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Articles by H Saito
Total Records ( 10 ) for H Saito
  M Koga , J Murai , H Saito , M Mukai , S Matsumoto and S. Kasayama

In gastrectomized subjects, oral glucose tolerance test often shows marked hyperglycaemia (oxyhyperglycaemia) after glucose loading. Because serum glycated albumin (GA) has been shown to better reflect postprandial and maximum plasma glucose levels, we investigated whether or not the clinical significance of serum GA and glycated haemoglobin (HbA1C) in non-diabetic gastrectomized subjects differs.


During health examinations, 62 non-diabetic subjects with a history of gastrectomy and 87 non-diabetic control subjects were selected in the present study. Body mass index (BMI) in the gastrectomy group was significantly lower than in the control group.


Fasting plasma glucose levels were significantly lower in the gastrectomized subjects than in the control subjects. Although both HbA1C and serum GA were significantly higher in the gastrectomized subjects, there was a significant difference in GA/HbA1C ratio between the gastrectomized subjects and the control subjects. BMI-adjusted serum GA, based on our previous finding of inverse influence of BMI on serum GA, was also significantly higher in the gastrectomized subjects than in the controls.


Serum GA is higher relative to HbA1C in gastrectomized subjects. This suggests that serum GA may be a better marker than HbA1C for glycaemic excursion in these subjects.

  M Koga , J Murai , H Saito , S Kasayama , A Imagawa , T Hanafusa , T Kobayashi and the Members of the Japan Diabetes Society's Committee on Research on Type 1 Diabetes

Fulminant type 1 diabetes mellitus (FT1DM), a subtype of type 1 diabetes mellitus, was first reported as a disease entity in 2000. Ketoacidosis at initial onset due to acute pancreatic cell destruction makes early diagnosis and treatment for FT1DM mandatory. In the early period of FT1DM, haemoglobin (Hb)A1C levels are not markedly elevated. This study investigated serum glycated albumin (GA), which reflects acute short-term changes in plasma glucose, as a new clinical index for FT1DM at disease onset.


Subjects comprised 35 patients with FT1DM who had undergone measurement of HbA1C and serum GA at initial visit and 42 patients with type 2 diabetes mellitus (T2DM) with HbA1C <8.5% and no history of diabetes treatment as controls.


HbA1C was significantly lower in FT1DM than in T2DM, whereas serum GA was significantly higher. GA/HbA1C ratio was thus significantly higher in FT1DM than in T2DM (3.9 ± 0.5 versus 2.8 ± 0.3; P < 0.0001). GA/HbA1C ratio was >3.2 in 41 of 42 FT1DM patients (98%), compared with only one of 32 T2DM patients (3%).


Serum GA is significantly higher in FT1DM than in T2DM, whereas HbA1C is significantly lower. FT1DM can thus be distinguished from untreated T2DM by GA/HbA1C ratio at initial visit before treatment for diabetes.

  H Hirasawa , A Tomidokoro , M Araie , S Konno , H Saito , A Iwase , M Shirakashi , H Abe , S Ohkubo , K Sugiyama , T Ootani , S Kishi , K Matsushita , N Maeda , M Hangai and N. Yoshimura

Objectives  To evaluate the peripapillary distribution of retinal nerve fiber layer thickness (RNFLT) in normal eyes using spectral-domain optical coherence tomography and to study potentially related factors.

Methods  In 7 institutes in Japan, RNFLT in 7 concentric peripapillary circles with diameters ranging from 2.2 to 4.0 mm were measured using spectral-domain optical coherence tomography in 251 ophthalmologically normal subjects. Multiple regression analysis for the association of RNFLT with sex, age, axial length, and disc area was performed.

Results  Retinal nerve fiber layer thickness decreased linearly from 125 to 89 µm as the measurement diameter increased (P < .001, mixed linear model). Retinal nerve fiber layer thickness correlated with age in all diameters (partial correlation coefficient [PCC] = –0.40 to –0.32; P < .001) and negatively correlated with disc area in the 2 innermost circles but positively correlated in the 3 outermost circles (PCC = –0.30 to –0.22 and 0.17 to 0.20; P ≤ .005). Sex and axial length did not correlate with RNFLT (P > .08). The decay slope was smallest in the temporal and largest in the nasal and inferior quadrants (P < .001); positively correlated with disc area (PCC = 0.13 to 0.51; P ≤ .04); and negatively correlated with RNFLT (PCC = –0.51 to –0.15; P ≤ .01).

Conclusions  In normal Japanese eyes, RNFLT significantly correlated with age and disc area, but not with sex or axial length. Retinal nerve fiber layer thickness decreased linearly as the measurement diameter increased. The decay slope of RNFLT was steepest in the nasal and inferior quadrants and steeper in eyes with increased RNFLT or smaller optic discs.

