Valilactone, an inhibitor of esterase, produced by actinomycetes.
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Biomedical subjects
Publications and source records attributed to M Asano.
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Vasoconstrictor effects of Bay k 8644, a dihydropyridine Ca++ agonist, and vasorelaxant effects of nifedipine were investigated in helical strips of dog cerebral (basilar, posterior cerebral and middle cerebral) and peripheral (coronary and mesenteric) arteries. The addition of Bay k 8644 produced a dose-dependent contraction in the absence of any contractile agent in the basilar artery with a pD2 value of 8.53. Similar sensitivity to Bay k 8644 was observed in the posterior cerebral, middle cerebral or coronary artery. Bay k 8644 was much less effective in producing a contraction in the mesenteric artery. An elevation of the concentration of extracellular K+ eliminated the difference between the responses to Bay k 8644 in the basilar and mesenteric artery. Contractile responses of the basilar artery to Bay k 8644 were antagonized competitively by nifedipine (pA2 = 8.17), but non-competitively by diltiazem. The pA2 values for nifedipine antagonism of Bay k 8644 responses with the elevated K+ were the same between the basilar and mesenteric arteries. Increased sensitivity to exogenously added K+ also was observed in cerebral and coronary arteries when compared with the mesenteric artery. The addition of nifedipine to an unstimulated strip produced a dose-dependent relaxation in cerebral and coronary arteries, but not in the mesenteric artery. When the cerebral and peripheral arteries were contracted with K+ to the same magnitude, nifedipine produced similar relaxations among these arteries. Nifedipine was less efficacious in antagonizing the contractile response to Bay k 8644 compared with the contractile response to K+ in cerebral arteries. These results suggest that 1) the voltage-dependent Ca++ channels in the cerebral and coronary arteries are in different states of activation from those in the mesenteric artery, 2) Bay k 8644 contracts the cerebral and coronary arteries by acting primarily on the same site, presumably dihydropyridine receptors of the voltage-dependent Ca++ channels at which nifedipine acts, 3) the dihydropyridine receptors were the same between the basilar and mesenteric arteries and 4) there may be a difference in the state of the Ca++ channel in the arteries between the stimulation with Bay k 8644 and K+-depolarization.
Calcium (Ca2+) channel functions were compared in femoral arteries isolated from 6-week-old spontaneously hypertensive rats (SHR) and from age-matched normotensive Wistar-Kyoto (WKY) rats. BAY k 8644 (BAY), a dihydropyridine Ca2+ channel agonist, elicited a dose-dependent contraction in strips of SHR femoral arteries with a pD2 value of 8.55. Maximum contraction induced by this agonist (1 X 10(-7) M) was comparable to the maximum developed by KCl (K+) depolarization. BAY was less effective in eliciting a contraction in strips of WKY rat femoral arteries. Increased sensitivity to K+ was also observed in SHR femoral arteries. Contractile responses of SHR femoral arteries to BAY were antagonized competitively by nifedipine with a pA2 value of 8.36. When the effects of an elevation in the level of extracellular K+ on the contractile responses to BAY were determined in SHR and WKY rat femoral arteries, dose-response curves for BAY were not significantly different between the SHR and WKY rats. Femoral arteries from SHR, but not from WKY rats, relaxed when placed in a Ca2+-free solution. The addition of nifedipine (10(-10)-10(-7) M) to unstimulated strips produced a dose-dependent relaxation in femoral arteries from SHR, but not from WKY rats. These results suggest that (1) the increased responsiveness to BAY seen in SHR femoral arteries appears to occur because these arteries are more depolarized than WKY rat femoral arteries; and (2) BAY acts primarily on the same site, presumably the dihydropyridine receptors of the voltage-dependent Ca2+ channels, at which nifedipine acts.
A 10-year-old girl was admitted displaying a medullary thyroid carcinoma, accompanying neurinomas of the tongue, marfanoid habitus, megacolon, and scoliosis. Although her adrenal glands were found to be unremarkable on both CT and ultrasonogram examination an MIBG scintiscan showed a 131-1 uptake, suggesting the presence of medullary hyperplasia. Remarkable nodal involvement with invasive features witnessed in the upper mediastinum during tertiary surgery four years later, following a total thyroidectomy. The TCT and CEA profiling was not sufficient enough to predict a recurrence. At the present state there is difficulty in providing an early diagnosis; through node dissection, however, is considered to be necessary at time of primary thyroid operation in cases with MEN type 2b.
