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C H Ahn

Publications and source records attributed to C H Ahn.

At least 37 records · Page 2Linked to original sources
PubMed1990

Stereostructure activity relationships of catecholamines on human platelet function.

The concentration-dependent effects of clonidine, isomers of epinephrine, norepinephrine (NE), isoproterenol, cobefrin and alpha-methyldopamine, and related desoxy analogs (epinine, dopamine, N-isopropyldopamine) were examined on human platelets. The rank order of aggregatory potency (pD2 values) was R(-)-epinephrine (6.3) greater than R(-)-NE (5.9) greater than (+/-)-erythro-cobefrin (5.3) greater than S(+)-epinephrine (4.7) = S(+)-NE (4.7) = clonidine (4.7) = dopamine (4.6) greater than epinine (4.4) greater than S(+)-alpha-methyldopamine (4.3) = R(-)-alpha-methyldopamine (4.3) greater than (+/-)-threo-cobefrin (3.7). The isoproterenol isomers and N-isopropyl-dopamine were inactive as agonists. In 9 of 16 platelet-rich plasma preparations, R(-)-epinephrine, R(-)-NE, and (+/-)erythro-cobefrin were agonists and the remaining analogs blocked R(-)-NE-induced aggregation with a rank order of inhibitory potencies (pKB values) of clonidine (6.2) greater than S(+)-alpha-methyldopamine (5.0) greater than dopamine (4.6) = R(-)-alpha-methyldopamine (4.4) greater than or equal to S(+)-NE (4.3) greater than N-isopropyldopamine (4.1) greater than S(+)-isoproterenol (3.7) = R(-)-isoproterenol (3.5). Each compound was also able to reverse prostaglandin E1 (PGE1) (0.1 microM)-induced blockade of the maximal aggregation response to ADP. At high concentrations, R(-)-isoproterenol was more potent than either the S(+)-isomer or desoxy analog, N-isopropyldopamine, in the reversal of PGE1 inhibition of ADP aggregation. Phentolamine blocked these alpha 2-adrenoceptor-mediated actions against PGE1 on ADP aggregation. The rank order of potency for the reversal of PGE1-mediated inhibition of ADP aggregation by these catecholamines was similar to that observed for platelet aggregation. Our results indicate that (i) the stereochemical requirements for the interaction of catecholamines with platelet alpha 2-adrenoceptors are in agreement with the Easson-Stedman hypothesis and other alpha-adrenoceptor tissues; (ii) catecholamines lacking a benzylic hydroxyl group in the R-configuration and/or possessing an N-isopropyl group were alpha 2-adrenoceptor antagonists; (iii) clonidine gave quantitatively different responses compared with catecholamines for interaction with alpha 2-adrenoceptors; and (iv) inhibition of platelet adenylate cyclase is correlated to the inhibition of epinephrine-induced aggregation response for this series of compounds.

Adenosine Diphosphate↗
PubMed1988

Characterization of the inhibition of U46619-mediated human platelet activation by the trimetoquinol isomers. Evidence for endoperoxide/thromboxane A2 receptor blockade.

