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Biomedical subjects

T Okano

Publications and source records attributed to T Okano.

At least 343 records · Page 19Linked to original sources

Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer.

Adriamycin (ADR), an anthracycline anticancer drug, was bound to the poly(aspartic acid) chain of poly(ethylene glycol)-poly(aspartic acid) block copolymer by amide bond formation between an amino group of Adriamycin and the carboxyl groups of the poly(aspartic acid) chain. The polymeric drug thus obtained was observed to form a micelle structure possessing diameter of approximately 50 nm, with a narrow distribution, in phosphate-buffered saline and to show excellent water solubility despite a large amount of ADR introduction. Further, it was able to be stored in lyophilized form without losing its water solubility in the redissolving procedure. Increased stability of the bound Adriamycin molecules in phosphate-buffered saline and elimination of binding affinity for bovine serum albumin due to the micelle formation were further advantages of this polymeric drug. In vivo high anticancer activity of this micelle-forming polymeric drug against P 388 mouse leukemia was obtained with less body weight loss than that seen with free ADR, due to low toxicity as compared with free ADR.

Animals↗

Poly(dimethylsiloxane)-poly(ethylene oxide)-heparin block copolymers. III: Surface and bulk compositional differences.

Previously observed bioactivity of poly(dimethylsiloxane)-poly(ethylene oxide)-heparin (PDMS-PEO-Hep) triblock copolymers has prompted studies of the surface and bulk character of this copolymer using angular-dependent electron spectroscopy for chemical analysis (ADESCA), static secondary mass spectroscopy (SIMS), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Because the low-energy PDMS phase dominates surfaces of this copolymer when solvent cast under air or vacuum conditions, attempts were made to explain surface restructuring and rearrangements induced in hydrated or aqueous environments that permit surface accessibility and bioactivity of heparin moieties. Based on comparisons with PDMS, PEO, and heparin homopolymers, PEO/heparin blends, and an unheparinized PDMS-PEO diblock copolymer, PDMS-PEO-heparin demonstrates both phase-mixed and phase-separated regions in DSC analysis. During annealing cycles above the Tg values of the copolymer constituents, phase-mixed regions become increasingly phase separated and PEO enriched. TGA analysis confirmed the presence block copolymer constituents and presented evidence of intermolecular segmental interactions, hence phase-mixing in the copolymers. ADESCA analysis indicates that the outer 5 A of both the PDMS-PEO and PDMS-PEO-Hep copolymers is essentially pure PDMS. However, significant amounts of PEO are detected 5 to 20 A below the surface. Static SIMS also detects the presence of PDMS at the surfaces of the PDMS-PEO and PDMS-PEO-Hep copolymers. Compositional models based on ADESCA, SIMS, and DSC data are presented for desiccated and hydrated copolymer surfaces.

Biocompatible Materials↗

Blood compatibility of PEO grafted polyurethane and HEMA/styrene block copolymer surfaces.

HEMA/styrene (HEMA/STY) block copolymers and poly(ethylene oxide) 4,000 M.W. (PEO4K) grafted Biomer (B-PEO4K) surfaces have been synthesized, characterized, and evaluated as blood-contacting materials. These surfaces have demonstrated improved blood compatibility, compared to Biomer, in in vitro and ex vivo experiments. Biomer vascular grafts (6 mm I.D. 7 cm in length) were fabricated by a dip coating process. The luminal surface was modified either with PEO grafting, HEMA/STY coating, or Biomer coating (control). These surface-modified grafts were implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. Surface protein layer thickness was measured by transmission electron microscopy (TEM). B-PEO4K and Biomer showed thick multilayers of adsorbed proteins (1000-2000 A) after 3 weeks to 1 month implantation. In contrast, HEMA/STY only showed a monolayer protein thickness (less than 200 A), even after 3 months. Visualization of adsorbed plasma proteins (albumin, IgG, and fibrinogen) was performed with scanning electron microscopy (SEM)/TEM using an immunogold double antibody technique. The pattern of protein distribution showed high concentrations of fibrinogen and IgG, and less albumin adsorbed onto Biomer and B-PEO4K. In contrast, HEMA/STY showed a patchy protein distribution pattern with high concentrations of albumin and IgG, and relatively less fibrinogen. Adsorbed monolayer patterns showed improved compatibility over multilayered proteins. The Biomer and B-PEO4K grafts occluded within 1 month, while HEMA/STY grafts were patent for over 3 months. The thin and stable adsorbed protein layer on HEMA/STY surfaces may be associated with the microdomain structures of the surface, and will play an important role in long-term in vivo blood compatibility. This manuscript will evaluate the long-term in vivo performance of these polymers, analyze the extent of protein adsorption onto the surfaces, and correlate protein layer thickness to the thrombogenicity of the polymer surfaces.

Adsorption↗

Digital subtraction of radiograph in evaluating alveolar bone changes after initial periodontal therapy.

The purpose of this study was to determine the effect of initial periodontal therapy on crestal bone remineralization with the use of a digital subtraction method for quantitative analysis. Fifteen crestal sites randomly selected from five patients were examined at the initial visit, after completion of oral hygiene instruction, and 1, 3, and 6 months after scaling and root planing with standardized radiographs. The radiographs were digitized by means of a drum-scanning microdensitometer with a sampling aperture of 50 microns producing 256 gray levels and corrected for difference of contrast between image pairs. Results were as follows: (1) statistically significant changes were observed even 1 month after the therapy and (2) the extent of changes was quantitatively expressed and monotonically increased with time. These results indicate that subtraction radiography may be a reproducible and quantitative method for the evaluation of periodontal therapy.

