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Biomedical subjects

S Imai

Publications and source records attributed to S Imai.

At least 469 records · Page 26Linked to original sources

[Role of PAF for the formation of gastric mucosal injury induced by ischemia-reinfusion in the rat].

Oxyradicals of neutrophils are supposed to play a role in the formation of gastric mucosal injury induced by ischemia-reinfusion (I-R). Recently, platelet-activating factor (PAF) is suggested to be involved in the I-R injury as one of chemical mediators since this substance may be produced in hypoxic tissue, stimulating oxyradical generation of neutrophils. In the present study, using CV-3988, a PAF antagonist, the severity of gastric mucosal damage and chemiluminescence (CL) activity of neutrophils of circulating blood were measured to evaluate the role of PAF in the I-R injury. SD rats fasted overnight were anesthetized and instilled 0.1N HCl into the stomach. Rats were then subjected to reduction of blood pressure to 20-30 mmHg for 20 min by bleeding followed by reinfusion of shed blood for 20 min. Two groups of rats each received 10 mg/kg CV-3988 (PAF-A grup) or saline (I-R group) i.v. 5 min prior to bleeding. After killing rats, the area of gross gastric lesions and the index of histologic damage were assessed. In separate PAF-A and I-R groups of rats, and control rats received saline i.v. and no hypotension, blood samples were collected from the portal vein and the abdominal aorta 45 min after acid instillation. Luminol-dependent CL stimulated by PMA of blood samples was measured using the photometer Monolight 401. CL activity was expressed as [peak CL/neutrophils number].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Evaluation of SOD activity in gastric mucosa of hemorrhagic shock rats].

UNLABELLED: Superoxide dismutase (SOD) exogenously administered has been documented to protect gastric mucosa against ischemia-reinfusion injury by scavenging oxygen radicals. However, the changes in levels of endogenous SOD in ischemic gastric mucosa are not known. To evaluate this, the present study was designed. METHODS: Fasted and anesthetized SD rats were given 0.1 N HCl i.g. and received the following procedures. Study 1: (1) Ischemia group--25 min after acid instillation, blood pressure was reduced to 20-30 mmHg for 20 min. (2) Ischemia-Reinfusion group--5 min after acid administration, rats received the same hypotension as above followed by reinfusion of shed blood for 20 min. (3) Control group-Rats were killed 45 min later without hypotension and reinfusion. Study 2: Three groups of rats treated with the same procedures as in Study 1 were given allopurinol (50 mg/kg/day) i.g. once daily for 2 days prior to the experiment. All rats were killed by exsanguination from the carotid artery to avoid as much as possible contamination of gastric mucosal samples with red blood cells rich in SOD. The supernatants of the corpus and antral mucosa homogenized were prepared for measuring their SOD activity using the nitrite method modified by Oyanagui. RESULTS: SOD activity in the gastric mucosa significantly increased in both the Ischemia (Ische.) and Ischemia-Reinfusion (I-R) groups compared to the control (Ische. vs. I-R vs. Cont'l: corpus-123.4 +/- 4.8 vs. 127.4 +/- 3.6 vs. 96.9 +/- 4.4 NU/Mg protein; antrum-71.6 +/- 2.8 vs. 81.4 +/- 6.8 vs. 62.1 +/- 3.1 NU/mg protein). No increase in SOD activity was observed in rats pretreated with allopurinol. CONCLUSION: SOD activity increases with oxyradicals generation in the rat stomach subjected to either hemorrhagic ischemia alone or hemorrhagic ischemia plus reinfusion. This also suggests that oxyradicals are generated even in the ischemic period.

Animals↗

Effects of two angiotensin converting enzyme inhibitors on the mechanical function and energy metabolism of isolated rat hearts. A nuclear magnetic resonance study with an active form of benazeprilat and captopril.

