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Biomedical subjects

W A Clark

Publications and source records attributed to W A Clark.

At least 55 records · Page 3Linked to original sources
PubMed1990

Relation between left ventricular systolic resistance and contractile rate processes.

To test the hypothesis that left ventricular (LV) systolic resistance is determined by the intrinsic rate processes of the contractile system, we studied 40 spontaneously hypertensive male rats (SHR). Thyroid hormone manipulation was used to alter isomyosin composition and consequently the rate processes of the contractile system. Seven groups of rats were studied: control (SHRC, n = 9); propylthiouracil (PTU) treated for 10 days (SHRP-10, n = 5), 20 days (SHRP-20, n = 5), and 30 days (SHRP-30, n = 6); and thyroxine treated for 5 days (SHRT-05, n = 5), 10 days (SHRT-10, n = 5), and 15 days (SHRT-15, n = 5). In situ (n = 40) and isolated (n = 14; 5 SHRP-30, 5 SHRC, and 4 SHRT-15) heart experiments were performed. In comparison to SHRC, we observed the following: 1) LV pump performance was not different in any of the thyroxine-treated groups, whereas with PTU, pump performance was significantly depressed in rats with greater than 80% slow myosin. 2) Normalized LV peak elastance (Emaxn) was significantly increased in the SHRP-30, whereas it was not altered after thyroxine. These observations were further confirmed in the isolated heart on the basis of peak isovolumetric stress-strain relations. 3) Thyroxine increased and PTU decreased theoretical maximum flow (Qmax; a measure of LV resistance); thus an inverse relation between Qmax and percent slow myosin was observed (r2 = 0.86). 4) The time to peak isovolumetric pressure was increased in SHRP-30 and decreased in SHRT-15. The relaxation process was significantly slower for SHRP-30 group and was unchanged for SHRT-15 group. These observations support our hypothesis that LV systolic resistance quantifies an intrinsic rate-dependent property of the myocardium and that isomyosin composition is one of its determinants. In addition, with changes in isomyosin composition toward predominantly slow myosin, the responses in Emaxn and Qmax are discordant, which may be responsible for the preservation of pump performance. This underscores the importance of quantifying both LV systolic resistance and elastance in the assessment of the functional status of the LV as a mechanical pump.

Animals↗
PubMed1990

Elderly mobility and mobility outcomes: households in the later stage of the life course.

Recent research has demonstrated that elderly residential mobility is conditioned more often by economic factors than is mobility in general. This article explores these issues, specifically those related to the effects of mobility, aging in place, and migration on elderly economic well-being. Using the American Housing Survey national file for 1985, different types of mobility and migration for households in the later stages of the life course are examined. The evidence reiterates central city/suburban locational differences for the elderly, emphasizes the role of house costs, and house cost/income ratios in creating stress for the elderly, and strongly suggests that the elderly population is not simply grouped into young-old, old, and old-old, but is better treated in a continuum of life course changes.

Aged↗
PubMed1990

Dose response of dairy cows to ammonium salts of volatile fatty acids.

In previous studies ammonium salts of a mixture of isobutyrate, 2-methylbutyrate, isovalerate, and valerate were fed in a corn silage, corn, corn gluten meal, and urea diet to Holstein cows throughout lactation to define the optimum level of ammonium salts of milk production. The objective of this work was to conduct another dose response study using other forage and protein sources and to determine the effects of decreasing VFA intakes as lactation advanced. The concentrate portion of the diet contained 0, .4, .8, 1.2, or 1.6% ammonium salts of VFA. The forage to concentrate ratio was 50:50, 60:40, and 70:30 for the first, middle, and last third of lactation, respectively. The study was conducted at four university locations using 191 Holstein cows. Feeds used included corn silage, alfalfa silage or hay, corn, soybean meal, minerals, and vitamins. Treatment x location interactions were significant for milk yield during early lactation. During mid- and late lactation, supplemental VFA (.8%) improved milk and protein yield. Milk composition was not greatly affected by feeding VFA. In mid-lactation, cows fed .8% ammonium salts of VFA ate more feed than did controls. Feed efficiencies were similar among groups throughout the experiment. Cows fed VFA tended to gain less BW during lactation than did controls. Health and reproduction were not different among groups.

Animal Feed↗
PubMed1989

Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis.

