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Biomedical subjects

Y Tabata

Publications and source records attributed to Y Tabata.

At least 73 records · Page 4Linked to original sources
PubMed2000

Relationship between breast milk feeding and atopic dermatitis in children.

OBJECTIVE: To determine whether or not the breast milk feeding has a role in the prevalence of atopic dermatitis among children. METHODS: The target population of the study was all children participating in health check-up program for 3-year-old children in 60 municipalities locating 10 selected prefectures during designated 2 months between October and December 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. RESULTS: Questionnaires from 3856 children (81.6% of those who were to participate in the programs, and 96.4% of children who participated them) were analyzed. After the adjustment for all potential confounding factors using unconditional logistic models, the risk of atopic dermatitis was slightly higher among children with breast milk (odds ratio [OR] = 1.16 with 95% confidence interval [CI] 0.96-1.40). Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.15; 95% CI, 0.96-1.37) and those with second or later parity orders (OR = 1.14, 95% CI; 0.95-1.35) showed odds ratios that were higher than unity without statistical significance. CONCLUSION: Breast milk elevates the risk of atopic dermatitis slightly without statistical significance; the risk may be, however, higher in children in second or later parity orders.

Adult↗
PubMed2000

Treatment strategies for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH).

In Epstein-Barr virus (EBV) infection, the virus immortalizes B lymphocytes and cytotoxic T lymphocytes (CTLs) are directed toward both latent and lytic viral antigens expressed on EBV-infected B-cells. Various EBV-associated diseases occur as a result of this disruption of immune surveillance. In the majority of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) cases, the major cell types containing EBV DNA are not B-cells, but clonally proliferating T-cells or NK-cells. Proliferation of these cells produces severe immune reactions in the host, and the clinical features related to massive cytokine production at the onset of disease are unique and distinct from other EBV-associated diseases. In the treatment of EBV-HLH, therapeutic infusion of EBV-specific CTLs appears to be ineffective, and eradication of EBV-containing cells is useful but not sufficient to save lives, because of high incidence of acute mortality due to cytokine-induced multiple organ failure and neutropenia-associated opportunistic infections. The optimal treatment strategy for this disease consists of three steps: (1) control of cytokine storm including coagulopathy and multiple organ failure, (2) control of opportunistic infections, and (3) eradication of clonally proliferating EBV-containing T- or NK- cells by immunochemotherapy and, if necessary, hemopoietic stem cell/bone marrow transplantation (SCT/BMT).

Antiviral Agents↗
PubMed2000

Outcome of clonal hemophagocytic lymphohistiocytosis: analysis of 32 cases.

We studied the impact of clonality, determined by analysis of Epstein-Barr virus genome termini, T-cell receptor genes and clonal chromosomal abnormality, on the clinical outcome in 32 patients with hemophagocytic lymphohistiocytosis (HLH). Of the cases studied, 23 cases were EBV-clonal, 15 cases were TCR-clonal and 7 cases were cytogenetically clonal. Thirty patients were treated with immuno-chemotherapy and/or multiagents' chemotherapy and 4 received bone marrow transplantation. All 7 cases, in which cytogenetically abnormal clones were identified, were fatal (3-year survival by Kaplan-Meier analysis; 14%, 95%CI: 0-40%). None of these 7 cases received bone marrow transplantation. On the other hand, the 3-year survival of 23 clonal EBV-positive HLH cases including 4 cytogenetically abnormal cases was 64 % (95%CI: 42-84%), while that of 15 TCR-clonal cases was 53% (95%CI: 26-78%). Our observations suggest that cytogenetically abnormal cases are at extremely high risk, requiring intensive immuno-chemotherapy followed by prompt and timely allogeneic bone marrow transplantation.

Adolescent↗
PubMed2000

Management of severe neutropenia with cyclosporin during initial treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis.

Severe neutropenia (absolute neutrophil count <500/gl) is probably due to the combined effects of dysregulated cytokine production and chemotherapeutic agents, and is one of the risk factors in the initial treatment of patients with Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH). We report here 9 cases of neutropenic HLH, of which 8 were treated with cyclosporin (CSA, 2-6 mg/kg/day; continuous infusion, or 6 mg/kg/day; per os, for periods ranging from 9 days to >8 weeks) in the initial neutropenic phase during induction treatment using corticosteroids and etoposide. Five of the 6 cases, in which CSA treatment was started early (before the second week of induction), survived the critical period with recovery of neutrophil counts within a week. The remaining 3 cases, in which CSA was introduced later or not at all, died of infection. Based on these results, we recommend a prompt short-term CSA infusion during neutropenic episodes in the most common treatment regimen of etoposide and corticosteroids in patients with HLH. Improved neutrophil recovery as a result of CSA treatment makes it possible to continue immunochemotherapy safely and obtain improved patient outcomes.

