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Biomedical subjects

S Yoshihara

Publications and source records attributed to S Yoshihara.

At least 73 records · Page 4Linked to original sources

Clinical application of transiently evoked otoacoustic emissions after glycerol administration for diagnosis of sensorineural hearing loss.

Pure-tone audiometry and transiently evoked otoacoustic emission (TEOAE) measurements were made before and after glycerol administration in the ears of sensorineural hearing loss with three different clinical entities, i.e. Meniere's disease, cochlear Meniere's disease and unilateral sensorineural hearing loss of unknown cause without hearing fluctuation (SNHLWF). TEOAE was evoked after glycerol administration in several ears of Meniere's disease and cochlear Meniere's disease, in which it was not evoked before glycerol administration. Especially in patients with cochlear Meniere's disease, TEOAE was altered without an accompanying significant change in mean hearing level. The change in TEOAE after glycerol administration indicates that the active motile property of outer hair cells may be affected by endolymphatic hydrops.

Adult↗

Long lasting smooth muscle relaxation by a novel PACAP analogue in guinea-pig and primate airways in vitro.

1. We compared the relaxant effect of pituitary adenylate cyclase activating peptide (PACAP) 1-27 with that of a newly developed PACAP 1-27 analogue, [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2, in the guinea-pig trachea and primate bronchi in vitro (n = 4-5). 2. In the guinea-pig trachea precontracted by a submaximally effective carbachol concentration (0.1 microM), cumulative administration of PACAP 1-27 and the beta 2-adrenoceptor agonist salbutamol (3 nM-3 microM) caused significant and concentration-dependent smooth muscle relaxation, with salbutamol being approximately one log-step more potent in this model. However, in primate bronchi precontracted by carbachol (0.1 microM), cumulative administration of PACAP 1-27 and salbutamol caused concentration-dependent smooth muscle relaxation with very similar potencies and maximum relaxant effects. 3. In the guinea-pig trachea, non-cumulative administration of the PACAP 1-27 analogue and the original PACAP 1-27 (0.3-3 microM) caused concentration-dependent relaxation with a very similar maximum relaxant effect and potency. However, the onset and offset of action was markedly slower for the PACAP 1-27 analogue than for the original PACAP 1-27 (< 90% versus < 10% of peak relaxation remaining 6 h after administration). Separate experiments confirmed that the PACAP 1-27 analogue also caused significant relaxation with slower onset and offset of action than did the original PACAP 1-27 in primate bronchi. 4. Peptidase inhibition by captopril (10 microM) and phosphoramidon (1 microM) significantly increased the maximum relaxant effect and duration of action of PACAP 1-27 but not of the PACAP 1-27 analogue, during the 3 h of observation in the guinea-pig trachea. 5. We conclude that [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2 produces significant, concentration-dependent and sustained airway smooth muscle relaxation in vitro. The sustained relaxant effect is due, at least in part, to the PACAP 1-27 analogue being less susceptible to cleavage by peptidases than the original peptide PACAP 1-27.

Albuterol↗

Early gastric cancer and lymph node metastasis.

A total of 1,845 cases of gastric cancer have been resected in our hospital during the past 18 years. Of these, 764 cases (41.5%) were early gastric cancer. The rate of lymph node metastasis was 2% in early mucosal cancer and 19.4% in early submucosal cancer (p < 0.001). In the cases of early mucosal cancer, the rate of lymph node metastasis was 0.9% for the elevated type and 2.4% for the depressed type. In the cases of early submucosal cancer, the rate of lymph node metastasis was 25.3% for the elevated type and 17.3% for the depressed type. In the mucosal cancers the rate of lymph node metastasis was high in the 0-IIc and IIc + III macroscopic type, and in the poorly differentiated microscopic type. In the submucosal cancers the rate of lymph node metastasis was 40% in mucinous adenocarcinoma and 33% in papillary adenocarcinoma. There was no lymph node metastasis in any case of early gastric cancer smaller than 1 cm surface diameter.

