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Biomedical subjects

H C Smith

Publications and source records attributed to H C Smith.

At least 145 records · Page 8Linked to original sources

Dynamic domains of DNA polymerase alpha in regenerating rat liver.

Intranuclear redistributions of DNA polymerase alpha activity (the presumptive replicative enzyme) are observed preceding and during in vivo replication in regenerating rat liver. The most marked induction of in vitro enzyme activity occurs coincident with the onset of in vivo replication and is seen in the high salt resistant domain of the nuclear matrix. Moreover, DNA polymerase alpha endogenous and exogenous template activities begin to redistribute prereplicatively from bulk chromatin directly to the high salt resistant matrix. These prereplicative subnuclear events are detectable prior to the induction of total cellular DNA polymerase alpha and appear to continue throughout replication. Maximal percent recovery of the total nuclear activity on the high salt resistant matrix (approximately 30%) occurs coincident with and during the time when in vivo replication rates are maximum. At the conclusion of replication, DNA polymerase alpha activities shift back into the bulk chromatin and are no longer high salt resistant. In contrast, DNA polymerase beta (presumptive repair enzyme) endogenous and exogenous template activities are randomly distributed in the nuclear subfractions through the proliferative response. We conclude that DNA polymerase alpha is dynamically assembled or activated on the nuclear matrix and that this process is initiated before the onset of in vivo replication.

Animals↗

Angiographic changes produced by percutaneous transluminal coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is being used with increasing frequency in the treatment of patients with symptomatic coronary artery disease. Balloon inflation results in diverse angiographic findings, reflecting the great variety of anatomic and pathologic changes produced. The long-term effects of inflation on the underlying atherosclerotic lesion and the clinical outcome are unknown but may depend in part on the anatomic changes caused by the dilatation itself. To facilitate communication and evaluation of the results of PTCA, a classification of the angiographic findings and their potential mechanisms is presented. Recognition and analysis of these angiographic findings may be helpful in evaluating the long-term outcome of patients undergoing PTCA.

Aneurysm↗

Follow-up of patients from the coronary artery surgery study (CASS) potentially suitable for percutaneous transluminal coronary angioplasty.

To determine the proper place for percutaneous transluminal coronary angioplasty (PTCA) among the therapeutic options available for patients with coronary heart disease, one must compare the results of PTCA with those obtained by conventional medical and surgical therapy. To develop a cohort comparison group, we interrogated the Coronary Artery Surgery Study (CASS) registry, and patients with proximal discrete subtotal stenosis (70% to 99%) involving the right, left anterior descending, circumflex, or left main coronary artery, singly or with stenoses in two of the three major coronary arteries, were selected; 796 patients (3.7% of all patients enrolled in CASS from 1975 to 1979) met these selection criteria. Surgical therapy was chosen in 53.3%; surgical mortality was low and there was excellent 4-year actuarial survival. There was significant improvement in functional class. Survival was also excellent in medically treated patients. Medically treated patients also had significant improvement in functional class in comparison with baseline values. The data presented here characterize a cohort group against which the clinical results of PTCA can be evaluated and compared.

Angina, Unstable↗

Effect of verapamil on left ventricular function: a randomized, placebo-controlled study.

Verapamil has a negative inotropic action in isolated cardiac muscle. Its effects on left ventricular function were tested in 25 patients with suspected coronary artery disease. A double-blind, randomized, placebo-controlled study design was used. Verapamil (0.2 mg/kg over 10 minutes) significantly lowered mean arterial pressure (from 105 to 89 mm Hg) while increasing the cardiac index (from 2.8 to 3.1 liters/min/m2). No statistically significant effect was seen on heart rate, left ventricular end-diastolic pressure or end-systolic volume index, ejection fraction, peak rates of systolic wall thickening or diastolic wall thinning, or percentage of hemiaxial shortening. However, there was a small increase in the left ventricular end-diastolic volume index (from 94 to 102 ml/m2). Important findings were a reduction in systemic vascular resistance (from 39 to 30 U . m2), an increase in left ventricular end-diastolic volume index consistent with a negative inotropic effect, and no evidence of improved regional wall dynamics in portions of the left ventricular wall considered hypokinetic because of myocardial ischemia.

Cardiac Catheterization↗

Plasma contamination accounts for thyroid hormone binding in nuclear protein extracts from human mononuclear cells.

