Biomedical subjects

B K Yeh

Publications and source records attributed to B K Yeh.

At least 19 recordsLinked to original sources

PubMed2000

Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization.

The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex at 3 A resolution has been determined. Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding. Heparin also interacts with FGFR in the adjoining 1:1 FGF:FGFR complex to promote FGFR dimerization. The 6-O-sulfate group of heparin plays a pivotal role in mediating both interactions. The unexpected stoichiometry of heparin binding in the structure led us to propose a revised model for FGFR dimerization. Biochemical data in support of this model are also presented. This model provides a structural basis for FGFR activation by small molecule heparin analogs and may facilitate the design of heparin mimetics capable of modulating FGF signaling.

Binding Sites↗

PubMed1997

Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.

A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.

3T3 Cells↗

PubMed1993

Liquid chromatographic analysis of amino acids: using dimethylamino-azobenzenesulfonyl chloride and Hypersil ODS column to analyze the composition of apo B peptides.

A reliable high-performance liquid chromatography (HPLC) method is described for the separation of dimethylamino-azobenzenesulfonyl-amino acid (DABS-AA). The separation is accomplished by reversed-phase chromatography on a Hypersil ODS column (4.6 x 150 mm) with a Hewlett-Packard liquid chromatography system. In addition to the developed sample and solvent preparation procedure, this precolumn modification method using dimethylaminoazobenzene sulfonyl chloride (DABS-CL) for amino acid analysis is proved reliable and sensitive. Five apolipoprotein B-100 tryptic peptides, two of them containing cysteine, were demonstrated as examples for the general application of this method in amino acid analysis. It is a useful method for analysis of cysteine- and cystine-containing peptide and, furthermore, for determination of sulfhydryl and disulfide linkages of proteins.

Amino Acid Sequence↗

PubMed1977

Sodium nitroprusside as a coronary vasodilator in man. I. Effect of intracoronary sodium nitroprusside on coronary arteries, angina pectoris, and coronary blood flow.

The effect of the intra-arterial injection of 5 to 10 microng of sodium nitroprusside on the caliber of normal and diseased coronary arteries was evaluated in 21 patients during diagnostic cardiac catheterization. In addition, the effect of intra-graft injection of 5 microng of the same agent on the blood flow in aorta-right coronary artery saphenous vein bypass grafts was also evaluated intra-operatively in two patients. The compound induced an increase in the caliber of both normal and stenosed coronary arteries as well as an increase of flow in the grafts. Consistent with measurements of coronary flow response to sodium nitroprusside, angina pectoris which developed in four patients during cardiac catheterization was immediately relieved and the ischemic ST-segment depression significantly reversed after injection of 5 to 10 microng of the drug into the left main coronary artery. Within the dose range used, the drug caused no significant effect on systemic blood pressure or apparently deleterious electrophysiologic changes. No side effects were observed. We conclude that the primary direct action of sodium nitroprusside in the human coronary artery is vasodilatory.

Adult↗

PubMed1976

Antiarrhythmic activity of potassium canrenoate in man.

The efficacy of potassium canrenoate in suppressing frequent ventricular premature depolarizations and ventricular bigeminal and trigeminal rhythms thought to be due to digitalis overdose was studied in seven men and five women (average age, 54.5 years). A mean dose of 525 mg. (1.31 mEq.) of potassium canrenoate administered intravenously effectively suppressed the ventricular rhythm disturbances in eight of the 12 patients for from several minutes to 4 hours. The mean serum digoxin level determined in seven patients was greater than 2.3 ng. per milliliter. The ability of potassium canrenoate to counteract digitalis intoxication suggests that the molecule of canrenoate is unique in the clinical setting since it shows both diuretic and antiarrhythmic properties.

Adult↗

PubMed1976

Sodium nitroprusside as a coronary vasodilator in man: a comparison of the effects of sodium nitroprusside and papaverine hydrochloride on aortocoronary saphenous vein graft flow.

Blood flow in aortocoronary saphenous vein grafts was studied in response to intragraft injection of sodium nitroprusside and papaverine hydrochloride. Following injection of 50 mug of sodium nitroprusside, mean graft flow increased from 40.1 +/- 4.5 to 81.3 +/- 8.5 ml per minute. Administration of 30 mg of papaverine hydrochloride caused mean graft flow to rise from 35.4 +/- 3.9 to 70 +/- 7.9 ml per minute. Sodium nitroprusside increases aortocoronary graft flow, the doubling effect of 50 mug of the drug being of the same order of magnitude as that induced by 30 mg of papaverine hydrochloride.

Adult↗

PubMed1975

Inotropic action of tolbutamide on human myocardium.

The inotropic action of tolbutamide previously demonstrated in vitro was evaluated in 15 nondiabetic subjects during diagnostic cardiac catheterization. Following bolus injection of 250 mg of tolbutamide intravenously, a rise of serum insulin and a slight fall of serum potassium were observed. Inotropic response was determined from significant fall in PEP/LVET ratio, significant fall of left ventricular end-diastolic pressure, shift to an augmented function curve in work-pressure relationships, and prominent rise of dP/dt values at comparable heart rates. The inotropic effect was greatest at 5-15 min with return to near control values at 30 min. An unusually marked inotropic response was observed in one subject. While the measurable net hemodynamic effect of tolbutamide in the human heart is small, its effect on ischemic and normal areas within the heart of a diabetic patient with atherosclerosis may be different. Thus, its ultimate effect on the diseased heart may be significant.