The effects of angiotensin converting enzyme inhibitors (ACEIs), CGS 14831 (CAS 86541-78-8) and captopril, on the mechanical function and energy metabolism were studied in isolated rat hearts using global ischemia-reperfusion model. The myocardial tissue levels of ATP, creatine phosphate (CP) and pH were determined with 31P-nuclear magnetic resonance (31P-NMR). Global ischemia was induced by cross-clamping of the inflow line for 40 min. While thiol containing ACEI, captopril, significantly inhibited the ATP depletion and pH fall produced by ischemia, non-thiol compound, CGS 14831, did not have any influence on the ATP degradation and pH fall during ischemia. Both CGS 14831 (20 micrograms/ml) and captopril (80 micrograms/ml) have little influence on the mechanical function during the ischemia-reperfusion period. L-Cysteine (44.6 micrograms/ml) inhibited the pH fall significantly during the ischemia without exerting influence on the ATP degradation. These data suggest that local renin-angiotensin-aldosterone system does not play an important role in maintenance of the myocardial mechanical function during ischemia-reperfusion. The thiol residue of captopril is not responsible for the inhibitory effect of this compound on ischemia-induced ATP degradation. Some specific effect of captopril may play a role in the protective effect.

Angiotensin-Converting Enzyme Inhibitors↗

[Elective prosthetic valve reoperation to relieve unacceptably high gradient].

Pressure gradients of Lillehei-Kaster valve (13 patients), Omniscience valve (26 patients) and Omnicarbon valve (7 patients) in the aortic position were evaluated by Doppler echocardiography. Twenty-three out of 46 patients revealed unacceptably high gradients. Seven prostheses were removed because the valve design that they had high gradients across them. Clinical findings including left ventricular function and symptoms improved after the reoperation. Patients who underwent aortic valve replacement with this series of valve prostheses should be followed up cautiously.

Aortic Valve↗

Studies on bilokinase, a biliary plasminogen activator: immunologic property and organ distribution.

The aim of the present study was to elucidate the immunologic difference between bilokinase, a plasminogen activator in bile, and urokinase, an urinary plasminogen activator, and to demonstrate the organ distribution of these antigens. Polyclonal antibodies against the highly purified activators (bovine-bilokinase, -urokinase and human urokinase) were raised in rabbits or guinea pigs. Immunologic precipitin reactions and quenching were found to occur only between the activators and their respective antisera. Histo-immunologic demonstration of the activators revealed that bilokinase-antigen was localized mainly in the hepatocytes as well as in the mucosa of the gall bladder, whereas urokinase-antigen was present in the epithelium of the urinary tubules. The liver may have a potential role in the hepatobiliary fibrinolytic system.

Animals↗

[Oral administration of OK-432 (picibanil). (8th report) clinical application: its immunomodulatory effects on the patients with gastrointestinal cancers].

A streptococcal preparation, OK-432 at a dose of 5 KE was orally administered to the patients with gastric or colorectal cancer for 7 approximately 14 days before operation, and its immunomodulatory effects on peripheral blood lymphocytes (PBL), regional lymph node lymphocytes (RLNL) and tumor infiltrating lymphocytes (TIL) were assessed. OK-432 treated group included 5 gastric and 6 colorectal cancers, and control group included 6 gastric and 8 colorectal cancers. After oral administration of OK-432 the proportion of Leu 7+ and Leu 11+ cells in PBL increased, and NK cell activity of PBL also was augmented. The proportion of OKT8+ cells increased in PBL and those of OKT3+ cells and OKT8+ cells decreased in RLNL after oral administration of OK-432. The responsiveness of TIL to autologous tumor extracts in the presence of interleukin-2 was enhanced in oral OK-432 group. These results indicate that oral OK-432 affects on NK and T cells and augments the antitumor immunity of the patients with gastrointestinal cancer.

Administration, Oral↗

Production of AMP and adenosine in the interstitial fluid compartment of the isolated perfused normoxic guinea pig heart.

