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Biomedical subjects

Y Tabata

Publications and source records attributed to Y Tabata.

At least 109 records · Page 6Linked to original sources
PubMed1998

Complexation of basic fibroblast growth factor with gelatin.

Polyion complexation between basic fibroblast growth factor (bFGF) and gelatin was studied by the turbidity change of mixed solution, heparin high performance liquid affinity chromatography (HPLAC), and isoelectric electrophoresis. When an aqueous solution of acidic gelatin with an isoelectric point (IEP) of 5.0 was mixed with that of bFGF, the turbidity of the mixed solution increased with time, whereas basic gelatin with and IEP of 9.0 did not cause any solution turbidity. A maximum turbidity of the mixed bFGF and acidic gelatin solution was observed around a bFGF/gelatin molar ratio of 1.0, irrespective of the gelatin concentration and solution temperature. The solution turbidity decreased with an increase in the ionic strength of the mixed solution. Complexation of bFGF with acidic gelatin was slower than that with poly(acrylic acid) probably because of the lower density of gelatin negative charge than that of poly(acrylic acid). HPLAC study revealed that complexation of bFGF with the acidic gelatin reduced the affinity of bFGF for heparin, in contrast to the basic gelatin, although the extent became smaller with the increasing ionic strength of the solution. An electrophoretic experiment showed that the IEP of bFGF shifted to a lower value after its gelatin complexation. These findings indicate that an electrostatic interaction is the main driving force for the complexation between acidic gelatin and basic bFGF.

Acrylic Resins↗
PubMed1997

Genotypes of aldehyde dehydrogenase and alcohol dehydrogenase polymorphisms in patients with Leber's hereditary optic neuropathy.

To define whether alcohol drinking provides a risk for Leber's hereditary optic neuropathy (LHON), the genotypes of low K(m) aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase type 2 (ADH2), major enzymes involving the alcohol metabolism, were examined in 29 unrelated Japanese patients with LHON associated with mitochondrial DNA 11778 mutation, 24 unrelated asymptomatic carriers with the mutation and 57 normal controls without the mutation. PCR-restriction detection revealed three genotypes of ALDH2 and ADH2. The allele frequencies of either enzyme in LHON patients, asymptomatic carriers, or both, did not differ from those in normal controls. There is no association between LHON and genotypes of alcohol-metabolizing enzymes. However, six of the LHON patients had frequent alcohol consumption, while none of the asymptomatic carriers claimed frequent drinking habit. Thus, we could not make a denial of drinking effects on optic nerve damage in LHON.

Adolescent↗
PubMed1997

Photodynamic effect of polyethylene glycol-modified fullerene on tumor.

Fullerence (C60) efficiently generates singlet oxygen when irradiated with light, and thus should have a photodynamic effect on tumors, if it is accumulated in the tumor tissue. To explore tumor targeting of C60, we chemically modified the water-insoluble C60 with polyethylene glycol (PEG), not only to make it soluble in water, but also to enlarge its molecular size. When injected intravenously into mice carrying a tumor mass in the back subcutis, the C60-PEG conjugate exhibited higher accumulation and more prolonged retention in the tumor tissue than in normal tissue. The conjugate was excreted without being accumulated in any specific organ. Following intravenous injection of C60-PEG conjugate or Photofrin to tumor-bearing mice, coupled with exposure of the tumor site to visible light, the volume increase of the tumor mass was suppressed and the C60 conjugate exhibited a stronger suppressive effect than Photofrin. Histological examination revealed that conjugate injection plus light irradiation strongly induced tumor necrosis without any damage to the overlying normal skin. The antitumor effect of the conjugate increased with increasing irradiation power and C60 dose, and cures were achieved by treatment with a dose of 424 micrograms/kg at an irradiation power of 107 J/cm2. These findings indicate that PEG-modified C60 is a candidate agent for photodynamic tumor therapy.

Animals↗
PubMed1997

Potential efficacy of basic fibroblast growth factor incorporated in biodegradable hydrogels for skull bone regeneration.