Sites of inhibition for the trimetoquinol (TMQ) isomers on 15S-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619)-, 12-O-tetradecanoylphorbol 13-acetate (TPA)- and A23187-induced human platelet activation were investigated. Experiments using washed human platelets were designed to characterize relationships among functional (aggregation, secretion) and biochemical (protein phosphorylation, metabolism of inositol phospholipids and radioligand displacement analysis) processes of platelet activation by U46619 and the specificity of inhibition by the TMQ isomers. Thromboxane A2 receptor stimulation by U46619 in human platelets resulted in a time- and concentration-dependent breakdown of inositol phospholipids [phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol (PI)], phosphatidic acid (PA) accumulation, phosphorylation of 20 and 45 kD proteins, aggregation and serotonin secretion. The TMQ isomers stereoselectively inhibited all U46619-mediated platelet activation processes. R(+)-TMQ was 40- and 22-fold more potent than S(-)-TMQ as an inhibitor of U46619-induced platelet aggregation and serotonin secretion respectively. In addition, R(+)-TMQ blocked U46619-induced 20 kD protein phosphorylation, 45 kD protein phosphorylation, PIP2, PIP and PI breakdown, and PA accumulation with a potency which was 8-, 13-, 45-, 37-, 33- and 33-fold greater than the S(-)-isomer respectively. In contrast to S(-)-TMQ, R(+)-TMQ produced a concentration-dependent inhibition of specific [3H]U46619 binding to endoperoxide/thromboxane A2 receptor sites in washed platelets. In other experiments, S(-)-TMQ was more potent than R(+)-TMQ as an inhibitor of TPA- and A23187-induced platelet aggregation and serotonin secretion, and of TPA-induced phosphorylation of 45 and 20 kD proteins. The inhibitory potencies of S(-)-TMQ against TPA- or A23187-induced responses were similar to those needed for antagonism of U46619-mediated platelet activation. In contrast, much higher concentrations of R(+)-TMQ were required for blockade of TPA or A23187 versus U46619-mediated responses in human platelets. Taken collectively, the data show that the TMQ isomers interfered with the endoperoxide/thromboxane A2 receptor-mediated phospholipase C-signal cascade of inositol phospholipid hydrolysis, calcium mobilization, and protein phosphorylation leading to platelet aggregation and secretion. R(+)-TMQ acted as a pharmacologically selective and highly stereospecific [R(+)-TMQ much greater than S(-)-TMQ] antagonist of endoperoxide/thromboxane A2 receptor sites in platelets.(ABSTRACT TRUNCATED AT 400 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Use of [3H]trimetoquinol as a radioligand in human platelets: interaction with putative endoperoxide/thromboxane A2 receptor sites.

We have recently shown that trimetoquinol [1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4- tetrahydroisoquinoline; TMQ] is a potent and stereoselective [R(+)-isomer greater than S(-)-isomer] antagonist of aggregation induced by thromboxane A2 and stable epoxymethano PGH2 analogues (U46619; U44069) in human platelets. The present study was undertaken to characterize the pharmacological specificity of binding sites for racemic- [3H]TMQ in washed human platelets. Specific binding of [3H]TMQ, determined by addition of 100 microM R(+)-TMQ, accounted for 12-26% of the total binding at 1.0 microM. Saturation data suggested two binding sites with apparent dissociation constants of 2.8 nM and 1.4 microM for the high and low affinity binding sites, respectively. Maximal binding densities (pmol/mg protein) were 2.3 and 42.9 for the respective high and low affinity sites. The optical isomers of TMQ, cis and trans-isomers of 13-azaprostanoic acid (13-APA), and U46619 inhibited [3H]TMQ specific binding to the low affinity site. R(+)-TMQ was 32-fold more potent than S(-)-TMQ at inhibiting [3H]TMQ binding, and the stereoselective potency difference and concentrations needed to inhibit binding were similar to those required for inhibition of U46619-induced platelet aggregation and serotonin secretion. Similarly, trans-13-APA was 90-fold more potent than cis-13-APA as a competitor of [3H]TMQ binding. U46619 also inhibited TMQ binding at concentrations (IC50 = 0.4 microM) similar to those required for aggregation (EC50 = 0.16 microM) and secretion (EC50 = 0.23 microM). At 1 mM, arachidonic acid inhibited [3H] TMQ binding by only 25%. Our studies indicate that [3H]TMQ interacts with specific binding sites with characteristics indicative of putative endoperoxide/thromboxane A2 receptors in human platelets.

Blood Platelets↗
PubMed1987

Sulfonamide-containing regimens for disease caused by rifampin-resistant Mycobacterium kansasii.

Fourteen wild strains and 14 relapse or treatment failure isolates of Mycobacterium kansasii were tested and found to be highly susceptible to sulfamethoxazole (SMX), with 26 of 28 isolates having minimal inhibitory concentrations (MIC) of less than or equal to 4 micrograms/ml), using a broth microdilution method. Treatment failure isolates frequently exhibited resistance to rifampin (RMP) (greater than 2 micrograms/ml), isoniazid (INH) (greater than 4 micrograms/ml), and ethambutol (EMB) (greater than 4 micrograms/ml) not seen among the wild strain isolates. Eight patients with cavitary disease caused by RMP-resistant M. kansasii were treated with SMX-containing regimens that also included high dose INH (900 mg), EMB (25 mg/kg), and an aminoglycoside (either streptomycin or amikacin). Patients were treated initially in the hospital for 4 to 10 wk. In 7 of the 8 patients, sputum cultures became negative in a mean of 10 wk (range, 7 to 14 wk). Acquired drug resistance to INH, RMP, and EMB can be demonstrated in M. kansasii, and SMX in combination with other agents chosen on the basis of MIC determinations are effective in the treatment of disease caused by RMP-resistant M. kansasii.

