PubMed Health⌕ Search

Biomedical subjects

D F Larson

Publications and source records attributed to D F Larson.

At least 37 records · Page 2Linked to original sources
PubMed1993

Putative vascular endothelial cell chemotactic factors: comparison in a standardized migration assay.

While a number of chemoattractants of vascular endothelial cells have now been identified in vitro, differences in methodology preclude comparisons of substances evaluated in different assays. Here, we report a standardized chemotactic assay in which the migration of calf pulmonary artery endothelial cells in a 48-well microchemotaxis chamber was determined. Nonstimulated (control) migration was remarkably constant (mean +/- SD, 96 +/- 14) from plate to plate, thus allowing the indexing of relative migration of stimulated cells to that of nonstimulated cells in the control wells of that plate. Based on the relative migrations observed in response to each of the substances evaluated, those proving to be stimulatory of migration were placed in rank order by potency. The growth factors epidermal growth factor, transforming growth factor-alpha, and basic fibroblast growth factor (followed by pentosan polysulfate, plasmin, fibronectin, fibrinogen, granulocyte-macrophage colony stimulating factor heparin, adenosine, and MgSO4) were the most potent. Only the platelet factors platelet-derived growth factor-BB and platelet activating factor proved inhibitory of migration. Combining fibrinogen with other chemoattractants produced either stimulation or inhibition in comparison to the migration observed with fibrinogen alone, suggesting that more than one signal transduction mechanism was, in all likelihood, invoked by the various agents. This assay will allow the rapid screening and rank ordering of additional putative chemoattractants, will facilitate the study of the biochemical mechanisms involved in endothelial cell migration, and will permit the evaluation of pharmacologic agents capable of modulating stimulated or unstimulated migration.

Adenosine↗
PubMed1990

Freund's complete adjuvant induces ornithine decarboxylase activity in the central nervous system of male rats and triggers the release of pituitary hormones.

In male rats, inoculation of Freund's complete adjuvant (FCA, 0.5 mg/rat of Mycobacterium butyricum in paraffin oil) induced high levels of ornithine decarboxylase (ODC) in the hypothalamus and pituitary gland (285% and 245% of controls, respectively, within 12 h to 2 days). ODC activity also was altered in the cerebellum and left neocortex, but not in the right neocortex. This activity reflected a dynamic equilibrium which is influenced by ODC synthesis, degradation, activation, etc. The circadian rhythms of pituitary ODC activity and plasma prolactin level, 3-4 days after FCA, showed that enhancement of enzymatic activity during the dark phase correlated with a marked release of prolactin (Prl). During this early period after FCA, changes in plasma levels of other pituitary hormones were not significant or were less important. Pretreatment with bromocriptine microcapsules inhibited both basal and FCA-induced pituitary ODC activity, as well as Prl secretion. Further, significant increases in plasma luteinizing hormone and adrenocorticotropic hormone were noted from days 4 and 8, respectively, and onwards. Finally, a phase of reduced corticosterone secretion occurred during the latency period. This study shows that FCA influences central nervous system pathways and supports the idea that endogenous Prl is involved in some early events which lead to the development of adjuvant arthritis.

Adrenocorticotropic Hormone↗
PubMed1987

A simplified mitral valve method for two-dimensional echo Doppler blood flow calculation: validation in an open-chest canine model and initial clinical studies.

Quantitative two-dimensional Doppler echocardiography is increasingly used for the calculation of cardiac blood volumes. This study evaluates a simplified method for measuring volume flow at the mitral valve orifice. In four open-chest dogs the simplified mitral valve method was compared to a previously described mitral orifice method for Doppler volume flow calculation and to data obtained by electromagnetic flow measurement. Cardiac output varied from 1.4 to 7.7 L/min. Correlation for both the Doppler method and the electromagnetic meter volume flows was r = 0.98 to 0.99, and there was no significant difference between the two methods. In a clinical pilot study, 10 children were studied in the catheterization laboratory, and the simplified Doppler flow method was compared to thermodilution cardiac output measurements with good results. The study indicates that the simplified mitral valve method provides acceptable accuracy for Doppler cardiac output measurement.

Animals↗
PubMed1985

Catecholamine-induced cardiac hypertrophy in a denervated, hemodynamically non-stressed heart transplant.

