[The multiple compartment analysis of N2 washout curve].
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Adult↗
Biomedical subjects
S Kubo
Publications and source records attributed to S Kubo.
A case of pheochromocytoma combined with catecholamine cardiomyopathy.
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Adrenal Gland Neoplasms↗
Clostridium botulinum type C toxin: a sketch of the molecule.
The purification and crystallization of type C botulinum toxin along with its physical characteristics are described. The shape of Clostridium botulinum type C toxin molecule is globular like a pressed ball with a 7.4 nm diameter and a 4.3 nm thickness. The molecular volume is approximately 185 nl and the molecular weight is 141000. The toxin molecule is composed of two parts, which are separable under appropriate conditions. These parts have some differences in the electrophoretic properties, amino acid distribution, immunological, and functional characteristics. The toxin molecule can be reconstituted by association of S-S bond between the two chains. The expression of the toxicity requires that the fragments of the polypeptide chain carrying the necessary information be functionally organized for the proper development of the specific tertiary structure for active conformation.
Clostridium botulinum↗
Four different monoclonal antibodies against type C1 toxin of Clostridium botulinum.
Monoclonal antibodies against type C1 toxin produced by Clostridium botulinum type C strain Stockholm (C-ST) were prepared by fusion of BALB/c myeloma cells P3X63-Ag8, with spleen cells from the mice immunized by C-ST toxoid. About 5% of single-cell colonies in wells were found to produce antibodies against the toxin as determined by an enzyme-linked immunosorbent assay (ELISA). Four different hybridoma cell lines, no. 9, 12, 14, and 17, were established, cloned by limiting dilution, and intraperitoneally injected into mice to obtain the ascites fluids containing high-titered antibodies. The reactions of these antibodies to type C1 and D toxins of strains C-ST, D-1873, and D-South African (D-SA) were observed by both neutralization and ELISA tests. Three monoclonal antibodies, no. 9, 14, and 17, reacted with C-ST toxin, but only no. 17 highly neutralized the toxin. These antibodies did not react with type D toxins. On the contrary, no. 12 reacted with toxins of both C-ST and D-SA (but not of D-1873) and commonly neutralized these two toxins. This indicates that there is a common antigenic part between C-ST and D-SA toxin molecules which participates in the toxin-neutralizing reaction. The neutralization profiles of C-ST toxin by no. 12 and 17 antibodies were different in a time-to-death test of mice. The mechanisms of neutralization by no. 12 and 17 may be different.
Animals↗
A clinical study on the role of the renin-angiotensin-aldosterone system and catecholamines in chronic congestive heart failure.
In order to evaluate the roles of the renin-angiotensin-aldosterone system and of catecholamines in 117 normotensive patients with chronic congestive heart failure (CHF), a study was made of the relationships between plasma concentrations, hepatic extraction of these humoral factors and hemodynamic parameters. In 6 patients with moderate to severe CHF, the acute effect of oral; administration of angiotensin I converting enzyme inhibitor, SQ 14225 (captopril), on mean arterial pressure (MAP), peripheral venous pressure (VP) and these humoral factors was investigated. In patients with CHF of Class III-IV (according to NYHA classification), the urinary norepinephrine (U-NE) excretion increased. Plasma norepinephrine (P-NE) levels increased in proportion to the severity of CHF (p less than 0.001) and had a positive correlation with systemic vascular resistance (SVR) (p less than 0.01), VP (p less than 0.05), pulmonary artery wedge pressure (PWP) (p less than 0.01) and plasma renin activity (PRA) (p less than 0.01). P-NE correlated negatively with the cardiac index (p less than 0.02). Hepatic extraction of norepinephrine (EX-NE) was reduced in patients with elevated right atrial pressure (RAP) (p less than 0.05) and negatively correlated with VP (p less than 0.05). In patients with elevated P-NE, U-NE increased significantly (p less than 0.01), despite their decreased renal clearance of norepinephrine (CNE) (p less than 0.02). There was no significant difference in EX-NE between these patients and patients with normal P-NE. PRA was higher in Class III-IV patients than in Class I-II patients in the prediuretic period (p less than 0.01). PA showed a significant positive correlation with PRA (p less than 0.001). Hepatic extraction of aldosterone (EX-A) was reduced in patients with elevated RAP (p less than 0.05) and was negatively correlated with VP (p less than 0.05). Following captopril administration, PRA increased consistently and PA decreased. MAP fell, especially in 2 patients with mitral stenosis. The heart rate tended to decrease. VP also fell with symptomatic improvement. The decline in VP was correlated with the decrease in P-NE (p less than 0.01). These findings suggest that the sympathetic nervous system contributes to the elevation of SVR and PWP even before frank heart failure develops. The rise of P-NE seems to be due to increased norepinephrine release from sympathetic nerve beds, whereas a decrease in hepatic extraction and renal clearance probably has only a minor effect. The renin-angiotensin system also seems to contribute to elevation of SVR, to maintain effective arterial pressure by enhanced sympathetic activity, and the renin-angiotensin system seems to be a main determinant of PA in CHF.