The pathway of production of AMP and adenosine in the myocardial interstitial fluid compartment was studied in the isolated perfused normoxic guinea pig heart by collecting the transmyocardial effluent (t.m.e.) with the method of De Deckere and Ten Hoor (1977). Besides adenosine and inosine, AMP was found in t.m.e. Infusion of alpha,beta-methylene adenosine 5'-diphosphate (AOPCP), a specific inhibitor of the ecto 5'-nucleotidase, resulted in increases in t.m.e. AMP and inosine and a decrease in adenosine. Infusion of acetate producing a nearly twofold increase in myocardial AMP content did not increase the t.m.e. AMP even in the presence of AOPCP. In preparations made from 6-OH dopamine treated animals, the t.m.e. adenosine and inosine were reduced and AOPCP produced smaller increases in AMP and inosine, indicating that most if not all of the t.m.e. AMP originated from the sympathetic nerve terminals. Infusions of beta,gamma-imidoadenosine and beta,gamma-methylene adenosine 5'-triphosphate (AMPPNP and AMPPCP), non-hydrolysable analogs of ATP, resulted in dose-dependent increases in the t.m.e. AMP, which were much augmented in the presence of AOPCP. AMPPNP produced similar effects in 6-OH dopamine-treated preparations. As AMPPNP and AMPPCP are good substrates of ATP pyrophosphohydrolase, these findings indicate the presence of ATP pyrophosphohydrolase in the myocardial interstitial space.

5'-Nucleotidase↗

Improvement of speech intelligibility by a secondary operation to mobilize the tongue after glossectomy.

To prove the hypothesis that speech after glossectomy would be improved more by increasing the mobility of the remaining tongue rather than by increasing its volume, the speech intelligibility of 4 glossectomy patients was investigated before and after a secondary operation in which a split skin graft was used to mobilize the residual tongue. In each case, the postoperative speech intelligibility scores were higher than preoperative ones (case 1:83.6 to 97.2%, case 2: 76.6 to 82.5%, case 3: 51.5 to 58.5%, case 4: 30.2 to 49.3%). Sounds produced with the rear portion of the tongue were improved in 3 cases, and plosive and affricative sounds were remarkably improved in all cases. These results were considered to be due to the increased mobility, especially the mid and rear portions of the tongue.

Adult↗

Fluorimetric determination of aluminium in serum.

A convenient fluorimetric method for the routine determination of aluminium in serum has been developed using lumogallion [4-chloro-3-(2,4-dihydroxyphenylazo)-2-hydroxybenzene-1-sulphonic acid]. Losses of aluminium during deproteinisation of the serum were prevented by treatment with a combination of 20 or 30% m/V trichloroacetic acid (TCA) and 5% m/VTCA. Iron(III) was removed by extraction into chloroform with capriquat (methyltrioctylammonium chloride) as an Fe3+-lumogallion-capriquat ternary complex. The interference from Cu2+ was eliminated by using thiosulphate as a masking agent. The detection limit was 3.6 ng ml-1 and the calibration graph was linear up to 1.4 micrograms ml-1 of aluminium. Using the proposed method, the average concentration of aluminium in the serum of healthy subjects was found to be 6.8 ng ml-1, in agreement with values reported in the literature.

Aluminum↗

Effect of MCI-176, a new calcium channel blocker, on large and small coronary arteries in dogs.

MCI-176, a new calcium channel blocker, increases coronary blood flow and may improve perfusion in ischaemic areas. Its vasodilating effects on large conductive coronary arteries and the resistive arterioles were therefore compared with those of diltiazem, nifedipine, glyceryl trinitrate and adenosine in anaesthetised open chest beagle dogs. Intracoronary injection of these compounds caused dose dependent increases in coronary flow associated with decreases in the resistance of resistive arterioles, and the rank order of potency was nifedipine greater than adenosine greater than MCI-176 greater than diltiazem greater than glyceryl trinitrate. The resistance of the large conductive vessels was likewise reduced by these agents, except for adenosine. Glyceryl trinitrate showed the highest selectivity to the large conductive vessels, while adenosine showed the lowest and calcium channel blockers were intermediate. Among three calcium channel blockers, MCI-176 had the highest selectivity to the large conductive vessels, while the duration of action was the longest with diltiazem; the duration of action of MCI-176 was intermediate. Thus, MCI-176 is a coronary vasodilator, the potency of which is intermediate between nifedipine and diltiazem, but it has the highest selectivity to the large conductive vessels among these three compounds.

Adenosine↗

Characterization of the CA125 antigen secreted from a newly established human ovarian cancer cell line (SHIN-3).

