Biomedical subjects

Masaya Yamamoto

Publications and source records attributed to Masaya Yamamoto.

At least 19 recordsLinked to original sources

PubMed2026

Genome-Wide Association Study of Contrast Media Hypersensitivity in Japanese Patients.

Iodinated contrast media (ICM), commonly used in radiological tests such as coronary angiography, can cause hypersensitivity reactions (HSRs). The mechanism of ICM HSRs is thought to be complex; while IgE-mediated allergic reactions appear to be involved, the details remain unclear. This study aims to elucidate the pathogenesis of ICM HSRs through genetic analysis. To date, a few case-control studies have been conducted exclusively on East Asians, but the results have been inconclusive and have not been replicated.We conducted a multistage GWAS for ICM HSRs in Japanese individuals. The study population comprised 153 cases with ICM HSRs (ranging from mild to severe form), 632 controls with no history of ICM-induced allergies, and < 38,721 individuals from the general population. We identified genome-wide significant association signals in the HLA region and also found that these signals originated from the three HLA alleles-B*52:01, C*12:02, DRB1*15:02-previously reported in a Korean candidate gene study. Using instrumental variable analysis with a polygenic score for pediatric asthma (PGSasthma) as a proxy, we demonstrated that ICM HSRs are associated with the allergic predisposition thought to be shared by asthma and ICM HSRs. There was a significant difference in the distribution of PGSasthma between ICM HSR patients and non-disease controls (per-SD odds ratio: 1.26, P = 0.021).Our genome-wide approach shows that HLA alleles are among the genetic factors underlying ICM HSRs. Furthermore, it provides evidence for the potential usefulness of predicting the risk of developing ICM HSRs based on allergic predisposition.

Allergic predisposition↗

PubMed2006

Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy.

A novel photosensitizer with magnetic resonance imaging (MRI) activity was designed from fullerene (C(60)) for efficient photodynamic therapy (PDT) of tumor. After chemical conjugation of polyethylene glycol (PEG) to C(60) (C(60)-PEG), diethylenetriaminepentaacetic acid (DTPA) was subsequently introduced to the terminal group of PEG to prepare PEG-conjugated C(60) (C(60)-PEG-DTPA). The C(60)-PEG-DTPA was mixed with gadolinium acetate solution to obtain Gd(3+)-chelated C(60)-PEG (C(60)-PEG-Gd). Following intravenous injection of C(60)-PEG-Gd into tumor-bearing mice, the PDT anti-tumor effect and the MRI tumor imaging were evaluated. The similar O(2)(*-)generation was observed with or without Gd(3+) chelation upon light irradiation. Both of the C(60)-PEG-Gd and Magnevist(R) aqueous solutions exhibited a similar MRI activity. When intravenously injected into tumor-bearing mice, the C(60)-PEG-Gd maintained an enhanced MRI signal at the tumor tissue for a longer time period than Magnevist(R). Injection of C(60)-PEG-Gd plus light irradiation showed significant tumor PDT effect although the effect depended on the timing of light irradiation. The PDT efficacy of C(60)-PEG-Gd was observed at the time when the tumor accumulation was detected by the enhanced intensity of MRI signal. This therapeutic and diagnostic hybrid system is a promising tool to enhance the PDT efficacy for tumor.

Animals↗

PubMed2006

Efficient gene transfer by pullulan-spermine occurs through both clathrin- and raft/caveolae-dependent mechanisms.

The feasibility and mechanism of gene delivery by pullulan-spermine, a recently developed cationic polysaccharide, were investigated. Pullulan-spermine-mediated transfection of plasmid DNA resulted in greatly reduced cytotoxicity and a 10-fold increase in the level of gene expression when compared to Lipofectamine 2000, a commercially available cationic lipid. Additionally, after transfection of p53-expressing plasmid DNA by pullulan-spermine but not Lipofectamine 2000, the in vitro proliferation of T24 cells was significantly reduced. Pullulan-spermine-mediated gene expression was inhibited by both chlorpromazine of clathrin-mediated endocytosis inhibitor and methyl-beta-cyclodextrin and filipin of raft/caveolae inhibitors. We conclude that pullulan-spermine is a promising carrier for gene transfection, and that cellular uptake of pullulan-spermine-plasmid DNA complexes is mediated by clathrin- and raft/caveolae-dependent endocytotic pathways.

Asialoglycoprotein Receptor↗

PubMed2006

Hypertonic stress increases phosphatidylinositol 4,5-bisphosphate levels by activating PIP5KIbeta.

