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Biomedical subjects

T Okano

Publications and source records attributed to T Okano.

At least 397 records · Page 22Linked to original sources
PubMed1988

H+ coupled transport of p.o. cephalosporins via dipeptide carriers in rabbit intestinal brush-border membranes: difference of transport characteristics between cefixime and cephradine.

We demonstrated previously that aminocephalosporins, such as cephradine, possessing a alpha-amino group and a carboxyl group, are transported via H+/dipeptide carrier system in the intestinal brush-border membranes. The present study examined the transport characteristics of cefixime, a new p.o. cephalosporin with two carboxyl groups, by the rabbit intestinal brush-border membrane vesicles in comparison with those of cephradine. With an intravesicular pH of 7.5, apparent optimum extravesicular pH was 6.0 for cephradine uptake and more acidic (pH 4.5-5.0) for cefixime uptake. An inward H+ gradient [( pH]i = 7.5, [pH]o = 5.0) induced overshoot uptake of cefixime, and this uptake was reduced in the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, a protonophore. Cefixime uptake at pH 5.0 was trans-stimulated (countertransport effect) and cis-inhibited by dipeptides and aminocephalosporins but not at pH 7.5. Cephradine uptake at pH 7.5 was stimulated by the countertransport effect of dipeptide but not by cefixime. Cefixime and cephradine uptake at pH 5.0 was greatly inhibited by 4,4'-diisothiocyano-2,2'-disulfonic stilbene. These findings indicate that cefixime is transported by an inward H+ gradient via dipeptide carrier only in an acidic pH region, whereas cephradine is transported via dipeptide carrier in both neutral and acidic pH regions, suggesting the existence of multiple transport systems for dipeptides; a neutral pH preferring system (Type I) and an acidic pH preferring system (Type II).

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Coexistence of CREST syndrome and primary biliary cirrhosis. Serological studies of two cases.

Two patients with characteristic features of CREST syndrome and primary biliary cirrhosis are reported. Sera of both patients contained autoantibodies to centromere and mitochondrial antigens. Immunodiffusion analysis identified the specificities of precipitating antibodies to mitochondria of the first case as anti-M-A and M-C, and of the second case as anti-M-A and M-B antibodies. Simultaneous occurrence of 2 marker antibodies in an individual patient indicates that the 2 patients reported here have CREST syndrome and primary biliary cirrhosis, both of which are considered as a distinct clinical entity.

Aged↗
PubMed1987

Prophylaxis of superficial bladder cancer with instillation of adriamycin or mitomycin C.

A multicenter trial for postoperative prophylaxis of superficial Ta-T1, G1-G2 bladder cancer was performed. Intravesical instillation using either 20-30 mg adriamycin or 20 mg mitomycin C per dose was carried out for 4 weeks or 2 years. Patients without instillation served as controls. A total of 259 patients was considered eligible for the evaluation. The instillation group showed a better disease free survival rate than the control group. Better prophylactic effects of instillation therapy were observed when one of following factors was present: multiple tumors, large tumors, T1 and G2 bladder cancer. The total dose of drug instilled seemed to correlate with the effects, but there were no differences between adriamycin and mitomycin C. The side effects were minimal and temporary.

Administration, Intravesical↗
PubMed1987

Neurochemical effects following AF64A injection into the basal nuclei of rats.

AF64A, a specific cholinergic neurotoxin, was injected into the basal nuclei of rats. The injected sites were the bilateral nucleus basalis of Meynert (NBM) and the medial septal nucleus (MSN), well known to be the nuclei of origin of the two major cholinergic pathways. The remote effects of injection were estimated by the regional choline acetyltransferase (CAT) activity in the frontal cortex, striatum and hippocampus. The injection of AF64A (1 nmol in 1 microliter) produced a reduction in the CAT activity in each projected site: NBM lesions in the frontal cortex and MSN lesions in the hippocampus after one and three weeks. Twelve weeks after the injection, the reduced CAT activity had returned to normal levels. This neurochemical effect shows plasticity and recovery with time. The injections of small amounts of AF64A (0.2 and 0.1 nmol in 1 microliter) produced no chemical changes after one week.

Acetylcholinesterase↗
PubMed1987

Effect of sulfhydryl reagents on tetraethylammonium transport in rat renal brush border membranes.

