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Biomedical subjects

Mitsuru Akashi

Publications and source records attributed to Mitsuru Akashi.

At least 55 records · Page 3Linked to original sources
PubMed2004

Synthesis of double-armed lariat ethers with pyrene moieties at each end of two sidearms and their fluorescence properties in the presence of alkali metal and alkaline earth metal cations.

Two types of double-armed lariat ether derivatives having pyrene moieties at each end of two sidearms, (3x + 1)-crown-x derivatives 1 (x = 5), 2 (x = 6), and 3 (x = 4) (type A) and 3y-crown-y derivatives, 6 (y = 5) and 7 (y = 6) (type B), were synthesized, and their complexation behavior toward alkali metal and alkaline earth metal cations was examined by fluorescence spectroscopy. Pyrene excimer emission decreased accompanied by an increase in monomer emission upon metal ion complexation. This finding is ascribed to the change of the spatial distance of two pyrene rings by movement suppression of both the crown ring and one of the two sidearms based on complexation with the metal cation. The selectivity for alkaline earth metal cations was highly dependent on the fitness of the host cavity and the guest size. Although most of the fluorophores did not respond to alkali metal cations, only trans-7a containing an 18-crown-6 ring showed K(+) selectivity.

Journal Article↗
PubMed2004

Polymerization within a molecular-scale stereoregular template.

Enzymes efficiently synthesize biopolymers by organizing monomer units within regularly structured molecular-scale spaces and exploiting weak non-covalent interactions, such as hydrogen bonds, to control the polymerization process. This 'template' approach is both attractive and challenging for synthetic polymer synthesis, where structurally regulated molecular-scale spaces could in principle provide solid-phase reaction sites for precision polymerization. Previously, free-radical polymerization of methyl methacrylate in solutions containing stereoregular isotactic (it) or syndiotactic (st) poly(methyl methacrylate) (PMMA) has been shown to result in template synthesis of the opposite PMMA based on stereocomplex formation with van der Waals interactions. However, using the structure of a solid to determine the stereochemical structure of a polymer has not been satisfactorily achieved. Here we show that macromolecularly porous ultrathin films, fabricated by a single assembly step, can be used for the highly efficient stereoregular template polymerization of methacrylates through stereocomplex formation. This reaction mould accurately transfers its structural properties of stereoregularity, molecular weight and organization within the template to the new polymer.

Journal Article↗
PubMed2004

Preparation and thermosensitivity of naturally occurring polypeptide poly(gamma-glutamic acid) derivatives modified by propyl groups.

Poly(gamma-glutamic acid) (gamma-PGA) is a biosynthetic polymer, and the carboxyl groups are able to undergo a chemical modification. In this study, poly(alpha-propyl gamma-glutamate) (gamma-PGA propylate) was synthesized by the esterification of these carboxyl groups to yield a thermosensitive and biodegradable polymer. In aqueous solution, the gamma-PGA propylate can impart thermosensitivity by controlling the hydrophobic-hydrophilic balance of the gamma-PGA polymeric chains.

Drug Stability↗
PubMed2004

Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques.

We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV-NS-immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV-NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS-immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU-2.

AIDS Vaccines↗
PubMed2004

Cell-adhesive and blood-coagulant properties of ultrathin poly(methyl methacrylate) stereocomplex films.

Isotactic (it) and syndiotactic (st) poly(methyl methacrylate)s (PMMAs) were assembled on a poly(ethylene terephthalate) cell disk (as a solid substrate), which is normally used for cell culture, to produce ultrathin stereocomplex films. Static contact angles of the films using air bubbles in aqueous phase revealed the stepwise assembly of both polymers. More L929 fibroblast cells adhered and were flattened on the ultrathin stereocomplex films, compared to homogeneous PMMA films and to spin-coated films comprised of a mixed solution of it- and st-PMMAs with a molar ratio of 1 : 2, which is the stoichiometry of a stereocomplex. The difference in the number of adherent cells was greatest after the first 3 h of incubation. Pre-adsorption of proteins, which are related to cell adhesion, onto the stereocomplex film potentially modulated the cell-adhesive properties. Fresh whole human blood did not coagulate on the complex film for 20 min, although blood coagulated after 15 min on the homogeneous films and on the 1 : 2 mixed film. Platelets did not adhere onto the complex films after 15 min of incubation, which was consistent with the results of blood coagulation. These observations indicate that the stereocomplex formation of PMMAs on the surface of films strongly affects the bioactivity of these films.

Animals↗
PubMed2004

IgG responses to intranasal immunization with cholera-toxin-immobilized polymeric nanospheres in mice.

