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Articles by K Inoue
Total Records ( 7 ) for K Inoue
  M Sone , A Koizumi , E Tamiya , K Inoue , I Ebihara , H Koide , S Okazaki , Y Kato , J Suzuki and H. Daida

Patients with pharyngeal pain are frequently encountered in the department of otorhinolaryngology. The pharyngeal pain is usually caused by an inflammation or a malignant disease. In some cases, anginal pain radiates to the pharynx. However, patients with angina pectoris who suffer from pharyngeal pain without chest pain are believed to be very rare. The patient was a 70-year-old man whose chief complaint was only pharyngeal pain on exertion. The pharyngeal pain was similar to acute pharyngitis with burning pain. Upon cardiac catheterization, no abnormality was found in the right coronary artery or in the circumflex artery, but 99% stenosis was found in the middle portion of the left anterior descending artery. There was no collateral circulation to the left anterior descending artery. Thus, percutaneous coronary intervention was performed, and the pharyngeal pain vanished.

  T Kurotobi , K Iwakura , K Inoue , R Kimura , A Okamura , Y Koyama , Y Tosyoshima , N Ito and K. Fujii

Background— The presence of multiple arrhythmogenic sources may be associated with the perpetuation of atrial fibrillation (AF). In this study, we investigated the hypothesis that multiple foci might be involved in the development of AF persistency.

Methods and Results— Two hundred fourteen consecutive patients with AF undergoing catheter ablation were enrolled in this study. The location of the arrhythmogenic foci was determined using simultaneous recordings from multipolar catheters before and after pulmonary vein isolation during an isoproterenol administration. We detected 500 arrhythmogenic foci (263 foci as AF initiators, and 237 foci as non-AF initiators). High-dose isoproterenol infusions (ranging from 2 to 20 µg/min) revealed potential arrhythmogenic foci, especially non–pulmonary vein foci (55%). Persistent AF was more highly associated with an incidence of multiple (>2) foci than paroxysmal AF (88% versus 65%, P=0.002), and a multivariate analysis demonstrated that multiple foci (>2) were an independent contributing factor for persistent AF (odds ratio; 95% confidence interval, 4.69; 1.82 to 12.09, P<0.001). In paroxysmal AF, the number of foci was higher in patients with long-term AF (>24 hours) than in those with short-lasting AF (2.64±0.14 versus 1.77±0.16, P=0.001). In the persistent AF group, the patients with short-lasting AF (<12 months) had a greater number of foci than did those with long-term AF (>12 months) (3.62±0.15 versus 1.92±0.16, P=0.04).

Conclusions— Multiple foci were likely to be involved in the development of persistent AF. However, if AF persisted for >12 months, they may not have had a significant effect on the AF perpetuation.

  K Yamaji , T Kimura , T Morimoto , Y Nakagawa , K Inoue , Y Soga , T Arita , S Shirai , K Ando , K Kondo , K Sakai , M Goya , M Iwabuchi , H Yokoi , H Nosaka and M. Nobuyoshi

We previously reported that the long-term luminal response after coronary bare metal stenting is triphasic, with an early restenosis phase spanning the 6 months after the index procedure, an intermediate-term regression phase from 6 months to 3 years, and a late renarrowing phase beyond 4 years. However, the clinical significance of late luminal renarrowing remains unknown.

Methods and Results—

Angiographic and clinical follow-up of the same cohort of 405 patients with successful Palmaz-Schatz stent placement was extended beyond 15 years. Clinical follow-up was completed in 98% of patients at 5 years and in 81% at 15 years. The incidence of death and cardiac death at 15 years was 45.4% and 20.6%, respectively. Paired long-term (4 to 10 years) and very long-term (>10 years) angiographic studies without intercurrent target lesion revascularization were performed in 55 lesions, and minimal luminal diameter further decreased from 1.88±0.50 mm to 1.60±0.73 mm (P=0.002). Late target lesion revascularization after initial stabilization of the stented segments occurred rarely within 4 years. Beyond 4 years, however, the incidence of late target lesion revascularization increased steadily from 3.3% at 4 years to 24.7% at 15 years. The incidence of definite very late stent thrombosis was low (1.5% at 15 years).


Luminal renarrowing of the stented segment beyond 4 years was a progressive process extending beyond 10 years. The angiographic observation of late in-stent restenosis was clinically relevant because a corresponding progressive increase in the incidence of late target lesion revascularization was observed beyond 4 years and up to 15 to 20 years after bare metal stent implantation.

