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Biomedical subjects

S Kotani

Publications and source records attributed to S Kotani.

At least 19 recordsLinked to original sources
PubMed1992

Acute nephrotoxicity as an adverse effect after intraperitoneal injection of massive amounts of bioactive ceramic powders in mice and rats.

Silicon elution from bioactive ceramic powders was measured using an in vitro solubility test, in which the powders were soaked in phosphate buffer solution. Silicon elution was highest in Bioglass (BG), followed by Ceravital (KGS), apatite-wollastonite-containing glass ceramics (A-W.GC), and hydroxyapatite (HA), respectively. Silicon elutions on this in vitro solubility test were correlated with the rates of rapid death in mice following intraperitoneal injection of each of these bioactive ceramic powders. Histopathological examination of the mice revealed nephropathy, which was considered to be the cause of death. The nephropathy was characterized by epithelial degeneration in the renal tubules and increased silicon content throughout the entire kidney, findings suggesting silicon nephropathy. It is considered that, because a large quantity of silicon eluted from the powder was absorbed from the peritoneum, concentration in the glomerular filtrate and urine increased until silicon polymerization occurred, after which the silicon polymer became deposited in the renal tubules. A single injection of furosemide prevented the acute nephrotoxicity of bioactive ceramic powder.

Animals↗
PubMed1992

Differences in ceramic-bone interface between surface-active ceramics and resorbable ceramics: a study by scanning and transmission electron microscopy.

The interface between bioactive ceramics and bone was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The materials were apatite-wollastonite-containing glass ceramic (A-W.GC) as a representative surface-active ceramic, and calcite and beta-tricalcium phosphate (beta-TCP) as resorbable ceramics. Particles of these materials, ranging between about 100 microns and 300 microns in diameter, were implanted into rat tibiae, and specimens were prepared for observation at 8 weeks after implantation. Both SEM and TEM demonstrated that A-W.GC was bonded to bone through a thin Ca-P-rich layer consisting of fine apatite crystals apparently different from those of bone in shape, size, and orientation. Collagen fibers of the bone reached the surface of this layer, and chemical bonding between A-W.GC and the bone was speculated. Calcite and beta-TCP, on the other hand, made direct contact with the bone, and no apatite layer was present at the interface. The surfaces of the implants became rough due to degradation, and bone grew into the finest surface irregularities. However, we were unable to demonstrate any continuity of crystals between the resorbable implants and bone by high-resolution TEM. Accordingly, the bonding strength was considered to be mainly attributable to mechanical interlocking.

Animals↗
PubMed1992

Mechanism and strength of bonding between two bioactive ceramics in vivo.

A study was conducted to examine the mechanism and strength of bonding between two bioactive ceramic plates in vivo. Rectangular plates (15 mm X 10 mm X 2 mm) of Bioglass, apatite-wollastonite-containing glass ceramic (designated A-W.GC), and two types of hydroxyapatite sintered at 900 degrees C and 1200 degrees C (designated HA900 and HA1200) were prepared. Two plates of the same materials tied together with silk thread were implanted subcutaneously into rats. The force required to detach the mutually bonded bioactive ceramic plates was measured 4, 8, 12, and 24 weeks after implantation. The interface between the two bonded plates was examined by SEM-EPMA and thin-film x-ray diffraction analysis. At 24 weeks after implantation, the mutual bonding of Bioglass and A-W.GC was stronger than that of the two HA types. SEM-EPMA and thin-film x-ray diffraction analysis of the bonded area of Bioglass and A-W.GC plates showed bonding zones with apatite in the margins, and a bonding zone with calcite in the center. The greater strength of bonding of Bioglass and A-W.GC plates compared with the two types of HA plate 24 weeks after implantation is explained by the wider bonding zone provided by the calcite layer formed in the center of the plates, which is considered to have been perfused with PO4-poor body fluids resulting from PO4 consumption for apatite formation in the margins.

Animals↗
PubMed1992

A comparative study of ultrastructures of the interfaces between four kinds of surface-active ceramic and bone.