Studies of stress-induced cardiac hypertrophy suggest that myocardial mass is regulated by the circulating level of epinephrine. The trophic effect is mediated by cardiac beta-adrenergic receptors, and in the murine, rat, and dog heart, specifically by beta 2-adrenergic receptors. The well-characterized functional effects of catecholamines on heart have obscured their role as myocardial trophic hormones. Therefore, we compared the effect of beta-adrenergic receptor stimulation on the myocardial mass of both a working innervated heart and an essentially nonworking denervated heterotopically transplanted heart in the same rat; in this model, the neural and stretch parameters are nonoperational in the transplanted heart. Ornithine decarboxylase (ODC), an enzyme elevated in a dose-dependent manner in heart by isoproterenol, was assayed in both hearts to determine the relationship between ODC activity and myocardial mass in response to isoproterenol administration in working, innervated heart compared to denervated, nonworking heart. In both recipient and donor heart, the myocardial mass paralleled the ability of an isoproterenol bolus to stimulate ODC in the respective heart. However, beta-adrenergic receptor activity in the donor heart was decreased 5 days after transplantation as assessed by the differential ability of a single dose of isoproterenol to stimulate ODC activity. Beta-receptor coupling to ODC activity in the donor heart exceeded that of the recipient heart at 10 days posttransplantation suggesting a time-dependent elevation of beta-adrenergic receptor activity in donor heart. At all times, alterations in myocardial mass paralleled beta-adrenoceptor activity as assessed by the ability of isoproterenol administration to elevate ODC activity. The results support the concept that myocardial mass is regulated by the level of circulating hormones, particularly epinephrine.

Animals↗
PubMed1985

Prolactin-induced polyamine biosynthesis in spleen and thymus: specific inhibition by cyclosporine.

The induction of ornithine decarboxylase (ODC) in the rat spleen and thymus in response to prolactin shows a dose-dependent sensitivity to cyclosporine (CsA), a known immunosuppressive drug. Marked inhibition of prolactin-stimulated ODC activity occurred at 0.12 mg CsA/kg body weight, and nearly total inhibition was detected at 1.2 mg CsA/kg, a dose comparable to that used to suppress organ rejection processes. CsA blocked ODC induction in response to prolactin injection in both intact and hypophysectomized rats, suggestive of a direct effect of prolactin on spleen and thymus. Furthermore, we were able to demonstrate specific 125I-prolactin binding sites on the rat spleen and thymus. Although growth hormone was capable of elevating ODC activity in spleen, this elevation was not inhibited by CsA. ODC activity in response to cyclic AMP-mediated hormones and to steroid analogs such as dexamethasone was not affected by CsA. Agents known to alter calcium channeling mostly had random enhancing capacity when administered with CsA. The most potent elevation occurred in spleens in response to aminophylline plus CsA. It should be noted, however, that aminophylline alone slightly inhibited the basal level of ODC in the spleen. Insulin, which elevated ODC in the thymus and spleen in a dose-dependent manner, also was not affected by concurrent CsA administration. Prolactin administration altered the RNA and DNA content of spleen and thymus indicating its ability to alter metabolic function. We conclude that prolactin may regulate immune function in spleen and thymus. Studies are in progress to identify the regulation of specific gene products by prolactin.

Animals↗
PubMed1985

A Doppler echocardiographic method for calculating volume flow across the tricuspid valve: correlative laboratory and clinical studies.

In this study we tested a two-dimensional Doppler echocardiographic method for measuring volume flow across the tricuspid valve. Five anesthetized, open-chest dogs had a calibrated electromagnetic flow probe placed on the ascending aorta. Volume flow across the tricuspid valve was controlled by creating a variable femoral-to-pulmonary arterial shunt. Since no standard plane provided a direct view of the tricuspid valve orifice, tricuspid flow area was estimated by calculating a fixed circular flow orifice from the maximal late diastolic diameter of the tricuspid anulus in a four-chamber view. Doppler-determined velocities across the tricuspid valve and tricuspid anulus images in the four-chamber view were obtained in inspiration and expiration. For 24 cardiac outputs (0.6 to 4.0 liters/min), inspiratory tricuspid flow determined by the Doppler method correlated minimally better (r = .90, SEE = 0.30 liter/min) than did expiratory measurements (r = .89, SEE = 0.35 liter/min) with the time-averaged systemic flow determined electromagnetically. Doppler-determined tricuspid volume flows in four-chamber and short-axis two-dimensional echocardiographic views from 10 children were then compared with values determined simultaneously by thermodilution during cardiac catheterization. In the children, Doppler-determined flows in short-axis and four-chamber views, both in inspiration and expiration, were similar; when results for the two views were averaged in inspiration and expiration, the tricuspid flows predicted by the Doppler method were highly correlated (r = .98, SEE = 0.48 liter/min) with the results of thermodilution. The two-dimensional Doppler echocardiographic method provides a means of estimating volume flow across the tricuspid valve noninvasively.

Adolescent↗
PubMed1985

Prolactin receptors on human T and B lymphocytes: antagonism of prolactin binding by cyclosporine.