IgG responses to antigen-nanosphere hybrids were studied in mice. Cholera toxin (CT) was covalently immobilized onto the surface of polymeric nanospheres (NS) with a nanophase-separated structure consisting of a polystyrene core and a poly(methacrylic acid) graft corona. Reaction conditions favoring the dehydroxide condensation reaction of the amino group of the CT with the carboxyl group of NS effectively immobilized CT onto their surface. When CT-immobilized nanospheres (CT-NS) were suspended in aqueous solution and administrated to mice either intranasally or intramuscularly, serum IgG titers elevated with increasing time and reached a maximum level at 8 weeks after immunization. On the other hand, intranasal administration of CT alone induced an even higher serum IgG titer than that of CT-NS at 4 weeks. However, the titer gradually decreased thereafter. Thus, polymeric NS may be an effective substrate to covalently immobilize antigen on their surface, steadily inducing a high level of IgG production in response to the intranasal administration.

Administration, Intranasal↗
PubMed2004

Optimal gamma-ray dose and irradiation conditions for producing low-molecular-weight chitosan that retains its chemical structure.

This study focuses on the optimal conditions for gamma irradiation to reduce the molecular weight of chitosan but still retain its chemical structure. Chitosan was irradiated under various conditions, i.e. flake solid state (condition 1), flake dispersed in water (condition 2), flake dispersed in 0.05, 0.1, 1 and 2% aqueous K(2)S(2)O(8) solution (conditions 3a, 3b, 3c and 3d, respectively), flake dispersed in 0.5, 1 and 2% aqueous H(2)O(2) solution (conditions 4a, 4b and 4c, respectively), and chitosan acetic acid solution (condition 5). Comparative studies were done using three types of chitosans with molecular weights of the order of 10(5) Da with degrees of deacetylation of 0.80, 0.85 and 0.90%. For all conditions, after irradiation, there were two regions of molecular weight reduction. A severe degradation occurred in the first region with decreases in the molecular weight of 80% for radiation doses up to 50 kGy for conditions 1, 2 and 3 (3a-3c) and 20 kGy for condition 4. In the second region, a slow degradation occurred, which resembled a plateau stage. The results for conditions 3d and 5 were the most dramatic, since the primary structure of chitosan was changed after the irradiation. The degradation of chitosan by gamma rays was found to be most effective for the amorphous structure. The retention of the structure of chitosan after gamma irradiation makes it possible to produce a low-molecular-weight chitosan that retains its functionality, as demonstrated by its activity in the coupling reaction with N,N'-carbonyldiimidazole.

Biocompatible Materials↗
PubMed2003

A facile synthesis of novel cyclodextrin derivatives incorporating one beta-(1,4)-glucosidic bond and their unique inclusion ability.

Novel cyclodextrin derivatives incorporating one (1,4)-glucosidic bond are easily synthesized in three steps from permethylated alpha- and beta-cyclodextrins, and such host molecules show inclusion selectivity for sodium m-nitrobenzoate over the corresponding p-isomer, in contrast to the cases of the parent permethylated alpha- and beta-cyclodextrins.

Cyclodextrins↗
PubMed2003

Bioinspired organic-inorganic composite materials prepared by an alternate soaking process as a tissue reconstitution matrix.

Poly(acrylic acid) (PAAc) grafted poly(ethylene) (PE) (PAAc-g-PE) film-apatite or calcium carbonate (CaCO3) composite materials were prepared by an alternate soaking process, which simply forms apatite or CaCO3 on the polymer materials by alternate soaking in Ca(2+)- and PO(3-)4- or CO(3)2- -containing solutions. X-ray diffraction analysis of the composite films indicated the presence of hydroxyapatite or CaCO3 on the film. Scanning electron microscopic observation revealed that the whole surface of the film was covered by the apatite or CaCO3. Cell compatibility tests of the apatite- or CaCO3-coated film suggested that the greater number of cells adhered on the films and that the cell proliferation properties were extremely greater on the films.

Animals↗
PubMed2003

Alternating gene expression in fibroblasts adhering to multilayers of chitosan and dextran sulfate.

The alternating compatibility of fibroblast cells adhering to multilayers of chitosan and dextran sulfate (Dex) on a substrate was analyzed at the gene expression level. A greater number of round-shaped cells adhered to the films with an outermost surface composed of Dex, although the total number of adherent cells was independent of the film surface. Greater expression of heat-shock protein 70B mRNA was demonstrated in cells adhering to films with the Dex surface. It was found that analysis of gene expression was a powerful tool for evaluating the bioactivity of multilayers.

Biocompatible Materials↗
PubMed2003

Osteoconductive and hemostatic properties of apatite formed on/in agarose gel as a bone-grafting material.

