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Biomedical subjects

Y Tabata

Publications and source records attributed to Y Tabata.

At least 37 records · Page 2Linked to original sources
PubMed2001

Peripheral nerve regeneration through a long detergent-denatured muscle autografts in rabbits.

Muscle segments excised from rabbit biceps femoris muscles were treated with detergent sodium dodecyl sulphate to denature cellular constituents, and each was autografted in a 5 cm gap of the sciatic nerve in the same rabbit. Axonal regrowth through the grafts and reinnervation into the host sciatic nerves and muscles were studied morphologically, and electrophysiologically, 4 months after grafting. Regenerating axons accompanied by Schwann cells extended through basal lamina tubes of the grafts into the distal host nerves. Reinnervation of the tibialis anterior muscles by motor nerves was confirmed by recovery of the compound muscle action potentials (CMAP) and the reinnervation of the muscle spindles was demonstrated by electron microscopy. These findings indicated that the basal lamina tubes of denatured muscles were effective scaffolds through which the regenerating nerve fibers grew across as large a gap as 5 cm.

Animals↗
PubMed2001

Recent progress in tissue engineering.

Tissue engineering is a newly emerging biomedical technique that involves the artificial manipulation of cells to promote tissue and organ regeneration. Its medical significance will undoubtedly increase in the 21st century. This review summarizes recent progress that has been made in tissue engineering as well as its future implications.

Journal Article↗
PubMed2001

Non-fermi-liquid scaling in Ce(Ru0.5Rh)2Si2.

We study the temperature and field dependence of the magnetic and transport properties of the non-Fermi-liquid (NFL) compound Ce(Ru0.5Rh0.5)2Si2. For fields H less, similar0.1 T the results suggest that the observed NFL behavior is disorder driven. For higher fields, however, magnetic and transport properties are dominated by the coupling of the conduction electrons to critical spin fluctuations. The temperature dependence of the susceptibility as well as the scaling properties of the magnetoresistance are in very good agreement with the predictions of recent dynamical mean-field theories of Kondo alloys close to a spin-glass quantum critical point.

Journal Article↗
PubMed2001

Evaluation of gelatin microspheres for nasal and intramuscular administrations of salmon calcitonin.

The suitability of gelatin microspheres for nasal and intramuscular delivery of salmon calcitonin (sCT) was examined. Negatively and positively charged gelatin microspheres were prepared using acidic gelatin [isoelectric point (IEP) value of 5.0] and basic gelatin (IEP=9.0), respectively. The average diameters of positively charged gelatin microspheres in their dried state were 3.4, 11.2, 22.5 and 71.5 microm, while that of negatively charged gelatin microspheres was 10.9 microm. Both types of gelatin microspheres were capable of adhering to the nasal mucosa. The mucoadhesion of positively charged gelatin microspheres was significantly higher than that of their negatively charged counterparts. The absorption of sCT after intranasal and intramuscular administration was evaluated by calculating the area above the hypocalcemic-time curve (AAC) in rats. The AAC values after nasal administration of sCT in positively and negatively charged gelatin microspheres were significantly greater than that in pH 7.0 PBS. Therefore, the nasal absorption of sCT was enhanced by both types of gelatin microspheres. The hypocalcemic effect after administration of sCT in positively charged gelatin microspheres of 11.2 microm was significantly greater than that of negatively charged gelatin microspheres of the same size. On the other hand, AAC values were not affected by their particle sizes. The AAC values after the intramuscular administration of sCT in positively and negatively charged gelatin microspheres were significantly increased compared to that in PBS. Furthermore, the time-courses of the plasma calcium levels differed between positively and negatively charged gelatin microspheres. The hypocalcemic effect of the negatively charged gelatin microspheres tended to appear more slowly and last longer compared to that of positively charged gelatin microspheres. The hypocalcemic effects after intramuscular administration of sCT in gelatin microspheres were not affected by their particle sizes as well as those after intranasal administration. In conclusion, the gelatin microspheres have been shown to be a useful vehicle for nasal or intramuscular delivery of sCT.