Effect of sulfhydryl reagents on the transport of tetraethylammonium, an organic cation, has been studied in brush border membrane vesicles isolated from rat renal cortex. H+ gradient-dependent uptake of tetraethylammonium by the vesicles was inhibited by various sulfhydryl reagents in a dose-dependent manner, and the potency of the reagents was followed in the order of HgCl2 greater than p-chloromercuribenzoate, p-chloromercuribenzene sulfonate (PCMBS) greater than N-ethylmaleimide. In the absence of H+ gradient, tetraethylammonium uptake and efflux also were inhibited by p-chloromercuribenzoate and PCMBS. The sulfhydryl reagents did not affect the dissipation rate of H+ gradient across the membranes. Pretreatment of brush border membranes with PCMBS resulted in an inhibition of tetraethylammonium uptake in the presence and absence of H+ gradient, and this inhibition was reversed by subsequent treatment of the vesicles with thiols such as dithiothreitol, glutathione and cysteine. The inhibitory effect by PCMBS pretreatment was protected in the preincubation with unlabeled tetraethylammonium. These results suggest that sulfhydryl reagents inhibit the transport of tetraethylammonium by their specific interaction with the active sites of the carrier, and that sulfhydryl groups are essential for organic cation transport system in renal brush border membranes.

4-Chloromercuribenzenesulfonate↗
PubMed1986

H+ coupled uphill transport of aminocephalosporins via the dipeptide transport system in rabbit intestinal brush-border membranes.

The transport characteristics of aminocephalosporin antibiotics, possessing an alpha-amino group and a carboxyl group, in brush-border membranes isolated from rabbit small intestine have been studied by a rapid filtration technique. The uptake of cephradine by brush-border membrane vesicles was stimulated by the countertransport effect of dipeptides, which indicates the existence of a common carrier transport system. An inward H+ gradient ([pH]i = 7.5 to 8.4, [pH]o = 6.0) stimulated cephradine uptake against a concentration gradient (overshoot phenomenon), and this stimulation was reduced when the H+ gradient was subjected to rapid dissipation by the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, a protonophore. A valinomycin-induced K+ diffusion potential (interior-negative) stimulated H+ gradient-dependent cephradine uptake without altering the equilibrium value. The uptake of other aminocephalosporins (cefadroxil, cefaclor, cephalexin) was also stimulated in the presence of an inward H+ gradient, while the uptake of cephalosporins without the alpha-amino group (cefazolin, cefotiam) was not changed in the presence or absence of the H+ gradient. These results suggest that the transport of aminocephalosporins can be driven actively by an inward H+ gradient via the dipeptide transport system in the intestinal brush-border membranes, and that the process results in the transfer of a positive charge.

Animals↗
PubMed1986

Specific binding of atrial natriuretic polypeptide to renal basolateral membranes in spontaneously hypertensive rats (SHR) and stroke-prone SHR.

The binding of alpha-human atrial natriuretic polypeptide (alpha-hANP) to basolateral membranes isolated from renal cortex of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHR-SP) was measured at 0 degree C and compared with that of Wistar-Kyoto rats (WKY). The binding of 125I-alpha-hANP in SHR and SHR-SP at 14-15 weeks old demonstrated different binding profiles compared with that in WKY, though there were no apparent differences of the profiles among WKY, SHR and SHR-SP at 5 weeks old. For the high affinity binding sites, the apparent dissociation constant and the maximal binding capacity in SHR and SHR-SP were significantly decreased in comparison with those in WKY. The present data suggest that the altered characteristics of specific receptors for atrial natriuretic polypeptide in SHR and SHR-SP may be involved in the development or maintenance of genetic hypertension.

Age Factors↗
PubMed1986

H+ gradient-dependent transport of aminocephalosporins in rat intestinal brush-border membrane vesicles. Role of dipeptide transport system.

The transport of cephalosporin antibiotics in brush-border membrane vesicles isolated from rat small intestine has been studied by a rapid filtration technique, demonstrating a carrier-mediated transport system for aminocephalosporins such as cephradine. In agreement with the transport mechanisms of dipeptides, the uptake of cephradine by brush-border membrane vesicles was Na+-independent and was stimulated in the presence of an inward H+ gradient ([H+]o greater than [H+]i). Cephradine uptake in the presence of an inward H+ gradient was a saturable process with an apparent Km of 9.4 mM, and was markedly inhibited by dipeptides but not inhibited by amino acids. The present data suggest that aminocephalosporins can be transported by a common carrier-mediated system with dipeptides in the intestinal brush-border membranes and this process may be driven by an H+ gradient.

