Biomedical subjects

Kenji Ashida

Publications and source records attributed to Kenji Ashida.

7 recordsLinked to original sources

PubMed2005

[Effectiveness of deep breath-hold SPECT in torso area: examination concerning improvement of resolution].

Because SPECT images are acquired under normal respiration, the respiratory motion induces artifacts and decreases resolution. In this study we developed a novel method of acquiring SPECT data during deep inhalation breath-hold (BrST) and assessed its efficacy in reducing motion artifacts and improving resolution. Reproducibility studies found that variations in SPECT image homogeneity were reduced using the BrST method to within a clinically non-problematic range. An experiment using a custom-built respiration phantom showed almost complete elimination of motion artifacts and significant improvement in resolution using the BrST method. Clinical assessment confirmed a significant reduction in motion artifacts along with the improvement in resolution. The BrST method enabled visualization of lesions that previously had been impossible to detect by standard acquisition under normal respiration. The BrST method is expected to both significantly reduce motion artifacts and improve resolution.

Artifacts↗

PubMed2005

Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase.

Dehydroepiandrosterone-sulfate, the sulfated form of dehydroepiandrosterone, is the most abundant steroid in young adults, but gradually declines with aging. In humans, the clinical application of dehydroepiandrosterone targeting some collagen diseases, such as systemic lupus erythematosus, as an adjunctive treatment has been applied in clinical trial. Here, we report that dehydroepiandrosterone may negatively regulate the mitogen-activated protein kinase pathway in humans via a novel dual specificity protein phosphatase, DDSP (dehydroepiandrosterone-enhanced dual specificity protein phosphatase). DDSP is highly homologous to LCPTP/HePTP, a tissue-specific protein tyrosine phosphatase (PTP) which negatively regulates both ERK and p38-mitogen-activated protein kinase, and is transcribed from the PTPN7 locus by alternative splicing. Although previous reports have shown that the mRNA expression of the LCPTP/HePTP gene was inducible by extracellular signals such as T-cell antigen receptor stimulation, reverse transcribed (RT)-PCR experiments using specific sets of primers suggested that the expression of LCPTP/HePTP was constitutive while the actual inducible sequence was that of DDSP. Furthermore DDSP was widely distributed among different types of human tissues and specifically interacted with p38-mitogen-activated protein kinase. This inducible negative regulation of the p38-mitogen-activated protein kinase-dependent pathway may help to clarify the broad range of dehydroepiandrosterone actions, thereby aiding the development of new preventive or adjunctive applications for human diseases.

Amino Acid Sequence↗

PubMed2005

Force requirements and insulin delivery profiles of four injection devices.

BACKGROUND: Injection force requirements for four insulin pen-type injection devices were evaluated using the AGS-IkNG Autograph force measurement device (Shimadzu Corp., Kyoto, Japan). RESULTS: Compared with the Humulin Pen (the Japanese brand name is Humacart kit; the same device as the Humalog Pen; Eli Lilly, Indianapolis, IN), HumaPen Ergo (Eli Lilly), and NovoPen 3 (Novo Nordisk A/S, Bagsvaerd, Denmark), the InnoLet(Novo Nordisk) required the lowest injection force to both initiate piston movement and commence insulin delivery and required the lowest overall force throughout delivery. InnoLet and NovoPen 3 showed the most even load-displacement curves, suggesting a smoother delivery of insulin during injection. In contrast, the Humulin Pen and HumaPen Ergo demonstrated marked fluctuations in the force required to complete injection. CONCLUSIONS: These performance characteristics appeared consistent with mechanical features of these insulin delivery devices, and the results highlight the potential importance of careful pen selection for patients with neuromuscular weakness or impaired manual coordination.

Diabetes Mellitus↗

PubMed2004

Adrenopause.

Dehydroepiandrosterone(DHEA) and DHEA-S are steroids that are abundantly produced by the adrenal gland. Plasma concentrations of DHEA and DHEA-S increase during adrenarche but decrease steadily after puberty. Although DHEA and DHEA-S have few intrinsic androgenic actions, they have recently attracted widespread attention due to their beneficial anti-aging effects. We clarified the beneficial effects of DHEA as an anti-aging steroid with regard to its stimulation of the immune system and its anti-diabetes, anti-atherosclerosis, anti-dementia (neurosteroid), anti-obesity and anti-osteoporosis effects. There are two possible biochemical and molecular mechanisms: direct action via the DHEA receptor on the target gene; and indirect action. We identified a high affinity of DHEA binding in human T-lymphocytes by searching for the target genes that are induced in activated T-lymphocytes in the presence of DHEA, determined the gene sequence and named DHEA-induced dual p38-specific phosphatase (DDSP). DDSP transgenic mice have been created to identify the anti-aging effects of DDSP. The conversion of DHEA to estrone by cytochrome P450 aromatase in primary cultured human osteoblasts was clarified. We are currently undertaking an open trial of DHEA replacement therapy.