Administration, Inhalation↗
PubMed2001

Enhanced formation of fibrosis in a rabbit aneurysm by gelatin hydrogel incorporating basic fibroblast growth factor.

OBJECTIVE: This study was undertaken to analyze whether the controlled release of basic fibroblast growth factor (bFGF) can promote intrasaccular thrombosis in an experimental aneurysmal model. METHODS: Carotid aneurysms were constructed in 80 rabbits with venous pouches and treated by placing gelatin hydrogels into each aneurysm incorporating 0, 25, 50, or 100 microg of bFGF or incorporating 100 microg of bFGF with different water contents. In the controls, the venous pouches either were not treated or were treated with gauze alone. Gelatin hydrogel was used for the controlled release of bFGF into the aneurysms. The formation of fibrosis in the aneurysms was histologically viewed to assess the area occupied by the fibrous tissues at 3 and 6 weeks after the hydrogel application. The effect of the bFGF dose and water content on obliterating the aneurysm by the hydrogels incorporating bFGF was also investigated. RESULTS: Six weeks after the application of gelatin hydrogels with a water content of 95 wt% incorporating 100 microg of bFGF, the lateral pouch orifice was completely closed, obliterating the aneurysm at the level of tissue appearance, in contrast to hydrogels incorporating lower doses of bFGF and other control agents. The venous pouch aneurysm was histologically occupied with the newly formed fibrous tissue, and the fibrous tissue area and percentage of the aneurysmal lumen occupied by the fibrosis-gauze complex were significantly larger than those of other hydrogel applications (P < 0.05). The neointima tissue was homogeneously covered with a monolayer of Factor VIII-positive cells. The fact that there was no difference in the water content in the fibrosis formation induced by the bFGF-incorporated gelatin hydrogels indicated that the hydrogel biodegradability did not affect the obliteration of the aneurysm. CONCLUSION: Local controlled release of bFGF stimulated the formation of in vivo fibrosis, resulting in obliteration of the aneurysm. The long-term results of the fibrous organization remain speculative.

Animals↗
PubMed2001

A trial to prepare biodegradable collagen-hydroxyapatite composites for bone repair.

This paper is a trial to prepare collagen-hydroxyapatite composites in vitro by an alternate immersion method. Collagen sponges of different biodegradabilities were prepared through chemical cross-linking of Type I collagen with glutaraldehyde (GA) at concentrations of 0.2, 1.0, and 2.0 wt%. The sponges were immersed at 37 degrees C in Tris-HCl-buffered solution containing 200 mM CaCl2 (pH 7.4) for 2 h and then in an aqueous solution of 120 mM Na2HPO4 (pH 9.3) for a 2 h further (one immersion cycle). The alternate immersion cycle was repeated for different times to obtain collagen-hydroxyapatite composites. The characterization of the resulting composites was performed by Fourier transform infrared spectroscopy (FT-IR). X-ray diffraction (XRD), and scanning electron microscopy (SEM). The weight of composites increased with an increase in immersion cycles and the rate of increase became greater with higher GA cross-linking levels for collagen sponge preparation. The pH of the phosphate solution decreased with the immersion cycle, which suggests H+ generation accompanied hydroxyapatite formation. Irrespective of the GA concentration and immersion cycle, every composite showed IR absorption bands attributable to phosphate and hydroxyl groups at 950-1100 or 550-650 and 3000-3500 cm(-1) and broad peaks specific to hydroxyapatite on the XRD charts. SEM study revealed small white clusters of hydroxyapatite interspersed uniformly on/in the collagen framework without any preferential orientation. The composite prepared from 0.2 wt% GA cross-linked collagen sponge which showed favourable characteristics was applied to a rat skull defect to evaluate its osteoconductivity as well as biodegradability. The formation of new bone tissue was histologically observed at the defect 12 weeks after application in marked contrast to the collagen sponge alone. The composite degraded without any inflammation reaction. It is concluded that the collagen-hydroxyapatite composite prepared by the present method is a biodegradable biomaterial of osteoconductivity applicable to bone repair.