Adolescent↗
PubMed2000

Bone regeneration at rabbit skull defects treated with transforming growth factor-beta1 incorporated into hydrogels with different levels of biodegradability.

OBJECT: Skull bone regeneration induced by transforming growth factor-beta1 (TGFbeta1)-containing gelatin hydrogels (TGFbeta1-hydrogels) was investigated using a rabbit skull defect model. Different strengths of TGFbeta1 were examined and compared: different TGFbeta1 doses in gelatin hydrogels with a fixed water content, different water contents in gelatin hydrogels with a fixed TGFbeta1 dose, and TGFbeta1 in solution form. In addition, regenerated skull bone was observed over long time periods after treatment. METHODS: Soft x-ray, dual energy x-ray absorptometry, and histological studies were performed to assess the time course of bone regeneration at a 6-mm-diameter skull defect in rabbits after treatment with TGFbeta1-hydrogels or other agents. The influence of TGFbeta1 dose and hydrogel water content on skull bone regeneration by TGFbeta1-hydrogels was evaluated. Gelatin hydrogels with a water content of 95 wt% that incorporated at least 0.1 microg of TGFbeta1 induced significant bone regeneration at the rabbit skull defect site 6 weeks after treatment, whereas TGFbeta1 in solution form was ineffective, regardless of dose. The in vivo degradability of the hydrogels, which varied according to water content, played an important role in skull bone regeneration induced by TGFbeta1 -hydrogels. In our hydrogel system, TGFbeta1 is released from hydrogels as a result of hydrogel degradation. When the hydrogel degrades too quickly, it does not retain TGFbeta1 or prevent ingrowth of soft tissues at the skull defect site and does not induce bone regeneration at the skull defect. It is likely that hydrogel that degrades too slowly physically impedes formation of new bone at the skull defect. Following treatment with 0.1-microg TGFbeta1-hydrogel (95 wt%), newly formed bone remained at the defect site without being resorbed 6 and 12 months later. The histological structure of the newly formed bone was similar to that of normal skull bone. Overgrowth of regenerated bone and tissue reaction were not observed after treatment with TGFbeta1 -hydrogels. CONCLUSIONS: A TGFbeta1-hydrogel with appropriate biodegradability will function not only as a release matrix for the TGFbeta1, but also as a space provider for bone regeneration. The TGFbeta1-hydrogel is a promising surgical tool for skull defect repair and skull base reconstruction.

Absorptiometry, Photon↗
PubMed2000

Development of an oral drug delivery system targeting immune-regulating cells in experimental inflammatory bowel disease: a new therapeutic strategy.

Several studies have indicated the involvement of macrophages and dendritic cells in active inflammatory bowel disease (IBD). Manipulation of these cells is considered a very important therapeutic strategy for patients with IBD. We evaluated the effect of a new drug delivery system targeting microfold cells and macrophages with poly(DL-lactic acid) microspheres containing dexamethasone (Dx). Colitis was induced in BALB/c mice by 5% dextran sodium sulfate. Dx microspheres (n = 10) and only Dx (n = 10) were orally administered to dextran sodium sulfate-treated mice. Thereafter, serum levels and tissue distributions of Dx were investigated. To estimate the efficacy of this drug delivery system, we measured the histological score, myeloperoxidase activity and nitric oxide production, and gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma in the colonic tissue. Serum Dx levels were not increased after oral administration of Dx microspheres. The tissue distribution of microspheres containing (125)I-labeled Dx in inflamed colon was significantly higher than in other organs. The histological score, myeloperoxidase activity, and nitric oxide production of the group treated with Dx microspheres were significantly lower than of those treated with Dx alone. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in mice treated with Dx microspheres. Microspheres containing glucocorticoids such as Dx, which target microfold cells and macrophages, can facilitate mucosal repair in experimental colitis and could be an ideal agent for treatment of human IBD.

Administration, Oral↗
PubMed1999

Targeting of tumor necrosis factor to tumor by use of dextran and metal coordination.