Alveolar Process↗

[High dose chemotherapy and autologous bone marrow transplantation for advanced germ cell tumor].

Six patients, with advanced germ cell tumor refractory to prior chemotherapy including cis-platinum and etoposide, were treated by high dose chemotherapy and autologous bone marrow transplantation. Etoposide (1200-1800 mg/m2), cyclophosphamide (120 mg/kg) and cis-platinum (60-120 mg/m2) were given and the autologous bone marrow was infused 72 hours after the last dose of chemotherapy. Two patients were treated by high dose chemotherapy three times. The regimen of the third high dose chemotherapy was etoposide (1800 mg/m2), cyclophosphamide (120 mg/kg), adriamycin (80 mg/m2), ACNU (200 mg/m2) and 254S (100 mg/m2). One patient died of cerebral hemorrhage 7 days after ABMT. Of the 5 patients evaluable for response, 4 responded: one patient obtained a complete response and 3 a partial response.

Adolescent↗

[A clinico-pathological study of small renal cell carcinoma].

Between 1960 and 1989, 50 patients with small renal cell carcinoma measuring below 3 cm in diameter were examined. Among them, 31 patients were nephrectomized, but in 19 patients, the renal cell carcinoma was found first at autopsy. The average tumor diameter of the unrecognized ones was smaller than that of nephrectomized patients with the minimum of 0.4 cm. Forty-one patients had clear cell carcinoma, 9 granular cell carcinoma, 40 grade 1 tumor, and 10 grade 2 tumor. The grade 3 tumor was not found in our study. Three out of the 50 patients had distant metastasis at the time of operation or autopsy. Six patients had microscopic tumor thrombi just close to the tumor pseudo-capsule. Two patients had apparent tumor thrombi in the main renal vein. The smallest tumor that showed microscopic tumor thrombi measured 1.5 cm in diameter. The incidence of tumor thrombi was correlated with tumor diameter. The step sections by 4 mm thick of nephrectomized specimens were examined on 16 patients. The daughter tumor was found in two patients. The tumor thrombi had close relationships with the presence of distant metastasis (p less than 0.001) and/or the daughter tumor (p less than 0.01). In conclusion, small renal carcinoma measuring less than 1.5 cm in diameter was considered to be treated by conservative surgery.

Adult↗

[Structure of medical X-ray films].

Characteristic comparisons were made on various medical and dental X-ray films such as Agfa-Gevart, Dupont, Hanshin, Kodak, Konica, Nix, Sun Dental film. 1) Silver grains coated on the film base of regular and dental films showed a round (polyhedron) or potato-like shape. Grains of orthochromatic films were hexagonal or triangular in shape, although those of Konica orthochromatic films were small and round. 2) Size of silver grains ranged from 1.09 microns in the Fuji HRS film to 2.09 microns in the Konica film. 3) Thickness of the film base was the same (170 microns) in all types of film. 4) Thickness of the emulsion layer was 7 microns for non-screen type film, whereas that in the screen type was 4 microns to 8 microns. 5) Size of the silver grain of Kodak Ekta speed was large, and the thickness of the emulsion of this film was thin when compared to others. 6) In screen type films, the silver grains were only sparsely coated. In the non-screen type, however, a large number of silver grains were coated compactly on the film base. 7) Kodak TMG (T-mat) showed flattened silver grains which were piled up on the film layer.

Radiography, Dental↗

Interaction of ofloxacin with organic cation transport system in rat renal brush-border membranes.

Ofloxacin, a pyridonecarboxylic acid derivative, was examined for its effects on the transport of tetraethylammonium (cation), cephalexin and cephradine (zwitterions), p-aminohippurate (anion) and D-glucose in brush-border membrane vesicles isolated from rat renal cortex. The initial uptake of tetraethylammonium in the presence or absence of an outward H+ gradient was inhibited by ofloxacin in a dose-dependent manner, although the equilibrium value of tetraethylammonium uptake was not affected. This inhibition occurred in a competitive manner (Ki = 0.11 mM). Ofloxacin also inhibited the initial uptake of cephalexin and cephradine, which can be transported via the H+/organic cation antiport system in renal brush-border membranes. In contrast, ofloxacin had no effect on p-aminohippurate. These data suggest that ofloxacin interacts with the organic cation transport system in renal brush-border membranes, and this system may play an important role in the tubular secretion of ofloxacin.

Animals↗

Transport mechanisms of bestatin in rabbit intestinal brush-border membranes: role of H+/dipeptide cotransport system.

Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine], a potent inhibitor of aminopeptidase B and leucine aminopeptidase, enhances the immune response to activate the defense mechanism of the living organism and suppresses the growth and metastasis of cancer. Bestatin has been effectively used by p.o. administration, but the mechanisms of intestinal absorption remain to be solved. The present study was undertaken to examine whether bestatin, a dipeptide containing an unusual amino acid, is transported via dipeptide carriers in intestinal brush-border membranes, by using cephradine as a probe for the H+/dipeptide cotransport system. The initial uptake of cephradine in the presence or absence of an inward H+ gradient, driving force, was inhibited by bestatin and this inhibition occurred in a competitive manner (Ki = 0.47 mM). The uptake of cephradine was stimulated by the countertransport effect of bestatin, the definitive criterion for ascertaining a common transport system. These findings indicate that bestatin, as well as cephradine and other p.o. cephalosporins, can be transported via dipeptide carriers in intestinal brush-border membranes.

Adjuvants, Immunologic↗