Adult↗
PubMed1986

Alpha-adrenoceptor-mediated actions of optical isomers and desoxy analogs of catecholimidazoline and norepinephrine in human platelets: in vitro.

Adrenoceptor-mediated effects of the enantiomers of optically active imidazoline, 2-(3,4,alpha-trihydroxybenzyl imidazoline (catecholimidazoline; CI), and norepinephrine (NE), and the corresponding desoxy derivatives, 2-(3,4-dihydroxybenzyl)imidazoline (desoxy-CI) and dopamine, have been investigated in human platelets. Differences between responsiveness of platelets from donor to donor were observed in the presence of the isomers and the desoxy analogs of NE and CI. In certain platelet preparations, all compounds gave concentration-dependent stimulatory responses, whereas in other preparations, only R(-)-NE and R(-)-CI were inducers of platelet aggregation and serotonin release. The rank order of stimulatory potencies (EC50; microM) for CI and NE was R(-)-NE (1.3) greater than R(-)-CI (7.5) greater than S(+)-NE (19) = S(+)-CI (20) = dopamine (22) greater than desoxy-CI (greater than 35). Unlike R(-)-CI, both S(+)-CI and desoxy-CI were either agonists or antagonists of human platelet function. In preparations unresponsive to the S(+)-isomers or desoxy analogs, the potencies (EC50) for R(-)-NE and R(-)-CI were 1.7 and 7.7 microM respectively. The corresponding inactive CIs [S(+)-CI and desoxy-CI] were inhibitors of both primary and secondary phases of aggregation and serotonin release responses to R(-)-CI and R(-)-NE, respectively. In contrast, the aggregation responses to ADP, arachidonic acid or U46619 were not blocked by S(+)-CI or desoxy CI. The rank order of inhibitory potencies for selected alpha-adrenoceptor agents against R(-)-NE was phentolamine greater than clonidine greater than desoxy-CI greater than S(+)-CI. Moreover, the relative inhibitory potencies of phentolamine and desoxy-CI against aggregation responses to R(-)-NE and R(-)-CI, respectively, were the same. These results suggest that the enantiomers and desoxy derivatives of CI and NE mediate their effects in human platelets by an interaction with alpha-adrenoceptors; catecholamines and imidazolines interact with the same alpha-adrenoceptors in human platelets; the stereochemical requirements of both chemical classes for stimulatory activity in human platelets adhere to the Easson-Stedman hypothesis in this alpha 2-adrenoceptor system; and desoxy-CI possessed the highest potency as an antagonist of alpha-adrenoceptors which suggests that the hydroxy group at the benzylic carbon atom of these imidazolines may not be required for maximal binding to adrenoceptors in platelets.

Blood Platelets↗
PubMed1986

Syntheses and beta-adrenergic agonist and antiaggregatory properties of N-substituted trimetoquinol analogues.

Trimetoquinol [1-(3,4,5-trimethoxybenzyl)-6,7- dihydroxy-1,2,3,4-tetrahydroisoquinoline, TMQ] is a potent beta-adrenergic receptor agonist and inhibitor of human platelet aggregation. Selective cleavage of O-benzyl groups in the presence of an N-benzyl group using HCl and formation of a cyclic sulfite ester from the reaction of a catechol with thionyl chloride were achieved. The N-substituents included methyl, benzyl, and beta-hydroxy- and beta-chloroethyl groups. Each N-substituted TMQ caused a concentration-dependent stimulation of beta 2 (trachea) and beta 1 (atria) adrenoceptor tissues and inhibition of 15(S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13(E)-dienoic acid (U46619, a thromboxane A2 mimetic) mediated human platelet activation. TMQ remained the most potent in the series. Structure-activity results indicated that the larger the N-substituent, the lower the beta-adrenergic activity but the higher the inhibition of platelet aggregatory activity. Thus, the structural requirements of these TMQ analogues for the two types of biological activity are different.