Hyperosmotic stress increases phosphoinositide levels, reorganizes the actin cytoskeleton, and induces multiple acute and adaptive physiological responses. Here we showed that phosphatidylinositol 4,5-bisphosphate (PIP(2)) level increased rapidly in HeLa cells during hypertonic treatment. Depletion of the human type I phosphatidylinositol 4-phosphate 5-kinase beta isoform (PIP5KIbeta) by RNA interference impaired both the PIP(2) and actin cytoskeletal responses. PIP5KIbeta was recruited to membranes and was activated by hypertonic stress through Ser/Thr dephosphorylation. Calyculin A, a protein phosphatase 1 inhibitor, blocked the hypertonicity-induced PIP5KIbeta dephosphorylation/activation as well as PIP(2) increase in cells. Urea, which raises osmolarity without inducing cell shrinkage, did not promote dephosphorylation nor increase PIP(2) levels. Disruption or stabilization of the actin cytoskeleton, or inhibition of the Rho kinase, did not block the PIP(2) increase nor PIP5KIbeta dephosphorylation. Therefore, PIP5KIbeta is dephosphorylated in a volume-dependent manner by a calyculin A-sensitive protein phosphatase, which is activated upstream of actin remodeling and independently of Rho kinase activation. Our results establish a cause-and-effect relation between PIP5KIbeta dephosphorylation, lipid kinase activation, and PIP(2) increase in cells. This PIP(2) increase can orchestrate multiple downstream responses, including the reorganization of the actin cytoskeleton.

Actins↗

PubMed2006

Tissue engineering by modulated gene delivery.

Tissue engineering is a newly emerging biomedical form to create a local environment which enables cells to promote the proliferation and differentiation for regeneration induction. The cell-induced regeneration of tissues and organs is achieved by making use of the tissue engineering technology or methodology. Several genetic approaches with virus and non-viral vectors or genetically engineered cells have been attempted to enhance tissue regeneration. The basic idea is to promote the cell proliferation and differentiation as well as the secretion of biological signal molecules for tissue regeneration from cells by gene transfection. For successful gene transfection and expression, it is important to develop drug delivery system (DDS) which allows a therapeutic gene to be delivered specifically to the target cell at an appropriate timing for a certain time period. This paper overviews the recent development of gene-modified tissue engineering, briefly explaining delivery technologies necessary to modulate the efficiency of gene transfection.

Animals↗

PubMed2006

Regulation of fibroblast growth factor-23 signaling by klotho.

The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.

Animals↗

PubMed2006

Enhanced bone regeneration at a segmental bone defect by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel.

The objective of this study is to investigate the feasibility of a biodegradable hydrogel of gelatin as the controlled release carrier of bone morphogenetic protein-2 (BMP-2) suitable for enhancement of bone regeneration at a segmental bone defect. Hydrogels with three different water contents were prepared through glutaraldehyde crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction conditions. Segmental critical-sized defects (20 mm) were created at the ulnar bone of skeletally mature New Zealand white rabbits, and gelatin hydrogels incorporating BMP-2 (17 microg/hydrogel) were implanted into the defects. When bone regeneration was evaluated by soft x-ray observation and bone mineral density (BMD) measurement, the gelatin hydrogels incorporating BMP- 2 exhibited significantly high osteoinduction activity compared with that of free BMP-2, although the activity depended on the water content of the hydrogels. Significantly higher BMD enhancement was observed in the gelatin hydrogel with a water content of 97.8 wt% than that with the lower or higher water content. We concluded that the biodegradable gelatin hydrogel is a promising controlled release carrier of BMP-2 for bone regeneration at the segmental bone defect.

Absorbable Implants↗

PubMed2005

Regulation of oxidative stress by the anti-aging hormone klotho.

klotho is an aging suppressor gene and extends life span when overexpressed in mice. Klotho protein was recently demonstrated to function as a hormone that inhibits insulin/insulin-like growth factor-1 (IGF-1) signaling. Here we show that Klotho protein increases resistance to oxidative stress at the cellular and organismal level in mammals. Klotho protein activates the FoxO forkhead transcription factors that are negatively regulated by insulin/IGF-1 signaling, thereby inducing expression of manganese superoxide dismutase. This in turn facilitates removal of reactive oxygen species and confers oxidative stress resistance. Thus, Klotho-induced inhibition of insulin/IGF-1 signaling is associated with increased resistance to oxidative stress, which potentially contributes to the anti-aging properties of klotho.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Enhanced ectopic bone formation using a combination of plasmid DNA impregnation into 3-D scaffold and bioreactor perfusion culture.