Adult↗

Bone bonding ability of bioactive bone cements.

The bone bonding ability of three types of bioactive bone cement A, B, and C consisting of glass or glass ceramic powder and bisphenol-alpha-glycidyl methacrylate resin was evaluated. Type A contained MgO-CaO-SiO2-P2O5-CaF2 glass powder; Type B, MgO-CaO-SiO2-P2O5-CaF2 glass ceramic powder; and Type C, MgO free CaO-SiO2-P2O5-CaF2 glass powder. Rectangular plates (2 x 10 x 15 mm) of Types A, B, C, and polymethylmethacrylate cements were implanted into the tibial metaphyses of male rabbits and the failure load measured by mechanical failure testing (detaching test) 10 and 25 weeks after implantation. The failure loads of Types A, B, C, and polymethylmethacrylate cements were respectively, 29.52, 41.48, 28.22, and 0.29 N at 10 weeks and 33.42, 41.27, 33.64, and 0.20 N at 25 weeks. Examination of the bone cement interface revealed that all the bioactive bone cements achieved direct bone contact with the bone. These results showed that all three types of bioactive bone cement have the ability to bond to bone, and the cement containing glass ceramic powder revealed higher bonding strength than did those containing glass powder.

Animals↗

The in vitro and in vivo indomethacin release from self-setting bioactive glass bone cement.

The in vivo and in vitro drug release profiles from a self-setting bioactive CaO-SiO2-P2O5 glass bone cement containing indomethacin as a model drug were investigated. The cement containing 2% and 5% indomethacin (IMC) powder hardened within 5 min after mixing with ammonium phosphate buffer. After setting, in vitro drug release from drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for two weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite during the drug release test in SBF. An IMC-loaded cement device (2% and 5% drug) was implanted in the subcutaneous tissue on the back of rats. The in vivo IMC release from the cement increased and attained maximum levels (Cmax of 2% and 5% drug-loaded cements was 0.27 and 3.37 micrograms/ml, respectively) at Tmax, 3 and 0.5 d, respectively, upon subcutaneous (s.c.) administration in rats. This suggested that the s.c. administration of the cement provided IMC release for a much longer period than s.c. administration of the solution, and the plasma IMC concentration was dependent on the drug concentration in the cement. The plasma IMC concentration and the area under the curve from 2% and 5% IMC-loaded cements in rats were dependent on the concentration of IMC in the cements. The in vivo IMC concentration in plasma obtained by the deconvolution method was much lower than that delivered in SBF in vitro. Scanning electron microscopy and photomicrographs of cross sections showed that the bioactive bone cement had excellent biocompatibility with the surrounding soft tissues.

Animals↗

Increased liposome extravasation in selected tissues: effect of substance P.

We have used a pharmacologic mediator to open intercellular connections in selected vessels to allow liposomes to escape from the blood stream and to extravasate into tissues that have appropriate receptors. We have examined the effects of substance P (SP), a peptide known to increase vascular permeability in selected tissues, such as trachea, esophagus, and urinary bladder in rats. We used quantitative fluorescence analysis of tissues to measure two fluorescent markers, one attached to the lipid (rhodamine-phosphatidylethanolamine) and another, doxorubicin (an anti-tumor drug), encapsulated within the aqueous interior. We have also examined the deposition of liposomes microscopically by the use of encapsulated colloidal gold and silver enhancement. Analysis of the biochemical and morphological observations indicate the following: (i) Injection of SP produces a striking increase in both liposome labels, but only in tissues that possess receptors for SP in postcapillary venules; (ii) liposome material in these tissues has extravasated and is found extracellularly near a variety of cells beyond the endothelial layer over the first few hours; (iii) 24 h following injection of liposomes and SP, liposome material is found in these tissues, localized intracellularly in both endothelial cells and macrophages. We propose that appropriate application of tissue-specific mediators can result in liposome extravasation deep within tissues that normally do not take up significant amounts of liposomes from the blood. Such liposomes are able to carry a variety of pharmacological agents that can be released locally within selected target tissues for therapeutic purposes.

