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Biomedical subjects

Y Tabata

Publications and source records attributed to Y Tabata.

210 records · Page 12Linked to original sources

Can a bone marrow cell contribute to organ regeneration? In vivo analysis using transgenic rats with reporter genes.

Although implantation of multipotent bone marrow-derived stem cells represents an attractive new cell therapy to repair damaged tissues, recent reports have raised serious concerns over the feasibility of using stem cells deriving from the bone marrow to promote cell transdifferentiation. We established transgenic (Tg) rats with reporter genes as specific molecular tags to examine the effect of bone marrow cells (BMCs) on transdifferentiation into tissues/organs. To monitor transdifferentiation events of locally transplanted BMCs into hepatocytes or capillary endothelial cells, a liver injury model and an ischemic hind-limb model were developed in rats. To test the ability of circulating bone marrow-derived cells to give rise to myocytes after skeletal muscle injury, we used a bone marrow cell transplantation model from Tg rats, which showed ubiquitous expression of beta-galactosidase (lacZ), into lethally irradiated non-Tg rats. Our results show that there was little transdifferentiation of BMCs into the targeted cells in these tissue injury models. However, in the ischemic hind-limb model, laser Doppler imaging and histologic analysis showed that both implantation of BMCs and treatment with microspheres incorporating basic fibroblast-like growth factor (bFGF), which enables the release of bFGF at the site of action over a period of time, effectively induced angiogenesis. In conclusion, rat BMCs with specific marker genes could be a useful tool for detecting transdifferentiation events in vivo.

Animals↗

Sorsby's fundus dystrophy in two Japanese families with unusual clinical features.

PURPOSE: To describe two Japanese families with Sorsby's fundus dystrophy (SFD) with unusual clinical features. METHODS: Two families from Kagoshima Prefecture with senile-onset macular dystrophy were examined. Three affected individuals through three successive generations of one family and three affected siblings in another family were examined and followed. RESULTS: The initial symptom of these patients was a rapid or slow central visual loss that occurred at an average age of 67.4 years. The major ophthalmoscopic changes consisted of soft drusen and hemorrhagic or atrophic lesions in the macula, which were progressive and ultimately led to disciform scarring. They had no difficulty with night vision. All the patients had normal peripheral retina with intact peripheral fields. They maintained good ambulatory vision and could walk unguided until late in life. These patients had a novel mutation in the tissue inhibitor of the metalloproteinases-3 (TIMP3) gene. CONCLUSIONS: This is the first report of SFD from the East. Its clinical features differ from those of SFD patients of the West, appearing closer to features of age-related macular degeneration. These two unrelated Japanese families with an identical mutation in the TIMP3 gene might be descendants of a common ancestor who carried the mutant gene.

Aged↗

Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogels.

The objective of this study is to enhance the bone induction activity of basic fibroblast growth factor (bFGF) for reconstruction of skull bone defects which has been clinically recognized as almost impossible. For this purpose, we prepared biodegradable hydrogels from gelatin with an isoelectric point of 4.9 which is capable of polyionic complexing with basic bFGF. When implanted in rabbit skull defects of 6 mm in diameter (6 defects per experimental group), the gelatin hydrogels incorporating 100 microg of bFGF promoted bone regeneration at the defect in marked contrast to free bFGF of the same dose, finally closing the bone defects after 12 weeks of implantation as is apparent from histological examination. In dual energy X-ray absorptometry analysis, the bone mineral density at the skull defects enhanced by the hydrogels was significantly higher than that by free bFGF at doses ranging from 2 to 200 microg/defect (P < 0.05). The extent of bone regeneration induced by gelatin hydrogels incorporating 100 microg of bFGF increased with a decrease in their water content. Histological examination indicated that more slowly degrading hydrogels of lower water content prolonged the retention period of osteoblasts in the bone defects. This led to enhanced bone regeneration compared with faster degrading hydrogels of higher water content. It was concluded that this biodegradable hydrogel system was a promising surgical tool to assist self-reconstruction of the skull bone.

Animals↗

An electron spin resonance study of free radicals in black dust deposited in human lungs.

An Electron Spin Resonance measurement was conducted on black dust deposited in autopsied human lungs. Free radicals were detected in all specimens examined, and the spectra indicated the presence of two types of radicals, both of which are apparently singlet lines. The amount of the respective component differed from sample to sample. The component with the narrower width, 2.7 G, and the smaller g factor, 2.0025, is attributable to carbon radicals associated with the combustion of hydrocarbons, and especially its relevance to the experience of smoking was inferred. The other component, with a width of about 10 G and g factor fo 2.0037, was found to be more common among the specimens. The assignment of the latter component is not very clear, but an oxygen-related radical is a possible candidate.

Adult↗

Usefulness of microspheres composed of gelatin with various cross-linking density.

The release rate of insulin, as a model peptide, from gelatin microspheres (GM) prepared with gelatin having various cross-linking densities in vitro was examined. The release of insulin from GM showed the burst effect, followed by a slow release phase regardless of the cross-linking density of gelatin. The total amount of insulin released in 2 weeks decreased with increasing cross-linking density of gelatin. The release rate of insulin within 6 h was well correlated with the cross-linking density of gelatin. The remaining amounts of both insulin and GM after injection of insulin incorporated in GM to mice femoral muscle tissue were also examined in vivo. Both insulin and GM rapidly disappeared from the injection site within 1 day, and thereafter slowly disappeared over 14 days. The time courses of the remaining amounts were fairly similar to each other. Furthermore, the remaining amount of insulin 1 day after administration was well correlated with the cross-linking density of gelatin. These data suggest that insulin was released from GM with the degradation of GM in mice muscular tissue and that the release rate of insulin can be controlled by modifying the cross-linking density of gelatin. In conclusion, the control of the release rate of insulin from GM can be achieved under both in vitro and in vivo conditions by gelatin through the alteration of cross-linking conditions.