Animals↗
PubMed2001

Controlled release of growth factors based on biodegradation of gelatin hydrogel.

To develop a carrier for the controlled release of biologically-active growth factors, biodegradable hydrogels were prepared through glutaraldehyde cross-linking of gelatin with isoelectric points (IEP) of 5.0 and 9.0, i.e. 'acidic' and 'basic' gelatins, respectively. Radioiodinated growth factors were used to investigate their sorption and desorption from the hydrogel of both types of gelatin. Basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1) were well sorbed with time to the acidic gelatin hydrogel, while less sorption was observed for the basic gelatin hydrogel. This could be explained in terms of the electrostatic interaction between the growth factors and the acidic gelatin. However, bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), though their IEPs are higher than 7.0, were sorbed to the acidic gelatin hydrogel to a smaller extent than the two other growth factors. Under in vitro non-degradation conditions, approximately 20% of the incorporated bFGF and TGF-beta1 was desorbed from the hydrogels within the initial 40 min, followed by no further substantial desorption, whereas large initial desorption was observed for BMP-2 and VEGF. When implanted in the back subcutis of mice, gelatin hydrogels were degraded over time. Each growth factor was retained in vivo being incorporated in the acidic gelatin hydrogel: the smaller the in vitro desorption amount from the hydrogel, the longer the in vivo retention time. The in vivo profile of bFGF and TGF-beta1 retention was in good accordance with that of the hydrogel. These findings indicate that the growth factor immobilized to the acidic gelatin hydrogel through ionic interaction was released in vivo as a result of hydrogel degradation.

Adsorption↗
PubMed2001

Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2.

One of the greatest needs in the clinical bone field is a bioactive agent to stimulate bone formation. We previously reported that fibroblast growth factor-2 (FGF-2) exhibited strong anabolic actions on bone formation in models of rodents and dogs. Aiming at a clinical application, this study was undertaken to clarify the effect of a single local application of recombinant human FGF-2 on fracture healing in nonhuman primates. After a fracture was created at the midshaft of the right ulna of animals and stabilized with an intramedullary nail, gelatin hydrogel alone (n = 10) or gelatin hydrogel containing 200 microg FGF-2 (n = 10) was injected into the fracture site. Although 4 of 10 animals treated with the vehicle alone remained in a nonunion state even after 10 weeks, bone union was complete at 6 weeks in all 10 animals treated with FGF-2. Significant differences in bone mineral content and density at the fracture site between the vehicle and FGF-2 groups were seen at 6 weeks and thereafter. FGF-2 also increased the mechanical property of the fracture site. We conclude that FGF-2 accelerates fracture healing and prevents nonunion in primates, and therefore propose that it is a potent bone anabolic agent for clinical use.

Alkaline Phosphatase↗
PubMed2001

Controlled release of hepatocyte growth factor from gelatin hydrogels based on hydrogel degradation.

