODS: In this open label trial, the efficacy, safety, and pharmacokinetics of repeated administration of infliximab were evaluated in 13 patients with BD accompanied by refractory uveoretinitis. Infliximab was administered 4 times at Weeks 0, 2, 6, and 10 at doses of either 5 or 10 mg/kg by intravenous drip infusion. Frequency of ocular attacks was used as the primary index for evaluation of efficacy, with visual acuity and extraocular symptoms as secondary indices. RESULTS: The mean numbers of ocular attacks, converted to frequency per 14 weeks, were 3.96 times for the 5 mg/kg group and 3.79 times for the 10 mg/kg group during the observation period. Following treatment with infliximab, they decreased to 0.98 times and 0.16 times, respectively. A serious adverse event, tuberculosis, was observed in one case in the 10 mg/kg group. Serum infliximab concentration increased with dosage. CONCLUSION: Administration of infliximab in patients with BD with refractory uveoretinitis suppressed the frequency of ocular attacks, and multiple administration was well tolerated, suggesting that infliximab is effective for this condition.
354 citations
Authors
Showing all 54156 results
Name | H-index | Papers | Citations |
---|---|---|---|
Shizuo Akira | 261 | 1308 | 320561 |
Yi Cui | 220 | 1015 | 199725 |
John F. Hartwig | 145 | 714 | 66472 |
Yoshihiro Kawaoka | 139 | 883 | 75087 |
David Y. Graham | 138 | 1047 | 80886 |
Takashi Kadowaki | 137 | 873 | 89729 |
Kazunari Domen | 130 | 908 | 77964 |
Susumu Kitagawa | 125 | 809 | 69594 |
Toshikazu Nakamura | 121 | 732 | 51374 |
Toshio Hirano | 120 | 401 | 55721 |
Li-Jun Wan | 113 | 639 | 52128 |
Wenbin Lin | 113 | 474 | 56786 |
Xiaoming Li | 113 | 1932 | 72445 |
Jinhua Ye | 112 | 658 | 49496 |
Terence Tao | 111 | 606 | 94316 |