Adrenal Glands↗

PubMed2003

Human pituitary tumor transforming gene (hPTTG) inhibits human lung cancer A549 cell growth through activation of p21(WAF1/CIP1 ).

Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4 cells. This gene was able to induce cell transformation in vitro and is also associated with p53-dependent and -independent apoptosis. In this study, we cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly inhibited cell growth, which was determined by the adherent cell growth properties, colony formation in soft agar and [3H] thymidine incorporation, respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was associated with the activation of p21WAF1/CIP1 in A549 cells, but not in HeLa cells. The hPTTG overexpression increased both the p21WAF1/CIP1 mRNA and protein expression levels as determined by both Northern and Western blot analysis, respectively, in A549 cells. The increased expression of p21WAF1/CIP1 mRNA was regulated at the transcription level and was independent on p53 expression because the luciferase activity increased after the co-transfection of hPTTG and p21WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The subcellular distribution of hPTTG was dependent on cell type, and was predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells. These results indicate that an overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21WAF1/CIP1 -dependent and -independent.

Animals↗

PubMed2003

[Estimation of glandular content rate and statistical analysis of the influence of age group and compressed breast thickness on the estimated value].

Because the glandular content rate is an important factor in evaluating breast cancer detection and average glandular dose, it is important in mammography research to estimate and analyze this rate. The purpose of this study was to obtain a formula for statistical estimation of the glandular content rate, to clarify statistically the influence of age group and compressed breast thickness (CBT) on estimating the glandular content rate, and to show statistically the general relation between glandular content rate and the factors of age and CBT. The subjects were 740 Japanese women aged 20-91 years (mean+/-SD: 48.3+/-12.8 years) who had undergone mammography. In our study, the glandular content rate was statistically estimated from age group, mAs-value, and CBT when subjects underwent mammography, from a phantom simulation, and from MR images of the breast. In addition, multivariate analysis was carried to examine statistically the influence of age group and CBT on glandular content rate. The mean glandular content rate as estimated by age group was as follows: 35.6% for those in their 20s, 33.4% in the 30s, 27.5% in the 40s, 23.8% in the 50s, and 21.8% in those 60 and over. The rate for the subjects as a whole was 27.1%. This study indicated that overestimation occurred if the estimated value of the glandular content rate was not corrected in the 3D-measurement by MRI. In addition, this study showed that the statistical influence on glandular content rate was significantly larger for CBT than age.

Adult↗

PubMed2002

Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S.

The plasma ACTH and cortisol levels do not change during aging. On the other hand, the plasma dehydroepiandrosterone sulfate (DHEA-S) changes remarkably during aging. Before puberty, the plasma DHEA-S level both in males and females is very low, however, it rapidly increases at puberty, and thereafter significantly decreases both linearly and age-dependently. Cytochrome P450c17 has two enzyme activities, 17-alpha-hydroxylase and 17,20-lyase. Cortisol is synthesized by 17-alpha-hydroxylase, and DHEA is synthesized by 17,20-lyase. The mechanism of dissociation of cortisol and DHEA synthesis in aging depends on another regulator of 17,20-lyase of cytochrome P450c17 such as cytochrome P450 reductase. We demonstrated significant decrease in cytochrome P450 reductase activity in bovine aged adrenal glands. We clarified the beneficial effects of DHEA as an anti-aging steroid based on both in vitro and in vivo experiments, such as the stimulatory effect of immune system, anti-diabetes mellitus, anti-atherosclerosis, anti-dementia (neurosteroid), anti-obesity and anti-osteoporosis. It is very important to identify the mechanism of action of DHEA. We clarified the conversion of DHEA to estrone by cytochrome P450 aromatase in primary cultured human osteoblasts. We indentified high affinity of DHEA binding with K(d)=6.6 nM in antigen and DHEA stimulated human T lymphocytes. We searched for the target genes that are specifically induced in activated T lymphocytes in the presence of DHEA by subtractive hybridization screening for differentially expressed transcripts. The double blind, randomized human replacement therapies utilizing DHEA are also reviewed.

Aging↗