Animals↗

Cold air-induced bronchoconstriction is mediated by tachykinin and kinin release in guinea pigs.

In the present study, we investigated the role of acetylcholine, tachykinins and kinins in the bronchoconstriction induced by cold air inhalation. Cold air was delivered to anaesthetised, artificially ventilated guinea pigs through a tracheal cannula. Inhalation of cold air increased the maximum total pulmonary resistance (RL) in a time-dependent manner, reaching a maximum after 15 min of exposure. The increase in RL induced by exposure to cold air for 10 min was not affected by pretreatment with atropine (1.4 mu mol/kg, i.v.); it was abolished by the tachykinin NK2 receptor antagonist, SR 48968 (0.3 mu mol/kg, i.v.) and was reduced by 58% by the kinin B2 receptor antagonist, HOE 140 (0.1 mu mol/kg, i.v.). These findings suggest that cold air induces bronchoconstriction in guinea pigs via a cascade that involves the release of kinins and tachykinins.

Animals↗

Mechanical and biological properties of two types of bioactive bone cements containing MgO-CaO-SiO2-P2O5-CaF2 glass and glass-ceramic powder.

In this study two types of bioactive bone cement containing either MgO-CaO-SiO2-P2O5-CaF2 glass (type A) or glass-ceramic powder (type B) were made to evaluate the effect of the crystalline phases on their mechanical and biological properties. Type A bone cement was produced from glass powder and bisphenol-a-glycidyl methacrylate (BIS-GMA) resin, and type B from glass-ceramic powder containing apatite and wollastonite crystals and BIS-GMA resin. Glass or glass-ceramic powder (30, 50, 70, and 80 by wt %) was added to the cement. The compressive strength of type A (153-180 MPa) and B (167-194 MPa) cement were more than twice that of conventional polymethylmethacrylate (PMMA) cement (68 MPa). Histological examination of rat tibiae showed that all the bioactive cements formed direct contact with the bone. A reactive layer was seen at the bone-cement interface. In specimens with type A cement the reactive layer consisted of two layers, a radiopaque outer layer (Ca-P-rich layer) and a relatively radiolucent inner layer (low-calcium-level layer). With type B cement, although the Ca-P-rich layer was seen, the radiolucent inner layer was absent. Up to 26 weeks there was progressive bone formation around each cement (70 wt %) and no evidence of biodegradation. The mechanical and biological properties of the cements were compared with those of a previously reported bone cement containing MgO-free CaO-SiO2-P2O5-CaF2 glass powder (designated type C).

Animals↗

Tachykinins mediate the potentiation of antigen-induced bronchoconstriction by cold air in guinea pigs.

The role of tachykinins in the potentiation of antigen-evoked bronchoconstriction induced by inhalation of cold air was studied in guinea pigs. Cold air was delivered through a tracheal cannula to anesthetized, artificially ventilated guinea pigs sensitized with ovalbumin and pretreated with atropine (1.4 micromol/kg). Inhalation of cold air increased total pulmonary resistance (RL) in a time-dependent manner; inhalation of cold air for 10 or 15 minutes, but not for 5 minutes, produced a significant increase in RL. Aerosolized ovalbumin (5 breaths) increased RL in a dose-dependent manner (0.5% to 5%). Inhalation of cold air for 5 minutes significantly enhanced both the peak and the duration of the increase in RL induced by 0.5% ovalbumin. The tachykinin neurokinin 2-receptor antagonist, SR 48968 (0.3 micromol/kg intravenously) inhibited both the peak and the duration of the bronchoconstriction induced by 5-minute inhalation of cold air and ovalbumin (0.5%), whereas it did not affect the response to ovalbumin (0.5%) alone. These findings suggest that exposure to cold air potentiates the bronchoconstriction response to antigen and that this potentiation is mediated by tachykinin release from sensory nerves.