The interfaces between four kinds of surface-active ceramic and bone were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) using undecalcified specimens. The materials were Bioglass-type glass (Bioglass), Ceravital-type glass-ceramic (KGS), apatite- and wollastonite-containing glass-ceramic (A-W.GC) and hydroxyapatite (HA). Particles of these materials, ranging between about 100 and 300 microns in diameter, were implanted into rat tibiae, and specimens were prepared for observation at 8 weeks after implantation. All materials were observed to bond to bone through a collagen-free layer consisting of fine apatite crystals distinct from those in bone. The crystals of this apatite layer and those of bone were intermingled at their interface, suggesting chemical bonding. In Bioglass, which had only a glassy phase, several tens of microns of the material surface had changed to such an apatite layer. In KGS and A-W.GC, which had macrocrystals in the glassy phase, an intervening apatite layer about 0.5 micron thick was observed between the materials and bone. Furthermore, fine apatite crystals were also observed among the macrocrystals near the surface of the materials. In HA, which had no glassy phase, an intervening apatite layer was much less distinct and sometimes absent. These differences were considered to be attributable to the differences in chemical composition, crystallization, and solubility of the materials.

Animals↗
PubMed1992

Enhancement of bone bonding to bioactive ceramics by demineralized bone powder.

In an attempt to enhance the bonding of bone to bioactive ceramics, allogeneic demineralized bone powder (DBP) was used in combination with bioactive ceramic implants in rabbit tibiae. Rectangular plates (10 x 15 x 2 mm) made of apatite-wollastonite-containing glass ceramics were implanted in the proximal metaphyses of the bilateral tibiae of 20 rabbits, with DBP packed into the medullary cavity. In the control group, only the plates of A-W GC were implanted in the bilateral tibiae of 20 rabbits. Four rabbits from each group were killed at two, four, eight, 12, and 25 weeks after implantation for the tensile test. Results of the tensile test and histologic examination of the undecalcified specimens by Giemsa surface stain and contact microradiography confirmed that DBP significantly accelerated the process of bone bonding to the implant and increased the strength of bone-implant bonding.

Animals↗
PubMed1991

Influence of adjuvants on the antibody specificity to the Plasmodium falciparum major merozoite surface protein, gp195.

The effect of adjuvants on the specificity of immune responses to the Plasmodium falciparum gp195 protein was investigated using adjuvant formulations based on synthetic muramyl dipeptide and monophosphoryl lipid A derivatives, in parallel with CFA and alum. Although these immunomodulators were as effective as CFA in inducing an antibody response to gp195, there were distinct differences in the recognition of B cell epitopes by these antibody populations. We have also demonstrated that MHC control of antibody specificity can be related to the adjuvant used for immunization. In general, the potency of adjuvants, their ability to induce antibodies of a particular specificity, or their ability to overcome MHC control of immune responsiveness varied independently. These findings suggest a critical role of adjuvants in the determination of the specificity of the immune response to protein Ag. Thus, the influence of adjuvants should be a major consideration in studies on immunologic recognition, as well as in the design of modern subunit vaccines.

Adjuvants, Immunologic↗
PubMed1991

Rabbit antibodies against two different extracellular domains of human thyrotropin receptor possess thyroid stimulating activities.

We have produced rabbit antibodies against synthetic peptides corresponding to the mid-region (amino acid residues 172-202, C peptide) and to the unique segment near the transmembrane region (amino acid residues 341-370, P peptide) in the extracellular component of the human thyrotropin (TSH) receptor and evaluated their biological activities. Both anti-C peptide antibodies raised in two rabbits showed strong thyroid stimulating activities (TSAb) (4127% and 2548%). Anti-P peptide antibodies raised in two rabbits were also strongly positive for TSAb activities (359% and 3468%). However, none of these antibodies had TSH-binding inhibitor immunoglobulin (TBII) activities. These results suggest that the domains responsible for TSAb are likely to span the entire extracellular component of the TSH receptor.

Amino Acid Sequence↗
PubMed1991

Effects of injecting massive amounts of bioactive ceramics in mice.