Amines↗
PubMed1986

Role of chloride on carrier-mediated transport of p-aminohippurate in rat renal basolateral membrane vesicles.

Effect of inorganic anions on p-amino[3H]hippurate transport in renal basolateral membranes has been studied using the vesicles preloaded with unlabeled p-aminohippurate (countertransport condition). The uptake of p-amino[3H]hippurate was stimulated by the outward gradient of unlabeled p-aminohippurate and the labeled substrate was accumulated into the vesicles against its concentration gradient in the presence of Cl-. The substitution of SCN- and SO4(2-) for Cl- in both sides of the vesicles depressed the initial rate and the overshoot magnitude of p-amino[3H]hippurate uptake. These results suggest that Cl- may play an important role for the carrier-mediated transport system of organic anion in renal basolateral membranes.

Aminohippuric Acids↗
PubMed1986

Adhesion behavior of rat lymphocyte subpopulations (B cell and T cell) on the surface of polystyrene/polypeptide graft copolymer.

Polyvinyl/polypeptide graft copolymers having microdomain structure on their surfaces were newly synthesized for the development of a specific cell separator, and the adhesion behavior of rat lymphnode lymphocytes with these materials was examined by column method. Morphologic change of lymphocytes adherent to the graft copolymers was found to be less than that of cells adherent to corresponding homopolymers, i.e., polystyrene and poly (gamma-benzyl L-glutamate). Separation of lymphocyte subpopulations (B cell and T cell) was examined in the absence of serum proteins. The adhesion selectivity for B cell was found to depend on the microdomain structure, since the highest value, 2,2, was observed for the graft copolymer with the polypeptide content of 50 wt%. Synthetic polypeptide derivatives may be promising materials which substitute for a conventional system with nylon fiber and fetal calf serum.

Animals↗
PubMed1986

Hydrophilic-hydrophobic microdomain surfaces having an ability to suppress platelet aggregation and their in vitro antithrombogenicity.

Block copolymers were synthesized by a coupling reaction of hydrophilic chains of poly(2-hydroxyethyl methacrylate) (PHEMA) with hydrophobic chains of polystyrene (PSt), or poly(dimethyl siloxane) (PDMS). Microstructures of films of the block copolymers exhibited a hydrophilic-hydrophobic microphase separated structure. For evaluation of in vivo antithrombogenicity, small diameter tubes (1.5 mm I.D. and 20 cm length) coated by the copolymers on their internal surfaces were implanted in rabbits as arteriovenous shunts. Occlusion times of the tubes, measured by formation of thrombus, were three days for PHEMA, two days for PSt, and three days for PDMS. The block copolymers showed excellent antithrombogenic properties: occlusion times were 20 days for HEMA-St block copolymer and 12 days for HEMA-DMS block copolymers. In vitro examination of polymer-platelet interaction in terms of platelet adhesion and aggregation, which are important initial processes of blood coagulation, demonstrated suppressed adhesion and aggregation on microdomain surfaces constructed of hydrophilic and hydrophobic block copolymers. From both in vivo and in vitro examination, it was concluded that HEMA-St and HEMA-DMS block copolymers showed promising antithrombogenic activities by suppressing activation and aggregation of platelets.

Animals↗
PubMed1986

Effect of microstructure of poly(propylene-oxide)-segmented polyamides on platelet adhesion.

The relationship between microstructure and platelet adhesivity of six types of poly(propylene oxide) (PPO)-segmented polyamides based on the polyamide segments nylon 210, 310, 410, 510, 610, and 710 were investigated. These multiblock PPO-segmented copolymers were prepared by interfacial polycondensation. Physical characterization of these copolymers was by means of thermal analysis, transmission electron microscope, wide-angle X-ray diffraction (WAXD), and small-angle X-ray scattering (SAXS). The WAXD and SAXS measurements showed that the copolymers had microstructures containing crystalline and amorphous phases and that these microstructures, represented by means of crystallite thickness and long period, varied with incorporation of PPO segments. Blood compatibility of these copolymers was evaluated by estimating the amount of adhering platelets on the copolymer surfaces. The amount of adhering platelets was minimum for the surfaces of the copolymers having a crystallite thickness of 6.0-6.5 nm and a long period of 12-13 nm. This result suggests that the particular size and distribution of the crystalline and amorphous phases in the copolymer could be determining factors for suppressing platelet adhesion on the copolymer surface, and that the control of these factors could lead to ideal antithrombogenic polymers.