Treatment of rats with the beta-adrenergic agonist isoproterenol results in cardiac hypertrophy, myocyte necrosis, and interstitial cell fibrosis. Our objectives in this study have been to examine whether hypertrophy and fibrosis occur in a compensatory and reparative response to myocyte loss or whether either process may be occurring independently of myocyte loss and thus be a reactive response to adrenergic hormone stimulation. We have examined this question by evaluating each of these responses in rats treated with different doses and forms of isoproterenol administration. Myocyte necrosis was evaluated using in vivo labeling with monoclonal antimyosin for identification of myocytes with permeable sarcolemma, which was indicative of irreversible injury. Myocardial fibrosis was evaluated by morphometric point counting of Gomori-stained tissue sections and by assessment of the stimulation of fibroblast proliferation by determination of increased levels of DNA synthesis. Stimulation of fibroblast DNA synthesis was determined from DNA specific radioactivities and radioautography after pulse labeling with [3H]thymidine. The evidence provided by this study suggests that the degree and timing of myocardial hypertrophy does not follow the course of myocyte loss and, thus, appears to be either a response to altered cardiac loading or a reactive response to beta-adrenergic hormone stimulation rather than a compensation for myocyte loss. Myocardial fibrosis, on the other hand, appears to be more closely related to myocyte necrosis with respect to collagen accumulation in the same areas of the heart, its dose-response relation to the amount of isoproterenol administered, and the timing of increased DNA synthesis, or fibroblast proliferation, after myocyte loss.

Animals↗
PubMed1989

Tissue plasminogen activator-mediated thrombolysis of cerebral emboli and its effect on hemorrhagic infarction in rabbits.

Tissue plasminogen activator (tPA) dissolves intravascular thrombus and restores blood flow after thromboembolic vascular occlusion. The utility of this agent for treatment of stroke in humans may be limited by post-reperfusion hemorrhagic complications. We studied tPA-mediated thrombolysis in an animal model of cerebrovascular occlusion in order to determine what factors, if any, predispose tPA-treated animals to suffer hemorrhage. Small blood clot emboli were injected into the internal carotid arteries of rabbits. Angiograms confirmed occlusion of the middle cerebral artery or internal carotid artery in 100% of subjects. tPA or saline was administered as a 30-minute infusion at various times after embolization. Hemorrhage rates were similar in all groups regardless of treatment. tPA increased the prothrombin time and the thrombin time but not the partial thromboplastin time. There was no correlation between these changes in blood coagulation and the finding of cerebral hemorrhage. We observed a significant association between stroke severity and cerebral hemorrhage. We conclude that tPA treatment successfully causes thrombolysis of cerebral emboli without causing an increase in the incidence of cerebral hemorrhage in rabbits.

Animals↗
PubMed1989

Cardiac myosin isoenzyme shifts in non-insulin treated spontaneously diabetic rats.

We evaluated myocardial myosin isoform distribution in a group of diabetic BB/W rats from which insulin was withheld for varying periods in order to evaluate the time course and extent of myosin isoform shifts in these animals. Prior studies of myosin isoform distribution in diabetic rats have utilized chemically induced diabetic rats or insulin-treated BB/W rats. Following a stabilization period on insulin therapy, insulin was withheld for 9-28 days during which the animals received supplemental parenteral bicarbonate and Ringer's lactate. Left ventricular myocardial myosin isoform distribution was determined by nondenaturing pyrophosphate gel electrophoresis. We found that the normal predominance of V1 isomyosin in these rats was shifted to V3 predominance by approximately two weeks after the cessation of insulin therapy. This was significantly sooner than was seen in another study which utilized insulin treated BB/W rats, and is similar to the time course seen with chemically induced diabetic rats. In addition, the normal V1 myosin isoform distribution observed during insulin therapy and the progressive shift to the V3 isoform distribution during increasing periods without insulin suggest that this shift can be prevented with insulin alone.

Animals↗
PubMed1988

Structural vs. contractile protein remodeling and myocardial stiffness in hypertrophied rat left ventricle.