Plasma protein contamination accounted for high affinity thyroid hormone binding to a nuclear protein extract from human blood mononuclear cells. The degree of contamination was directly related to the number of times the cells were washed before the nuclear protein was extracted. After three washes, no specific binding was detected. Plasma contamination was estimated to be 0.3-0.5 microliter/assay tube. The TBG concentration in this volume of plasma was consistent with the concentration of 0.2 micrograms/ml measured by RIA in the nuclear extract. Total specific binding of [125I] T4 and [125I] T3 can be attributed to plasma contamination, as 0.3 microliter of plasma gave identical binding. Furthermore, a TBG antiserum abolished specific T4 and T3 binding to the nuclear protein extract. These data are consistent with TBG being the major plasma contaminant. In fourteen normal, euthyroid subjects, the higher mean maximum binding capacity (MBC) for T4 (1.63 +/- 0.27 SD) compared to T3 (0.25 +/- 0.21 pmol/mg protein; P less than 0.001) and the same binding affinity (Ka, 2.0 +/- 0.7 x 10(9)/mol) for both T4 and T3 are the same as found in plasma. The higher MBC for T4 (5.8 +/- 1.0) and T3 (0.69 +/- 0.2 pmol/mg protein) in two hypothyroid subjects are consistent with the higher mean TBG concentration of 28 +/- 5 micrograms/ml compared to the level in ten normal subjects (19.2 +/- 1.8 micrograms/ml; P less than 0.001). In two subjects with low normal TBG concentrations of 15 micrograms/ml, the T4 maximum specific binding of 9% was lower than found in normal subjects 16.6 +/- 7.6%. We conclude that the methodology described previously and used in this study is invalid for measuring thyroid hormone nuclear receptor status in humans.

Blood Proteins↗

Balloon angioplasty in multivessel coronary artery disease.

Coronary angioplasty with use of the balloon catheter was initially performed only in patients with single-vessel coronary artery disease. Most symptomatic patients with coronary artery disease who require revascularization for control of their symptoms, however, have stenoses in more than one major coronary artery. Therefore, we have evaluated the results of balloon angioplasty in patients with multivessel disease. Of 261 patients who underwent percutaneous transluminal coronary angioplasty at our institution up to February 1983, 100 had multivessel disease. Of these 100 patients, 72 had an initially successful procedure, defined as successful dilation of one or more major coronary arteries without significant complication. Of the remaining 28 patients, 25 underwent coronary artery bypass grafting (6 on an urgent basis for coronary occlusion). No deaths occurred. In selected patients with multivessel disease, coronary angioplasty is associated with low morbidity and mortality and might be an excellent alternative to coronary artery bypass grafting when medical treatment fails. Percutaneous transluminal coronary angioplasty merits the critical comparison with standard therapy that can be achieved only in a properly designed clinical trial.

Angiography↗

Pericardiocentesis assisted by two-dimensional echocardiography.

Pericardiocentesis assisted by two-dimensional echocardiography was performed in 40 patients with effusions of various types and causes; no complications occurred. This approach combines several advantages, including visualization of the fluid-filled sac and determination of its location, estimation of the amount of fluid, and identification of structures intervening between the body surface and the pericardial sac (for example, the liver). The ideal point of needle entry caned. This approach combines several advantages, including visualization of the fluid-filled sac and determination of its location, estimation of the amount of fluid, and identification of structures intervening between the body surface and the pericardial sac (for example, the liver). The ideal point of needle entry caned. This approach combines several advantages, including visualization of the fluid-filled sac and determination of its location, estimation of the amount of fluid, and identification of structures intervening between the body surface and the pericardial sac (for example, the liver). The ideal point of needle entry can be selected to avoid contact with the heart and can be marked on the body wall. This method combines the safety and visibility of the open (surgical) approach with the simplicity of the direct ("blind") puncture method. Locating the optimal point on the body wall, closest to the pericardial fluid, allows a short, plastic-sheathed needle to be used. Pericardiocentesis by this method can be performed with ease and safety.

Adolescent↗

Nuclear matrix-bound deoxyribonucleic acid synthesis: an in vitro system.

A nuclear matrix-bound in vitro replicational system that utilizes alpha-polymerase and matrix-attached DNA has been isolated from regenerating rat liver and characterized for in vitro requirements. beta-Polymerase is a minor component of the matrix in vitro system. Evidence is presented for the native association of alpha-polymerase with the nuclear matrix and for the parallel induction of matrix-bound alpha-polymerase and in vivo DNA synthesis during the proliferative response following partial hepatectomy. Our data suggest that the attachment of alpha-polymerase to the matrix may be an important step in the assembly of functional replisomes. We also demonstrate prereplicative and late-replicative rises in nuclear and matrix-bound beta-polymerase activity and discuss these results in terms of possible genome screening.

