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Biomedical subjects

S Imai

Publications and source records attributed to S Imai.

At least 649 records · Page 36Linked to original sources

Ability of various oral bacteria to bind human plasma fibronectin.

The present study describes the ability of various oral bacteria to bind human plasma fibronectin (PFN). Avid binding of 125I-PFN was found for Streptococcus mutans (serotypes a to h), Streptococcus sanguis, group A Streptococcus pyogenes and Staphylococcus aureus, while other gram-positive bacterial species tested demonstrated only weak or negligible PFN binding ability. Two gram-negative bacterial species, Bacteroides gingivalis and Escherichia coli, did not significantly bind PFN. 125I-PFN binding to S. mutans 6715 cells was decreased by pretreatment with unlabeled PFN, and the radiolabeled PFN bound to the cell surface was released on addition of unlabeled PFN. Strong inhibition of 125I-PFN binding to S. mutans 6715 cells was obtained by protease pretreatment, while partial inhibition was also observed following treatment with acid, alkali, lipase, and monoclonal anti-polyglycerophosphate. These results suggest that PFN binding to S. mutans cells is reversible and that PFN receptors on the cell surface appear to be heat-stable multiple proteins.

Bacteria↗

Anti-arrhythmic effects of (-)-carnitine chloride and its acetyl analogue on canine late ventricular arrhythmia induced by ligation of the coronary artery as related to improvement of mitochondrial function.

Using the two-stage coronary ligation method, first described by Harris, (1950), anti-arrhythmic effects (AAE) of (-)-carnitine chloride (LCC) and acetyl (-)-carnitine chloride (ALCC) were studied in conscious unrestrained dogs in comparison with those of disopyramide (D). Two-stage ligation of the coronary artery resulted in a significant decrease in the myocardial free carnitine content. Intravenous administration of LCC (300 mg kg-1) and D (5 mg kg-1) suppressed the ventricular arrhythmia induced by coronary ligation after 24 hours. ALCC (300 mg kg-1) was found to be less potent. An improvement of the mitochondrial function (respiratory control index (RCI) and oxidative phosphorylation rate (OPR) ) was noted with LCC and ALCC and there was a linear correlation between AAE expressed as reduction of arrhythmic ratio and improvement in the OPR, whereas there was no improvement in mitochondrial function after D. Plasma carnitine concentration was increased after administration of LCC, attaining the value of around 8 mM at 10 min after 300 mg kg-1. At 60 min, the plasma carnitine concentration was still about half as high as at 10 min. After ALCC, both acetyl carnitine and free carnitine were found in the plasma. The concentration of the former was decreased after attaining a peak value of around 0.2 mM at 10 min, while the plasma concentration of free carnitine was gradually increased. The anti-arrhythmic effects of LCC and ALCC were ascribed to the improvement of mitochondrial oxidative phosphorylation, while effects other than the improvement of the mitochondrial activity were suggested as mechanisms of anti-arrhythmic effects of D.

Acetylcarnitine↗

Screening of sugars inhibitory against sucrose-dependent synthesis and adherence of insoluble glucan and acid production by Streptococcus mutans.

Various sucrose derivatives and a sucrose analogue were enzymatically synthesized on the assumption that structural similarities of the sugars to sucrose would endow them with an ability to inhibit the cariogenicity of sucrose. The effect of these sugars on sucrose-dependent synthesis and adherence of insoluble glucan and on acid fermentation of sucrose by Streptococcus mutans was examined in vitro. Although none of them inhibited the acid fermentation, several sugars not only inhibited the synthesis and adherence of insoluble glucan, but were themselves only slightly fermented as well.

Acids↗

Differences of global and regional left ventricular function in anterior and inferior myocardial infarction: assessment by the use of a regional ejection fraction.

Radionuclide angiography was performed on 41 patients with transmural myocardial infarction (MI) [17: anterior MI, 24: inferior MI] and 10 normal subjects in order to evaluate the influence of the infarct site on the global and the regional left ventricular function. The severity of the wall motion abnormality agreed closely with the reduction in the relative regional ejection fraction (%REF). The depression of the left ventricular ejection fraction (LVEF) in anterior MI was greater than that in inferior MI (p less than 0.01). We also found that the depression of the performance in the infarcted zone in anterior MI was more marked than that in inferior MI (p less than 0.01). However, function in the non-infarcted zone was almost the same in the anterior MI as in the inferior MI. As to the extent of the hypokinetic area, there was no significant difference between the patients with anterior MI and those with inferior MI. The above results indicated that the infarct site is an important determinant of the regional and the global left ventricular function after MI.

