Biomedical subjects

Yukihiko Kinoshita

Publications and source records attributed to Yukihiko Kinoshita.

4 recordsLinked to original sources

PubMed2006

Age-dependent changes in the racemisation ratio of aspartic acid in human alveolar bone.

We investigated the racemisation ratio of aspartic acid (Asp) in alveolar bone. In addition, we designed and created a new column to detect Asp in a short period of time, which allowed us to detect d-Asp and l-Asp separately from each other within 5min. Comparing identical ages, the racemisation ratio of alveolar bone was generally lower than that of other bones reported so far. This result suggests that alveolar bone is metabolically more active than other bones, as expected. The rate constant for the racemisation reaction (k(y)) of alveolar bone was calculated to be 0.000338 in males and 0.000084 in females. The rate constants in males and females were each similar to the respective ratios of the femur. This result suggests that the age-dependent reduction in metabolic turnover in alveolar bone proceeds similarly to that in the femur, although those changes proceed more slowly in females than in males. The correlation coefficient between the racemisation ratio of alveolar bone and chronological age was 0.660. It was high in males (r=0.912) and low in females (r=0.527), and this gender difference was statistically significant (P: 0.01-0.001), as in the femur.

Adolescent↗

PubMed2006

Cationized gelatin delivery of a plasmid DNA expressing small interference RNA for VEGF inhibits murine squamous cell carcinoma.

Double-stranded RNA (dsRNA) plays a major role in RNA interference (RNAi), a process in which segments of dsRNA are initially cleaved by the Dicer into shorter segments (21-23 nt) called small interfering RNA (siRNA). These siRNA then specifically target homologous mRNA molecules causing them to be degraded by cellular ribonucleases. RNAi down regulates endogenous gene expression in mammalian cells. Vascular endothelial growth factor (VEGF) is a key molecule in vasculogenesis as well as in angiogenesis. Tumor growth is an angiogenesis-dependent process, and therapeutic strategies aimed at inhibiting angiogenesis are theoretically attractive. To investigate the feasibility of using siRNA for VEGF in the specific knockdown of VEGF mRNA, thereby inhibiting angiogenesis, we have performed experiments with a DNA vector based on a siRNA system that targets VEGF (siVEGF). It almost completely inhibited the expression of three different isoforms (VEGF120, VEGF164 and VEGF188) of VEGF mRNA and the secretion of VEGF protein in mouse squamous cell carcinoma NRS-1 cells. The siVEGF released from cationized gelatin microspheres suppressed tumor growth in vivo. A marked reduction in vascularity accompanied the inhibition of a siVEGF-transfected tumor. Fluorescent microscopic study showed that the complex of siVEGF with cationized gelatin microspheres was still present around the tumor 10 days after injection, while free siVEGF had vanished by that time. siVEGF gene therapy increased the fraction of vessels covered by pericytes and induced expression of angiopoietin-1 by pericytes. These data suggest that cationized-gelatin microspheres containing siVEGF can be used to normalize tumor vasculature and inhibit tumor growth in a NRS-1 squamous cell carcinoma xenograft model.

Angiopoietin-1↗

PubMed2005

[Tissue engineering for jawbone].

One goal of jawbone reconstruction is to regenerate bone that is strong enough to support dentures or dental implants. Here we describe mandibular reconstructions using bioabsorbable poly (L-lactic acid) (PLLA) mesh and particulate cancellous bone and marrow (PCBM). PLLA mesh is made of monofilaments spun from molecular weight 20.5 x 10(4) that is elongated and woven into mesh. Mandibles of 62 patients with tumors, cysts, or alveolar atrophy were reconstructed with PLLA mesh trays/sheets and PCBM. The operative procedures were as follows: 1) a heat-softened PLLA mesh sheet or tray was cut and bent to conform to the shape and size of the bone defect; 2) PLLA mesh was fixed to the residual bone with stainless steel wire; and 3) the tray was filled with PCBM harvested from the ilium. Clinical evaluations six months after surgery showed that in 35 cases (56.5%) the results were judged to be excellent (bone formation range: beyond 2/3), in 17 cases (27.4%) they were good (bone formation range under 2/3, but re-operation unnecessary), and in 10 cases (16.1%) they were poor (cases not falling into either category above). Long-term observations showed that in 32 cases (80.0%) bone resorption was less than 10% of the regenerated bone. Among the patients wearing early dentures or dental implants, bone resorption was less. There is a good success rate for jawbone reconstruction surgery using PLLA mesh and PCBM, and patients can expect to have mandibles strong enough to support dentures and dental implants. In addition, there is an advantage of regenerating in the donor site as well. However, we need to develop therapies that combine bioactive factors to promote angiogenesis and osteogenesis or hybrid artificial bone for patients with poor regional blood circulation and for elderly patients who have too few osteoprogenitor cells.

Adolescent↗

PubMedDate not supplied

Proliferation and differentiation of rat bone marrow stromal cells on poly(glycolic acid)-collagen sponge.

We studied the effects of dexamethasone (Dex) and basic fibroblast growth factor (bFGF) on proliferation and differentiation of rat bone marrow stromal cells (RBMSCs), using three scaffolds: collagen sponge, poly(glycolic acid) (PGA)-collagen sponge, and PGA-collagen (UV) sponge. RBMSCs were seeded into the sponges, and cultured in primary medium, primary medium with Dex, and primary medium with bFGF and Dex. Three weeks after cultivation, we examined alkaline phosphatase (ALP) activity and cell number in the sponges, and also performed macroscopic, light microscopic, and scanning electron microscopic (SEM) observations. Collagen sponge shrank considerably, but PGA-collagen and PGA-collagen (UV) sponges maintained most of their original shape. PGA-collagen (UV) sponge supplemented with bFGF and Dex together had the highest ALP activity and cell number, followed by PGA-collagen sponge. Although collagen sponge showed cell proliferation only on the surface, the other two sponges showed cell proliferation in the interior. SEM showed the best cell attachment to PGA-collagen (UV) sponge in the presence of bFGF and Dex, followed by PGA-collagen sponge. In conclusion, PGA-collagen (UV) and PGA-collagen sponges proved to be much more useful as scaffolding for bone regeneration when combined with bFGF and Dex.

Alkaline Phosphatase↗