This paper investigates the controlled release of hepatocyte growth factor (HGF) by biodegradable gelatin hydrogels and their HGF-induced angiogenic effect. Hydrogels of different degradabilities were prepared through chemical crosslinking gelatin with varied amounts of glutaraldehyde. When the gelatin hydrogels were radioiodinated and subcutaneously implanted into the back of mice, the remaining radioactivity of the hydrogels decreased with time. However, the remaining period became longer when the concentration of glutaraldehyde used for hydrogel preparation increased. Following implantation of gelatin hydrogels incorporating 125I-labeled HGF, the HGF radioactivity retained in the mouse subcutis for longer time periods as the glutaraldehyde concentration becomes higher. The time profile of HGF remaining in every gelatin hydrogel was in good accordance with that of hydrogel degradation, indicating HGF release as a result of hydrogel biodegradation. The gelatin hydrogel incorporating HGF histologically induced angiogenic change around the implanted hydrogel. Gelatin hydrogels incorporating 5 and 10 microg HGF significantly enhanced the number of capillaries newly formed around the implanted site. This was in marked contrast to free HGF of same dose form and HGF-free, empty gelatin hydrogel. The gelatin hydrogel incorporating HGF induced VEGF around the implanted site. In vitro bioassay revealed that HGF molecules interacting with gelatin, still exhibited the biological activity. The interacted HGF would be released from gelatin hydrogels only when they were degraded to generate water-soluble gelatin fragments. It is possible that the HGF associating gelatin fragments of bioactivating, results in induced angiogenic effect.

Animals↗
PubMed2001

An oral drug delivery system targeting immune-regulating cells ameliorates mucosal injury in trinitrobenzene sulfonic acid-induced colitis.

Control of immune-regulating cells in the colonic mucosa is important in the treatment of patients with inflammatory bowel disease (IBD). The aim of study was to examine the therapeutic effect of dexamethasone (DX) microspheres on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, a model for human Crohn's disease. DX microspheres and DX alone were administered orally to rats with TNBS-induced colitis. The macroscopic score, histological score, myeloperoxidase (MPO) activity, nitric oxide (NO) production, and gene expressions of proinflammatory cytokines, cyclooxygenase (COX)-1, and COX-2 in the colonic tissue were determined. Proliferating cell nuclear antigen (PCNA) staining and expression of nuclear transcription factor (NF)-kappaB in colonic tissues were also investigated. Macroscopic score, histological score, MPO activity, and NO production in rats treated with DX microspheres were significantly lower than in those treated with DX alone. The gene expression of proinflammatory cytokines and COX-2 in rats treated with DX microspheres was down-regulated, compared with that in rats treated with DX alone. The number of PCNA-positive cells in the DX microsphere group was larger than in the group treated with DX alone. DX microspheres suppressed NF-kappaB activation in TNBS-induced colitis more strongly than DX alone. Oral administration of DX microspheres appears to ameliorate mucosal injury in TNBS-induced colitis. This drug delivery system could be an ideal therapy for human IBD.

Administration, Oral↗
PubMed2001

Liver targeting of interferon-beta with a liver-affinity polysaccharide based on metal coordination in mice.

Frequent and high-dose i.v. injections of interferon-beta (IFN-beta) have been used clinically to treat patients with viral hepatitis despite various side effects. Because side effects are caused by the systemic effects of IFN-beta, the purpose of this study was to target the drug specifically to the liver, thus reducing the adverse events. A chelating residue, diethylenetriaminepentaacetic acid (DTPA), was introduced to pullulan, a water-soluble polysaccharide with a high affinity for the liver. Murine IFN-beta could be coordinately conjugated with the DTPA-pullulan by simple mixing in an aqueous solution containing zinc ion (Zn2+). Intravenous injection of the IFN-beta-DTPA-pullulan conjugate with Zn2+ coordination enhanced liver induction of an antiviral enzyme, 2',5'-oligoadenylate synthetase (2-5AS), to a greater extent than that by free IFN-beta, although the 2-5AS levels in the liver depended on the mixing ratio of the IFN-beta/DTPA residue of DTPA-pullulan/Zn2+. In addition, the duration of the liver 2-5AS induction by the IFN-beta-DTPA-pullulan conjugate with Zn2+ coordination was longer than that by free IFN-beta. The liver targeting of IFN-beta by DTPA-pullulan with Zn2+ coordination may be a promising IFN therapy.

Animals↗
PubMed2001

[AML(M7) associated with t(16;21)(p11;q22) showing relapse after unrelated bone marrow transplantation and disappearance of TLS/FUS-ERG mRNA].