Aldosterone↗
Mitochondrial adenylate kinase from chicken liver. Purification characterization and its cell-free synthesis.
Mitochondrial adenylate kinase has been purified 5400-fold from chicken liver extract in an overall yield of 36%. The purified enzyme has a specific activity of 810 U/mg, a molecular weight of 28 000, and the following amino acid composition: 21 aspartic acid or asparagine, 14 threonine, 17 serine, 27 glutamic acid or glutamine, 16 proline, 22 glycine, 22 alanine, 15 valine, 6 methionine, 11 isoleucine, 29 leucine, 5 tyrosine, 7 phenylalanine, 16 lysine, 7 histidine, 19 arginine, 3 half-cystine, and no tryptophan, totalling 257 residues. The purified enzyme has one disulfide bond and one sulfhydryl group. The disulfide bond is related to the active conformation of the enzyme, whereas the sulfhydryl group does not contribute to the enzyme activity. The sulfhydryl group is easily oxidized in the presence of Cu2+ resulting in the formation of dimer with about one half of the specific activity of the monomer. The enzyme is similar to porcine heart mitochondrial adenylate kinase in antigenicity but different from chicken cytosolic adenylate kinase. Mitochondrial adenylate kinase was synthesized in the mRNA-dependent rabbit reticulocyte lysate system programmed with total chicken liver RNA. The mobility in sodium dodecylsulfate gel electrophoresis of the product obtained in vitro was the same as that of the purified mitochondrial adenylate kinase. This evidence indicates that the mitochondrial adenylate kinase is synthesized as a polypeptide with a molecular weight indistinguishable from that of the mature protein.
Adenylate Kinase↗
[Investigation on uneven distribution of inspired gas in human lung by mathematical analysis of N2 clearance curve].
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Humans↗
Separation and characterization of heavy and light chains from Clostridium botulinum type C toxin and their reconstitution.
Clostridium botulinum type C toxin consists of a heavy and a light chain with molecular weights of 98,000 and 53,000, respectively, which are linked by one disulfide bond. The two components were separated from each other by quaternary aminoethyl Sephadex A-50 column chromatography by stepwise elution with NaCl in 27.5 mM borax-45 mM sodium dihydrogen phosphate buffer, pH 8.0, containing 5% 2-mercaptoethanol at 0 degrees C. The purified components had different amino acid compositions and antigenicities, and the toxicity of the toxin was neutralized completely by either anti-heavy chain Fab or anti-light chain Fab. the two components could be reconstituted to form an active molecule with recovered toxicity which varied according to the method used. Maximum recovery was obtained in a system in which the intersubunit S--S bond was first formed in the presence of high concentration of neutral salts, after which the concentration of salt was gradually decreased. The reconstituted preparation was highly toxic and had the same properties as the parental toxin on chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunodiffusion. By the use of three perturbants, the fractions of exposed tryptophans and tyrosines of the preparation were found to be almost the same as that of the parental toxin.
Amino Acids↗
Correlative ontogenetic development of catecholamine- and LHRH-containing nerve endings in the median eminence of the rat.
The ontogenetic development of catecholamine (CA)- and LHRH-containing nerve endings in the median eminence of the rat was investigated by combining fluorescence histochemistry and immunohistochemistry in the same tissue section. LHRH-terminals appeared earlier than CA-terminals and were already detectable in the lateral part of the external layer of the central ME on the first day after birth. CA-nerve endings were first seen in a corresponding region of the ME on the seventh postnatal day. At this stage both types of terminals showed the earliest manifestation of a correlative pattern of their distribution. Subsequently the development of both types of nerve endings proceeded rapidly, and at 14 days their distribution pattern corresponded to that in adult animals. The authors conclude that at this stage the CA-neurons play a constant and significant role in the release of LHRH into the portal capillaries. The correlation between both types of nerve endings and the ontogenetic development of the capillary plexuses of the hypophysial portal system is discussed.