Adrenergic beta-Agonists↗
PubMed1986

A four-drug regimen for initial treatment of cavitary disease caused by Mycobacterium avium complex.

Forty-six patients with positive sputum cultures for Mycobacterium avium complex and cavitary disease were placed on a 4-drug regimen consisting of isoniazid, rifampin, and ethambutol daily and streptomycin twice weekly. Forty-two (91.3%) converted their sputum to negative and 4 (8.7%) failed to convert. All of the 4 nonconverters had prior subtotal gastrectomy. Twenty-two patients were available for long-term follow-up: 12 patients completed 24 months of chemotherapy, all experienced sputum conversion, but 2 reactivated, 1 at 9 and the other at 27 months after termination of chemotherapy. These 2 patients had prior subtotal gastrectomy. Ten patients completed 18 months of chemotherapy with sputum conversion, 2 of these reactivated but had not had prior subtotal gastrectomy. In this group of patients, subtotal gastrectomy appeared to be an adverse risk factor for both initial treatment response and reactivation in pulmonary disease caused by Mycobacterium avium complex.

Antitubercular Agents↗
PubMed1983

Short-course chemotherapy for pulmonary disease caused by Mycobacterium kansasii.

Forty patients with pulmonary disease caused by Mycobacterium kansasii were treated initially with rifampin, isoniazid, and ethambutol daily for 12 months, and with streptomycin twice weekly for the first 3 months. Postchemotherapy follow-up examinations have ranged from 6 to 68 months, with an average of 31 months. One of the 40 patients (2.5%) relapsed 6 months after completion of chemotherapy. In vitro susceptibility of the mycobacteria to the drugs used, extent of disease, and/or the coexistence of other diseases did not seem to influence the outcome. This 12-month chemotherapy regimen is considered to be sufficient for the initial treatment of pulmonary disease caused by M. kansasii.

Adult↗
PubMed1982

Diagnostic criteria for pulmonary disease caused by Mycobacterium kansasii and Mycobacterium intracellulare.

A study of 271 patients infected with Mycobacterium kansasii and 226 patients with Mycobacterium avium-intracellulare complex has led to the proposal of new diagnostic criteria. These criteria, based on the presence or absence of cavitation and on the duration of sputum positivity after initiation of therapy, are proposed to more accurately distinguish colonizations from active invasion of tissue than the current diagnostic criteria.

Humans↗
PubMed1981

Initial roentgenographic manifestations of pulmonary Mycobacterium tuberculosis, M kansasii, and M intracellularis infections.

The initial radiographic features of 188 patients with pulmonary infections due to Mycobacterium tuberculosis were compared to 184 patients with M kansasii and 100 patients with M intracellularis infections. The patients were all from the University of Texas Health Center at Tyler, all had at least two positive sputum cultures and no other potential pathogen, and none had a past medical history of any type of tuberculosis. The comparison showed that all three organisms have a strong tendency to produce cavitary infiltrates in the posterior portions of the upper lobes. No distinctive or pathognomonic feature could be found. The atypical organisms were more likely to produce thin-walled cavities and far advanced unilateral disease, but both of these patterns also occurred with M tuberculosis. Endobronchial spread and volume loss were common in all three diseases. The only definite difference seems to be the absence of a primary or juvenile form of atypical tuberculosis and a much greater incidence of empyema and postprimary pleural effusions with M tuberculosis. In an individual case, the roentgenographic manifestations of the three diseases are indistinguishable.

Aged↗
PubMed1979

A demographic study of disease due to Mycobacterium kansasii or M intracellulare-avium in Texas.

The number of patients reported th have disease due to Mycobacterium kansasii or M intracellulare-avium has increased in Texas from January 1967 to December 1976, in contrast to a decrease in tuberculosis. Presented is an analysis of 1,409 patients infected with M kansasii and 706 patients infected with M intracellulare-avium. The former group clustered in urban areas with more than twice the incidence compared to nonurban areas (P less than 0.001). The latter group was more diffusely distributed with approximately twice the incidence in nonurban areas compared to urban areas (P less than 0.001). The average age of the group infected with M kansasii was 50 years and of the group infected with M intracellulare-avium 58 years. In patients infected with M kansasii only, the average age was significantly higher for men than women. There was a male predominance in both groups, ie, 3:1 in M kansasii and 2:1 in M intracellulare-avium. Persons with Spanish surnames had a low incidence of disease due to M kansasii. No other racial or ethnic association was noted. The various factors involved in determining the atypical mycobacterial diseases are discussed.