  A Tsubota , K Matsumoto , K Mogushi , K Nariai , Y Namiki , S Hoshina , H Hano , H Tanaka , H Saito and N. Tada

To identify key genes involved in the complex multistep process of hepatotumorigenesis, we reduced multivariate clinicopathological variables by using the Long–Evans Cinnamon rat, a model with naturally occurring and oxidative stress-induced hepatotumorigenesis. Gene expression patterns were analyzed serially by profiling liver tissues from rats of a naive status (4 weeks old), through to those with chronic hepatitis (26 and 39 weeks old) to tumor development (67 weeks old). Of 31 099 probe sets used for microarray analysis, 87 were identified as being upregulated in a stepwise manner during disease progression and tumor development. Quantitative real-time reverse transcription–polymerase chain reaction and statistical analyses verified that IQGAP1 and vimentin mRNA expression levels increased significantly throughout hepatotumorigenesis. A hierarchical clustering algorithm showed both genes clustered together and in the same cluster group. Immunohistochemical and western blot analyses showed similar increases in protein levels of IAGAP1 and vimentin. Finally, pathway analyses using text-mining technology with more comprehensive and recent gene–gene interaction data identified IQGAP1 and vimentin as important nodes in underlying gene regulatory networks. These findings enhance our understanding of the multistep hepatotumorigenesis and identification of target molecules for novel treatments.

  C Hamashima , T Nakayama , M Sagawa , H Saito and T. Sobue

In 2005, there were 9264 deaths from prostate cancer, accounting for 4.7% of the total number of cancer deaths in Japan. As the population continues to age, interest in prostate cancer screening has increased, and opportunistic screening for prostate cancer has been conducted worldwide. The guideline for prostate cancer screening was developed based on the established method. The efficacies of prostate-specific antigen (PSA) and digital rectal examination (DRE) were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screening were formulated. Two methods of prostate cancer screening were evaluated. Based on the analytic framework involving key questions, 1186 articles published from January 1985 to October 2006 were selected using MEDLINE and other methods. After the systematic literature review, 28 articles were identified as providing evidence of mortality reduction from prostate cancer, including 5 observational studies for DRE screening, 1 meta-analysis, 3 randomized controlled trials and 19 observational studies for PSA screening. Although several studies showed that PSA screening had a beneficial effect, the results of the selected studies were inconsistent. Overall, the evidence that screening reduced mortality from prostate cancer was insufficient. Furthermore, prostate cancer screening is associated with serious harms, including overdiagnosis, adverse effects of needle biopsy and adverse effects of local prostatectomy. At present, the evidence for the effect of prostate cancer screening is insufficient. Both PSA and DRE were not recommended for population-based screening programs, but they could be conducted as individual-based screening if basic requirements were met.

  E. T Alexander , M Tanaka , M Kono , H Saito , D. J Rader and M. C. Phillips

Carriers of the apolipoprotein A-IMilano (apoA-IM) variant, R173C, have reduced levels of plasma HDL but no increase in cardiovascular disease. Despite intensive study, it is not clear whether the removal of the arginine or the introduction of the cysteine is responsible for this altered functionality. We investigated this question using two engineered variations of the apoA-IM mutation: R173S apoA-I, similar to apoA-IM but incapable of forming a disulfide bond, and R173K apoA-I, a conservative mutation. Characterization of the lipid-free proteins showed that the order of stability was wild typeR173K>R173S>R173C. Compared with wild-type apoA-I, apoA-IM had a lower affinity for lipids, while R173S apoA-I displayed intermediate affinity. The in vivo effects of the apoA-I variants were measured by injecting apoA-I-expressing adeno-associated virus into apoA-I-null mice. Mice that expressed the R173S variant again showed an intermediate phenotype. Thus, both the loss of the arginine and its replacement by a cysteine contribute to the altered properties of apoA-IM. The arginine is potentially involved in an intrahelical salt bridge with E169 that is disrupted by the loss of the positively charged arginine and repelled by the cysteine, destabilizing the helix bundle domain in the apoA-I molecule and modifying its lipid binding characteristics.

