104 research outputs found

    No association of the Trp 64 Arg mutation of the β3-adrenergic receptor gene with obesity, type 2 diabetes mellitus, hyperlipidemia, and hypertension in Japanese patients with schizophrenia

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    This study was conducted to address the question of whether the β3-adrenergic receptor gene mutation (Trp 64 Arg) is associated with metabolic disease in Japanese patients with schizophrenia. Methods : In a cross-sectional study, 89 participants were grouped into three genotypes. The 64 Arg allelic frequency in patients with or without metabolic disease was analyzed. Anthropometrics variables and biochemical parameters were compared among the genotypes. Results : The 64 Arg allele, which had a frequency of 0.22, was not associated with obesity, type 2 diabetes mellitus, dyslipidemias, or hypertension. No significant differences among the genotypes were found in current age, age at diagnosis with schizophrenia, body mass index, waist-hip ratio, plasma glucose, plasma insulin, triglycerides, free fatty acids. Patients with the 64 Arg allele had greater 24-h excretion of norepinephrine than those lacking the variant (p=0.019). Conclusion : The 64Arg allelic mutation is not associated with obesity, type 2 diabetes mellitus, lipid metabolism dysfunction, or hypertension in Japanese patients with schizophrenia

    トクシマ ダイガク ビョウイン ノウソッチュウ センター ニ ハンソウ サレタ rt-PA ジョウチュウ リョウホウ ノ Drip and Ship ショウレイ ニオケル ケントウ

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    Recently,“Drip and Ship”treatment conducted in collaboration of a hospital in remote area and an institution capable of emergency stroke treatment under guidance by a stroke specialist has been reported to be effective. “Drip and Ship” treatment refers to initiating intravenous recombinant tissue-type plasminogen activator(rt-PA)infusion at a remote hospital(Drip)and then transporting patients to an institution capable of multimodality management and endovascular treatment of stroke(Ship). We report here a case analysis and examinations on treatment methods, prognosis, and some other parameters in 16 patients who were transported to the Stroke Care Unit(SCU)of the Tokushima University Hospital while undergoing“Drip and Ship”treatment between June 2013 and November 2015. Occluded vessels were recanalized by rt-PA administration in 5/12patients (42%). For 6 cases in which recanalization was not achieved with rt-PA, endovascular treatment was performed, and recanalization was obtained in 3 patients(50%). There was a marked improvement(8.4points on average)in NIHSS at the time of discharge compared to that before rt-PA administration. A representative case showed a 26‐point improvement in NIHSS at the time of discharge compared to the pretreatment value. The advantage of“Drip and Ship”treatment is two-fold : It allows for rt-PA treatment of acute ischemic stroke patients at remote-area institutions incapable of multimodality stroke management, and also makes it possible to add endovascular treatment for rt-PA-irresponsive cases in which recanalization of occluded vessels could not be achieved with rt-PA therapy. The results suggest that the“Drip and Ship”treatment is a safe and effective means to eliminate regional disparities in intravenous rt-PA therapy and can make more contributions to the collaborative stroke care in the Tokushima prefecture in the future

    miR-1246 in tumor extracellular vesicles promotes metastasis via increased tumor cell adhesion and endothelial cell barrier destruction

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    BackgroundTumor blood vessels play a key role in tumor metastasis. We have previously reported that tumor endothelial cells (TECs) exhibit abnormalities compared to normal endothelial cells. However, it is unclear how TECs acquire these abnormalities. Tumor cells secrete extracellular vesicles (EVs) to create a suitable environment for themselves. We have previously identified miR-1246 to be more abundant in high metastatic melanoma EVs than in low metastatic melanoma EVs. In the current study, we focused on miR-1246 as primarily responsible for acquiring abnormalities in TECs and examined whether the alteration of endothelial cell (EC) character by miR-1246 promotes cancer metastasis.MethodsWe analyzed the effect of miR-1246 in metastatic melanoma, A375SM-EVs, in vivo metastasis. The role of tumor EV-miR-1246 in the adhesion between ECs and tumor cells and the EC barrier was addressed. Changes in the expression of adhesion molecule and endothelial permeability were examined.ResultsIntravenous administration of A375SM-EVs induced tumor cell colonization in the lung resulting in lung metastasis. In contrast, miR-1246 knockdown in A375SM decreased lung metastasis in vivo. miR-1246 transfection in ECs increased the expression of adhesion molecule ICAM-1 via activation of STAT3, followed by increased tumor cell adhesion to ECs. Furthermore, the expression of VE-Cadherin was downregulated in miR-1246 overexpressed EC. A375SM-EV treatment enhanced endothelial permeability. VE-Cadherin was validated as the potential target gene of miR-1246 via the target gene prediction database and 3′ UTR assay.ConclusionmiR-1246 in high metastatic tumor EVs promotes lung metastasis by inducing the adhesion of tumor cells to ECs and destroying the EC barrier
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