The biologic behavior of hydroxyapatite formed on/in agarose (HA/agarose) gels with the use of a novel alternate soaking process was compared with commercially available Bone Ject (True-Bone ceramic-collagen combined bone-graft material, Koken, Japan) as a filler for the tooth-extraction sockets of six adult monkeys (Macasa fascicularis). After the monkeys' first premolars were extracted, the defects created were replaced with one of the following materials: (a). HA/agarose created by 12 soaking cycles, (b). HA/agarose created by 9 soaking cycles, (c). Bone Ject, and (d). no material implantation (control). The time of hemostasis in each extraction site was estimated, and the samples were then studied histologically. In the controls, the time of hemostasis was about 5 min. The Bone Ject particles were easily washed out by bleeding, and the time of hemostasis was about 15 min. The HA/agarose gel was densely packed into the bony defect. The hemorrhage from the defects stopped within a few seconds after graft placement. This hemostasis was most likely related to the compactibility and adhesiveness of the material. After 12 weeks of implantation, free Bone Ject particles surrounded by inflammatory cells were observed. The bony defect filled with the HA/agarose gels was completely absorbed and replaced by newly formed bone possessing bone marrow. There was no difference in the biologic behavior of HA/agarose gels created by 9 versus 12 soaking cycles. The present study suggests that HA/agarose gels may play an important role as an alternative biodegradable bone-graft material for autogenous bone in humans.

Animals↗
PubMed2003

Novel Guglielmi detachable coils (GDCs) for the treatment of brain aneurysms. In vitro study of hydroxyapatite coating on Pt plate as GDCs model.

With the use of an alternate soaking process a thin layer of hydroxyapatite (HAp) was formed on a platinum plate (Pt plate) which was used as a model for Guglielmi detachable coils (GDCs). The in vitro coagulant activity of the HAp-coated Pt plate was evaluated for the purpose of brain aneurysm treatment. In order to fix and to form the apatite layer homogeneously, beta-mercaptopropionic acid was immobilized onto the Pt surface prior to use. The HAp layer was formed on the beta-mercaptopropionic acid-fixed Pt plate surface, and quantitative control of apatite formation was achieved by controlling the number of alternate soaking process cycles. The HAp formed on the Pt plate surface was confirmed by X-ray diffraction and X-ray photoelectron spectroscopy studies. Blood interaction with the Pt plate was altered from nonthrombotic to highly thrombotic by forming a HAp layer on the surface. The alternate soaking process is an appropriate method to modify the GDCs. Complete treatment of brain aneurysms is expected with the use of HAp-coated GDCs, which would allow formation of a stable blood clot.

3-Mercaptopropionic Acid↗
PubMed2003

Controlled hydrophobic/hydrophilicity of chitosan for spheres without specific processing technique.

Chitosan is functionalized with phthalic anhydride at the amino group and poly(ethylene glycol) methyl ether at the hydroxyl group via homogeneous reaction. The product regenerated forms particles in either aqueous solution or organic solvents. The particles are spheres with the size of few micrometers as observed from scanning electronmicroscopy. The present work demonstrates that by simply adjusting the hydrophilicity and hydrophobicity, we can directly obtain spheres without a specific processing technique.

Biocompatible Materials↗
PubMed2003

Mucosal immunization with inactivated HIV-1-capturing nanospheres induces a significant HIV-1-specific vaginal antibody response in mice.

Mucosal secretory IgA is considered to have an important role in the prevention of human immunodeficiency virus type 1 (HIV-1) transmission through sexual intercourse. Therefore, substances that induce HIV-1-specific IgA antibody in the genital tract may become promising candidates for prophylactic vaccine against HIV-1 infection. We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and gp120 antigens on their surface and that intravaginal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody in mice. In this study, various strategies for immunization with HIV-NS were undertaken to induce HIV-1-specific IgA response in the mouse genital tract. HIV-NS were administered intravaginally, orally, intranasally or intraperitoneally to mice. Progesterone treatment enhanced the anti-HIV-1 IgA response to intravaginal immunization significantly, but intranasal immunization with HIV-NS was more effective compared with other immunization routes in terms of vaginal IgA response. In addition, vaginal washes from intranasally immunized mice were capable of neutralizing HIV-1(IIIB). Thus, application of HIV-NS is a practical approach to promote HIV-1-specific IgA response by the vaginal mucosa in the mouse and intranasal appears to be an effective immunization route in this animal model. Intranasal immunization with HIV-NS should be further pursued for its potential as an HIV-1 prophylactic vaccine.

AIDS Vaccines↗