Blood Glucose↗

PubMed1975

Antiarrhythmic activity of four pteridine compounds in ouabain intoxication.

The antiarrhythmic effects of 4 pteridine analogues, 2 of which are potassium-sparing diuretics, triamterene (2, 4, 7-triamino-6-phenylpteridine) and [2-phenyl-4, 7 diaminopteridine-6-(N-diethylaminoethyl) carboxamide] and 2 of which have no diuretic effects [2-phenyl-4, 7-diaminopteridine-6-(N-2-hydroxyethyl) carboxamide], on ouabain-induced ventricular tachycardia in intact pentobarbital-anesthetized dogs were investigated. Ouabain was given as a continuous infusion 2 mug/kg/min intravenously until 5 min after the onset of a sustained ventricular tachycardia. It was found that both 6-(N-dimethylaminopropyl) and 6-(N-diethylaminoethyl) carboxamide derivates of the pteridine had a significant protective effect against ouabain-induced ventricular tachycardia in dogs that had been pretreated with a dose of 5 mg/kg intravenously. At this dose the 2 pteridine compounds with diuretic activity exhibited a transient antiarrhythmic effect in abolishing the ouabain-induced ventricular tachycardia while those without diuretic properties failed to suppress the ventricular tachycardia.

Animals↗

PubMed1975

A His bundle electrocardiographic analysis of cardiac conduction in the pediatric and adolescent patient.

Bipolar electrode catheter recordings of His bundle electrograms with three simultaneously recorded surface electrocardiographic leads were obtained from 30 pediatric and adolescent patients (aged 3 to 18 years). In 14 patients, cardiac murmurs were proved to be innocent by cardiac catheterization. The control conduction intervals were compared to those of 13 patients with congenital heart disease, and three with acquired heart disease (myocardiopathy, rheumatic valvular disease, and Friedreich's ataxia). P-R, intra-atrial (P-A), A-V nodal (A-H), and intraventricular (H-V) conduction intervals were measured to the nearest 5 msec. Conduction delays were analyzed in each of the three components of the P-R interval. These delays occurred both in single components of the system as well as in combined conduction delays and were not always demonstrable by surface electrocardiograms. The Wenckebach phenomenon induced by atrial pacing was localized to the A-V node as well as the His-Purkinje system. This technique of intracardiac electrogram recordings is safe, does not significantly prolong cardiac atheterization time, and often yields unique and useful data concerning A-V conduction.

Adolescent↗

PubMed1975

Electrophysiologic effects of the antiarrhythmic agent disopyramide phosphate.

The electrophysiologic effects of the antiarrhythmic agent disopyramide phosphate given intravenously were studied in 10 patients with cardiac disease. Studies included determinations of sinus recovery time and refractoriness of the atria, the atrioventricular (A-V) node and the His-Purkinje system. Measurements were performed at rest and 15 and 30 minutes after administration of disopyramide. Serum drug levels were measured at these times. Sinus recovery time was shortened at both 15 and 30 minutes, with an average decrease of 39.5 and 146.2 msec, respectively (P less than 0.01). Atrial refractoriness was not altered significantly, but tended to be reduced; the mean effective refractory period was 289.5 msec before administration of disopyramide and 259 and 270 msec 15 and 30 minutes, respectively, after administration. The functional refractory period of the atrioventricular (A-V) node was definitely prolonged in seven patients 15 minutes after administration of disopyramide. The relative refractory period of the His-Purkinje System was not altered. Although this study does not elucidate the mechanism by which disopyramide acheives its antiarrhythmic effects, animal work has shown that it is similar to that of quinidine. In the doses used the drug does not seem to cause first, second or third degree A-V block or fascicular or bundle branch block; it did not increase the severity of first degree A-V block in the three patients with this disturbance. The drug may be particularly useful when arrhythmias are associated with slow sinus rates.

Adult↗

PubMed1975

Potassium canrenoate in the treatment of long-term digoxin-induced arrhythmias in conscious dogs.

The effects of potassium canrenoate on arrhythmias induced by long-term progressive digoxin toxicity were studied in eight conscious beagle dogs. Sinus bradycardia and sinoatrial block, as well as atrioventricular (A-V) conduction disturbances, were consistently alleviated by administration of potassium canrenoate. Premature supraventricular (including junctional) and ventricular depolarizations as well as ventricular tachycardias were also suppressed. Although potassium canrenoate always terminated the digitalis-induced arrhythmias, it usually converted the rhythm to sinus arrhythmia rather than to normal sinus rhythm. Equimolar sodium canrenoate, but not potassium chloride, had similar reversal effects on arrhythmias induced by long-term digoxin intoxication. These data indicate that canrenoate, a diuretic agent with reported positive inotropic effects, may be useful in the treatment of digitalis-induced arrhythmias in man.

Animals↗

PubMed1975