Adult↗

Beta-receptor blocking potencies of the three newly synthesized beta-adrenergic antagonists (S-596, K-351, N-696) as assessed with the radioligand binding assay method in rat cardiac muscle membrane treated with neuraminidase.

To assess the beta-blocking potencies of three newly synthesized beta-blockers, i.e., S-596: dl-2-(3'-t-butylamino-2'-hydroxypropylthio)-4-(5'- carbamoyl-2'-thienyl)-thiazole hydrochloride, K-351: 3,4-dihydro-8-(2-hydroxy-3-isopropyl-aminopropoxy)-3-nitroxy -2H-1-benzopyran, and N-696: 4,3-(tert-butylamino)-2-hydroxypropoxy)-N-methylisocarbostyril hydrochloride, values of Ki (inhibition constant) were obtained by the radioligand binding assay method using rat heart membrane treated with neuraminidase. The pA2 values of these blockers as antagonists against the positive chronotropic and inotropic actions of isoproterenol were also determined by pharmacological methods using guinea pig atria. To assess the selectivity of these beta-blockers, pA2 values were also obtained in the isolated trachea using isoproterenol as an agonist. The order of potencies as assessed by Ki and pA2 values were S-596 greater than K-351 greater than N-696. When the Ki values were plotted against the pA2 values together with the Ki and pA2 values of our previous study (Horii et al., 1974; Nakazawa et al., 1978; Nakagawa et al., 1980; Nakagawa et al., 1983; Nagatomo et al., 1983), straight lines were obtained with r values of 0.93 (P less than 0.001) (positive chronotropic action) and 0.91 (P less than 0.001) (positive inotropic action), respectively. Thus, the validity of using the beta-adrenoceptor binding assay method developed in this laboratory using cardiac membrane treated with neuraminidase for assessment of the potencies of beta-adrenoceptor blockers in cardiac muscle was further substantiated.

Adrenergic beta-Antagonists↗

31P-topical nuclear magnetic resonance (31P-TMR) studies of cardiotoxic effects of 5-fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR).

Using the 31P-topical nuclear magnetic resonance method (TMR), an attempt was made to determine the myocardial high-energy phosphate compounds (HEP) contents under in situ conditions in closed-chest animals, and the effects of opening the thorax on the myocardial energy metabolism were studied comparing the cardiotoxic effects of 5-fluorouracil (5-FU) in closed-chest and open-chest animals. It was found that the depletion of myocardial HEP produced by 5-FU was much more marked in open-chest animals than in closed-chest ones, indicating the necessity of conducting the experiments in closed-chest animals for the proper evaluation of the cardiotoxicity of certain types of compounds. Therefore, the cardiotoxicity of a prodrug of 5-FU was assessed in closed-chest animals, and it was found to be less cardiotoxic than 5-FU.

Adenosine Triphosphate↗

Effects of etafenone on myocardial energy metabolism as studied by an organ redoximeter and biochemical analyses.

Direct recording of reduced nicotinamide adenine dinucleotide (NADH) fluorescence was conducted with an organ redoximeter in isolated perfused guinea pig heart. Cross-clamping of the aortic inflow line resulted in an increase in NADH fluorescence. After etafenone (10(-6) M), there was a significant prolongation of the time to the detectable or the maximum increase in NADH fluorescence. The magnitude of the increase in NADH fluorescence tended to be reduced (135% as compared with 145% in the control group). Supplemental chemical analyses revealed a significant increase in creatine phosphate, adenosine triphosphate (ATP) and total adenine nucleotide in the etafenone-pretreated group 15 min after postischemic reperfusion, although the ischemia-induced changes were not improved by this compound. It was suggested that the better recovery of myocardial high energy phosphate levels produced by etafenone was brought about by a decrease in oxygen consumption due to a decrease in mechanical performance of the heart and possibly by a better resynthesis of ATP.

