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Biomedical subjects

M C Yang

Publications and source records attributed to M C Yang.

At least 127 records · Page 7Linked to original sources

Studies of the vasorelaxant effect of acetate.

Sodium acetate caused dose-dependent relaxation of helical rat tail artery strips constricted by phenylephrine, potassium chloride and arginine vasopressin. Substantial relaxation was evident at acetate concentrations as low as 4 mM. The results suggest that the vasodilatation of acetate is not limited to receptor-dependent or voltage-dependent mechanisms. Acute increases in bath sodium chloride concentration resulted in marked relaxation of vessel strips constricted by phenylephrine and potassium chloride. Arginine vasopressin-constricted strips were quite resistant to the vasorelaxant effect of increased bath sodium chloride.

Acetates↗

Chronotropic actions of bPTH-(1-34) in the right atrium of the rat.

Bovine parathyroid hormone and its N-terminal (1-34) peptide fragment (bPTH-(1-34] are known to possess direct hypotensive activity in the rat. The purpose of the present study was to determine if bPTH-(1-34) possessed a direct chronotropic action as well. In vivo studies revealed that bPTH-(1-34) did produce a chronotropic effect in the rat comprising both a direct component as well as a reflex tachycardia related to its hypotensive actions. In vitro studies of isolated right atria indicated that while bPTH-(1-34) had no positive inotropic effect, it did produce significant chronotropic effects which were direct and dose-dependent. The potency of bPTH-(1-34) was found to be similar to that of isoproterenol, however, it was only one-third as effective as isoproterenol in maximally increasing atrial rate. A slight but significant increase in atrial cyclic AMP was generated prior to the chronotropic actions of bPTH-(1-34).

Adrenergic Fibers↗

Parathyroid hormone (PTH) fragments relax the guinea-pig trachea in vitro.

Synthetic bovine parathyroid hormone fragment containing the N-terminal 1-34 amino acids (bPTH-(1-34) ) relaxed the guinea-pig trachea constricted with histamine in vitro. Peptides with bovine and human sequences purchased from Peninsula Laboratories and Beckman Bioproducts produced similar effects. Substitution of methionine in positions 8 and 18 by norleucine did not affect this property of bPTH-(1-34). However, when the methionines were oxidized by treating the peptide with hydrogen peroxide, the peptide could no longer produce relaxation in the trachea. Oxidation of the methionine-replaced analog did not affect the action of the peptide on the trachea. It seems that the methionines per se are not necessary, but once oxidized the conformation of the molecule may be sufficiently altered to affect its ability to relax the trachea. While propranolol can block the relaxing action of isoproterenol, this blocking agent produces no inhibition of the bPTH-(1-34) effect. This action of PTH on the trachea may be related to cAMP because isobutyryl-methylxanthine, a phosphodiesterase inhibitor, potentiates and imidazole, a phosphodiesterase stimulator, inhibits the trachea relaxing action of bPTH-(1-34).

1-Methyl-3-isobutylxanthine↗

Structure activity relationship of parathyroid hormone: separation of the hypotensive and the hypercalcemic properties.

The present study was conducted to show that the hypercalcemic and the vascular relaxing activities of PTH are two separable properties. During the hypotensive action of the synthetic fragment bovine (b) PTH-(1-34), plasma calcium levels were not significantly changed. Mild oxidation with hydrogen peroxide abolished the hypotensive and hypercalcemic actions of bPTH-(1-84). However, the same treatment on bPTH-(1-34) abolished only the hypotensive and not the hypercalcemic action. Analysis of the amino acid composition revealed only the oxidation of the methionines to methionine sulfoxides. The other amino acids remained unchanged. In addition, the analog with methionines replaced by norleucine, [Nle8,Nle18,Tyr34]bPTH-(1-34), was active in all the vascular assays, and these activities were unaffected by hydrogen peroxide treatment of the molecule. Perhaps the methionine sulfoxides in the hydrogen peroxide-treated bPTH-(1-34) affected the changes of the molecule in such a manner that the part of the molecule for the vascular action but not that for the hypercalcemic action was no longer accessible to the receptors of the target organs. The hypotensive pentapeptide, bPTH-(24-28), was not active in the hypercalcemic assay. All these data are consistent with our hypothesis that the vascular relaxing and the hypercalcemic actions of PTH are two separate properties of the molecule.