The objective of this study is to enhance in vivo ectopic bone formation by combination of plasmid DNA impregnation into three-dimensional (3-D) cell scaffolds and a developed in vitro culture method. Gelatin was cationized by introducing spermine (Sm) to the carboxyl groups for complexation with the plasmid DNA. As the MSC scaffold, collagen sponge reinforced by incorporation of poly(glycolic acid) (PGA) fibers was used. A complex of the cationized gelatin and plasmid DNA of BMP-2 was impregnated into the scaffold. MCS were seeded into each scaffold and cultured by a static and perfusion methods. When MSC were cultured in the PGA-reinforced collagen sponge, the level of BMP-2 expression was significantly enhanced by the perfusion culture compared with static method. When the osteoinduction activity of the PGA-reinforced collagen sponges seeded with PBS, MSC, naked plasmid DNA-BMP-2, cationized gelatin-plasmid DNA-BMP-2 complex, and transfected MSC by static and perfusion method, were studied following the implantation into the back subcutis of rats in terms of histological and biochemical examinations, homogeneous bone formation was histologically observed throughout the sponges seeded with cationized gelatin-plasmid DNA of BMP-2 complex and transfected MSC by perfusion method, although the extent of bone formation was higher for the later one. The level of alkaline phosphatase activity and osteocalcin content at the implanted sites of sponges seeded with transfected MSC by perfusion method were significantly high compared with those seeded with other agents. We conclude that combination of plasmid DNA-impregnated PGA-reinforced collagen sponge and the perfusion method was promising to promote the in vitro gene expression for MSC and in vivo ectopic bone formation.

Animals↗

PubMed2005

Administration of control-released hepatocyte growth factor enhances the efficacy of skeletal myoblast transplantation in rat infarcted hearts by greatly increasing both quantity and quality of the graft.

BACKGROUND: We investigated whether simultaneous administration of control-released hepatocyte growth factor (HGF) enhances the efficacy of skeletal myoblast (SM) transplantation (Tx) through its antiapoptotic, angiogenic, and antifibrotic effects in myocardial infarction (MI). METHODS AND RESULTS: Forty-eight Lewis rats with chronic MI were divided into 4 groups. In Group I (n=14), neonatal SMs (5 x 10(6)) were transplanted in the MI area with a gelatin sheet incorporating 40 microg (1 g/L) of HGF applied. Group II (n=14) had SM Tx and placement of a saline sheet. Groups III (n=10) and IV (n=10) had culture medium injection plus HGF and saline sheet application, respectively. Four rats each from Groups I and II were sacrificed at day 1 for TUNEL assay on donor SMs. The percentage of TUNEL-positive donor cells was much lower in Group I than in Group II (P<0.05). At 4 weeks, in Group I, left ventricular diastolic dimension was smallest in echocardiography, end-systolic elastance was highest, and tau was the lowest (both P<0.0005 in ANOVA) in cardiac catheterization. Vascular density inside the graft was higher in Group I than in Group II (P<0.0001). The percentage of fibrotic area inside the graft was smaller in Group I than in Group II (P<0.001). The graft volume as estimated by fast skeletal myosin heavy chain-positive areas was approximately 7-fold larger in Group I than in Group II (P<0.0001). CONCLUSIONS: In SM Tx, HGF can greatly increase the graft volume and vascularity and reduce fibrosis inside the graft, which enhances the efficacy of SM Tx to infarcted hearts.

Animals↗

PubMed2005

Suppression of aging in mice by the hormone Klotho.

A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.

Aging↗

PubMed2005

Fate of unprotected side branches as related to embolic complications during stent implantation for acute coronary syndromes using a distal protection procedure.

Coronary lesion stenting with aspiration and distal balloon occlusion is more often associated with embolic occlusion of interposed side branches when the branch arises at an angle of </=45 degrees and the artery containing the lesion is large. However, this event is infrequent, often resolving during the procedure and uniformly resolving by 6 months.

Aged↗

PubMed2005

Control-released hepatocyte growth factor prevents the progression of heart failure in stroke-prone spontaneously hypertensive rats.