Animals↗

Functional and metabolic effects of cardioplegia induced by a young's solution (YNG solution) as assessed in isolated atrial preparations and in isolated perfused heart preparations of the guinea pig.

p6e protective effects of Young's solution (YNG solution), a cardioplegic solution, on the myocardial function and metabolism were assessed in isolated atrial preparations and isolated perfused heart preparations of the guinea pig. In atrial preparations, the time to arrest of the contraction became shorter as the concentrations of the K+, Mg++, and K+-Mg++ solutions increased, while the time to resumption of the contraction was lengthened. There was no difference in the time to arrest between K+ and K+-Mg++ solutions, but the time to resumption was reduced with K+-Mg++ solution to about half the value with K+ solution. YNG solution represented an optimum solution for obtaining a quick cardiac arrest and quick resumption of contraction. In the isolated perfused heart, the time to arrest was similar for all the cardioplegic solutions used and the heart stopped in diastole. However, the time to arrest was longer with cold Krebs-Henseleit's solution (cold cardioplegia). The time to resumption of the contraction was the shortest with YNG solution, which yielded the highest mitochondrial respiratory control ratio (RCR) and ADP/O ratio. There was a negative correlation between the time to resumption of contraction and mitochondrial RCR or ADP/O ratio (r = -0.50 and -0.58, respectively).

Animals↗

Effects of cardioplegia induced by a Young's solution (YNG solution) on the blood-perfused canine papillary muscle preparation.

Experiments were carried out in the blood-perfused canine papillary muscle preparation to evaluate the protective effect of a cardioplegic solution, Young's solution (YNG solution), on the myocardial function. Both in spontaneously contracting preparations and in electrically paced (2 Hz) preparations, the time to the cardiac arrest and the time to the maximum blood flow were found to be significantly shorter when the cardiac arrest was induced with cardioplegic solutions than when it was induced with the cold modified Krebs-Ringer's solution (cold cardioplegia). The maximum blood flow of the paced preparation tended to be greater with cardioplegic solutions. The time to resumption of regular contractions was significantly shorter with YNG solution as compared with cold cardioplegia. The developed tension and the blood flow at the time of resumption of the regular contractions tended to approach the control value more quickly with YNG solution, as compared with other cardioplegic solutions and cold cardioplegia. It is concluded that YNG solution represents an optimal cardioplegic solution.

Animals↗

The sequence and correlation of the changes in several parameters of energy metabolism induced by ischemic insult in heart muscle.

Samples of myocardium with varying degrees of ischemia were obtained from subendo- and subepicardium of nonischemic, ischemic border and center zones of canine left ventricles to assess the sequence of rapid alterations of several parameters of energy metabolism induced by myocardial ischemia. Ischemia was induced by occluding the left anterior descending coronary artery. The contents of creatine phosphate (CP) and ATP decreased significantly. There was a significant accumulation of lactate. The redox potential (Eh) and phosphorylation potential (l') also decreased sharply, but only a slight decrease in energy charge (E.C.) was noted. A close correlation was found between ATP and total adenine nucleotide (r = 0.99). There were various degrees of linear correlation between other parameters, except for ATP (and total adenine nucleotide) and Pi, and CP and l', which were uncorrelated. The sequence of rapid alterations in the parameters of energy metabolism induced by ischemia was: (1) l' and CP, (2) Pi, ATP and Eh, and finally (3) lactate and E.C. A significant increase of the heart rate and a decline of the mean blood pressure and left ventricular pressure (LVP) were also observed in association with a slight change in the maximum rate of rise of the left ventricular pressure (dP/dtmax).

Adenine Nucleotides↗

The antispermatogenic effect and toxicity of 2, 4-dinitro-6-tert-butylphenyl methanesulfonate on Sprague-Dawley rat.

The antispermatogenic effects of 2, 4-dinitro-6-tert-. butylphenyl methanesulfonate (HE-166) were studied in Sprague-Dawley rats. They were fed 25, 100 and 400 ppm of HE-166 in the basal died for one year. Laboratory data showed no significant changes except for increases in gamma-globulin, alkaline phosphatase, GOT and GPT values in the 100 ppm group. Macroscopically, significant changes were found in the testes in the experimental group, which showed marked atrophy. Histologically, the testes were filled with fibrin exudate in the stroma and there was reduced spermatogonia, cellular debris and giant cells, and even calcification, depending on the dose of HE-166. The anti-fertility effects of HE-166 were also observed by mating rats and checking the pregnancy rate during three generations. These effects might be due to the direct cytotoxic effect of HE-166 on post-meiotic cells as epididymal spermatozoa and testicular sperm and spermatids. As far as tumor incidence was concerned, one case of fibroadenoma of the mammary gland, one case of leiomyosarcoma in the uterus in the 100 ppm group and one case of leiomyoma in the uterus in the 25 ppm group developed at around 8 months, but no other tumors developed.