Animals↗

Cardiac-catheterization and cardiac-surgical facilities: use, trends, and future requirements.

Cardiac catheterizations and cardiac operations were evaluated in the population of Olmsted County, Minnesota, from 1973 through 1980, and trends in this region were compared with nationwide trends based on data from several sources. The rates of coronary arteriography and coronary-artery bypass operations in Olmsted county have increased over time, but overall, the rates of catheterization and operation appeared to be leveling off. For the country as a whole, the data appear to show similar trends, but there are wide differences among regions in the rates of operation and catheterization. In 1980 40 per cent of hospitals with cardiac-catheterization laboratories and 55 per cent of those with facilities for open-heart surgery were doing fewer than the suggested minimum numbers of these procedures necessary to achieve optimum results. The data support the view that further growth in the number of cardiac centers should be avoided. We believe there is a need for continued evaluation of the use of cardiac services if quality is to be protected and costs controlled.

Adult↗

A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency.

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in th placebo group. This benefit in graft patency persisted in each of over 50 subgroups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation.

Adult↗

Thyroid hormone binding to putative nuclear receptors in human mononuclear blood cells.

Nuclear protein extracts from mononuclear cells in normal subjects, subjects with the clinical syndrome of thyroid hormone resistance and cultured B lymphocytes bound thyroxine (T4) Ka; 1 . 3-3 . 5 X 10(9) m-1) and triiodothyronine (T3) (Ka; 1 . 2-3 . 9 X 10(9) m-1) with similar affinities. When an extra wash step was introduced, the maximum specific binding of T4 and T3 was reduced by 75% and binding was abolished by three washes. These data suggest binding is to a serum protein contaminant present in the mononuclear cell preparation.

Adolescent↗

Employment status after coronary artery bypass surgery.

Factors that influence the effect of coronary artery bypass graft surgery (CABG) on employment were examined in 1427 2-year survivors from entry into the nonrandomized Mayo Clinic portion of the National Heart, Lung, and Blood Institute's prospective Coronary Artery Surgery Study. Five hundred seventy-nine patients (41%) were treated medically, 769 (54%) were treated surgically and 79 (5%) were initially treated medically but later had CABG. All groups were similar at entry with respect to age and percent working, retired or quitting work for cardiac reasons. There was a similar decline in employment from entry to 2 years in all three groups. The number who quit work for cardiac reasons was twice the number of previously disabled workers who returned to work with all three modes of therapy. Univariate and multivariate analyses were used to test the independent prognostic values of a number of variables for subsequent employment in the largest homogeneous surgical subset--496 nonretired males. Postoperative angina was the most powerful factor reducing postoperative employment. Postoperative employment was also lower if the patient was not working before surgery, was a laborer, or older than age 55 years (all p less than 0.01). Although the level of nonwork physical activity was generally increased after CABG, there was no relationship between physical activity and employment. This study confirms that employment declines after CABG, but three of the four most powerful prognostic variables were not related to surgery.

Age Factors↗

Left ventricular performance before and after aortocoronary artery bypass surgery.

Left ventricular performance was studied before and late (mean 12-17 months) after aortocoronary artery bypass surgery by quantitative, computer-based videoangiography. We measured total function (left ventricular ejection fraction, volumes and end-diastolic pressure) at rest (in 60 patients) and before and after exercise (abnormal exercise hemodynamics preoperatively in 32 patients) and regional function (peak rate of systolic wall thickening) at rest (in 60 patients) and before and after administration of nitroglycerin (in 19 patients). Total left ventricular function at rest is usually unchanged postoperatively. Exercise hemodynamics are more sensitive indexes of performance and, if abnormal, usually improve postoperatively if revascularization has been complete and extensive myocardial infarction has not occurred. Regional myocardial function usually improves postoperatively if the bypass graft to the region is patent and has a blood flow of more than 60 ml/min (measured late postoperatively by videodensitometry) and if no previous infarction was present in the region. Myocardial infarction and graft blood flow of 40 ml/min or less are the two main factors that prevent improvement in abnormal regions defined by the regional wall thickening method when bypass grafts are patent. Regions supplied by occluded grafts show decreases in regional function. The preoperative wall-thickening response to administration of nitroglycerin can be used to distinguish ischemia and significant myocardial infarction and to predict the successful response to aortocoronary bypass graft surgery.

Blood Pressure↗