Airway Resistance↗

Effect of cilostazol, a novel anti-platelet drug, on restenosis after percutaneous transluminal coronary angioplasty.

The possible preventive effect of cilostazol, a novel anti-platelet drug, on restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) was examined. One hundred and two consecutive patients, who underwent successful PTCA, were followed for 3 to 6 months. To prevent restenosis, 46 patients (60 PTCA sites) were treated with cilostazol alone (200 mg/day) (cilostazol group) and the remaining 56 (61 PTCA sites) were treated with other anti-platelet drugs and/or warfarin potassium (control group). Restenosis was defined as a more than 50% loss of the initial gain of the coronary diameter achieved by PTCA. Cilostazol did not significantly reduce the patient or lesion restenosis rate; the patient restenosis rate was 32% in the control group and 22% in the cilostazol group (P = 0.24), and the lesion restenosis rate was 30% in the control group and 23% in the cilostazol group (P = 0.44). However, the lesion non-progression rate, which was defined as the incidence of lesions with either no change or regression of coronary stenosis at the PTCA site, was significantly greater with cilostazol (37%) than in the control group (16%) (p < 0.05). Although cilostazol failed to show a significant reduction in restenosis after PTCA, the present results suggest that a further trial with a larger number of patients is needed to confirm its usefulness.

Aged↗

Granulocyte activation in restenosis after percutaneous transluminal coronary angioplasty.

To examine whether or not granulocyte activation is involved in restenosis after percutaneous transluminal coronary angioplasty (PTCA), we prospectively followed the time course of the plasma level of granulocyte elastase, which is an index of granulocyte activation, before and after successful angioplasty in 43 consecutive patients. Restenosis was defined as a more than 50% loss of the initial gain in the coronary diameter achieved by PTCA with more than a 50% resultant stenosis in the follow-up coronary arteriography performed 3 months after PTCA. There was no difference in the level of granulocyte elastase between the 2 groups with (n = 15) and without (n = 28) restenosis before, the day after and 1 month after PTCA. However, 3 months after PTCA, the level of granulocyte elastase was significantly higher in the group with restenosis than in that without restenosis (171 +/- 13 vs 147 +/- 6 mg/l, P < 0.05). The level of granulocyte elastase at 3 months after PTCA also correlated significantly with the percent luminal stenosis at the angioplasty site (P < 0.05). These results suggest that granulocyte activation may be involved in restenosis after PTCA.

Adult↗

Corticotropin-releasing factor inhibits antigen-induced plasma extravasation in airways.

We investigated the potential of corticotropin-releasing factor (CRF) to reduce neurogenic plasma extravasation in sensitised guinea pig airways evoked by antigen challenge. Inhalation of 5% ovalbumin for 2 min in the presence of phosphoramidon (2.5 mg/kg, i.v.) increased extravasation of Evans blue dye in the trachea and main bronchi. The increase in plasma extravasation induced by antigen challenge was significantly reduced by pretreatment with CRF (30 nmol/kg, i.v.) (73% in the trachea and 42% in the main bronchi). The inhibition of plasma extravasation by CRF (30 nmol/kg, i.v.) alone was not different from the inhibition induced by the combination of CRF and the tachykinin NK1 receptor antagonist, CP-99,994 (4 mg/kg, i.v.) (73% in the trachea and 38% in the main bronchi). CRF (30 nmol/kg, i.v.) inhibited by 32% in the trachea and by 43% in the main bronchi plasma extravasation induced by aerosolised bradykinin but did not reduce the plasma extravasation caused by aerosolised substance P in the presence of phosphoramidon. These findings suggest that CRF reduces ovalbumin-induced plasma extravasation in guinea pig airways by inhibiting the release of tachykinins from primary sensory nerves.

Animals↗

Drug release from a novel self-setting bioactive glass bone cement containing cephalexin and its physicochemical properties.