Biodegradable gelatin hydrogels incorporating basic fibroblast growth factor (bFGF) were evaluated for their efficacy in bone regeneration using a rabbit model. Hydrogels with water contents of 85% and 98% were prepared using chemical crosslinking of gelatin with an isoelectric point of 4.9 in aqueous solution and, after freeze drying, were impregnated with an aqueous solution of bFGF to obtain bFGF-incorporated gelatin hydrogels. When they were implanted into bone defects measuring 6 mm in diameter in rabbit skulls (six animals/group), complete closure of the defect was observed at 12 weeks after implantation, regardless of the water content of the hydrogels. In contrast, bFGF did not enhance bone regeneration when applied to the skull defect in solution with phosphate-buffered saline (PBS). Also, gelatin hydrogels lacking bFGF were not effective in inducing bone formation, with fibrous tissue growing into the defect instead, similar to the skull defect seen in control rabbits treated with PBS. This indicates that the presence of hydrogels did not interfere with bone regeneration at the skull defect, probably because of their disappearance during biodegradation. It is concluded that the gelatin hydrogel is a promising matrix for effective induction of biological activity of bFGF for bone regeneration in skull and sinus defects.

Animals↗
PubMed1997

PF1092A, B and C, new nonsteroidal progesterone receptor ligands produced by Penicillium oblatum. I. Taxonomy of producing strain, fermentation, isolation and biological activities.

Three new nonsteroidal progesterone receptor ligands, PF1092A, B and C, have been isolated from Penicillium oblatum. They were purified from the solid cultures of rice media using ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies, and crystallization. All three ligands competitively inhibited [3H]-progesterone binding to porcine uteri cytosol preparations with IC50 of 3.0 x 10 nM (PF1092A), 2.2 x 10(2) nM (PF1092B) and 2.2 x 10(3) nM (PF1092C).

Animals↗
PubMed1997

PF1092A, B and C, new nonsteroidal progesterone receptor ligands produced by Penicillium oblatum. II. Physico-chemical properties and structure elucidation.

The structures of PF1092A (1), B (2) and C (3), new nonsteroidal progesterone receptor ligands produced by Penicillium oblatum, were elucidated by spectroscopic analyses. These compounds possess an eremophilane-type sesquiterpene carbon skeleton and differ only in that 1 and 2 are different monoacetates of 3. The absolute configurations of 1-3 were determined by single crystal X-ray diffraction analysis of the 4-bromobenzoyl ester of PF1092A and by measuring the optical rotations of the acetylation products of these compounds.

Furans↗
PubMed1996

Secondary lymphoid malignancy in two children with neuroblastoma.

Secondary lymphoid malignancy, particularly acute lymphoblastic leukemia (ALL), is rare. We report one case of ALL and another case of mediastinal lymphoblastic lymphoma developed after treatment for neuroblastoma. The secondary ALL characterized by short latency period and an 11q23 translocation apparently was induced by etoposide treatment. The pathogenesis of the secondary lymphoma is less certain and may be related to previous treatment with cyclophosphamide and radiotherapy, host susceptibility, or chance occurrence. One child died of progressive lymphoma and the other remains in remission 1 year following allogeneic bone marrow transplantation. Additional studies are needed to determine the risk, pathogenesis, and optimal treatment for secondary lymphoid malignancy.

Child↗
PubMed1996

A new biological glue from gelatin and poly (L-glutamic acid).

This study describes the potentiality of hydrogels composed of gelatin and poly(L-glutamic acid) (PLGA) as a biological glue for soft tissues and compares its effectiveness with that of a conventional fibrin glue. Water-soluble carbodiimides (WSC) were used to crosslink the aqueous mixture of gelatin and PLGA. The mixed aqueous solution of gelatin and PLGA set to a hydrogel by use of WSC as rapidly as BOLHEAL fibrin glue. An addition of PLGA to gelatin aqueous solution reduced not only its gelation time but also the WSC concentration necessary for hydrogel formation. The cured hydrogel exhibited firm adhesion to the mouse skin and other soft tissues with a higher bonding strength than BOLHEAL fibrin glue. Cohesive failure in the hydrogel was observed when the gel-tissue bond was broken, in contrast to BOLHEAL fibrin glue. The bonding strength of the gelatin-PLGA hydrogel became higher with the increasing PLGA concentration. The inflammatory reaction around the gelatin-PLGA hydrogel subcutaneously implanted in mice was mild, and the hydrogel was gradually absorbed with time in vivo. A toxicity test demonstrated that the concentration of WSC necessary as a biological glue was low enough not to induce its toxicity.

Adhesives↗
PubMed1996

Production of interleukin 1 from macrophages incubated with poly (DL-lactic acid) granules containing ovalbumin.

