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Articles by M Kimura
Total Records ( 10 ) for M Kimura
  R. S Vasan , S Demissie , M Kimura , L. A Cupples , C White , J. P Gardner , X Cao , D Levy , E. J Benjamin and A. Aviv

Background— Leukocyte telomere length (LTL) decreases over the adult life course owing to the cumulative burden of oxidative stress, inflammation, and exposure to vascular risk factors. Left ventricular (LV) mass is a biomarker of long-standing exposure to cardiovascular disease risk factors. We hypothesized that LTL is related inversely to LV mass.

Methods and Results— We related LTL (measured by Southern blot analysis) to echocardiographic LV mass and its components (LV diastolic dimension and LV wall thickness) in 850 Framingham Heart Study participants (mean age 58 years, 58% women) using multivariable linear regression with adjustment for age, sex, height, weight, systolic blood pressure, hypertension treatment, and smoking. Overall, multivariable-adjusted LTL was positively related to LV mass (β-coefficient per SD increase 0.072; P=0.001), LV wall thickness (β=0.053; P=0.01), and LV diastolic dimension (β=0.035; P=0.09). We observed effect modification by hypertension status (P for interaction=0.02 for LV mass); LTL was more strongly associated with LV mass and LV wall thickness in individuals with hypertension (β-coefficient per SD increment of 0.10 and 0.08, respectively; P<0.01 for both). Participants with hypertension who were in the top quartile of LV mass had LTL that was 250 base pairs longer than those in the lowest quartile (P for trend across quartiles=0.009).

Conclusions— In contrast to our expectation, in the present community-based sample, LTL was positively associated with LV mass and wall thickness, especially so in participants with hypertension. These data are consistent with the hypothesis that longer LTL may be a marker of propensity to LV hypertrophy.

  S Rathore , O Katoh , H Matsuo , M Terashima , N Tanaka , Y Kinoshita , M Kimura , E Tsuchikane , K Nasu , M Ehara , K Asakura , Y Asakura and T. Suzuki

Background— Retrograde approach through collaterals has been introduced for percutaneous recanalization of chronic total occlusion (CTO) of the coronary arteries. We investigated the safety and efficacy of retrograde approaches used for percutaneous recanalization of CTO in a consecutive series of patients.

Methods and Results— We studied 157 consecutive patients who underwent retrograde CTO recanalization between 2003 and 2008 at a single center. A total of 118 (75.2%) of these patients have had previously failed antegrade attempts. Septal, epicardial, and saphenous vein graft collaterals were used in 67.5%, 24.8%, and 7.6% of cases, respectively. Collateral channel was crossed by guide wire successfully in 115 (73.2%) cases, and the procedure was successful by retrograde approach in 103 (65.6%) cases. Collateral channels (CCs) were graded as follows: CC0, no continuous connection; CC1, continuous thread-like connection; and CC2, continuous, small sidebranch-like connection. CC1, collateral tortuosity <90°, and angle with recipient vessel <90° (P<0.0001) were significant predictors of success. Epicardial channel use (P=0.01), CC0, corkscrew channel (P<0.0001), angle with recipient vessel >90° (P=0.0007), and nonvisibility of connection with recipient vessel were found to be significant predictors of procedural failure. The CC dissection was observed in 6 patients, with 1 needing coil embolization and others who were managed conservatively. The major adverse cardiac events were low, with 1 coronary artery bypass graft, 1 Q-wave myocardial infarction, 5 non–Q-wave myocardial infarctions, and no deaths in this group of patients.

Conclusions— The retrograde approach in CTO percutaneous coronary intervention is effective in recanalizing CTO. The success rate by retrograde approach was 65.6%, and final success was 85% in this group with acceptable overall adverse events. We have identified predictors of failure related to collateral morphology.