A cell line (designated SHIN-3) was established from a 56-year-old Japanese woman diagnosed as having serous cystadenocarcinoma of the ovary. SHIN-3 produced the tumor marker, CA125. When samples were subjected to one-dimensional gel electrophoresis followed by immunoblotting with anti-CA125 antibody, antigen binding appeared in the low-molecular-mass fraction around 50 KDa as well as in the high-molecular-mass fraction (more than 200 KDa). Subsequent resolution of this lower-molecular-mass component by two-dimensional gel electrophoresis gave rise to bands of 49 KDa near an isoelectric point of 7.3. Treatment of the CA125 antigen with 10 mM periodic acid resulted in no loss of activity. However, reduction and alkylation in 6 M guanidine-HCl or treatment at 100 degrees C for 20 min resulted in complete loss of activity. Treatment with various glycosidases did not inhibit activity, whereas digestion with proteases (except for papain) produced complete loss of activity, suggesting that the CA125 antigenic determinant is composed of conformationally dependent peptides.

Antigens, Tumor-Associated, Carbohydrate↗

Inotropic and chronotropic effects of N6-substituted derivatives of cyclic AMP as assessed in guinea-pig isolated right atria and papillary muscle.

1. The inotropic and chronotropic actions of N6-substituted adenosine 3':5'-cyclic monophosphate (cyclic AMP) derivatives (N6-R cyclic AMPs) were studied in guinea-pig isolated right atrial preparations and in the papillary muscle preparations from guinea-pig right ventricle. 2. All the N6-R cyclic AMPs except N6-C14H29 produced positive inotropic effects in papillary muscle. The C5H11, C6H13, C7H15, C8H17 and C9H19 compounds were the most potent as inotropic agents, the potency being lower with compounds having longer or shorter N6-side chains than these. 3. In right atria N6-C2H5-C7H15 cyclic AMPs produced negative chronotropic effects. However, after treatment of the preparations with 8-phenyltheophylline the negative chronotropic effects were either much attenuated or abolished, indicating the involvement of adenosine receptors. 4. All the N6-R cyclic AMPs except N6-C14H29 were more potent activators of bovine myocardial protein kinase than cyclic AMP. The partition coefficients between octanol and an aqueous phase of N6-R cyclic AMPs became greater as the numbers of carbon atoms increased, and there appeared to be a relationship between partition coefficient and inotropic potency. It was concluded that membrane penetrativeness rather than potency as activators of protein kinase determined the potencies of N6-R cyclic AMPs as positive inotropic agents. 5. Derivatives such as N6-C7H15 cyclic AMP, which have positive inotropic activity without any marked negative chronotropic effect, may be useful as cardiotonic agents in heart failure.

Animals↗

Composition of the rumen ciliate population in experimental herds of cattle and sheep in Lethbridge, Alberta, Western Canada.

Rumen ciliate populations were surveyed in 11 Holstein cattle and 6 sheep in Lethbridge (Alta., Canada) to determine species distribution in this Western Canadian environment. A total of 28 ciliate species were identified in cattle and 17 in sheep. The average total number of ciliates per millilitre of rumen content was 6.9 X 10(4) in cattle and 1.9 X 10(5) in sheep. The average number of species per host was 20.5 in cattle and 13.8 in sheep. Of the ciliate species detected, species of Entodinium appeared most frequently both in cattle and in sheep. Diplodinium polygonale, Eodinium lobatum, Eo. monolobum, Eremoplastron rostratum, Ostracodinium clipeolum, Os. mammosum, and Ophryoscolex purkynjei were not detected in sheep. In contrast, Ophryoscolex caudatus was not found in cattle. These data indicate that the ciliate faunas of cattle and sheep in this Western Canadian environment are similar to those found in Japan.

Alberta↗

Three binding sites of 125I-iodocyanopindolol, i.e. beta 1, beta 2-adrenergic and 5HT1B-serotonergic receptors in rat brain determined by the displacement and Scatchard analysis.