Left ventricular pressure overload will result in the hypertrophic growth of the myocardium and in the rat may include a remodeling of both the structural and contractile proteins. As a result, an adaptive rise in active stiffness, or the force generating capacity of the myocardium, may occur. The relative importance of structural vs. contractile protein remodeling to the hypertrophic response and active stiffness is unclear. Accordingly, we monitored the ratio of V1/V3 isomyosin and the fibrillar nature and volume fraction of myocardial collagen, together with the developed systolic stress-strain relation of the intact myocardium in the adult male Wistar rat after 8 weeks of abdominal aorta banding. In comparison to controls and for the 20% increase in left ventricular mass obtained with banding we found: (a) collagen volume fraction had increased significantly (6.2 +/- 2.0 vs. 3.6 +/- 1.0%) while the V1/V3 ratio did not change; (b) interstitial compartment remodeling included a perivascular accumulation of collagen around small intramyocardial coronary arteries and the appearance of more extensive fibrillar collagens; and (c) active stiffness increased significantly. Thus, the increase in active stiffness of the hypertrophied adult rat myocardium, seen with abdominal aorta banding, appears to be related to interstitial fibrosis and not a conversion of myosin isoforms.

Animals↗
PubMed1987

Primary structure and comparative sequence analysis of an insect apolipoprotein. Apolipophorin-III from Manduca sexta.

The amino acid sequence of an insect apolipoprotein, apolipophorin-III from Manduca sexta, was determined by a combination of cDNA and protein sequencing. The mature hemolymph protein consists of 166 amino acids. The cDNA also encodes for an amino-terminal extension of 23 amino acids which is not represented in the mature hemolymph protein. The existence of a precursor protein was confirmed by in vitro translation of fat body mRNA. Computer-assisted comparative sequence analysis revealed the following points: 1) the protein is composed of tandemly repeating tetradecapeptide units with a high potential for forming amphiphilic helical structures. Compared to mammalian apolipoproteins the repeat units in the insect apolipoprotein show considerable length variability; 2) the sequence has a striking resemblance to several human apolipoproteins including apoE, AIV, AI, and CI. However, the homology seems to be entirely functional since, although the insect and mammalian apoproteins contain very similar types of amino acid residues, the actual degree of sequence identity is quite low. Whether the mammalian and insect apoproteins are derived from a common ancestral amphiphilic helix forming, lipid-binding protein, or arose by convergent evolution can not be determined at present. This represents the first complete amino acid sequence for an insect apolipoprotein.

Algorithms↗
PubMed1987

The influence of domestic position on health status.

Data from the Robert Wood Johnson Foundation 1982 survey of access to health care are used to examine the influence of household composition and members' domestic position--e.g. age, sex, marital status, and presence of children, on health status and use of health services. A hierarchical analysis was undertaken to sort groups of individuals and households having different domestic structures. The results of the analyses of use and access for these groups show that, after controlling for age, domestic position and household arrangements are significant explanatory variables. Ways to refine the approach are discussed.

Adolescent↗
PubMed1987

Trichomonas gallinae in columbiform birds from the Galapagos Islands.

Domestic pigeons were introduced into the Galapagos Islands in 1972 or 1973. There is a high prevalence of Trichomonas gallinae among them and some evidence of canker. Trichomonas gallinae can be found also in endemic Galapagos doves in the vicinity of Puerto Ayora on Santa Cruz Island. Doves examined on pigeon-free islands were not found infected.

Animals↗
PubMed1987

The Roepke Lecture in Economic Geography: urban restructuring from a demographic perspective.

"The central argument of this paper is that recent research has overemphasized the notions of urban restructuring and undervalued the role of spatial demographics in understanding urban and [regional] spatial patterns. The paper examines the notions embedded in urban restructuring and suggests that a focus on several elements of demographic processes is an equally important component of understanding urban and [regional] spatial structure. A specific discussion of the Los Angeles region indicates that there is a high level of complexity in social-spatial change. Social-spatial change is not simply explained by reference to an unspecified urban restructuring."

Americas↗
PubMed1987

Physiologic versus pathologic hypertrophy and the pressure-overloaded myocardium.