Tumor targeting of recombinant human tumor necrosis factor alpha (TNF) and consequently an enhanced anti-tumor effect were achieved through conjugation with dextran having metal chelating, diethylenetriaminepentaacetic acid (DTPA) residues based on metal coordination. A simple mixing with the DTPA-dextran in an aqueous solution containing Cu2+ enabled TNF to coordinately conjugate to dextran. Following intravenous (i.v.) injection into tumor-bearing mice, the TNF-DTPA-dextran conjugate caused a significantly higher tumor accumulation of TNF and the longer retention period than free TNF or its mixture with the DTPA-dextran. Intravenous injection of the TNF-DTPA-dextran conjugate suppressed tumor growth to a significantly greater extent than that of free TNF at a lower injection dose. It is concluded that dextran conjugation based on Cu2+ coordination is a promising way to enhance the anti-tumor effect of TNF as a result of its passive tumor targeting.

Animals↗
PubMed1999

In vitro and in vivo comparison of bulk and surface hydrolysis in absorbable polymer scaffolds for tissue engineering.

This article describes preliminary in vitro and in vivo studies comparing bulk and surface hydrolysis in absorbable polymer scaffolds proposed for tissue engineering of bone. The two polymers systems used were a bulk hydrolyzing 50:50 poly(DL-lactide-co-glycolide) (PLGA) and a surface hydrolyzing self-catalytic poly(ortho ester) (POE). Polymer scaffolds were exposed to physiological saline at body temperature and changes in polymer mass loss and inherent viscosity were monitored over time. New bone formation and local tissue response were evaluated by implanting scaffold disks of both polymer systems into non-critical-size calvarial defects in rabbits. New bone formation was determined by bone mineral density measurements, and local tissue response was determined by qualitative histology. Preliminary results confirmed that one of the main design characteristics for absorbable polymers in tissue engineering of bone, coordination of controlled polymer mass loss with new tissue formation, appeared to be achieved better using a surface hydrolyzing POE, rather than with a bulk hydrolyzing 50:50 PLGA. Bone mineral density at 6 and 12 weeks was an average 25% higher in the surface hydrolyzing scaffold. Unfortunately, the amount of bone formed was so inconsequential that this observation is of little relevance. Use of a water-soluble signaling factor such as basic fibroblast growth factor (bFGF) failed to increase bone formation. The histological response of these two polymer systems was similar and unaffected by the presence or absence of bFGF. The persistence of structural integrity for self-catalytic POE scaffolds after 6 and 12 weeks implantation, while 50:50 PLGA scaffolds had partially collapsed after 6 weeks, suggests surface hydrolyzing scaffolds may have some advantage over bulk hydrolyzing scaffolds in resisting normal in vivo stresses when used in a calvarial defect.

Animals↗
PubMed1999

Sealing effect of rapidly curable gelatin-poly (L-glutamic acid) hydrogel glue on lung air leak.

BACKGROUND: Air leak is a problem commonly occurring in lung and thoracic operations. In this study, a rapidly curable hydrogel glue was prepared as the seal for lung air leak. METHODS: Mixing an aqueous solution of gelatin and poly(L-glutamic acid) with a water-soluble carbodiimide produced a hydrogel. The sealing effect on the air leak wound of rat lung was compared with that of conventional fibrin glue. RESULTS: The gelatin-poly(L-glutamic acid) hydrogel glue was solidified as rapidly as the fibrin glue, and was significantly more effective in sealing the lung air leak than the fibrin glue. Approximately 80% of the lungs treated with the hydrogel glue exhibited no air leak at the lung pressure of 50 cm H2O. Urea addition could prevent spontaneous gelatination of the mixed solution at room temperature and did not affect the hydrogel sealing effect. The bonding strength of the hydrogel glue both with and without urea to the lung tissue was significantly higher than that of the fibrin glue. CONCLUSIONS: We concluded that this strong lung adhesion of the gelatin-poly(L-glutamic acid) hydrogel glue resulted in its superior sealing effect.

Animals↗
PubMed1999

Fabrication of porous gelatin scaffolds for tissue engineering.

A novel method which employs water present in swollen hydrogels as a porogen for shape template was suggested for preparing porous materials. Biodegradable hydrogels were prepared through crosslinking of gelatin with glutaraldehyde in aqueous solution, followed by rinsing and washing. After freezing the swollen hydrogels, the ice formed within the hydrogel network was sublimated by freeze-drying. This simple method produced porous hydrogels. Irrespective of any rinsing and washing processes, water was homogeneously distributed into the hydrogel network, allowing the hydrogel network to uniformly enlarge and the ice to act as a porogen during the freezing process. Different porous structures were obtained by varying the freezing temperature. Hydrogels frozen in liquid nitrogen, had a two-dimensionally ordered structure, while the hydrogels prepared at freezing temperatures near -20 degrees C, showed a three-dimensional structure with interconnected pores. As the freezing temperature was lowered, the hydrogel structure gradually became more two-dimensionally ordered. These results suggest that the porosity of dried hydrogels can be controlled by the size of ice crystals formed during freezing. It was concluded that the present freeze-drying procedure is a bio-clean method for formulating biodegradable sponges of different pore structures without use of any additives and organic solvents.