The selectivity of binding of 125I-iodocyanopindolol (125I-ICYP) to beta 1-, beta 2-adrenergic and 5HT1B-serotonergic receptors were analysed using both the Scatchard and displacement methods. When the binding of 125I-ICYP to the rat brain membrane was examined by means of the displacement analysis with l-metoprolol, triphasic displacement curves were observed. Analyses carried out on the basis of the displacement of 125I-ICYP by beta-selective antagonists, alpha-adrenergic agonists and antagonists, and serotonergic agonists and antagonists indicated the correspondence of the super high, high- and low-affinity sites of 125I-ICYP binding to beta 2-, beta 1-adrenergic and 5HT1B-receptors, respectively. By contrast, the Scatchard analysis revealed the biphasic character of the 125I-ICYP binding and the complete inhibition of the binding to high- and low-affinity sites by l-metoprolol (30 microM) and 5-hydroxytryptamine (5HT, 10 microM), respectively, suggesting the correspondence of the high- and low-affinity sites to beta-adrenergic and 5HT1B-receptors. Thus, regarding the determination of the selectivity of binding of a radioligand, the displacement analysis is more informative than the Scatchard analysis. In the case of 125I-ICYP the separation of beta 1- and beta 2-adrenergic receptors becomes feasible only with the displacement method.

Animals↗

[Beta-blocking actions and the partial agonist activity of bopindolol, a new beta-adrenoceptor antagonist, and its two metabolites].

The beta-blocking effects of bopindolol, a new long-acting beta-adrenoceptor antagonist, and its two metabolites, 18-502 and 20-785, were studied in the isolated atria and trachea preparations of the guinea pig. The partial agonist activity (PAA) and the membrane stabilizing activity (MSA) were studied in the pithed rat and the right ventricular papillary muscle preparations of the guinea pig, respectively. Antagonistic effect of bopindolol against isoproterenol was 1.1-2.8 and 14.1 times more potent than propranolol in the atria and the trachea preparations, respectively, while those of 18-502 were 34.7-38.0 (in atria) and 29.0 (in trachea) times more potent than propranolol. beta-Blocking potencies of 20-785 were 50% (in atria) and 10% (in trachea) of those of propranolol. Bopindolol, 18-502 and 20-785 increased the heart rate of the pithed rat dose-dependently. The effects were inhibited by pretreatment of the preparation with propranolol. The onset of action of bopindolol was slower and the duration, longer than those of its two metabolites. Bopindolol and 18-502 were more potent membrane stabilizers than propranolol, while 20-785 produced only a minimal stabilizing effect. These results indicate that not only bopindolol, but also the metabolites of bopindolol, 18-502 and 20-785 are potent beta-blocking agents with PAA. It is presumed that the long duration of action of bopindolol is due to the potent activities of its metabolites 18-502 and 20-785.

Adrenergic beta-Antagonists↗

Selectivity of bunitrolol for beta 1- and beta 2-adrenergic receptors and 5HT1B-receptors: assessment by biphasic Scatchard plots and biphasic displacement curve analysis with 125I-iodocyanopindolol and 3H-CGP12177.

The preference by bunitrolol for beta 1- and beta 2-adrenoceptors of the rat brain, heart and/or lung was assessed by the radioligand binding assay method with 125I-iodocyanopindolol (125I-ICYP) or 3H-CGP12177. Scatchard plots of 125I-ICYP binding in the presence of bunitrolol were found to be non-linear. The inhibition constants (Ki) of bunitrolol for high (beta 2-) and low affinity sites (beta 1-) were: 0.42 +/- 0.16 nM for beta 1 and 3.55 +/- 1.61 nM for beta 2 (beta 1 greater than beta 2), respectively. Displacement experiments conducted with the preparations of the rat brain using 125I-ICYP or with the preparations of the rat heart using 3H-CGP12177 yielded Ki values for bunitrolol of 0.53 +/- 0.20 (beta 1) and 2.37 +/- 0.78 (beta 2) nM for 125I-ICYP binding and 2.01 +/- 0.38 (beta 1) and 12.67 +/- 6.54 (beta 2) nM for 3H-CGP12177 binding. In addition, the Ki value for 5HT1B-receptors assessed in displacement experiments conducted with 125I-ICYP in the presence of 30 microM I-metoprolol in the rat brain was 10.54 +/- 5.92 nM. Thus, bunitrolol is a beta 1-selective antagonist.

Adrenergic beta-Antagonists↗