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Intravenous cimetidine treatment was prescribed for patients suffering from anaphylaxis, urticaria, pruritus, and contact dermatitis. Most of these patients recovered promptly from shock status, itching, and/or flushing after the administration of cimetidine. Intravenous cimetidine therefore may be an effective treatment for those allergic reactions.
Ascertainment of breast cancer incidence among the cohort of the RERF Life Span Study extended sample identified 574 breast cancers among 564 cases diagnosed during 1950-1980 of which 412 cancers were reviewed microscopically. There were no dose-dependent differences with respect to diagnostic certainty or histological type. As in previous studies, the dose response appeared to be roughly linear and did not differ between the two cities. The most remarkable new finding was the emergence of a radiation-related excess among women under 10 years of age at exposure. The risk of radiogenic breast cancer appears to decrease with increasing age at exposure, whether expressed in relative or absolute terms. These results suggest that exposure of female breast tissue to ionizing radiation at any time during the first four decades of life, even during the premature stage, can cause breast cancer later in life, and that the length of time that tumor promoters such as endogenous hormones operate following exposure has an important influence on the development of radiation-induced breast cancer. An unresolved question is whether breast cancer risk is increased by radiation exposure at ages older than 40.
A simple method for the simultaneous determination of acetylcholine, choline, noradrenaline, dopamine and serotonin in brain tissue was developed by using high-performance liquid chromatography with electrochemical detection. These compounds are analysed in a single chromatographic run within 30 min with a simple sample clean-up procedure. The detection system consists of two electrochemical detector cells aligned in series: a glassy-carbon electrode for catecholamines and serotonin, and a platinum electrode for acetylcholine and choline. For the detection of the latter compounds, they were converted enzymatically into hydrogen peroxide through a column reactor with immobilized acetylcholinesterase and choline oxidase. A column of boronic acid gel was placed just ahead of the immobilized enzyme column to remove catecholamines, which caused interfering responses on the platinum electrode. Two equivalent analytical columns and a column switching were employed to speed up the serotonin assay. Simultaneous determination of these major neurotransmitters in rat brain regions was successfully carried out with the system described.
Luteinizing hormone-releasing hormone (LH X RH) agonist can be administered daily to patients with prostatic cancer with resulting clinical efficacy. A sustained drug release formulation of an LH X RH agonist, (D-Leu6)-des Gly-NH2(10)-LH X RH ethylamide (leuprolide)-vinyl polymer composite, was prepared by means of radiation-induced polymerization under a supercooled state. The sustained release of leuprolide from subcutaneously implanted leuprolide-vinyl polymer composite (14 mm in diameter and 4 mm in thickness) was obtained over a period of several months in five patients with prostatic cancer. Serum testosterone levels began to decrease on the tenth day, fell below 1 ng/ml after three weeks of implantation, and thereafter remained at the castration level until removal of the polymer composite. Clinical improvement was associated with serum hormonal changes, and support this as a novel and superior method of administration of LH X RH agonist.
Positive electron impact (EI), positive chemical ionization (CI), and negative CI mass spectra of eight tricyclic antidepressants are presented. In the positive EI mode, peak(s) at m/z 193 and/or 195, which corresponded to the tricyclic nucleus, appeared for five compounds; a peak at m/z 58 was common to compounds having a gamma-dimethylaminopropyl group as their side chain. Molecular ions appeared for all compounds though they were very small in some compounds in the positive EI mode. In the positive CI mode, [M + H]+ quasi-molecular peaks appeared together with [M + C2H5]+ peaks in five compounds; the ion at m/z 196, which corresponded to the tricyclic nucleus also appeared in five compounds. In the negative CI mode with 1 Torr chamber pressure, [M - 1]- quasi-molecular ions were observed for all compounds except for lofepramine; [M + 43]- anions, which probably corresponded to [M + C3H4]-, appeared in five compounds; strong [M + Cl]- ions appeared in carpipramine and clocapramine. The anions due to the tricyclic nucleus also appeared in this mode. In the negative CI mode at low pressure (0.01 Torr), the spectra were generally similar to those in the 1 Torr negative CI mode. However, the cluster anions never appeared at the low pressure. Some data on extraction for some antidepressants from human urine and plasma, and their separation by gas chromatography, are also presented.