The myocardium consists of myocytes and capillaries embedded in a connective tissue matrix. Myocardial mass, which is predominantly a function of myocyte size, is determined by systolic tension; when systolic pressure is gradually elevated above the normal range, mass will increase. The hypertrophic process is a continuum consisting of subtle transitions that take place within the muscular, collagenous, and vascular compartments; these transitions, however, need not be temporarily concordant. We would identify three phases to the hypertrophic process. First, there is an evolutionary phase, whereby the structural and biochemical remodeling of the various compartments of the myocardium is in transition, with each compartment having its own rate of adjustment. During this evolutionary phase, myocardial contractility, as reflected by stress-length and stress-velocity relations, may or may not be normal, but ventricular pump function and O2 delivery are preserved. Second, there is a physiologic phase during which the structural and biochemical remodeling of the compartments reaches a coordinated balance. The myocardial stress-length relation and ventricular function are each normal, but rate-dependent indices of contractility may be abnormal. During the physiologic phase of hypertrophy, the remodeled myocardium will revert to normal when the abnormal loading condition is removed. Finally, there is a pathologic phase. In this phase, compartment remodeling is no longer balanced (e.g., the ratio of structural versus maintenance proteins), and length and rate-dependent indices of myocardial contractility are depressed. Ventricular pump function is also abnormal in the pathologic phase; consequently. O2 delivery to the tissues is impaired. This imbalance in O2 demand and supply may be apparent at rest in more advanced expressions of disease or may appear during the physiologic stress of exercise in less severe disease. In the latter case, the patient's aerobic capacity is reduced to the extent that it can be used to grade the severity of heart failure and to predict the cardiac reserve. During the pathologic phase of hypertrophy, the structural and biochemical remodeling of the myocardium may be irreversible, although this may not be the case for each compartment. Finally, it is important to distinguish cardiac (or myocardial) failure from the clinical syndrome of congestive heart failure. The latter arises from congested organs and hypoperfused tissues; its clinical manifestations are dependent on the activation of the adrenergic nervous and renin-angiotensin-aldosterone systems and the presence of a salt-avid kidney. Congestive heart failure is a late clinical feature of chronic pressure overload and pathologic hypertrophy.

Animals↗
PubMed1986

Modeling mobility in the Dutch context: current issues and dilemmas.

The author assesses recent research on modeling residential mobility. "The review and analysis in this article are designed to...examine the question of the trade off between theoretical concerns and policy relevance. The review emphasizes recent research in the Dutch housing market context....[Three critical issues are highlighted.] The first is the link between the aggregate and micro approaches. The second is the role of the interface between the studies of mobility and the larger demographic processes. And the third is the nature of the modeling strategies themselves. The last will lead quite naturally into the concluding remarks--the usefulness of modeling for policy makers."

Demography↗
PubMed1984

Replacement perfusion of cultured eucaryotic cells: a method for the accurate measurement of the rates of growth, protein synthesis, and protein turnover.

The fractional rates of protein synthesis (ks) and degradation (kp) were studied in the myeloma cell line SP2/0-AG14 grown at different rates (kg). Cells in spinner flask suspension cultures were maintained at constant cellular density for prolonged periods by replacement perfusion of labeling medium at a rate equivalent to the rate of growth. Total protein synthesis was calculated from the specific radioactivity of labeled L-leucine in the precursor (medium) and cellular protein. Fractional synthesis rates determined by approach to equilibrium labeling were the same as those determined by equilibrium-pulse labeling kinetics and pulse-chase kinetics. The rate of protein degradation was determined from the established relationship Kg = ks - kp. Protein synthesis rates remained constant over a threefold range in the rate of cell growth. At relatively slow growth rates (kg = 0.017/hr) turnover represented a major fraction of total synthesis (kp = 0.032/hr = 0.65ks). At rapid growth rates (kg = 0.058/hr) the value of kp was less than 0.005/hr. No major difference was observed between the ks determined for individual cellular proteins (separated by SDS-polyacrylamide (7.5%) gel electrophoresis) from rapid- and slow-growing cultures. Thus, with an invariable ks, any change in growth rate is due to an inverse change in the rate of turnover. Since turnover is the balance between synthesis and degradation and since synthesis is unchanging, then changes in the growth rate of SP2/0-AG14 should be due to changes in the rate of protein degradation. Experiments were therefore performed to determine the origin of the degradative machinery, ie, cytosolic or lysosomal; autolysis of prelabeled cellular protein (in vitro) was observed only at acidic pH (4.2) and was totally inhibited by addition of leupeptin (10 microM) and pepstatin (2 microM), the specific inhibitors of lysosomal cathepsins B (&L) and D, respectively. Since growth rate appears to be regulated by the alterations in the rate of protein degradation and degradation (in vitro) in SP2/0-AG14 appears to be lysosomal, then one should be able to alter the rate of cellular growth by interfering with rate of lysosomal proteolysis. Indeed, when the lysosomotropic amine NH4Cl (10 mM) is added to cells growing with a kg of 0.018/hr +/- 0.001 (ks = 0.050/hr +/- 0.002) the growth rate increased to 0.051/hr +/- 0.002 without change in the rate of protein synthesis (ks = 0.049/hr +/- 0.003).(ABSTRACT TRUNCATED AT 400 WORDS)

Cells↗