Animals↗

Positively charged gelatin microspheres as gastric mucoadhesive drug delivery system for eradication of H. pylori.

Gastric mucoadhesive drug delivery systems are very promising for eradication of Helicobacter pylori (H. pylori), a spiral bacterium that resides in the gastric mucus layer and at the mucus-epithelial cell interface. New positively charged biodegradable microspheres were prepared using aminated gelatin by surfactant-free emulsification in olive oil, followed by a cross-linking reaction with glutaraldehyde. The amino group contents of the modified gelatin and the microspheres were determined using a 2,4,6-trinitrobenzenesulfonic acid method. With the increase of glutaraldehyde concentration, the amino group content of the microspheres decreased accordingly. The influence of glutaraldehyde concentration, cross-linking reaction time, drug-loading patterns, and type of release media on the in vitro release characteristics of amoxicillin from the microspheres was investigated. Amoxicillin release rate from the modified gelatin microspheres was significantly reduced compared with that from gelatin microspheres. Furthermore, the release was decreased with the increase of glutaraldehyde concentration and/or cross-linking time. On the other hand, a faster release was observed in a lower pH release medium and/or using a lower pH solution for amoxicillin loading. The gastric mucoadhesive properties of the microspheres were evaluated using RITC-labeled microspheres in an isolated rat stomach. The gastric mucoadhesion of the modified gelatin microspheres was markedly improved compared with that of gelatin microspheres. The modified gelatin microsphere proves to be a possible candidate delivery system for the effective eradication of H. pylori.

Adhesives↗

Novel collagen sponge reinforced with polyglycolic acid fiber produces robust, normal hair in murine hair reconstitution model.

The hair reconstitution assay is a useful system for studying cell-cell and epithelial-mesenchymal interaction. The current method consists of transplantation of both epidermal and dermal cells, using a silicone chamber placed on an athymic nude mouse. However, because of leakage and tilting of the grafted cells, the rate and area of hair growth vary depending on the chamber. We modified this method by using a collagen sponge as a scaffold and compared two types of collagen sponges, each having different tensile strengths. A conventional collagen sponge disturbed normal hair follicle formation; in contrast, a collagen sponge containing polyglycolic acid (PGA) fiber supported proper restructuring of skin and hair follicles. These data suggested the usefulness of PGA fiber-containing collagen sponges for hair reconstitution in research and clinical applications.

Absorbable Implants↗

Tissue blood flow in brain, liver, renal cortex, and renal medulla in experimental hemorrhagic shock.

Cerebral, hepatic, renal cortical, and medullary tissue blood flows of the dog during hemorrhagic shock were measured continuously using the thermoelectrical method. The effects of blood replacement, adrenergic alpha-stimulator and -blockade and hydrocortisone on the tissue blood flows were studied. After hemorrhage, cerebral blood flow was well maintained while renal cortical blood flow was poorly maintained. Following retransfusion, the blood flow returned rapidly to the brain and slowly to the renal cortex. Norepinephrine, phentolamine, and hydrocortisone were not effective in maintaining the organ blood flows in shock. However, when norepinephrine was given systemically and phentolamine administered to the renal artery simultaneously during shock, both cerebral and renal flows were well maintained. After the blood replacement and administration of alpha-blockade or hydrocortisone, all the measured blood flows returned to normal levels.

Animals↗

Experimental corneal neovascularization by basic fibroblast growth factor incorporated into gelatin hydrogel.

The study was designed to investigate the feasibility of using an acidic gelatin hydrogel as a biodegradable vehicle for basic fibroblast growth factor (bFGF). bFGF was incorporated by polyion complexation into a biodegradable hydrogel prepared by cross-linking acidic gelatin with the isoelectric point of 4.9. The dried hydrogel (sized to 2x1 mm) was hydrated with bFGF aqueous solution including different doses of bFGF (20, 50, 125, 250 and 500 ng) and implanted into a rabbit corneal pocket (2.5x2 mm). As a control group, the gelatin hydrogel without bFGF or bFGF alone (500 ng) was used. Corneal angiogenesis was evaluated by biomicroscopy, corneal fluorescein angiography and histology for 21 days. Photographs were taken and corneal angiogenesis was evaluated by image analysis. The hydrogel degraded with time after its implantation into the corneal pocket. Experimental eyes receiving the hydrogel containing more than 50 ng of bFGF demonstrated significant corneal angiogenesis. Control eyes and eyes receiving the hydrogel containing 20 ng of bFGF showed no corneal angiogenesis. Corneal angiogenesis, which occurred on the 3rd or 4th day after implantation, reached maximal growth on about day 7 and regressed from day 10 after implantation. The area of angiogenesis showed a dose-dependency on bFGF. The gelatin hydrogel itself induced neither angiogenesis nor inflammation. These results suggested that acidic gelatin hydrogel releases bioactive bFGF with its biodegradation, resulting in corneal neovascularization.

Absorbable Implants↗