Age Factors↗
Homogeneity and heterogeneity of toxins produced by Clostridium botulinum type C and D strains.
Five Clostridium botulinum strains were used in the present work, two of type C, C-Stockholm (C-ST) and C-CB19, and three of type D, D-South African (D-SA), D-1873, and D-CB16. The toxins, except for those of C-CB19 and D-CB16, were purified, and antisera were prepared in rabbits. To clarify the antigenicity of the toxins, neutralization and agar gel double-diffusion tests were performed. Anti-C-ST toxin serum neutralized two kinds of type C(1) toxin to a similar extent. Antisera against D-SA and D-1873 toxins, however, showed different neutralizing activity toward three type D toxins. Precipitin lines formed between D-SA and D-1873 toxins, and their antisera spurred to each other. From anti-D-SA toxin serum, two neutralizing fractions, one which neutralized D-SA, D-1873, and D-CB16 and one which neutralized only D-SA, were obtained. These results indicate that the antigenicities of D-SA and D-1873 toxins are not identical. Anti-C-ST toxin serum produced cross-neutralization on type D toxins, although the neutralization titer differed depending on the kind of toxin used. A precipitin line was formed with D-SA toxin, but not with D-1873; the developed line spurred to the C-ST toxin precipitin line. Two anti-D toxin sera also caused cross-neutralization on type C(1) toxins. However, the neutralizing activity of each serum to the same type C(1) toxin was different, and only anti-D-SA toxin serum developed a precipitin line with C-ST toxin which spurred to the D-SA toxin precipitin line. From anti-D-SA toxin serum, two different fractions capable of neutralizing C(1) and D toxins were obtained; one neutralized C-ST, C-CB19, and D-SA toxins, but not D-1873 and D-CB16, and the other neutralized all five toxins. There may be at least two common parts among C-ST, C-CB16, and D-SA toxin molecules.
Antigens, Bacterial↗
Nonsteroidal antiinflammatory agents. IV. Syntheses of pyridobenzoxepin, pyridobenzothiepin and their acetic acid derivatives.
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Animals↗
[Pharmacological studies on antispasmodics. I. Selectivity to antispasmodic activity of diarylmethylene-5-methyl-trans-quinolizidinium bromides (author's transl)].
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Acetylcholine↗
Studies on the mechanism of "exaggerated natriuresis" in essential hypertension.
Prompt and exaggerated natriuresis and diuresis were seen one to two hours after the starting of an infusion of 300 ml of 3% saline for one hour in patients with essential hypertension on a high sodium chloride intake. There were no significant differences in urinary volume and sodium excretion after the saline load in patients with normal and low plasma renin activity. The inhibition of angiotensin converting enzyme with SQ 14225 in patients with normal plasma renin activity did not produce additional natriuresis and diuresis after the saline load. Mean arterial blood pressure and/or changes in mean arterial blood pressure after the saline load showed a positive correlation with urinary volume and sodium excretion in each collection period in hypertensive subjects. Free water reabsorption in hypertensives was lower at high levels of osmolar clearance than that in control subjects. These results suggest that "exaggerated natriuresis" in essential hypertension is due to a decrease in tubular sodium reabsorption, which may be the result of intrarenal hemodynamic changes related to high blood pressure per se. The decreased medullary osmolar gradient is a possible contributing factor in the enhanced sodium and water excretion, while the renin-angiotensin-aldosterone system does not seem to play an important role.
Aldosterone↗
[Controlled electrophoresis of serum proteins on polyacrylamide gel (author's transl)].
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Animals↗
Electrocardiographic and echocardiographic changes after one to two-years' treatment of hypertension. Analyses of voltages (Sv1+RV5), wall thickness, cavity, mass, and hemodynamics of the left ventricle.
The changes of left ventricular anatomy and function following treatment with antihypertensive agents for 1 to 2 years were studied by echo-cardiography in 34 patients with hypertension whose blood pressures and electrocardiographic voltages (SV1+RV5) were significantly decreased (p less than 0.001 and 0.01, respectively). The drugs administered or used were trichlormethiazide, beta-blockers, alpha-methyldopa, clonidine hydrochloride, and guanethidine. Most patients received 2 or more of the above drugs. The interventricular septal thickness, the left ventricular posterior wall thickness, the calculated left ventricular mass, the atrial dimensions, all decreased following treatment of hypertension for 1 to 2 years (p less than 0.001-0.05), and the ejection fraction improved (p less than 0.001). It is concluded that cardiac hypertrophy is not irreversible in patients with hypertension if their blood pressure is adequately controlled.