A 3-year-old boy with poorly prognostic acute megakaryoblastic leukemia (AML M7) showing t(16;21)(p11;q22) karyotype underwent unrelated bone marrow transplantation (U-BMT) during his first hematological remission. The conditioning regimen consisted of BU, VP-16 and L-PAM. Engraftment was smooth, but the patient developed grade I acute GVHD. During hematological remission before U-BMT, the TLS/FUS-ERG chimeric transcript of t(16;21)(p11;q22) was consistently detectable as minimal residual disease (MRD) by RT-PCR. However, after U-BMT it soon became undetectable. There was no detectable MRD until 7 months after U-BMT, but bone marrow relapse occurred 10 months after U-BMT. We consider that U-BMT is a promising treatment for t(16;21)(p11;q22) AML. However, an intensified conditioning regimen or modification of GVHD prophylaxis is needed.

Bone Marrow Transplantation↗
PubMed2001

Evaluation of insulin secretion of isolated rat islets cultured in extracellular matrix.

Islet isolation involves enzymatic digestion of the interstitial matrix and mechanical disruption of the tissue. It is possible that a fundamental change of islet biology resulting from the loss of critical factors required for islet function or survival will occur. Extracellular matrix (ECM) is one of the most important components of the islet microenvironment. Reconstruction of the cell-matrix relationship seems to be effective for improving the loss of differentiated islet structure and function. The purpose of this study was to characterize and compare the effects of collagen gel mixture or Matrigel on beta-cell function and islet cell survival. After isolation by the collagenase digestion technique, rat islets were divided and cultured with various types of collagen gel mixture. They were assessed for their glucose-stimulated insulin secretion and cell viability. Glucose-induced insulin secretion of islets cultured with collagen type I gel or a mixture of collagen type I and IV was improved after 11 days in culture. In conclusion, a type of gel composed of collagen type I and/or type IV as an islet microenvironment is sufficient to maintain glucose responsiveness and may be useful for islet transplantation.

Animals↗
PubMed2001

Development of a new method to induce angiogenesis at subcutaneous site of streptozotocin-induced diabetic rats for islet transplantation.

The subcutaneous space is a potential site for clinical islet transplantation. Even though there are several advantages, poor blood supply at this site mainly causes failure of islet survival. In this study, angiogenesis was induced in advance at the diabetic rats subcutis for islet transplantation by implanting a polyethylene terephthalate (PET) mesh bag containing gelatin microspheres incorporating basic fibroblast growth factor (bFGF) (MS/bFGF) and a collagen sponge. The bFGF was incorporated into gelatin microspheres for controlled release of bFGF. As controls, a PET mesh bag with or without either collagen sponges or MS/bFGF was implanted at the subcutaneous site of diabetic rats. Macroscopic and microscopic examinations revealed the formation of capillary network in and around the PET mesh bag containing MS/bFGF and collagen sponges 7 days after implantation when compare with other control groups. When tissue hemoglobin level was also measured, a significantly high level of hemoglobin amount was observed compared with that of control groups. When allogeneic islets mixed with 5% agarose were transplanted into the prevascularized rat subcutis, normoglycemia was maintained for more than 40 days, while other control groups were ineffective. This study demonstrated that combination of gelatin microspheres incorporating bFGF and collagen sponges enabled the mesh to induce neovascularization even at the subcutaneous site of streptozotocin-induced diabetic rats, resulting in improved function of islet transplantation.

Animals↗
PubMed2001

Monoclonal antibody-mediated drug targeting to choroidal neovascularization in the rat.