Adolescent↗
PubMed1979

Elimination of Mycobacterium intracellulare from sputum after bronchial hygiene.

Three cases are presented, each of which had more than 20 positive cultures of sputum for Mycobacterium intracellulare, infiltrations, and a history of bronchiectasis. Two had complete and the third nearly complete, sputum conversion during a program of bronchial hygiene without chemotherapy. It is probable that these cases were only noninvasive colonizations in previously diseases lungs. Recommendations are given for a therapeutic approach in such cases.

Aged↗
PubMed1979

Pulmonary manifestations of Mycobacterium intracellularis.

Pulmonary manifestations in 114 patients with at least two sputum cultures positive for M. intracellularis, no history of any kind of tuberculosis, and not other potential pathogen are described. Even with these stringent diagnostic criteria, seven patients had normal chest radiographs and another seven had reticulonodular-appearing disease without a definite focus of infection. In the other 100 patients, 92% had infiltrates in the apical and/or posterior segments of the upper lobes, and 88% had cavitary disease. The cavities were usually multiple and frequently measured over 4 cm. Scarring and volume loss were common, occurring to some degree in 70% of upper lobe foci. Pleural effusions were uncommon (5%) and usually small. Adenopathy was less common (4%) and usually occurred with upper lobe disease in younger patients. Most patients had some degree of endobronchial spread (81%). The radiographic characteristics of Mycobacterium intracellularis are not believed distinctive enought to differentiate it from Mycobacterium tuberculosis.

Aged↗
PubMed1978

Radiographic manifestations of pulmonary Mycobacterium kansasii infections.

The radiographic characteristics of 187 pristine cases of pulmonary Mycobacterium kansasii infection are reviewed. The cases were selected from a total of 309 patients with two positive sputum cultures. All but three of the 187 patients had pulmonary disease. The progenitive focus of disease almost always involved the upper lobes, the right side (72%) more often than the left (50%). Upper lobe disease began posterior to the trachea in every case. Only one patient had disease that originated in an atypical location, that is, in the superior segment of the right lower lobe. The most frequent radiographic abnormality was cavitation (96% of diseased patients). The classical description of a thin walled cavity (or cavities) occurred in 33% of patients. A cicatricial reaction was common (two-thirds of cases). About 63% of patients had endobronchial spread. The likelihood of endobronchial disease decreased as the distance from the progenitive focus increased. Pleural effusions and adenopathy were rare. In an individual case, it is not possible to differentiate between pulmonary M. tuberculosis and M. kansasii infections.

Adolescent↗
PubMed1976

Ventilatory defects in atypical mycobacteriosis. A comparison study with tuberculosis.

Two hundred thirty-two patients infected with Mycobacterium kansasii and 120 patients infected with M. intracellulare who were admitted to the East Texas Chest Hospital between 1965 and 1974 were individually matched according to age (+/- 5 years), sex, and extent of disease with an equal number of patients infected with M. tuberculosis. The ventilatory function in these patients was compared. The frequency of obstructive ventilatory defect, defined as forced expiratory volume in 1 sec less than 70 per cent of forced vital capacity, was greater among M. kansasii patients (68.9 per cent of 232) than among M. tuberculosis patients less than 80 per cent of predicted, was greater among M. intracellulare patients (68.3 per cent of 120) than among M. tuberculosis patients (57.5 per cent of 120). Above age 40, obstructive ventilatory defects tended to be more common in M. kansasii patients, whereas restricted ventilatory defects tended to be more common in M. intracellulare patients when compared with the same age group of M. tuberculosis patients. As expected, ventilatory function values among the M. tuberculosis groups decreased as extent of disease increased. In contrast, among the M. kansasii and M. intracellulare groups, these values were poorly related to the extent of disease; values were relatively low even with minimal extent of disease. It is suggested that the increased ventilatory defects among the M. kansasii and M. intracellulare patients could be accounted for by coexistent lung disease.

Adolescent↗