Amino Acids↗

The effect of the propagation coefficient on size distribution in micellar systems.

In this study the effect of the propagation coefficient on the molar distribution function in a modified shell model for micellar systems was examined. The sharpness of the micelle size distribution boundary was found to depend less on the degree of polymerization, n, than on the propagation coefficient, P. Although Kegeles (J. Phys. Chem. 83 (1979) 1728) has reported a marked sharpening of the distribution boundary when P = 2.0. we found the boundary to be fairly broad at this point. However, as values of the propagation coefficient were increased from 3 to 10, the micelle distribution boundary became increasingly sharp. The possibility of such a change in the reaction boundary arising from a structural transition, accompanied by a change in the rate of dissociation of monomer from the shell, is also discussed.

Journal Article↗

Structure and vascular activity relationship of parathyroid hormone and some hypotensive peptides.

The synthetic fragment of bovine PTH [bPTH-(1-34)] had direct vasodilatory action in the coronary, renal, hepatic and some visceral vascular beds. The vascular action of bPTH-(1-34) was separable from its hypercalcemic action. We attempted to identify the amino acid sequence responsible for this vascular action. The methionines in positions 8 and 18 were not necessary for vascular relaxation since [Nle8, Nle18, Tyr34]-bPTH-(1-34) was active. However, when these methionine residues were oxidized, the vascular action of this peptide disappeared. This would suggest conformational changes of this oxidized peptide, resulting in loss of activity. Adjacent basic amino acids in positions 25, 26 and 27 may play an important role in the hypotensive action of peptides. Other hypotensive peptides such as neurotensin, xenopsin and VIP which also possess adjacent basic amino acids but are not known to be vasoactive were also hypotensive in our assays.

Animals↗

Lack of histamine involvement in parathyroid hormone hypotensive action.

Promethazine and cimetidine blocked the hypotensive actions of 2-pyridylethylamine, and H1 agonist and dimaprit, an H2 agonist, respectively, but not that of bovine parathyroid hormone fragment [bPTH-(1-34)]. Rats were treated repeatedly with the histamine releaser, compound 48/80, until the release could no longer produce a decrease in blood pressure. The hypotensive action of bPTH-(1-34) could still be seen. Rats with histamine partially depleted with one injection of compound 48/80 were injected with cimetidine and pyrilamine, and H1 antagonist, which together blocked the hypotensive action of subsequent injections of compound 48/80, but not that of bPTH-(1-34). These data suggest that the vasodilatory action of bPTH-(1-34) does not involve the release or action of histamine.

Animals↗

Hypotensive action of synthetic fragments of parathyroid hormone.

Parathyroid hormone (PTH) and its N-terminal 1-34 fragment were shown to be hypotensive in dogs. In this study, synthetic bovine PTH fragments containing the N-terminal amino acids 1-34, 24-34, 24-28 and 25-27 [bPTH-(1-34), bPTH-(24-34), bPTH-(24-28) and bPTH-(24-27)] were synthesized and tested for hypotensive activity in dogs. bPTH-(1-34) is the most potent of these. The tripeptide is ineffective at doses as high as 2 mg/kg. bPTH-(24-34) and bPTH-(24-28) exhibited hypotensive activity but were less effective than bPTH-(1-34). A decrease in chain length decreased the hypotensive activity. The maximum response produced by bPTH-(1-34) was greater than that of either bPTH-(24-34) or bPTH-(24-28). The maximum responses, however, of bPTH-(24-34) and bPTH-(24-28) were similar. Another striking difference between bPTH-(1-34) and the other two effective fragments was the duration of action. Whereas the action of bPTH-(1-34) at ED50 lasted for up to 6 min the action of bPTH-(24-34) and bPTH-(24-28) lasted for less than 1 min. The hypotensive effect of these three bPTH fragments was not affected by propranolol, phentolamine, atropine, promethazine or cimetidine. In the perfused rat hindlimb, bPTH-(24-28) produced log dose-related sustained vasodilation.

Animals↗

Scanning molecular sieve chromatography of interacting protein systems. III. Effect of kinetic parameters on the large zone boundary profiles for local equilibration between mobile and stationary phases.