Animals↗
PubMed1986

Suppression of platelet activity on microdomain surfaces of 2-hydroxyethyl methacrylate-polyether block copolymers.

Block copolymers constructed from chains of poly(2-hydroxyethyl methacrylate) (PHEMA) and either poly-ethyleneoxide (PEO) or poly-propyleneoxide (PPO) were synthesized. These block copolymers exhibited microdomain structure. Platelet adhesion on their surfaces was investigated by a column elution method to examine the effect of microdomain structure. The number of platelets adhered from whole blood was smaller for the block copolymer systems than for the homopolymers. Minimum points of platelet adhesion appeared at approximately 0.38 mol fraction of HEMA in the HEMA-PO system. Both block copolymer surfaces showed microdomains of alternate lamellar structure. Furthermore, the percent of platelets released from the column after incubation was investigated using PRP. In the case of homopolymers, released platelet percentages decreased with an increase of incubation time. Released platelet percentages from the block copolymers, however, were nearly constant with changing incubation time. These results show that HEMA-EO and HEMA-PO block copolymers had the ability to suppress both reversible and irreversible adhesion of platelets to their respective microdomain surfaces.

Animals↗
PubMed1986

Streptococcal preparation (OK-432) inhibits development of type I diabetes in NOD mice.

OK-432 (a streptococcal preparation) has been widely used for cancer immunotherapy in Japan. It is the most potent immunomodulator in activating both macrophages and killer T cells and in increasing interleukin 2 production. Two K.E. (Klinische Einheit, clinical unit) of OK-432 were given intraperitoneally to each of 17 female nonobese diabetic (NOD) mice every week from 4-24 wk of age. NOD mice as well as BB rats spontaneously develop type I diabetes. During administration of OK-432, the development of diabetes was inhibited in 17 of 17 mice over the 24-wk observation period, whereas 14 of 17 female NOD mice given physiological saline had developed diabetes by 24 wk of age. At the onset of diabetes, nonfasting blood glucose was 511 +/- 82 mg/dl. Histologic examination showed that in the OK-432-treated NOD mice, 98% of total islets were intact or mildly infiltrated with mononuclear cells, whereas in saline-treated NOD mice, 79% of total islets exhibited severe insulitis. In OK-432-treated NOD mice, both the number of the mononuclear spleen cells and their natural killer cell activity was significantly increased.

Animals↗
PubMed1986

Tissue distribution of 7-dehydrocholesterol, vitamin D3 and 25-hydroxyvitamin D3 in several species of fishes.

A high-performance liquid chromatographic (HPLC) method for simultaneous determination of 7-dehydrocholesterol (7-DHC), vitamin D3 and 25-hydroxyvitamin D3 (25-OH-D3) in tissues of fishes was established, and using this method the tissue distribution of the sterols in lamprey (Entosphenus japonicus), great blue shark (Prionace glauca), skipjack (Katsuwonus pelamis) and albacore (Thunnus alalunga) was investigated. The results are summarized in the following: Although the alimentary canal, gall bladder and roe of lamprey and the alimentary canal of great blue shark contained comparatively high levels of 7-DHC (higher than 2,000 ng/wet tissue g), the other tissues of lamprey and great blue shark and all tissues of skipjack and albacore contained only low levels of 7-DHC (lower than 1,000 ng/g). There was no significant correlation between the levels of 7-DHC and vitamin D3. The contents of 7-DHC in the skin of skipjack and albacore were only 1/1,000 of those in the skin of rats. Although the contents of vitamin D3 in the liver of skipjack and albacore were extremely high (41,240 and 21,000 ng/g, respectively), those in the skin were very low (454 and 257 ng/g, respectively). 25-OH-D3 was detected in the viscera of skipjack, but the levels were not very high (lower than 150 ng/g). These levels were not significantly correlated with those of vitamin D3. The results suggest that large quantities of vitamin D3 in the liver of skipjack and albacore are supplied by other biosynthetic routes or by intake of vitamin D3 rather than by photochemical biosynthesis.

Animals↗