Biocompatible Materials↗
PubMed1999

Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities.

Biodegradable gelatin hydrogels were prepared through the glutaraldehyde crosslinking of acidic gelatin with an isoelectric point (IEP) of 5.0 and the basic gelatin with an IEP of 9.0. The hydrogel water content was changed by the concentration of both gelatin and glutaraldehyde, used for hydrogel preparation. An aqueous solution of basic fibroblast growth factor (bFGF) was sorbed into the gelatin hydrogel freeze-dried to obtain a bFGF-incorporating gelatin hydrogel. Irrespective of the hydrogel water content, approximately 30% of the incorporated bFGF was released from the bFGF-incorporating acidic gelatin hydrogel, within the first day into phosphate-buffered saline solution at 37 degrees C, followed by no substantial release. Probably, the basic bFGF complexed with the acidic gelatin through poly-ion complexation would not be released under the in vitro non-degradation condition of gelatin. On the contrary, almost 100% of the incorporated bFGF was initially released from all types of basic gelatin hydrogels. This is due to the simple diffusion of bFGF because of no complexation between bFGF and the basic gelatin. When implanted subcutaneously into the mouse back, bFGF-incorporating acidic and basic gelatin hydrogels with higher water contents were degraded with time faster than those with lower water contents. Significant neovascularization was induced around the implanted site of the bFGF-incorporating acidic gelatin hydrogel. The induction period prolonged with the decrease in hydrogel water content. On the other hand, such a prolonged vascularization effect was not achieved by the bFGF-incorporating basic gelatin hydrogel and the hydrogel initially exhibited less enhanced effect, irrespective of the water content. These findings indicate that the controlled release of biologically active bFGF is caused by biodegradation of the acidic gelatin hydrogel, resulting in induction of vascularization effect dependent on the water content. It is possible that only the transient vascularization by the basic gelatin hydrogel is due to the initial large burst in bFGF release, probably because of the down regulation of bFGF receptor.

Animals↗
PubMed1999

Suppression of experimental corneal angiogenesis by focal X-ray irradiation.

PURPOSE: To investigate the effect of focal X-ray irradiation on experimental corneal angiogenesis in the rabbit. METHODS: A gelatin hydrogel sheet impregnated with basic fibroblast growth factor was implanted into the corneal stroma of rabbits; this induced corneal angiogenesis. After the first sign of corneal angiogenesis was noted, the corneal region was irradiated with a dose of 10 Gy or 20 Gy. The control rabbits received no irradiation. The eyes were examined by slitlamp biomicroscopy and photographed, over a period of 28 days. The maximum length and total surface area of corneal angiogenesis were quantified by computerized image analysis. RESULTS: Corneal angiogenesis was noted on day 3 following implantation of the hydrogel sheet. In the rabbits irradiated with 10 Gy, the maximum length and total surface area of corneal angiogenesis were both significantly lower on day 4 and 7 following irradiation, compared to the respective measurement in the controls. In the rabbits irradiated with 20 Gy, the maximum length and total surface area of corneal angiogenesis were significantly lower between days 4 and 21, and between days 4 and 14, respectively, compared to the respective measurement in the controls. CONCLUSIONS: Focal X-ray irradiation to the corneal region suppressed corneal angiogenesis in a dose-dependent manner. Focal X-ray irradiation may be beneficial in treating ocular angiogenesis.

Animals↗
PubMed1999

Simple mixing of IFN with a polysaccharide having high liver affinity enables IFN to target to the liver.

Interferon (IFN) therapy is only one method that is clinically effective in controlling disease activity in patients with chronic hepatitis. A chelating residue (diethylenetriamine pentaacetic acid, DTPA) was introduced to pullulan, which is a polysaccharide with high liver affinity. This DTPA-pullulan could conjugate with IFN through Zn2+ coordination on mixing these three components. Intravenous injection of the IFN-DTPA-pullulan conjugate with Zn2+ coordination induced activity in the liver of an antiviral enzyme. 2',5'-oligoadenylate synthetase at IFN doses lower than those used for free IFN injection. In addition, synthetase induction by the conjugate continued for a longer time than did induction by free IFN. Liver targeting of IFN by this conjugation technique based on Zn2+ coordination opens a new method of IFN therapy.