PURPOSE: Active drug targeting mediated by monoclonal antibodies (mAbs) of vascular endothelial cells in tumors is a new concept in cancer therapy. Integrin alphavbeta3 has been reported to be strongly expressed in vascular endothelial cells of surgically excised choroidal neovascular membranes and is thought to be a potential antigen for mAb-mediated drug targeting of choroidal neovascularization (CNV). The objective of this study was to evaluate the efficacy of drug targeting mediated by anti-integrin alphavbeta3 mAbs in a laser-induced CNV rat model. METHODS: The mitomycin C (MMC)-dextran (MMCD) conjugate was synthesized with a carbodiimide-catalyzed reaction. The mAb was conjugated with MMCD (MMCD-mAb). To evaluate the feasibility of mAb-mediated drug targeting in vitro, we investigated the effect of the immunoconjugates involving dextran-binding MMC on the proliferation of human umbilical vein endothelial cells (HUVECs). CNV was induced by laser photocoagulation in male Brown Norway rats. Immunolocalization of integrin alphavbeta3 in CNV lesions was assessed immunohistochemically with the anti-von Willebrand factor antibody as an endothelial cell marker. Intravenous administration of saline (n = 7), 1 mg/day mAb (n = 7), 100 microg/kg per day free MMC (n = 7), MMCD with irrelevant Ab (n = 7), unconjugated MMCD with unconjugated mAb (MMCD+mAb; n = 7), or MMCD with mAb (MMCD-mAb; n = 8) containing an equal amount of free MMC, was performed daily for 3 days from day 14 after CNV induction. CNV was assessed by fluorescein angiography 2 weeks after treatment. Fluorescein leakage was scored on a four-grade scale. The animals were killed 2 weeks after treatment, and the lesions were evaluated histologically. RESULTS: The inhibition of immunoconjugates on the proliferation of HUVECs was enhanced specifically by the mediatory effect of the mAb. Endothelial cells demonstrated strong immunoreactivity of integrin alphavbeta3 in the CNV. In the vehicle-treated group, fluorescein leakage equal to that before treatment was observed 2 weeks after treatment, with an average score of 2.00 +/- 0.17 (mean +/- SEM). MMCD-mAb significantly inhibited the development of CNV in rats (P < 0.01). Moreover, the thickness of the lesions was significantly reduced in the MMCD-mAb-treated group (P < 0.01). CONCLUSIONS: Immunoconjugates effectively inhibited progression of CNV in this model. The results suggest that mAb-mediated drug targeting may be beneficial in the treatment of CNV.

Animals↗
PubMed2001

The efficacy of prevascularization by basic FGF for hepatocyte transplantation using polymer devices in rats.

This study used polymer devices implanted in rats to investigate the effect of prevascularization by basic fibroblast growth factor (bFGF) on hepatocyte transplantation (HTx). Lewis rats served as both donors and recipients. Polyvinyl alcohol (PVA) sponges with either hydrogel containing bFGF (bFGF group) or distilled water (control group) were implanted between the mesenteric leaves of recipient rats. Hepatotrophic stimulation was induced by a portacaval shunt and a 70% partial hepatectomy. After 1 week of prevascularization, hepatocytes harvested from the donor Lewis rats using a collagenase digestive method were injected into the sponges. Specimens were harvested at 2 weeks, 1 month, and 2 months after HTx. Histologic examination revealed that the control groups contained small numbers of hepatocytes restricted to the peripheral areas of the sponges. However, a large number of hepatocytes, including clusters, was found distributed uniformly in the bFGF group. In the bFGF group at 2 weeks, 1 month, and 2 months, the percentage of the sponge occupied by hepatocytes was 7.21+/-2.64%, 6.98+/-2.59%, and 5.58+/-3.77%, respectively. The corresponding ratios for the control group were 0.40+/-0.39%, 0.40+/-0.40%, and 0.87+/-1.51%. In addition, the mean number of new blood vessels in the bFGF group was significantly greater than that in the control group at 0 days, 2 weeks, and 1 month after HTx. These results suggest that bFGF strongly induced vascularization, which enabled a large number of hepatocytes to survive in the polymer devices.

Animals↗