  Y Fukatsu , T Noguchi , T Hosooka , T Ogura , K Kotani , T Abe , T Shibakusa , K Inoue , M Sakai , K Tobimatsu , K Inagaki , T Yoshioka , M Matsuo , J Nakae , Y Matsuki , R Hiramatsu , K Kaku , H Okamura , T Fushiki and M. Kasuga

Physical exercise ameliorates metabolic disorders such as type 2 diabetes mellitus and obesity, but the molecular basis of these effects remains elusive. In the present study, we found that exercise up-regulates heparin-binding epidermal growth factor-like growth factor (HB-EGF) in skeletal muscle. To address the metabolic consequences of such gain of HB-EGF function, we generated mice that overexpress this protein specifically in muscle. The transgenic animals exhibited a higher respiratory quotient than did wild-type mice during indirect calorimetry, indicative of their selective use of carbohydrate rather than fat as an energy substrate. They also showed substantial increases in glucose tolerance, insulin sensitivity, and glucose uptake by skeletal muscle. These changes were accompanied by increased kinase activity of Akt in skeletal muscle and consequent inhibition of Forkhead box O1-dependent expression of the pyruvate dehydrogenase kinase 4 gene. Furthermore, mice with a high level of transgene expression were largely protected from obesity, hepatic steatosis, and insulin resistance, even when maintained on a high-fat diet. Our results suggest that HB-EGF produced by contracting muscle acts as an insulin sensitizer that facilitates peripheral glucose disposal.

  N Ozaki , N Wakita , K Inoue and A. Yamada

A 58-year-old female was referred to our hospital with an abnormal shadow on her chest X-ray. Further examination revealed the left anterior descending coronary artery to pulmonary artery fistula with aneurysms. The patient was successfully repaired with operation and had no residual fistulas and aneurysms.

  M Ohshima , K Inoue , H Hayashi , D Tsuji , M Mizugaki and K. Itoh

DNA methylation is involved in many diseases such as cancer and autoimmunity. We generated recombinant single-chain Fv (scFv) antibodies against 5-methyl-2'-deoxycytidine (m5dCyd) using phage display technology and a hyperimmunized mouse, and the scFv of most interest were contructed as fusion proteins with green fluorescent protein obtained from Aequorea coerulescens GFP (AcGFP). Using RNA isolated from mouse spleens, we constructed a scFv library consisting of light chains. The scFv library was selected against m5Cyd-BSA and enriched through four rounds of panning. The scFv library was concentrated about 390-fold and an individual clone was reacted with m5Cyd-BSA. Two scFvs with high reactivity for m5Cyd-BSA termed 1–2 and 1–12 were produced. Furthermore, methylated DNA-binding activities of the scFvs were confirmed using an indirect immunofluorescence assay. Additionally, N- and C-terminal scFv 1–2 fusion with AcGFP were constructed, and we observed the N-terminal AcGFP exhibited much higher fluorescence intensity than the C-terminal fusions. The AcGFP-scFv 1–2 modified N-terminus of scFv with AcGFP had high fluorescence intensity, but the scFv 1-2-AcGFP modified C-terminus of scFv with AcGFP had low fluorescence intensity. The cross-reactivity of AcGFP-scFv 1–2 was similar to scFv 1–2, and thus, AcGFP-scFv 1–2 could be used in a direct immunofluorescence assay. The scFv fusion proteins may be useful for the detection and quantification of cellular methylated DNA in various specimens.

  M Ohshima , T Tadakuma , H Hayashi , K Inoue and K. Itoh

We generated a single-chain variable fragment (scFv) against 5-methyl-2'-deoxycytidine (m5dCyd) using phage display technology. The heavy and light chain variable region genes were amplified by the polymerase chain reaction (PCR) from hybridoma cell line FMC9 and assembled as an scFv fragment with a flexible linker (Gly4-Ser)3. The scFv DNA fragment was then cloned into pCANTAB-5E, and a phage displaying the scFv was produced. Antigen-positive phage clones were successfully selected by enzyme-linked immunosorbent assay (ELISA). The scFv was modified with FLAG and His tags for detection and purification. The scFv reacted strongly with m5dCyd and weakly with 5-methylcytidine (m5Cyd) but not with cytidine (Cyd) and 1-methyladenosine in a manner similar to the monoclonal antibody (MoAb). Although the specificities of scFv and MoAb were almost identical, the sensitivity of the scFv (IC50 0.054 µg/ml) was ~80 times higher than that of the parent MoAb (IC50 4.27 µg/ml), determined by inhibition ELISA. As a biochemical application of this scFv, we quantified the m5dCyd content of genomic DNA by enzymatic hydrolysis using inhibition ELISA. The cancer cell lines HeLa, HeLa S3 and MDA-MB-453 contained ~1% of the methylated DNA in total genomic DNA, as did peripheral blood cell genomic DNA from healthy volunteers, but HT29 and T-47D showed hypomethylation compared with the HeLa, HeLa S3 and MDA-MB-453 cell lines. The scFv generated here may be applicable to the assessment of cellular DNA methylation levels and is more sensitive than the MoAb.

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