  H. J Kimura , R Rocchi , M. A Landek Salgado , K Suzuki , C. Y Chen , M Kimura , N. R Rose and P. Caturegli

Interferon (IFN)- has been involved in the pathogenesis of Hashimoto thyroiditis. It is a cytokine released by infiltrating mononuclear cells that mediates its actions mainly through signal transducer and activator of transcription-1 (STAT1) but also through other transcription factors. To dissect the effect of IFN on thyroid morphology and function, we crossed transgenic mice that express IFN specifically in the thyroid gland to mice deficient in STAT1. Lack of STAT1 ameliorated the abnormal thyroid morphology and the primary hypothyroidism typical of IFN transgenic mice but not the suppressed iodine accumulation. Interestingly, lack of STAT1 alone decreased iodine accumulation, seemingly through expression of TGFβ. These results indicate that STAT1 is required to mediate some but not all of the phenotypic changes induced by IFN and that it also regulates iodine accumulation via TGFβ signaling.

  T Tominaga , I Kimijima , M Kimura , Y Takatsuka , S Takashima , Y Nomura , F Kasumi , A Yamaguchi , N Masuda , S Noguchi and N. Eshima

Toremifene and tamoxifen have been used for adjuvant therapy in post-menopausal patients with breast cancer in Japan. Dyslipidemias are common in post-menopausal women. However, limited data are available on the effects of these agents on lipid profiles in Japanese patients. The Japan Toremifene Cooperative Study Group has been conducting a Phase III randomized trial of post-menopausal patients with breast cancer. One of its secondary endpoints is to confirm the effects of these agents on serum lipid profiles.


The subjects were post-menopausal Japanese patients who had undergone surgery for early breast cancer. Toremifene or tamoxifen was administered for 2 years. Lipid levels were measured before and up to 24 months after initiation.


Compared with baseline, at 24 months, the toremifene group (n = 123) showed significantly decreased total cholesterol (P < 0.001) and low-density lipoprotein cholesterol levels (P < 0.001), and significantly increased high-density lipoprotein cholesterol levels (P < 0.001). Their triglyceride levels were not affected (P = 0.677). The tamoxifen group (n = 120) also showed significantly decreased total cholesterol (P < 0.001) and low-density lipoprotein cholesterol levels (P < 0.001); no significant changes occurred in high-density lipoprotein cholesterol (P = 0.297) or triglyceride levels (P = 0.120).


Distinct differences between two selective estrogen receptor modulators on lipids were observed. Toremifene improved lipid profiles, particularly as an enhancer of high-density lipoprotein cholesterol. To a large extent, tamoxifen improved low-density lipoprotein cholesterol levels. The impact of these improved lipid profiles on the risk of cardiovascular diseases needs further confirmation.

  Y Kobayashi , K Yasuda , E Kondo , T Katsura , Y Tanabe , M Kimura and H. Tohyama

Concerning meniscal tissue regeneration, many investigators have studied the development of a tissue-engineered meniscus. However, the utility still remains unknown.


Implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect may significantly enhance fibrocartilage regeneration in vivo in the defect.

Study Design

Controlled laboratory study.


Seventy-five mature rabbits were used in this study. In each animal, an anterior one-third of the right medial meniscus was resected. Then, the animals were divided into the following 3 groups of 25 rabbits each: In group 1, no treatment was applied to the meniscal defect. In group 2, the defect was covered with a fascia sheath. In group 3, after the resected meniscus was fragmented into small pieces, the fragments were grafted into the defect. Then, the defect with the meniscal fragments was covered with a fascia sheath. In each group, 5 rabbits were used for histological evaluation at 3, 6, and 12 weeks after surgery, and 5 rabbits were used for biomechanical evaluation at 6 and 12 weeks after surgery.


Histologically, large round cells in group 3 were scattered in the core portion of the meniscus-shaped tissue, and the matrix around these cells was positively stained by safranin O and toluisin blue at 12 weeks. The histological score of group 3 was significantly higher than that of group 1 and group 2. Biomechanically, the maximal load and stiffness of group 3 were significantly greater than those of groups 1 and 2.


This study clearly demonstrated that implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect significantly enhanced fibrocartilage regeneration in vivo in the defect at 12 weeks after implantation in the rabbit.