BACKGROUND: We have developed a hepatocyte growth factor (HGF)-incorporating gelatin hydrogel sheet (HGF sheet), which was designed to release HGF more than 2 weeks in vivo. The present study investigated whether the HGF sheet could prevent the progression of heart failure in stroke-prone spontaneously hypertensive rats. METHODS: Stroke-prone spontaneously hypertensive rats at the age of 25 weeks received placement of an HGF sheet on the left ventricular free wall (HGF, n = 10) or sham-operation (control, n = 10). All animals were followed up with Doppler echocardiography during the next 4 weeks and then underwent histologic analysis. The influence of the hydrogel sheet alone was assessed by echocardiography and left ventricular pressure measurements. Survival study was performed (each group, n = 11) at the age of 30 weeks. RESULTS: There were two deaths in the control group and no deaths in the HGF group during the 4 weeks. Fractional shortening was significantly higher, and left ventricular diastolic dimension was significantly smaller in the HGF than in the control group. The slope of the peak early diastolic filling velocity and the ratio of that slope to the slope of the peak filling velocity at atrial contraction were significantly lower in the HGF than the control group. Myocardial fibrosis was lower and capillary density was significantly higher in the HGF than the control group. Placement of the hydrogel sheet alone did not affect any cardiac function compared with sham operation. The survival rate at 10 weeks after the surgery was much higher in the HGF than the control group. CONCLUSIONS: The HGF sheet improves cardiac function, reverses left ventricular remodeling, and markedly improves survival in spontaneously hypertensive rats. These beneficial effects are associated with angiogenesis and reduced fibrosis in the left ventricular myocardium.

Animals↗

PubMed2005

Osteogenic differentiation of mesenchymal stem cells in biodegradable sponges composed of gelatin and beta-tricalcium phosphate.

Biodegradable gelatin sponges incorporating various amounts of beta-tricalcium phosphate (betaTCP) (gelatin-betaTCP) were fabricated and the in vitro osteogenic differentiation of mesenchymal stem cells (MSC) isolated from the rat bone marrow in the sponges was investigated. The gelatin sponges incorporating betaTCP have an interconnected pore structure with the average size of 180-200 microm, irrespective of the betaTCP amount. The stiffness of the sponges became higher with an increase in the amount of betaTCP. When seeded into the sponges by an agitated method, MSC were homogeneously distributed throughout the sponge. The morphology of cells attached got more spreaded with the increased betaTCP amount. The rate of MSC proliferation depended on the betaTCP amount and culture method: the higher the betaTCP amount in the stirring culture, the higher the proliferation rate. The deformed extent of gelatin-betaTCP sponges was suppressed with the increased amount of betaTCP. When measured to evaluate the osteogenic differentiation of MSC, the alkaline phosphatase activity and osteocalcin content became maximum for the sponge with a betaTCP amount of 50 wt%, although both the values were significantly high in the stirring culture compared with those in the static culture. We concluded that the attachment, proliferation, and osteogenic differentiation of MSC were influenced by sponge composition of gelatin and betaTCP as the cell scaffold.

Absorbable Implants↗

PubMed2005

Enhanced osteoinduction by controlled release of bone morphogenetic protein-2 from biodegradable sponge composed of gelatin and beta-tricalcium phosphate.

Biodegradable gelatin sponges at different contents of beta-tricalcium phosphate (beta-TCP) were fabricated to allow bone morphogenetic protein (BMP)-2 to incorporate into them. The in vivo osteoinduction activity of the sponges incorporating BMP-2 was investigated, while their in vivo profile of BMP-2 release was evaluated. The sponges prepared had an interconnected pore structure with an average pore size of 200 microm, irrespective of the beta-TCP content. The in vivo release test revealed that BMP-2 was released in vivo at a similar time profile, irrespective of the beta-TCP content. The in vivo time period of BMP-2 retention was longer than 28 days. When the osteoinduction activity of gelatin or gelatin-beta-TCP sponges incorporating BMP-2 was studied following the implantation into the back subcutis of rats in terms of histological and biochemical examinations, homogeneous bone formation was histologically observed throughout the sponges, although the extent of bone formation was higher in the sponges with the lower contents of beta-TCP. On the other hand, the level of alkaline phosphatase activity and osteocalcin content at the implanted sites of sponges decreased with an increase in the content of beta-TCP. The gelatin sponge exhibited significantly higher osteoinduction activity than that of any gelatin-beta-TCP sponge, although every sponge with or without beta-TCP showed a similar in vivo profile of BMP-2 release. In addition, the in vitro collagenase digestion experiments revealed that the gelatin-beta-TCP sponge collapsed easier than the gelatin sponge without beta-TCP incorporation. These results suggest that the maintenance of the intrasponge space necessary for the osteoinduction is one factor contributing to the osteoinduction extent of BMP-2-incorporating sponges.

Absorbable Implants↗

PubMed2005

Simultaneous application of basic fibroblast growth factor and hepatocyte growth factor to enhance the blood vessels formation.