The effects of massive administration of bioactive ceramic powder (Bioglass (45S5), Ceravital (KGS), apatite-wollastnite containing glass ceramics (A-W GC), and hydroxyapatite (HA], by intraperitoneal (IP), intramuscular (IM), or subcutaneous (SC) injection in Balb/c mice were examined in this investigation. Alumina, Silica Glass (SG), and A-W-Al (containing the same amount of crystal as A-W GC and 6.3% Alumina) were used as nonbioactive controls. The particle size of each material injected was smaller than 44 microns. In addition to the above, two more sizes (smaller than 105 microns and smaller than 255 microns) of A-W GC powder, and a 1 x 1 x 0.2 cm plate of the A-W GC were also evaluated. When the particle size was smaller than 44 microns, intraperitoneal injections of 5 mg per g of body weight of BG, KGS, A-W GC, and A-W-Al were lethal to the mice. Ceramics in fine powder form, which are generally believed to have higher bioactivity, are associated with higher mortality except A-W-Al. On the other hand, when the particle size of the ceramic was increased, the fatal effects of ceramic powders in mice decreased. Plate form of ceramics implanted I.P. had no systemic effects. Intramuscular or SC injections of bioactive ceramic powder with a particle size smaller than 44 microns had almost no systemic effects. Both the particle size of the ceramic powder and the route of administration influenced the reactivity of the bioactive ceramics in the mice. In conclusion, regardless of particle size, neither SC nor IM injection of large doses of highly bioactive ceramics had an adverse effect on the host (mouse).

Animals↗
PubMed1991

The bonding behavior of calcite to bone.

Plates of calcite (CaCO3) were implanted in rabbit tibiae, and their biocompatibility and bonding ability to bone were studied. The plates were also implanted subfascially in rabbit muscle for 8 weeks, and changes on their surfaces in the body were examined. Contact microradiography and Giemsa surface stain demonstrated direct bonding between calcite and bone without interpositions. The average failure load of the interface between calcite and bone was 4.11 kg, indicating an adequate strength of bonding. However, a Ca-P-rich layer, which formed on the surfaces of other bioactive ceramics in vivo, was not detected by a scanning electron microscope-electron probe x-ray microanalyzer. Scanning electron micrographs of the surface of calcite implanted subfascially for 8 weeks showed marked degradation and a rough surface. However, the surface apatite layer was not detected by thin-film x-ray diffraction analysis and Fourier transform infrared reflection spectroscopy. Calcite is a biodegradable material that bonds to bone without a surface apatite layer. The mechanical bonding provided by the anchoring effect of the newly formed bone into the surface roughness of calcite is considered to be a major factor in calcite-bone bonding.

Animals↗
PubMed1991

Bone bonding mechanism of beta-tricalcium phosphate.

It has been proposed that the formation of a surface apatite layer in vivo on surface active ceramics is an essential condition for chemical bonding between ceramics and bone tissue. To clarify the difference in bone-bonding mechanisms between surface active ceramics and bioresorbable ceramics, two experiments were performed using plates of dense beta-tricalcium phosphate (beta-TCP). First, plates of beta-TCP were implanted subcutaneously in rats for 8 weeks. Surface change due to bioresorption was observed with scanning electron microscopy. Formation of the apatite layer on the surface was investigated using thin-film x-ray diffraction and Fourier transform infrared reflection spectroscopy. Second, plates of beta-TCP were implanted in tibiae of rabbits for 8 and 25 weeks and subjected to the detaching test to measure bone-bonding strength. beta-TCP bonded strongly to bone. Undecalcified sections of the interface of bone and beta-TCP were examined with SEM-EPMA. However, by physicochemical methods, no formation of surface apatite layer was observed. These results suggest that beta-TCP bonds to bone through microanchoring between bone and rough surface of resorbed beta-TCP.

Animals↗
PubMed1991

Apatite formation on the surface of Ceravital-type glass-ceramic in the body.