Adult↗
The effect of small doses of kainic acid on the area CA3 of the hippocampal formation. An electron microscopic study.
The toxic effect on area CA3 of the hippocampus of the rat of small doses of kainic acid (KA) injected into the lateral ventricles was examined by electron microscopy. The most characteristic feature revealed was degeneration in the pyramidal cell somata and in their dendrites from as early as 3 hr after injection. We found four types of degenerating pyramidal cells probably corresponding to their susceptibility to KA intoxication. We also detected degenerating preterminal axons and terminals in addition to degenerating pyramidal cells and dendrites. Temporary structural alterations of the mossy fiber endings and intimate adhesional contacts the mossy fiber endings were also observed. The response of the glia to the damage area CA3 was an increase in the number of astroglia and macrophages in the early stage followed later by mobilization of microglia and astroglia for the formation of scar tissue.
Animals↗
[Pharmacological studies on antispasmodics. IV. Ganglion blocking activity of 3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide (HSR-902) and the correlation between its blocking activity and its inhibitory activity towards urinary bladder contraction (author's transl)].
The ganglion blocking activity of HSR-902, a new antispasmodic agent, was compared with those of atropine sulfate, butylscopolamine bromide, timepidium bromide, prifinium bromide and hexamethonium chloride. These agents inhibited the postganglionic action potential induced by preganglionic cervical sympathetic nerve stimulation in cat and the order of potency was as follows: hexamethonium chloride much greater than timepidium bromide in equilibrium with butylscopolamine bromide greater than prifinium bromide greater than HSR-902 much greater than atropine sulfate. Moreover, the inhibitory activities were correlated with the inhibitory activities of these agents on urinary bladder contraction induced by pelvic nerve stimulation in cat which had been demonstrated in a previous report. On the nictitating membrane contraction induced by postganglionic cervical sympathetic nerve stimulation in cat, HSR-902 alone exhibited a slight inhibition. HSR-902, as well as tolazoline hydrochloride, an alpha-blocking agent, shifted the dose-response curve of noradrenaline-contraction in parallel to the right without decreasing maximal response in the isolated aorta of guinea pig, and the plots of Schild were found to be linear. These results suggested that the weak inhibitory activity of HSR-902 on urinary bladder contraction would be due to the weakness of its ganglion blocking activity and that it is a new antispasmodic agent with a slight alpha-blocking activity.
Action Potentials↗
[Pharmacological studies on antispasmodics. V. Effect of 3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide (HSR-902) on the junctional transmission of pelvic nerve ending in isolated urinary bladder (author's transl)].
Effects of HSR-902, a new antispasmodic agent, on the junctional transmission of pelvic nerve ending in isolated urinary bladder was compared with those of atropine sulfate, butylscopolamine bromide, timepidium bromide and prifinium bromide. Tetrodotoxin (3 x 10(-8)g/ml) completely inhibited the contraction of isolated guinea pig urinary bladder induced by transmural stimulation (TM contraction), but hexamethonium chloride (1 x 10(-4)g/ml) and atropine sulfate (1 x 10(-5)g/ml) exhibited no inhibition and a slight inhibition, respectively. Neostigmine bromide (1 x 10(-7)g/ml) increased TM contraction, and the effect was completely inhibited by atropine sulfate (1 x 10(-5)g/ml). Antispasmodic agents (1 x 10(-7) - 1x 10(-5)g/ml), excluding HSR-902, showed slight inhibition on TM contraction. In contrast, HSR-902 (1 x 10(-6) - 1x10(-5)g/ml) increased TM contraction and/or resting tone (1 x 10(-5)g/ml). Phenoxybenzamine hydrochloride (1 x 10(-8)g/ml) and tolazoline hydrochloride (1 x 10(-5)g/ml), alpha-blocking agents, increased both TM contraction and resting tone. Increasing effects of HSR-902 on TM contraction and/or resting tone were completely inhibited by noradrenaline (1 x 10(-5)g/ml) with propranolol hydrochloride (1 x 10(-5)g/ml). These results suggested that these antispasmodic agents scarcely inhibited the junctional transmission in postganglionic cholinergic nerve ending induced by transmural stimulation of isolated guinea pig urinary bladder, and HSR-902 rather increased the transmission. Since it was also suggested that there was alpha-adrenoceptor inhibiting acetylcholine-release in the postganglionic cholinergic nerve terminal, the transmission increasing action of HSR-902 would be due to its alpha-blocking action.
Animals↗