2',5'-Oligoadenylate Synthetase↗
PubMed1999

Biodegradation of hydrogel carrier incorporating fibroblast growth factor.

In vivo release of basic fibroblast growth factor (bFGF) from a biodegradable gelatin hydrogel carrier was compared with the in vivo degradation of hydrogel. When gelatin hydrogels incorporating 125I-labeled bFGF were implanted into the back subcutis of mice, the bFGF radioactivity remaining decreased with time and the retention period was prolonged with a decrease in the water content of the hydrogels. The lower the water content of 125I-labeled gelatin hydrogels, the faster both the weight of the hydrogels and the gelatin radioactivity remaining decreased with time. The decrement profile of bFGF remaining in hydrogels was correlated with that of hydrogel weight and gelatin radioactivity, irrespective of the water content. Subcutaneous implantation of bFGF-incorporating gelatin hydrogels into the mice induced significant neovascularization. The retention period of neovascularization became longer as the water content of the hydrogels decreased. To study the decrease of activity of bFGF when implanted, bFGF-incorporating hydrogels were placed in diffusion chamber and implanted in the mouse subcutis for certain periods of time. When hydrogels explanted from the mice were again implanted, significant neovascularization was still observed, indicating that most of the biological activity of bFGF was retained in the hydrogels. It was concluded that, in our hydrogel system, biologically active bFGF was released as a result of in vivo degradation of the hydrogel. The release profile was controllable by changing the water content of hydrogels.

Animals↗
PubMed1999

Neovascularization effect of biodegradable gelatin microspheres incorporating basic fibroblast growth factor.

Biodegradable microspheres were prepared through glutaraldehyde cross-linking of gelatin without using any surfactants as a carrier matrix of basic fibroblast growth factor (bFGF). In the in vitro system, bFGF was sorbed to microspheres of acidic gelatin with an isoelectric point (IEP) of 5.0, but not to those of basic gelatin with an IEP of 9.0. The rate of bFGF sorption to the acidic gelatin microsphere in phosphate-buffered saline solution (pH 7.4) was smaller than that in water. Following incorporation of bFGF into the microspheres at 4 degrees C for 12 h, bFGF release from the bFGF-incorporating microspheres was studied. Approximately 30% of incorporated bFGF was released from the acidic gelatin microsphere within the initial 3 h, followed by no substantial release, whereas the basic gelatin microsphere released almost completely the incorporated bFGF within 1 day. It is likely that when basic bFGF molecules were immobilized to the acidic gelatin constituting microspheres through polyion complexation, they were not readily released under the in vitro nondegradation condition of gelatin. Incorporation of anionic carboxylmethyl cellulose (CMC) into the acidic gelatin microspheres reduced the amount of bFGF desorbed initially. This indicates that the initial burst is ascribed to free bFGF which is not ionically interacted with the acidic gelatin. CMC will function as a bFGF sorbent to suppress the initial leakage from the microspheres. When injected subcutaneously into the mouse back, bFGF-incorporating acidic gelatin microspheres were degraded over time and induced neovascularization around the injection site, in marked contrast to bFGF in the solution form. CMC incorporation slowed down the biodegradation and vascularization effect of bFGF-incorporating gelatin microspheres. It was concluded that the gelatin microsphere was a promising carrier matrix of bFGF to enhance the vascularization effect.

Animals↗
PubMed1999

Vascularization into a porous sponge by sustained release of basic fibroblast growth factor.

Vascularization into a poly(vinyl alcohol) (PVA) sponge was investigated using basic fibroblast growth factor (bFGF). This growth factor was impregnated into biodegradable gelatin microspheres for its sustained release and then the bFGF-containing microspheres or free bFGF were incorporated into PVA sponges. Following subcutaneous implantation into the back of mice, the bFGF-containing gelatin microspheres induced vascularization in and around the sponge to a significantly greater extent than that of free bFGF from 3 days after implantation. Significant ingrowth of fibrous tissue into the sponge was also observed when bFGF-containing microspheres were added to the sponge in contrast to free bFGF. Tissue ingrowth occurred into the deeper portion of the sponge over time while it accompanied formation of new capillaries. Empty gelatin microspheres had no effect on vascularization and the level of fibrous tissue ingrowth into the sponge was similar to that of the control group. It was concluded that incorporation of gelatin microspheres containing bFGF into the PVA sponge was effective in prevascularization of the sponge pores.

Animals↗