New proteinase inhibitors have recently been found in seminal plasma which specifically inhibit cysteine proteinases such as ficin, papain, cathepsin H and cathepsin B. The inhibitors consist of two components, In-A and In-B, both of which are effective in native semen. In the present work, a method of assay is devised to determine activities of both components separately. Under conditions in which In-B is denatured completely while In-A is not, inhibitory activity of In-A alone is determined. The mean In-A inhibitory level is 1.52 +/- 0.28 inhibitor unit/mL and the level is independent of the number of spermatozoa. In-B level is calculated by subtracting In-A level from the total ficin inhibition level of the semen. The mean In-B level is 1.47 +/- 0.52 inhibitor unit/ml. In-B level has a tendency to increase with increasing number of spermatozoa. The correlation coefficient is 0.307 and statistical significance p less than 0.005.
The effective refractory period (ERP) during the period of the alternation of the ST-T complex (STTA) in the ischemic myocardium was determined using a synchronized system of electrical stimulators and a bipolar epicardial electrode during acute coronary occlusion in anesthetized dogs. Epicardial unipolar electrograms (UP), epicardial bipolar electrograms (BP) and monophasic action potentials (MAP) were also recorded from ischemic areas. ERP in ischemic areas was prolonged, as ischemia progressed, and during the period of STTA ERP also alternately changed. A lower or negative deflection of the ST-T complex was accompanied by a longer ERP, and a higher or monophasic ST-T complex was accompanied by a shorter ERP. A good correlation was observed between the degrees of alternation in ERP and of STTA. MAP also showed an alternation in its duration and its amplitude. The alternation in duration preceded the alternation in amplitude. A lower or negative deflection of the ST-T complex corresponded to a MAP with a longer duration and a larger amplitude. During the period of STTA, a long conduction delay followed the negative deflection of the ST-T complex. A marked conduction delay appeared only during a period of STTA. Diltiazem and nifedipine inhibited STTA and an alternation in ERP. In conclusion, STTA is associated with an alternation in ERP and in conduction delay, and calcium antagonists attenuate both STTA and an alternation in ERP.
The purpose of this paper is to investigate the inhibitory effect of Lactobacillus casei (LC 9018) on the growth of transplantable murine bladder tumor. Lactobacillus casei, viable and/or heat-killed bacteria, either in oral or intravenous administration, produced a significant inhibitory effect on the tumor growth and much less pulmonary metastasis.
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Vasoconstrictor effects of Bay K 8644 (an agonist known to increase Ca2+ influx through the voltage-dependent Ca2+ channels) on femoral arteries of 6 week old spontaneously hypertensive rats (SHR) were investigated, and data compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). The addition of Bay K 8644 (1 X 10(-10)-3 X 10(-7) M) elicited a dose-dependent contraction in SHR femoral artery in the absence of any contractile agent. Maximum contraction induced by this agonist was the same as the maximum induced by either K+-depolarization or alpha-adrenoceptor stimulation. Bay K 8644 was less effective in eliciting a contraction in the WKY femoral artery. Increased sensitivity to K+ was also observed in the SHR femoral artery. In contrast, contractions in response to alpha-adrenoceptor stimulation were the same in the SHR as those in the WKY. The addition of nifedipine, a Ca2+ channel antagonist, to an unstimulated preparation produced a dose-dependent relaxation in femoral arteries from SHR, but not from WKY. When the arteries were contracted with 60 mM K+, nifedipine produced similar relaxations in the SHR as those in the WKY, suggesting that the Ca2+ channels in the SHR femoral arteries are more activated than those in the WKY femoral arteries. Contractile responses to SHR femoral arteries to Bay K 8644 were antagonized competitively by nifedipine. Contractile responses to Ca2+ determined in K+-depolarized strips were also antagonized competitively by nifedipine. However, Schild plot analysis demonstrated a different pA2 value for nifedipine, suggesting that there may be a difference in the state of voltage-dependent Ca2+ channels in SHR femoral artery between the stimulation with Bay K 8644 and K+-depolarization.
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