A novel device containing cephalexin as a model drug using a self-setting bioactive cement based on CaO-SiO2-P2O5 glass was investigated. The device consisted of 95 wt/wt% glass powders and 5 wt/wt% cephalexin powder hardened within 5 min after mixing with a phosphate buffer. After setting, in vitro drug release from homogeneous or heterogeneous drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for over 4 weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite with high bioactivity in hard bone tissue and reduced in volume by about 5% during dissolution testing in SBF. Consequently, 30% of the loaded drug was squeezed from the cement system at the initial stage of the drug release, and the remainder released more slowly. Because the heterogeneous system consisting of the cement and drug-loaded pellet avoided the drug-squeezing effect, it showed a longer drug release term than the homogeneous drug-loaded cement. The heterogeneous system using the hardened cement after soaking in SBF at 37 degrees C for 10 days showed very slow drug release at the initial stage because it completely avoided the drug-squeezing effect, and the release was a zero-order pattern.

Cephalexin↗

Bioactive bone cement: the effect of amounts of glass powder and histologic changes with time.

A study was conducted to examine the influence of the amount of glass powder added to a bioactive bone cement of our formula on its mechanical and biologic properties. Serial changes in the cement with time were also examined. The bioactive bone cement consisted of CaO-SiO2-P2O5-CaF2 glass powder and bisphenol-a-glycidyl methacrylate resin. Glass powder was added to the cement in 30, 50, 70, and 80% weight ratios. The compressive strengths of the resulting cements (171-239 MPa) were more than double that of polymethylmethacrylate cement (68 MPa). Histologic examination of rat tibiae bearing artificial defects packed with each bioactive cement showed direct bone contact 4 weeks after surgery. The cement with a higher percentage of glass powder showed better direct formation of bone around its periphery with a thicker reactive layer. Under scanning electron microscopic observation, the reactive layer showed increased levels of calcium and phosphorus. Examination of histologic changes up to 26 weeks showed progressive bone formation around the cement and no sign of biodegradation.

Animals↗

Possible role of hepatic bile mucus glycoprotein in development of intrahepatic gallstones.

To study the role played by hepatic bile mucus glycoprotein in the development of hepatolithiasis, mucus glycoprotein, isolated from the bile of patients with intrahepatic gallstones by gel filtration and ultracentrifugation, was examined for precipitability in control hepatic bile obtained postoperatively from patients successfully treated for cholecysto- and/or choledocho-lithiasis. When the mucus glycoprotein was incubated at 38 degrees C for 48 h in the control hepatic bile in the presence of calcium ions, massive precipitation was produced. The precipitation was inhibited by treating the mucus glycoprotein with acid, alkali, a reducing reagent, or protease, the inhibition being most effective with acid, which splits up carbohydrate chains. This suggests that the precipitability of the mucus glycoprotein resides mainly in its carbohydrate chains. These observations imply that the development of intrahepatic gallstones, calcium bilirubinate stones in particular, could be prevented by degrading mucus glycoprotein in hepatic bile.

Bile↗

Chemical structure of the carbohydrate moiety of fucose-rich glycopeptides from human pancreatic juice.

Human pancreatic juice, obtained from nine patients after partial excision of the pancreas for bile duct cancer, was fractionated in order to isolate its glycopeptides. Three glycopeptides were purified employing ion-exchange chromatography and gel filtration. All the glycopeptides were found to be free of sialic acid and galactosamine but to have an unusually high content of L-fucose. The chemical structures of the three glycopeptides were determined using 500-MHz [1H]-NMR spectroscopy. One of them, glycopeptide, GP-4, possessed a biantennary structure with three L-fucose residues. The second glycopeptide, GP-3, had a triantennary structure with four L-fucose residues, and the third one, G-2, had a tetra-antennary structure with five L-fucose residues. The chemical compositions of these glycopeptides, including the absence of sialic acid and the high L-fucose content, indicate that they represent a new class of glycopeptide present in the normal human pancreas.

Carbohydrate Sequence↗