Previous studies on surface structural changes in vitro as well as in vivo of bioactive A-W-type glass-ceramics and Bio-glass-type glasses showed that the essential condition for glasses and glass-ceramics to bond to living bone is formation of a bonelike apatite layer on their surfaces in the body. Gross et al., however, had explained the bone-bonding mechanism of Ceravital-type apatite-containing glass-ceramic without mentioning formation of the surface apatite layer. In the present study, apatite formation on the surface of one of Ceravital-type glass-ceramics was investigated in vitro as well as in vivo. An apatite-containing glass-ceramic of the composition Na2O 5, CaO 33, SiO2 46, Ca(PO3)2 16 wt%, which was named KGS by Gross et al., was soaked in an acellular simulated body fluid which had ion concentrations almost equal to those of the human blood plasma. The same kind of glass-ceramic was implanted into a rabbit tibia. Thin-film x-ray diffraction, Fourier transform infrared reflection spectroscopy, and scanning electron microscopic observation of the surfaces of the specimens soaked in the simulated body fluid showed that Ceravital-type glass-ceramic also forms a layer of carbonate-containing hydroxyapatite of small crystallites and/or a defective structure on its surface in the fluid. Electron probe x-ray microanalysis of the interface between the glass-ceramic and the surrounding bone showed that a thin layer rich in Ca and P is present at the interface. These findings indicated that Ceravital-type glass-ceramics also form the bonelike apatite layer on its surface in the body and bond to living bone through the apatite layer.

Animals↗
PubMed1991

Synthetic low-toxicity muramyl dipeptide and monophosphoryl lipid A replace Freund complete adjuvant in inducing growth-inhibitory antibodies to the Plasmodium falciparum major merozoite surface protein, gp195.

The Plasmodium falciparum major merozoite surface protein (gp195) is a protective antigen against lethal malaria. However, increasing evidence indicates that the efficacy of a malaria vaccine will require a strong adjuvant that is safe for human use. We compared the efficacies of two low-toxicity synthetic immunomodulators, B30-MDP (a lipophilic muramyl dipeptide derivative) and LA-15-PH (a synthetic equivalent of monophosphoryl lipid A), with that of Freund complete adjuvant (FCA) in eliciting an antibody response to gp195. Rabbits were immunized with native gp195 and B30-MDP, LA-15-PH, or the two in combination, with liposomes as the vehicle. Aluminum hydroxide and FCA were used as reference adjuvants. Results showed that adjuvant formulations based on B30-MDP alone or in combination with LA-15-PH induced high antibody titers to gp195, as compared with FCA. LA-15-PH alone was less effective. Aluminum hydroxide induced significantly lower antibody titers. The functional activity of the rabbit anti-gp195 antibodies induced by different adjuvants was evaluated in an in vitro parasite growth inhibition assay previously shown to correlate with anti-gp195 immunity in the Aotus monkey model. All rabbits immunized with B30-MDP-LA-15-PH and two of three rabbits immunized with B30-MDP alone produced sera that strongly inhibited parasite growth. The degree of growth inhibition was similar to that with FCA. The antibody titers of the rabbits receiving B30-MDP-LA-15-PH strongly correlated with the degree of in vitro growth inhibition. Our findings provided strong evidence that adjuvant formulations based on synthetic B30-MDP and LA-15-PH can replace FCA as adjuvants in stimulating protective immunity specific for gp195.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Partial degradation and biological activities of an antitumor polysaccharide from rice bran.

A rice bran polysaccharide designated RON was subjected either to partial hydrolysis with formic acid or to partial degradation by ultrasonic irradiation. A significant change in the molecular size was also observed during simple chromatography of RON on a strongly acidic ion exchange resin, although the apparent molecular weight of RON had been assumed to be more than 1 x 10(6) daltons (Da). This fact indicates that RON exists as molecular aggregates, presumably mediated by metal cations. Degradation products with average molecular weights above ca. 1 x 10(4) Da which were obtained by any of the three methods still retained the following activities of RON: in vivo antitumor activity against Meth-A fibrosarcoma in mice by oral administration, and in vitro macrophage stimulatory effects to induce tumoricidal activity and interleukin 1 production. This molecular size was proven to be the minimum requisite for these activities because smaller fragments were scarcely active. The aggregation was characteristic of RON but not essential for its antitumor activity because definite, though slightly reduced, activity was exhibited even by the smaller fragments obtained after the ion exchange resin treatment.

Animals↗
PubMed1991

[Tumor-forming type IgA (kappa) multiple myeloma developed into polyclonal hyper gamma-globulinemia after M-protein loss].

