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Biomedical subjects

C E Rackley

Publications and source records attributed to C E Rackley.

At least 55 records · Page 3Linked to original sources

Role of isosorbide dinitrate in patients with unstable angina pectoris.

The development of hemodynamic facilities permitted observations after isosorbide dinitrate (ISDN) administration over a 4-hour period in patients with a history of unstable angina pectoris and documented anatomic coronary artery disease. The patients had no evidence of left ventricular failure and were free of pain during the period of sublingual and oral ISDN administration. Beneficial influences on venous return and arterial blood pressure were manifested as declines in preload and afterload, along with reduction in the mechanical work of the ventricle and, finally, increases in the diastolic compliance of the ventricle. These hemodynamic changes were shown to persist 8 to 12 times as long as the brief influence of nitroglycerin. Thus hemodynamic evidence was provided for the first time on the beneficial influence of oral and sublingual ISDN on venous, arterial, and left ventricular myocardial muscle in patients with unstable angina pectoris.

Angina Pectoris↗

Inhibition of a physiologic pacing system due to its anti-pacemaker-mediated tachycardia mode.

Newer programmable DDD pacemakers prevent pacemaker-mediated tachycardia by automatic extension of the atrial refractory period after a detected premature ventricular contraction. We present an example in which the automatic extension of the atrial refractory period resulted in pacemaker inhibition, which should not automatically be assumed to represent pacemaker malfunction. A careful understanding of pacemaker timing intervals may allow for identification and correction of this problem.

Cardiac Pacing, Artificial↗

Distribution of insulin receptors in human erythrocyte membranes. Insulin binding to sealed right-side-out and inside-out human erythrocyte vesicles.

Analyses of insulin binding to human erythrocytes and to resealed right-side-out and inside-out erythrocyte membrane vesicles have revealed that high affinity insulin binding receptors are present on both sides of the erythrocyte membranes. Insulin binding to human erythrocytes was examined with the use of a binding assay designed to minimize the potential errors arising from the low binding capacity of this cell type and from non-specific binding in the assay. Scatchard analysis of equilibrium binding to the cells revealed a class of high affinity sites with a dissociation constant (Kd) of (1.5 +/- 0.5) X 10(-8) M and a maximum binding capacity of 50 +/- 5 sites per cell. Interestingly, both resealed right-side-out and inside-out membrane vesicles exhibited nearly identical specific sites for insulin binding. At the high affinity binding sites, for both right-side-out and inside-out vesicles, the dissociation constant (Kd) was (1.5 +/- 0.5) X 10(-8) M, and the maximum binding capacity was 17 +/- 3 sites per cell equivalent. These findings suggest that insulin receptors are present on both sides of the plasma membrane and are consistent with the participation of the erythrocyte insulin receptors in an endocytic/recycling pathway which mediates receptor-ligand internalization/externalization.

Binding Sites↗

Developmental changes in insulin receptors of pig red blood cells.

Scatchard analysis of the insulin binding to pig reticulocytes, fetal red cells, and adult erythrocytes showed the maximum number of high-affinity binding sites per cell to be 274, 147, and 29, respectively. All three cell types displayed a practically identical dissociation constant of approximately 1.22 X 10(-8) M at the high-affinity region. A long-term in vitro incubation of the fetal red cells and reticulocytes under tissue culture conditions was accompanied by a significant loss of insulin-binding capacity without any appreciable alteration of the dissociation constant. The isolation and characterization of insulin-receptor complexes from these cell types were carried out to establish whether the difference in insulin-binding capacity was due to the difference in the amount of the same species or due to different species of insulin receptors. Membrane proteins were extracted with Triton X-102 and fractionated by DEAE-Sephacel ion-exchange column chromatography. Each peak sample was complexed with 125I-insulin, and the complexes were covalently crosslinked and then applied to a Sepharose CL-6B column. A 95,000-Da complex was obtained from adult pig erythrocyte membranes; 220,000- and and 95,000-Da complex was obtained from adult pig erythrocyte membranes; 220,000- and 95,000-Da complexes from pig reticulocyte membranes; and greater than 600,000-, 220,000-, and 95,000-Da complexes from pig fetal cell membranes. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis under a nonreducing condition, the 95,000-Da complex was dissociated into a 53,000-Da component; the greater than 600,000-Da complex into greater than 320,000-, 130,000-, and 53,000-Da components; and the 220,000-Da complex was dissociated into 220,000-, 130,000-, and 53,000-Da components. These findings strongly suggest that the decrease in insulin binding during the developmental changes of red blood cells is due to a disappearance of high-molecular-weight insulin receptors rather than a decrease in the amount of the smaller receptor molecules.

Aging↗

Isolation and characterization of beta 1-adrenergic receptors from adult, rat cardiac myocytes.

The beta-receptors were isolated from rat cardiac myocytes and characterized. Isolated myocytes were prepared from adult rat hearts and characterized for viability. Membrane proteins were solubilized from myocytes with 1% Triton X-102. The solubilized membrane proteins were fractionated by DEAE-Sephacel ion exchange column chromatography. Two major protein peaks were obtained. The second protein peak sample was found to contain beta-receptors to which 125I-15-(4'-azido-3'-iodobenzyl)-carazolol (125I-ABC) was specifically bound. This sample was labeled covalently with 125I-ABC by UV irradiation. The radiolabeled sample was applied to a Sepharose CL-6B gel column. Two radiolabeled protein peaks, one with a molecular weight of approximately 570,000 and the other with a molecular weight of approximately 95,000 were found. When the 570,000-dalton complex was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions, it was dissociated into a component with a molecular weight of 66,000. The 95,000-dalton complex was dissociated into a 58,000-dalton component upon SDS-PAGE under reducing conditions. An excess amount of isoproterenol and propranolol decreased photolabeling of the beta-receptors with 125I-ABC by 60% and 40%, respectively.