  T Isada , A Kuwata , H Saito , T Ono , M Ishii , H Yoshikawa Inoue and K. Suzuki

Diel and seasonal changes in the photosynthetic physiology of phytoplankton and primary productivity were investigated during 2005, together with community composition in the Oyashio (OY) and Kuroshio–Oyashio transition (TR) regions of the northwest Pacific. In both regions, diel changes in the maximum photosynthetic rate (P*max) and the light saturation index (Ek) in the photosynthesis–irradiance (P–E) curve were observed, due to diel differences in photo-physiology. In the OY region, the highest values of chlorophyll a concentration, depth-integrated primary production and the maximum quantum yield of carbon fixation in photosynthesis (c max) were observed in May when diatom blooms occurred. Furthermore, a higher water-column light utilization efficiency () of photosynthesis for phytoplankton was found in the OY region in both May and September. In contrast, in the TR and warm-core ring regions, c max was nearly constant, while depth-integrated primary production in May was significantly lower than in the OY region. These results show that the spring phytoplankton assemblages in OY waters had a higher light utilization ability during photosynthesis. Such a high photosynthetic property would contribute to the highest seasonal biological drawdown of surface pCO2 among the world's oceans (Takahashi, T., Sutherland, S. C., Sweeney, C. et al. (2002) Global sea–air CO2 flux based on climatological surface ocean pCO2, and seasonal biological and temperature effects. Deep-Sea Res. II, 49, 1601–1622).

  M Ito , K Miyado , K Nakagawa , M Muraki , M Imai , N Yamakawa , J Qin , Y Hosoi , H Saito and Y. Takahashi

p38 MAPK (p38) plays pivotal roles in aging and reproductive physiology. Nevertheless, involvement of p38 in female reproductive aging is uncertain. To improve knowledge of the role of p38 in age-associated reproductive failure, the expression and subcellular localization of phosphorylated p38 was investigated in human granulosa cells. p38 was 7-fold more activated in cells from older subjects than in those from younger subjects. Similar results were obtained in human granulosa-like KGN cells treated with hydrogen peroxide (H2O2). Interestingly, phosphorylated p38 was detected in the nucleus less frequently in older cells than in younger cells (Younger: 58.6%; Older: 29.8%, P< 0.01). Similarly cytoplasmic localization of phosphorylated p38 in KGN cells was observed after treatment with H2O2. The activation and cytoplasmic localization of p38 in H2O2-treated KGN cells were blocked by N-acetylcysteine and SB203580. Although the p38 activators, FSH and tumor necrosis factor-, induced a similar localization of phosphorylated p38 in KGN cells, the expression and localization patterns of p38 were distinct from those in older granulosa cells and H2O2-treated KGN cells. These results indicate that the characteristic localization of p38 in older granulosa cells is induced by oxidative stress.

  K Nishida , A Hasegawa , S Nakae , K Oboki , H Saito , S Yamasaki and T. Hirano

Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency. However, it remains unknown how Zn homeostasis is regulated in mast cells and if Zn transporters are involved in allergic reactions. We show that Znt5/Slc30a5 is required for contact hypersensitivity and mast cell–mediated delayed-type allergic response but not for immediate passive cutaneous anaphylaxis. In mast cells from Znt5–/– mice, Fc receptor I (FcRI)–induced cytokine production was diminished, but degranulation was intact. Znt5 was involved in FcRI-induced translocation of protein kinase C (PKC) to the plasma membrane and the nuclear translocation of nuclear factor B. In addition, the Zn finger–like motif of PKC was required for its plasma membrane translocation and binding to diacylglycerol. Thus, Znt5 is selectively required for the mast cell–mediated delayed-type allergic response, and it is a novel player in mast cell activation.

  T Ebihara , M Azuma , H Oshiumi , J Kasamatsu , K Iwabuchi , K Matsumoto , H Saito , T Taniguchi , M Matsumoto and T. Seya

In myeloid dendritic cells (mDCs), TLR3 is expressed in the endosomal membrane and interacts with the adaptor toll/interleukin 1 receptor homology domain–containing adaptor molecule 1 (TICAM-1; TRIF). TICAM-1 signals culminate in interferon (IFN) regulatory factor (IRF) 3 activation. Co-culture of mDC pretreated with the TLR3 ligand polyI:C and natural killer (NK) cells resulted in NK cell activation. This activation was triggered by cell-to-cell contact but not cytokines. Using expression profiling and gain/loss-of-function analyses of mDC genes, we tried to identify a TICAM-1–inducing membrane protein that participates in mDC-mediated NK activation. Of the nine candidates screened, one contained a tetraspanin-like sequence and satisfied the screening criteria. The protein, referred to as IRF-3–dependent NK-activating molecule (INAM), functioned in both the mDC and NK cell to facilitate NK activation. In the mDC, TICAM-1, IFN promoter stimulator 1, and IRF-3, but not IRF-7, were required for mDC-mediated NK activation. INAM was minimally expressed on NK cells, was up-regulated in response to polyI:C, and contributed to mDC–NK reciprocal activation via its cytoplasmic tail, which was crucial for the activation signal in NK cells. Adoptive transfer of INAM-expressing mDCs into mice implanted with NK-sensitive tumors caused NK-mediated tumor regression. We identify a new pathway for mDC–NK contact-mediated NK activation that is governed by a TLR signal-derived membrane molecule.

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