A 77 year-old female admitted with costal and right clavicular tumors and multiple osteolytic lesions. In January 1983, a diagnosis of mature type plasmacytoma was made based on the histopathological examination of the right clavicular tumor. The amounts of serum protein and IgA (kappa) M-protein were 7.5 g/dl and 2.1 g/dl, respectively. A myelogram revealed 21% of mature plasma cells with 31.3 x 10(4) nucleated cells/microliter. Four months later following a chemotherapy started in March 1983, the tumor size became smaller with undetected M-protein by an immunofixation method. Besides, a serum protein analysis showed 24.6% of gamma-globulin and 1,980 mg/dl of IgG. However, in December 1983, the right clavicular and costal tumors regrew. The second biopsy specimen showed diffuse proliferated plasmablastoid cells which reacted only to anti-kappa antibody. By August 1984, the patient had systemic subcutaneous tumors as well as polyclonal IgG up to 3,356 mg/dl suggesting rapid progression of the disease. A myelogram showed 7.4% of mature plasma cells. In December 1984, the patient died of complicated obstructive ileus due to multiple mesenteric tumor. In this study we discussed on the role of M-protein loss and increased of normal globulin level in a tumor-forming type multiple myeloma.

Aged↗
PubMed1990

Interaction mechanism between microtubule-associated proteins and microtubules. A proton nuclear magnetic resonance analysis on the binding of synthetic peptide to tubulin.

An amino acid sequence essential for microtubule-associated proteins (MAPs) to bind to microtubules is presented [Aizawa et al. (1989) J. Biol. Chem. 264, 5885-5890]. A synthetic peptide of 23 amino acid residues which corresponded to the sequence [tubulin binding peptide (TBP)] was active in binding to tubulin and inducing its assembly. The TBP-tubulin interaction mechanism was analyzed by proton nuclear magnetic resonance spectroscopy as a simplified model for MAP-microtubule interactions. Intraresidue transferred nuclear Overhauser effects (TRNOEs) of TBP in TBP-tubulin mixtures were analyzed, and strong binding of two Val and two Lys residues of TBP to tubulin was detected. Among the sharply peaked signals from tubulin aromatic residues, those due to Tyr ring protons broadened upon mixing with TBP, suggesting the involvement of Tyr residue(s) in the binding with TBP. Irradiation of the tubulin Tyr protons resulted in an intermolecular TRNOE at TBP methyl proton resonances. Evidently, hydrophobic interactions between Val and Tyr residues are important for the binding of TBP to tubulin. Hydrophobic interactions have not been taken into account previously in the widely accepted electrostatic model for the binding of MAPs to microtubules.

Amino Acid Sequence↗
PubMed1990

Microtubule assembly inhibitor protein consists of a rigid globule essential for its activity and highly mobile coils.

The structure of microtubule assembly inhibitor protein (MIP) was studied by proton nuclear magnetic resonance (NMR) and limited proteolysis. Spin-diffusion experiments revealed that MIP has a tightly folded structure, a "rigid globule." This globule was irreversibly denatured by heat treatment at 80 degrees C, and the denatured MIP showed little ability to inhibit microtubule assembly. This indicates that the native globular structure is essential for the activity. By spin-diffusion and spin-echo experiments, the other part of the molecule was found to be highly mobile. We termed the region "highly mobile coils." Most of the acidic residues appeared to be clustered in the highly mobile coils. By limited proteolysis using subtilisin, the mobile region was digested into shorter pieces, and a single 17-kDa fragment remained. Proton NMR spectrum of this fragment was much the same as the spin-diffusion subspectra of the rigid globule in the intact MIP molecule. Furthermore, the 17-kDa fragment was found to retain the activity to inhibit the microtubule assembly. These results indicate that MIP consists of two moieties; one domain forms a rigid globule which is essential for its activity to inhibit microtubule assembly, and the other acidic one is highly mobile and tails from the globule. The tertiary structures of these two domains appear to be independent from each other. These domains may be responsible for two different functions of MIP, the interaction with the cytoskeleton and the interaction with, for example, nuclear components.

Amino Acids↗