Prolactin (PRL) receptors have been identified recently on human peripheral blood mononuclear cells (MNC) and may be involved in the regulation of cell-mediated immunity. Cyclosporine (CsA), an immunosuppressive cyclic endecapeptide utilized to prolong graft survival in human organ transplant patients, affects PRL binding to MNC. At concentrations of CsA from 10(-10) through 10(-8) M, the amount of PRL bound to MNC markedly increased to ca. 400% of controls, whereas CsA concentrations of 10(-6) and 10(-5) M totally inhibited PRL binding to lymphocytes. The ability of low concentrations of CsA to enhance PRL binding was temperature-dependent and did not occur when binding assays were conducted at 4 degrees C. PRL displaced [3H]CsA from lymphocytes with ca. 50% displacement at 10(-9) M PRL and total displacement at concentrations of 10(-7), 10(-6), and 10(-5) M. Growth hormone did not displace [3H]CsA in similar experiments. CsA also did not alter the binding of a beta-receptor antagonist to MNC, again suggesting that CsA was specific in its antagonism of PRL binding. A CsA analog with no immunosuppressive action, cyclosporin H, did not alter PRL binding to MNC. Furthermore, PRL receptors were demonstrated on four cell lines of human and mouse origin. Finally, PRL receptors were identified on purified populations of T and B lymphocytes isolated from human spleens, and CsA again inhibited PRL binding at concentrations of 10(-7) and 10(-6) M. The presence of PRL receptors on T and B lymphocytes suggests that PRL may be involved in the regulation of humoral and cell-mediated immunity, and that one effect of CsA on immune function may be its ability to inhibit the effects of PRL action on these lymphocytes.

Animals↗
PubMed1984

Prolactin receptors on human lymphocytes and their modulation by cyclosporine.

Prolactin receptors have been identified for the first time on human peripheral blood lymphocytes. These receptors are present on T- and B-cells as well as monocytes. The specific binding of [125I]prolactin to these cells can be selectively enhanced at certain concentrations and blocked by higher concentrations of cyclosporine , a known immunosuppressive agent which inhibits the mitogenesis of T-cells. Prolactin also induces ornithine decarboxylase, a key growth regulatory enzyme, in lymphocytes. Therefore, we suggest that the lymphocyte prolactin receptor may be involved in regulating lymphocyte function, and that one of the actions of cyclosporine is to block this rather ubiquitously occurring receptor.

B-Lymphocytes↗
PubMed1984

Rapid elevation of rat serum prolactin concentration by cyclosporine, a novel immunosuppressive drug.

Within one hr of the administration of cyclosporine to rats, there was a 4-fold elevation in the serum prolactin concentration. Doses of 0.12, 1.2, and 12 micrograms/100 g body weight cyclosporine significantly elevated the serum prolactin level. Higher doses, 120 or 1200 micrograms/100 g body weight cyclosporine resulted in small but insignificant elevations of the serum prolactin concentration. Bromocriptine, a dopamine agonist which inhibits prolactin release from the anterior pituitary, completely blocked the elevation in serum prolactin in response to cyclosporine alone. These data suggest that the ability of cyclosporine to suppress immune function may involve its ability to rapidly produce hyperprolactinemia.

Animals↗
PubMed1984

Cyclosporine inhibits prolactin induction of ornithine decarboxylase in rat tissues.

Cyclosporine (CyA), formerly cyclosporin A, significantly inhibited the ability of prolactin (PRL) to elevate ornithine decarboxylase (ODC) activity in a variety of rat tissues. Administration of PRL to hypophysectomized rats also resulted in an induction of ODC activity which was inhibited markedly in all tissues studied in the presence of CyA. Transglutaminase ( TGase ) activity was not affected in any significant manner by PRL or CyA in most tissues studied. However, it was elevated in the adrenal by 10(-8) M PRL. Bromocryptine, which selectively antagonizes pituitary PRL release, decreased the kidney ODC basal levels to 30% of vehicle control and serum PRL level to 4.3 +/- 1.4 compared to 28 +/- 10 in controls, suggestive of PRL maintenance of steady-state ODC activity in the kidney. CyA administration did not affect the action of glucagon, a known cyclic AMP-mediated hormone, or 8-bromo-cyclic AMP on kidney ODC activity. The elevation of rat kidney ODC activity by dexamethasone and triiodothyronine (T3), compounds which elevated serum prolactin levels in all cases, was also blocked by administration of CyA. Epidermal growth factor (EGF), which did not induce rat kidney ODC activity by itself, was capable of producing a small increment in ODC activity in the presence of CyA. The marked effect of CyA to selectively block ODC induction by PRL may be due to the ability of CyA to interact with receptor-required phospholipids in membranes and thus to antagonize hormone-receptor interaction.