Adrenergic beta-Antagonists↗

Platelet function abnormalities in response to arachidonic acid in the acute phase of myocardial infarction.

The aggregation of platelets to arachidonic acid was studied serially in patients admitted to the hospital with suspected acute myocardial infarction (MI) and no history of platelet-altering drug ingestion. Of 17 patients studied within the first 48 hours after MI, 16 had a marked decrease in aggregation, to 0.5 mM arachidonic acid (15 +/- 12% compared with 64 +/- 15% for control subjects, p less than 0.01). The exception was a patient with documented coronary artery spasm who was receiving nifedipine at the time of MI. He had a delayed but normal final percent aggregation. The aggregation response returned to normal at 2 to 4 days and was slightly above normal at 6 to 10 days (change not statistically significant). Thromboxane B2 formation correlated with the response of patients' platelets to arachidonic acid (38 +/- 15 ng in the low responders versus 161 +/- 30 ng/3 X 10(8) platelets/4 min in the normal responders, p less than 0.05). Low responding platelets after washing had normal adenosine diphosphate and adenosine triphosphate contents and aggregated and formed thromboxane B2 normally with arachidonic acid. The plasma of patients with MI was found to inhibit platelet aggregation and thromboxane B2 formation to arachidonic acid.

Adenosine Diphosphate↗

Isolation and characterization of human erythrocyte insulin receptors.

The noncovalently associated 125I-insulin-receptor complex was isolated from human erythrocyte membranes after allowing 125I-insulin to interact with the membranes followed by extraction of the 125I-insulin-receptor complex with Triton X-102 or, alternatively, by complete solubilization of the membranes with sodium dodecyl sulfate (SDS), removal of SDS, and then treatment of the solubilized sample with 125I-insulin. Sepharose CL-6B column chromatography of the 125I-insulin-receptor complex obtained by both of the above procedures yielded a highly radioactive 140,000-Da complex which was dissociated into small peptides when subjected to SDS-polyacrylamide gel electrophoresis. In contrast, when the 125I-insulin-treated membrane sample was extracted with Triton X-102, purified by DEAE-Sephacel ion exchange chromatography, covalently cross-linked with disuccinimidyl suberate, and then subjected to SDS-polyacrylamide gel electrophoresis, a highly radioactive component with Mr = 53,000 was obtained. On the other hand, when the Triton X-102-solubilized membrane receptor sample was fractionated by DEAE-Sephacel ion exchange chromatography, complexed with 125I-insulin, covalently crosslinked, and then applied to a Sepharose CL-6B column, a 95,000-Da complex with high specific radioactivity was obtained. Upon SDS-polyacrylamide gel electrophoresis, the 95,000-Da complex was dissociated into a 53,000-Da component which appeared identical with that obtained from the receptor complex described above which was obtained by direct interaction of the membranes with 125I-insulin.

Chromatography, Gel↗

Quantitative axial oblique contrast left ventriculography: validation of the method by demonstrating improved visualization of regional wall motion and mitral valve function with accurate volume determinations.

To compare the relative merits of conventional and axial RAO/LAO angiography, we performed biplane left ventricular (LV) cineangiograms in 36 patients in both the conventional 30-degree RAO/60-degree LAO projection and in the axial 45-degree RAO/60-degree LAO/25-degree cranial projection, in random sequence. LV volumes were calculated by a computerized system utilizing modification of the area-length method. Eng-diastolic volume, end-systolic volume, and ejection fraction correlated closely between the two projections (r = 0.93, 0.95, and 0.86, respectively). The axial 60-degree LAO view projected the LV apex inferiorly, the LV outflow tract superiorly, reduced LV foreshortening, and "uncovered" the LV outflow tract in all cases. Segmental wall motion abnormalities of the ventricular septum, apex, and posterior wall were better evaluated by the axial 60-degree LAO view in patients with regional asynergy in these zones. The 45-degree RAO, compared to the 30-degree RAO view, allowed a true tangential view of the mitral valve and provided a large "clear area" between the mitral valve and descending aorta, which improved the ability to quantify mitral regurgitation. Thus, axial oblique LV angiography improves evaluation of LV regional wall motion and mitral valve function without compromising LV volume quantitation.

Angiocardiography↗

Unstable angina pectoris: management based on available information.

Several prospective randomized studies of medical or surgical therapy have not shown that either form of management alone is uniformly superior with respect to mortality for unstable angina pectoris. Patients managed medically have a greater incidence of angina pectoris. Earlier studies indicated a higher rate of nonfatal myocardial infarction with urgent surgery. Present management includes hospitalization and early intensive medical therapy with nitrates and, usually, beta-blocking agents. Coronary arteriography is advised within a few days. If the patient has left main coronary artery disease or three-vessel disease, early coronary artery bypass graft surgery within days to a couple of weeks is advised. Otherwise, medical management is advised and elective surgery can be performed if the patient remains symptomatic.

Angina Pectoris↗