Clinical relevance

This study proposed a novel strategy to treat a large defect after a meniscectomy.

  Md. M Hossain , Y Kawarabayasi , M Kimura and Y. Kakuta

Sulphatase family enzymes hydrolyse the sulphate ester, found on the pathogens cell surface and playing an important role for host–pathogen interaction. The AtsG, homologue of arylsulphatase, predicted in the Mycobacterium tuberculosis genomic data, was successfully expressed in Escherichia coli. The recombinant AtsG protein exhibited hydrolysis of para-nitrophenyl sulphate and para-nitrocatechol sulphate, and binding affinity to the heparin–sepharose resin. This is the first report of molecular evidence for an arylsulphatase activity of the AtsG protein. The maximum activity was detected at pH 8.0 and 37°C. As EDTA completely inhibited this activity, a divalent cation was required for the activity.

  M Yamaguchi , S Takemori , M Kimura , Y Tanishima , T Nakayoshi , S Kimura , T Ohno , N Yagi , J. F. Y Hoh and Y. Umazume

To characterize the structure of jaw muscle fibres expressing masticatory (superfast) myosin, X-ray diffraction patterns of glycerinated fibres of dog masseter were compared with those of dog tibialis anterior in the relaxed state. Meridional reflections of masseter fibres were laterally broad, indicating that myosin filaments are staggered along the filament axis. Compared with tibialis anterior fibres, the peak of the first myosin layer line of masseter fibres was lower in intensity and shifted towards the meridian, while lattice spacings were larger at a similar sarcomere length. These suggest that the myosin heads of masticatory fibres are mobile, and tend to protrude from the filament shaft towards actin filaments. Lowering temperature or treating with N-phenylmaleimide shifted the peak of the first myosin layer line of tibialis anterior fibres towards the meridian and the resulting profile resembled that of masseter fibres. This suggests that the protruding mobile heads in the non-treated masticatory fibres are in the ATP-bound state. The increased population of weakly binding cross-bridges may contribute towards the high specific force of masticatory fibres during contraction. Electron micrographs confirmed the staggered alignment of thick filaments along the filament axis within sarcomeres of masticatory fibres, a feature that may confer efficient force development over a wide range of the sarcomere lengths.

  M Maeda , M Kimura and Y. Kimura

As a part of the study to reveal the biological significance of de-N-glycosylation in plants, we analysed the structural features of free N-glycans (FNGs) accumulated inside cells and secreted to the extracellular space using a rice cell culture system. The structural analysis of FNGs obtained from the intracellular fraction revealed that the high-mannose type N-glycans with one GlcNAc residue (GN1-type) occurred at a concentration of ~10 nmol/g, while the truncated complex type N-glycans with a N, N'-diacetylchitobiosyl unit (GN2-type) occurred at a concentration of ~1 nmol/g. This result suggested that two kinds of glycoenzymes, cytosolic endo-β-N-acetylglucosaminidase (ENGase) and intracellular acidic peptide:N-glycanse (PNGase), are involved in the production of FNGs in rice cell as well as in other plant cells. On the other hand, in the culture medium, Lewis a epitope-containing complex and high-mannose type FNGs with the N, N'-diacetylchitobiosyl unit were found, suggesting extracellular acidic PNGase to be involved in the release of N-glycans from folded/processed glycoproteins in extracellular space. Furthermore, in the culture medium, we found unusual GN1-FNGs that have a biantennary complex type structure harbouring the Lewis a epitope, suggesting cytosolic ENGase and golgi N-glycan-processing enzymes to be involved in the production of these plant complex type FNGs.

  N Matsuda , S Sato , K Shiba , K Okatsu , K Saisho , C. A Gautier , Y. s Sou , S Saiki , S Kawajiri , F Sato , M Kimura , M Komatsu , N Hattori and K. Tanaka

Defective mitochondrial quality control is shown to be a mechanism for neurodegeneration in some forms of Parkinson's disease.

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