The production profile of interleukin 1 (IL-1) from mouse peritoneal macrophages (M phi) was determined following their incubation with poly(DL-lactic acid) (PDLLA) granules containing ovalbumin (OVA). Upon incubation, M phi produced IL-1 at a significantly high rate compared with those incubated with OVA in the free form or OVA-free granules. A simple mixture of empty granules and free OVA exhibited the same level of IL-1 production as induced by free OVA alone. IL-1 production by the granules with a fixed OVA loading increased with an increase in their amount added to M phi. When incubated with a fixed amount of granules containing OVA of different loadings, M phi produced more IL-1 with an increase in the total OVA amount, but the IL-1 production decreased at OVA loadings higher than 10%. The presence of free OVA enhanced IL-1 production with the increased addition of empty granules, but the level induced by OVA loaded in granules was higher than that by mixtures of free OVA and empty granules, when compared at a similar OVA dose, irrespective of the absolute amount of PDLLA added. These findings indicate that the sustained release of OVA from the granules is critical to enhance the OVA-induced IL-1 production, in contrast to the OVA release accompanying a large initial burst, which reduced IL-1 production. It was concluded that the direct contact of PDLLA granules with M phi and the subsequent sustained release of OVA around M phi effectively activated M phi, resulting in enhanced IL-1 production.

Animals↗
PubMed1996

Rapidly curable biological glue composed of gelatin and poly(L-glutamic acid).

The tissue adhesion property of a hydrogel cross-linked with water-soluble carbodiimide (WSC) was investigated and compared with that of the conventional fibrin glue. The biodegradable hydrogel was composed of gelatin and poly(L-glutamic acid) (PLGA). This study focused on the mouse skin bonding by the WSC-formed hydrogel prepared from a low-molecular-weight (Mw) gelatin whose aqueous solution did not spontaneously set to a gel at 25 degrees C, in contrast to the conventional gelatin with high Mw. At polymer concentrations lower than the incipient gelation concentration, the bonding strength of mouse skin by the WSC-cross-linked gelatin-PLGA hydrogel increased with an increase in the concentration of gelatin and PLGA, irrespective of Mw of gelatin. When compared at the highest gelatin concentration which did not cause gelation, the bonding strength of the hydrogel composed of lower Mw gelatin and PLGA was higher than that of higher Mw gelatin hydrogel with or without PLGA or the conventional fibrin glue. The mixed aqueous solution from the gelatin with Mw of 10,000 and PLGA was gelled by use of WSC as rapidly as the fibrin glue. It was concluded that the gelatin-PLGA hydrogel is a safe biological glue with the adhesion property superior to the fibrin glue.

Adhesives↗
PubMed1996

Size effect on the antibody production induced by biodegradable microspheres containing antigen.

Poly(L-lactic acid) (PLLA) microspheres containing a model antigen, ovalbumin (OVA), were prepared by the evaporation method using double emulsion, and fractionated into different sizes by counterflow elutriation. Following the intraperitoneal (i.p.) and subcutaneous (s.c.) injection of the microspheres to mice, the titer of anti-OVA antibody in the serum was measured to assess the size effect on the profile of antibody production. OVA was released from the microspheres for 80 days, irrespective of the microsphere size. In both the s.c. and i.p. immunization, the serum level of anti-OVA IgG antibody in the mice induced by the microspheres containing OVA was higher than that of free OVA when compared at the same dose. The serum level of antibody in the mice i.p. injected with the microspheres tended to increase with the decreasing size. On the other hand, in the s.c. immunization, the microsphere size had little influence on the antibody production. It is possible that the injected microspheres tend to aggregate in the s.c. tissue, disappearing the size effect on the antibody production. Since the amount of microspheres injected increases with the decreasing size when their OVA loading is fixed, the increase in the amount will promote the interaction with immune cells, resulting in an enhanced antibody production. The cell interaction with the microspheres in the peritoneal cavity seems to be influenced by their size to a greater extent than in the s.c. tissue, probably because of their more frequent interaction with immune cells.

Animals↗
PubMed1996

Adjuvant effect of biodegradable poly(DL-lactic acid) granules capable for antigen release following intraperitoneal injection.