Large zone reaction boundary profiles for molecular sieve chromatography as affected by kinetic parameters have been simulated for local equilibration between the mobile and stationary phases. Our studies of monomer-dimer and monomer-tetramer systems indicate that in a slowly equilibrating system, the kinetic controls operating between the mobile and stationary phases contribute most significantly to the overall boundary profile. In a rapidly equilibrating system, however, the kinetic parameters kij and kji operating in the mobile phase are the principal determinants of the reaction boundary, while the kinetic effects of kii and k-ii between the mobile and stationary phases are minimal.

Chromatography, Gel↗

Scanning molecular sieve chromatography of interacting protein systems. Simulation of large zone behavior for self-associating solutes undergoing rapid chemical equilibration under kinetic control.

Theoretical large zone reaction boundaries for molecular sieve chromatography have been simulated by computer for a self-associating solute undergoing rapid chemical equilibration under kinetic control. These patterns show that the kinetically-controlled reaction rate between the mobile and stationary phases is the principal determinant of the elution boundary profile in molecular sieve chromatography. The overall chemical reaction rate in the mobile phase was found to have a much greater role in a rapidly equilibrating system than did the effect of axial dispersion within the gel matrix.

Chromatography, Gel↗

Multiple leukocyte abnormalities in chronic granulomatous disease: a familial study.

A variety of leukocyte enzyme activities were studied in an 11-year-old female with chronic granulomatous disease (CGD) and several members of her family. Leukocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity was 17 nmol/min/mg protein in the patient; two brothers with symptoms of recurrent bacterial infections have G-6-PD activities of 58 and 37 nmol/min/mg protein; the activites of this enzyme in both parents, maternal grandmother, and one additional brother were within normal limits. Storage at 4 degrees or heating at 37 degrees over a 120-min period revealed a marked lability of G-6-PD activity in the patient's cells which could not be stabilized by the addition of NADP and 2-mercaptoethanol; this lability was not seen in other family members tested. Activities of leukocyte glutathione reductase were reduced in both parents and the two affected male siblings with values of 18, 23, 23, and 24 nmol/min/mg protein, respectively. Activities of leukocyte glutathione peroxidase were reduced in all of the immediate family members tested, with values ranging from 11.2 to 43 nmol/min/mg protein; the activity of this enzyme in the patient was 38.5. Leukocyte NADP content in the patient, father, and two affected male siblings were 16.5, 23.4, 22.2, and 28.2 nmol/15 min/10(7) leukocytes, respectively.

Adolescent↗

Scanning molecular sieve chromatography of interacting protein systems. III. Effect of kinetic parameters on the large zone boundary profiles for local equilibration between mobile and stationary phases.

Large zone reaction boundary profiles for molecular sieve chromatography as affected by kinetic parameters have been simulated for local equilibration between the mobile and stationary phases. Our studies of monomer-dimer and monomer-tetramer systems indicate that in a slowly equilibrating system, the kinetic controls operating between the mobile and stationary phases contribute most significantly to the overall boundary profile. In a rapidly equilibrating system, however, the kinetic parameters k(ij) and k(ji) operating in the mobile phase are the principal determinants of the reaction boundary, while the kinetic effects of k(ii) and k-(ii) between the mobile and stationary phases are minimal.

Journal Article↗

Correlation of structural changes in parathyroid hormone with its vascular action.

The analysis of the spectrum of circular dichroism (CD) of methionine-oxidized bovine parathyroid hormone peptide, bPTH(1-34) revealed that approximately 43% of the orderly conformation (alpha-helix and beta-sheet) was converted into random coil structure. This peptide failed to elicit any hypotensive response in rats at any of the tested doses from 0.01 to 0.05 mg/ml. The blue shift of tryptophan fluorescence and the increase in the fluorescence intensity of the fluorescence probe 2-p-toluidinylnaphthalene-6-sulfonate (TNS) bound to the oxidized peptide indicated that the more hydrophobic environment was generated in the tryptophan domain as well as the molecule as a whole when the methionines in the peptide were oxidized. Modification of arginine with 1,2-cyclohexanedione (CHD) reduced 30% to 50% of the hypotensive action of the peptide hormone. Similar results in the increase of hydrophobicity of the arginine-modified peptide were also observed. These studies suggest that the conformational changes due to the methionine oxidation or arginine modification may be related to the inactivation of the vascular activity of bPTH(1-34).

Animals↗