OBJECTIVE: The present study investigated whether the simultaneous application of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) enhances blood vessel formation in murine ischemic hindlimb compared with bFGF or HGF applied alone. METHODS: Unilateral hindlimb ischemia was created in C57BL/6 mice. Hindlimb blood flow was evaluated by laser Doppler perfusion image index (LDPII) (ratio (%) of ischemic-to-normal-limb blood flow). The ischemic limbs were treated with bFGF and HGF separately, or bFGF and HGF together, and their therapeutic effects were assessed. Collagen microspheres (CM) were used as a sustained-release carrier for bFGF and HGF. RESULTS: A single intramuscular injection of 5 microg or less of bFGF-incorporated CM (bFGF/CM) into the ischemic limb did not significantly increase the LDPII compared with the control (no treatment) 4 weeks after the treatment. Similarly, 20 microg or less of HGF/CM did not increase LDPII. Based on these results, we compared the dual release of CM incorporating 5 microg of bFGF and 20 microg of HGF with either the single release of 5 mug of bFGF/CM alone or 20 microg of HGF/CM alone. The LDPII of the dual release (94.2% +/- 10.9%) was higher than either single release (51.2% +/- 5.8% or 52.5% +/- 8.0%, P < .01). Furthermore, the LDPII in the dual release (94.2% +/- 10.9%) was equivalent to that with 80 microg of bFGF/CM (95.1% +/- 7.6%) alone or 80 microg of HGF/CM (92.8% +/- 7.6%) alone. A histologic evaluation at 4 weeks showed capillary density in the dual release (868 +/- 173 vessels/mm(2)) was higher than that in either single release (204 +/- 68 vessels/mm(2) or 185 +/- 98 vessels/mm(2) , P < .01). The percentage of mature vessels assessed by alpha-smooth muscle actin staining was also higher in the dual release (43.8% +/- 7.8% vs 9.5% +/- 3.0% or 11.7% +/- 3.8%, respectively; P < .01). CONCLUSIONS: This study demonstrates that the sustained dual release of a lower dose of bFGF and HGF from a carrier matrix can achieve equivalent blood perfusion recovery and more mature vasculature in the ischemic limb than a higher dose of bFGF or HGF alone. This approach may be a highly promising strategy for the future treatment of peripheral vascular disease.

Animals↗

PubMed2004

Type I collagen can function as a reservoir of basic fibroblast growth factor.

Storage and release of endogenous growth factors by the extracellular matrix (ECM) are important biological events that control tissue homeostasis and regeneration. The interaction between basic fibroblast growth factor (bFGF) and heparan sulfate proteoglycans has been extensively studied and used as a prototype model of such a system, while the lower affinity of fibrillar type I collagen for bFGF has generally been considered biologically insignificant. However, our present investigation revealed that bFGF spontaneously interacts with type I collagen solution and sponges under in vitro and in vivo physiological conditions, and is protected from the proteolytic environment by the collagen. bFGF incorporated in a collagen sponge sheet was sustainedly released in the mouse subcutis according to the biodegradation of the sponge matrix, and exhibited local angiogenic activity in a dose-dependent manner. Intramuscular injection of collagen microsponges incorporating bFGF induced a significant increase in the blood flow in the murine ischemic hindlimb, which could never have been attained by bolus injection of bFGF. These results suggest the significance and therapeutic utility of type I collagen as a reservoir of bFGF.

Animals↗

PubMed2004

The female partner's satisfaction with sildenafil citrate treatment of erectile dysfunction.

BACKGROUND: Data on female partners' satisfaction are scarce, although there have been many articles on patient satisfaction after sildenafil citrate treatment. The aim of this study was to evaluate the satisfaction of female partners of patients receiving sildenafil citrate for their erectile dysfunction (ED) and to assess the female partners' sexual function. METHODS: Ninety-eight patients with ED were treated. Their female partners were asked to answer a questionnaire we have prepared to evaluate the efficacy of treatment, sexual satisfaction and changes in quality of life. It also included a question about female sexual function. From the results, the relationship between their female partner's satisfaction and efficacy of treatment, as well as female sexual function, were assessed. RESULTS: Thirty (31%) questionnaires were returned to us for analysis. Effectiveness of the treatment was acknowledged by 90% of the partners. An improvement in their partner's quality of life was noticed by 60% of the women. The majority (66.7%) of the female partners were satisfied with sildenafil citrate treatment and 20% were disappointed. Moreover, 20% of the female partners were concerned about adverse events. Regarding female sexual function, some form of sexual dysfunction affected 46.7% of the women. Furthermore, a significant number (P = 0.0230) of the female partners disappointed with the treatment had some kind of sexual dysfunction. CONCLUSIONS: The results indicated that female partners reported relatively high levels of treatment satisfaction. Female partners' sexual function and anxiety regarding adverse events should be evaluated when their satisfaction with sildenafil citrate treatment is poor despite an improvement of erectile function.

Adult↗