Ovalbumin (OVA)-containing poly(DL-lactic acid) (PDLLA) granules were prepared with different conditions. Following the intraperitoneal (i.p.) immunization of mice with the granules containing OVA, production of anti-OVA IgG antibody in the mouse serum was investigated. The i.p. injection of the granules induced a strong antibody production compared with that of free OVA, irrespective of the amount of OVA released for initial a few weeks and the period of OVA release. The serum level of IgG antibody induced by the granules was retained at a high level over 16 weeks although the period of OVA release and the amount of OVA released initially were different from each other. The initial OVA release for a few weeks was essential to induce the enhanced antibody production. Comparison of mice immunization by granules with different OVA loadings but at a similar dose revealed that antibody level was higher for the granules with lower loading than for those with the higher loading. However, when the granules were injected after encapsulation into a poly(vinyl alcohol) (PVA) hydrogel tube, the difference in their antibody level became insignificant. Because PVA encapsulation did not affect the OVA release profile, this finding indicates that the injection amount of the granules seems to have influenced the antibody production. We conclude that the release profile of OVA is not always a key factor to enhance the antibody production of OVA-containing granules so far as the initial OVA controlled release is achieved.

Adjuvants, Immunologic↗
PubMed1996

Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres.

Induction of systemic and mucosal immune responses following oral administration of biodegradable poly(D,L-lactic acid) (PDLLA) microspheres containing a model antigen, ovalbunin (OVA) was studied using microspheres with different average diameters of 0.6, 1.0, 4.0, 7.0, 11.0, 15.0, 21.0, and 26.0 microns. They were prepared from double emulsion with the solvent evaporation method, followed by size fractionation on counterflow elutriation. OVA was released from the microspheres in vitro over 80 days, irrespective of their size. Production of the serum anti-OVA IgG antibody and secretory OVA-specific IgA antibody in the mice gut was assessed following the oral administration of PDLLA microspheres containing OVA. Microspheres with a diameter of 4.0 microns enhanced the serum antibody in contrast with that of free OVA, but were not effective in inducing the gut secretion of IgA antibody. On the other hand, OVA-containing microspheres with a diameter of 7.0 microns enhanced IgA secretion to a significant extent compared with free OVA, whereas those with 26.0 microns in diameter were ineffective. Body distribution study revealed that the amount of microspheres taken up into Peyer's patches (PP) increased with the increasing size up to 11.0 microns, thereafter decreased, and finally became zero when their diameters were 21.0 microns or larger. The microspheres taken up into PP were translocated to the spleen, but no microspheres were noticed in the spleen when the size was larger than 5 microns. After being taken up inot PP, microspheres < 5 microns in diameter seemed to be transported to the spleen, a systemic lymphoid tissue, where the released antigen stimulated a serum antibody response, but larger microspheres probably remained at PP without being translocated to the spleen over the course of their antigen release, leading to induction of IgA secretion. It was concluded that the body distribution pattern of microspheres following the PP uptake was a key factor to regulate the induction of systemic and mucosal immune responses.

Administration, Oral↗
PubMed1996

Liver targeting of interferon through pullulan conjugation.

PURPOSE: The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver. METHODS: Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2', 5'-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated. RESULTS: The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7-9% of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice. CONCLUSIONS: IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

New formulation of 5-fluorouracil in microspheres reduces toxicity in mice.

A new dosage formulation of 5-fluorouracil incorporated in microspheres (5-FU-MS) was developed for the treatment of peritoneal carcinomatosis. We studied the acute toxicity and side effects of i.p. 5-FU-MS in mice. The 50% lethal dose value for 5-FU-MS was 535.4 mg/kg of 5-FU, which was 2.22 times that of the aqueous 5-FU solution. Deaths occurred 12-17 days after the administration of 5-FU-MS, but within 11 days after the administration of aqueous 5-FU. Thus, lethal toxicity appeared later with 5-FU-MS than with aqueous 5-FU. There were no differences in pathologic findings on autopsy between mice given the two dosage formulations.

Animals↗
PubMed1996

Changes in serum erythropoietin and the reticulocyte count during chemotherapy for leukemias.

We serially determined serum erythropoietin (Epo) and the reticulocyte count in patients with various types of leukemia during chemotherapy. Serum Epo increased soon after the initiation of chemotherapy and decreased after the termination of therapy irrespective of the types of leukemia or treatment regimen. However, it did not stay at low level but fluctuated. The reticulocyte count, on the other hand, showed a transient rise while serum Epo level descended. The value of serum Epo when increased was higher than the value expected from hemoglobin concentration; this finding was similar to that in aplastic anemia. These results suggest that myelosuppression is a major factor for the increase in serum Epo level during leukemia chemotherapy.

Adult↗