Acyltransferases↗
PubMed1984

Urinary polyamine levels are markers of altered T lymphocyte proliferation/loss and rejection in heart transplant patients.

The studies of urinary polyamine excretion in heart transplant patients reported in this article indicate that (1) total urinary polyamine excretion is increased one to three days before a biopsy-proved rejection in conventionally treated patients, (2) the acetylputrescine to N1-acetylspermidine ratio becomes elevated before rejection in cyclosporine-treated patients, and (3) the response to elevated ATG therapy during rejection can be evaluated by monitoring urinary polyamine concentrations. We conclude that daily monitoring of urinary polyamine levels may provide a noninvasive biochemical marker that precedes rejection and which parallels the extent of T lymphocyte suppression during the course of immunosuppressive drug therapy.

Biopsy, Needle↗
PubMed1983

Diuresis with continuous infusion of furosemide after cardiac surgery.

We prospectively evaluated the diuretic effect of furosemide administered by bolus injection and by continuous infusion in 18 cardiac surgery patients. Nine patients were randomly assigned to receive 0.3 mg/kg of furosemide as a bolus injection at time 0 and again 6 hours later (nine patients) or 0.05 mg/kg per hour of furosemide as a constant infusion for 12 hours (nine patients). There were no significant differences between groups with respect to age, weight, creatinine clearance, changes in serum sodium and potassium levels, total urinary concentrations of sodium and potassium, or total urine volume for 12 hours. Diuresis during continuous infusion of furosemide was less variable from hour to hour than after bolus injection of furosemide and was sustained throughout the infusion period. Although the continuous infusion of furosemide will not provide the rapid and vigorous diuresis that is necessary in some clinical situations, it may be useful whenever a gentle, sustained diuresis is desired.

Cardiac Surgical Procedures↗
PubMed1983

The interrelationship of factors controlling cardiac output.

Our understanding of the mechanics of circulation may be broadened by testing old and new concepts on a new hydraulic model made possible by a unique pump which resulted from the evolution of open heart surgical equipment. Findings in human physiology which have corollaries in the model can be analyzed more easily in the model, with the resulting conclusions transferable with reasonable validity. Factors thought to control cardiac output were tested. The results indicate that there are two separate and distinct sets of control factors, with only one set being operative at a time. It is the set that is potentially limiting cardiac output the most that is the determinant at any time. Past paradoxes in our perception of human circulatory physiology are accommodated by the resulting concept.

Cardiac Output↗
PubMed1982

A model of delayed aortic coarctation employing arterial and venous catheters for chronic blood sampling in conscious dogs.

We have developed a reproducible model of cardiac hypertrophy in conscious, unrestrained dogs after recovery from surgical trauma. The model has many potential applications due to the availability of non-stressful blood sampling from four arterial and/or venous vascular locations. Samples of blood for biochemical or pharmacological measurements were obtained from the carotid and femoral arteries as well as the pulmonary artery and inferior vena cava. Left ventricular hypertrophy up to 128% of the non-operated control animals was produced at 96 h post-intraluminal aortic coarctation. Inflation of a balloon in the descending aorta increased outflow resistance and resulted in hypertrophy. Hemodynamic parameters of cardiac function were obtained via a Swan-Ganz cardiac output catheter located permanently in the pulmonary artery. Complications observed in the dog model were minimal and mortality did not occur during the experimental period. This animal model employing multiple implanted catheters for blood sampling plus the ability to impose aortic coarctation in the unrestrained animal provides a flexible model system for biochemical and pharmacological research.

Animals↗
PubMed1982

beta 2-Adrenoceptors regulate induction of myocardial ornithine decarboxylase in mice in vivo.

The pharmacological characteristics of the myocardial adrenoceptor of the mouse have been examined during embryogenesis by measuring ornithine decarboxylase (ODC, EC 4.1.1.17) induction. 2 A four fold elevation of ODC activity was observed after isoprenaline (10 mg/kg, s.c.), and enzyme activity was increased two to three fold following adrenaline (1 mg/kg, s.c.) or terbutaline given by direct injection to the foetus (10 microgram/500 mg). 3 Pretreatment with the beta-adrenoceptor antagonist, propranolol (10 mg/kg), totally blocked the increase in ODC activity. 4 Elevation of myocardial ODC activity was not inhibited by metoprolol, a relatively specific beta-adrenoceptor antagonist, at a dose of 10 mg/kg. 5 Since the increase in ODC activity was blocked by a beta-adrenoceptor antagonist (propranolol) and enzyme activity was stimulated by terbutaline, a beta 2-agonist, we conclude that beta 2-adrenoceptors are selectively coupled to the regulation of murine cardiac ODC activity following catecholamine stimulation.

Adrenergic beta-Agonists↗