Animals↗

[Teratogenicity study on bromperidol in rats].

A teratogenicity study on bromperidol, a neuroleptic, was carried out in Wistar-Imamichi rats. Bromperidol was administered orally at the dose levels of 0.2, 1.5 and 10.0 mg/kg/day for 11 days from day 7 to day 17 of gestation. About two-thirds of pregnant females in each group were sacrificed on day 21 of gestation, and their fetuses were examined. The remaining dams were allowed to litter naturally, and the post-natal development of the offspring was observed. Treatment of bromperidol caused sedation of pregnant females in 1.5 and 10.0 mg/kg groups with concomitant decrease in body weight and in food and water intake in dose-dependent manner. Effect of bromperidol treatment on F1 generation was observed mainly in animals of 10.0 mg/kg group, suggesting overall growth retardation such as decrease in live fetal weight, retarded ossification of metacarpals and metatarsals, a slight decrease in day 1 viability index, a marginal delay in eyelid opening, reduction in growth rate and decrease in organ weight. No treatment-related external and internal abnormalities were observed in fetuses (F1), and no apparent effect on behavior, learning ability and reproductive function of offspring (F1) was found.

Abnormalities, Drug-Induced↗

Urethan-induced mammary tumorigenesis in a murine mammary tumor virus (MuMTV)-positive mouse strain: evidence for a keratinized nodule as an MuMTV-negative precursor lesion for squamous cell tumors.

Administration of urethan (CAS: 51-79-6; carbamic acid, ethyl ester) in the drinking water of breeding female mice of the murine mammary tumor virus (MuMTV)-positive DD/Tbr strain and the MuMTV-negative DDf strain induced so-called keratinized nodules, which were demonstrable in wholemount preparations of mammary glands. It also induced squamous cell tumors (also called adenoacanthoma) at an extremely early age. The keratinized lesions appearing in the lobular areas of the mammary glands showed heavy infiltration with lymphocytes and as such were very different from hyperplastic alveolar nodules, the preneoplastic lesions for adenocarcinomas. Immunoperoxidase tests with antibodies against the MuMTV revealed that positivity of normal mammary gland epithelium in the DD/Tbr strain was not found in the keratinized nodules, which was further evidence that in squamous cell tumorigenesis of the mammary gland the MuMTV is not expressed overtly even at an early stage in tumorigenesis, in contrast to the case with adenocarcinoma tumorigenesis. These findings substantiate previous conclusions that the MuMTV is not involved in chemical carcinogenesis of the mouse mammary gland.

Animals↗

Pharmacological profile of a new beta-adrenoceptor blocker, 4-[3-(tert-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride (N-696).

To characterize the pharmacological profile of a new beta-adrenoceptor blocker, 4-[3-(tert-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride (N-696), experiments were performed in the isolated atria and trachea of the guinea pig, in the pithed rat, in the anesthetized rabbit, in anesthetized dogs and in anesthetized open-chest dogs. Antiarrhythmic action was assessed in conscious as well as in anesthetized dogs. Although N-696 was a non-selective beta-blocker 15-20 times less potent than propranolol under in vitro conditions, it was as effective a blocker as propranolol under in vivo conditions. N-696 produced a fall of the blood pressure in the pithed rat and attenuated the blood pressure rise produced by stimulation of the preganglionic sympathetic nerve. In the anesthetized rabbits, it produced a hypotensive effect associated with an increased discharge of the renal nerve. In anesthetized dogs it produced a hypotensive effect and a decrease in the myocardial blood flow. However, the decrease in the myocardial blood flow was smaller than that produced by propranolol. All these findings indicate that N-696 has a direct vasodilatory effect besides its beta-blocking action. As a beta-blocker N-696 was unique in that it produced a potent antiarrhythmic effect in two-stage coronary ligation arrhythmia.

Adrenergic alpha-Antagonists↗